bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition
Authors: Mignogna Maria Lidia , Giannandrea Maila , Gurgone Antonia , Fanelli Francesca , Raimondi Francesco , Mapelli Lisa , Bassani Silvia , Fang Huaqiang , Van Anken Eelco , Alessio Massimo , Passafaro Maria , Gatti Silvia , Esteban José A. , Huganir Richard , D’Adamo Patrizia 
Published: March 2015

AbstractRAB39B is a member of the RAB family of small GTPases that controls intracellular vesicular trafficking in a compartment-specific manner. Mutations in the RAB39B gene cause intellectual disability comorbid with autism spectrum disorder and epilepsy, but the impact of RAB39B loss of function on synaptic activity is largely unexplained. Here we show that protein interacting with C-kinase 1 (PICK1) is a downstream effector of GTP-bound RAB39B and that RAB39B-PICK1 controls trafficking from the endoplasmic reticulum to the Golgi and, hence, surface expression of GluA2, a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). The role of AMPARs in synaptic transmission varies depending on the combination of subunits (GluA1, GluA2 and GluA3) they incorporate. RAB39B downregulation in mouse hippocampal neurons skews AMPAR composition towards non GluA2-containing Ca2+-permeable forms and thereby alters synaptic activity, specifically in hippocampal neurons. We posit that the resulting alteration in synaptic function underlies cognitive dysfunction in RAB39B-related disorders.
RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling
Authors: Patel Jyoti , McNeill Eileen , Douglas Gillian , Hale Ashley B. , de Bono Joseph , Lee Regent , Iqbal Asif J. , Regan-Komito Daniel , Stylianou Elena , Greaves David R. , Channon Keith M. 
Published: March 2015

AbstractChemokine signalling drives monocyte recruitment in atherosclerosis and aortic aneurysms. The mechanisms that lead to retention and accumulation of macrophages in the vascular wall remain unclear. Regulator of G-Protein Signalling-1 (RGS1) deactivates G-protein signalling, reducing the response to sustained chemokine stimulation. Here we show that Rgs1 is upregulated in atherosclerotic plaque and aortic aneurysms. Rgs1 reduces macrophage chemotaxis and desensitizes chemokine receptor signalling. In early atherosclerotic lesions, Rgs1 regulates macrophage accumulation and is required for the formation and rupture of Angiotensin II-induced aortic aneurysms, through effects on leukocyte retention. Collectively, these data reveal a role for Rgs1 in leukocyte trafficking and vascular inflammation and identify Rgs1, and inhibition of chemokine receptor signalling as potential therapeutic targets in vascular disease.
Allometry and growth of eight tree taxa in United Kingdom woodlands
Authors: Evans Matthew R , Moustakas Aristides , Carey Gregory , Malhi Yadvinder , Butt Nathalie , Benham Sue , Pallett Denise , Schäfer Stefanie 
Published: March 2015

AbstractAs part of a project to develop predictive ecosystem models of United Kingdom woodlands we have collated data from two United Kingdom woodlands - Wytham Woods and Alice Holt. Here we present data from 582 individual trees of eight taxa in the form of summary variables relating to the allometric relationships between trunk diameter, height, crown height, crown radius and trunk radial growth rate to the tree’s light environment and diameter at breast height. In addition the raw data files containing the variables from which the summary data were obtained. Large sample sizes with longitudinal data spanning 22 years make these datasets useful for future studies concerned with the way trees change in size and shape over their life-span.
Network-based proteomic approaches reveal the neurodegenerative, neuroprotective and pain-related mechanisms involved after retrograde axonal damage
Authors: Casas Caty , Isus Laura , Herrando-Grabulosa Mireia , Mancuso Francesco M. , Borrás Eva , Sabidó Eduardo , Forés Joaquim , Aloy Patrick 
Published: March 2015

AbstractNeurodegenerative processes are preceded by neuronal dysfunction and synaptic disconnection. Disconnection between spinal motoneuron (MN) soma and synaptic target leads either to a retrograde degenerative process or to a regenerative reaction, depending injury proximity among other factors. Distinguished key events associated with one or other processes may give some clues towards new therapeutical approaches based on boosting endogenous neuroprotective mechanisms. Root mechanical traction leads to retrograde MN degeneration, but share common initial molecular mechanisms with a regenerative process triggered by distal axotomy and suture. By 7 days post-injury, key molecular events starts to diverge and sign apart each destiny. We used comparative unbiased proteomics to define these signatures, coupled to a novel network-based analysis to get biological meaning. The procedure implicated the previous generation of combined topological information from manual curated 19 associated biological processes to be contrasted with the proteomic list using gene enrichment analysis tools. The novel and unexpected results suggested that motoneurodegeneration is better explained mainly by the concomitant triggering of anoikis, anti-apoptotic and neuropathic-pain related programs. In contrast, the endogenous neuroprotective mechanisms engaged after distal axotomy included specifically rather anti-anoikis and selective autophagy. Validated protein-nodes and processes are highlighted across discussion.
Detection of BRAF mutation in Chinese tumor patients using a highly sensitive antibody immunohistochemistry assay
Authors: Qiu Tian , Lu Haizhen , Guo Lei , Huang Wenting , Ling Yun , Shan Ling , Li Wenbin , Ying Jianming , Lv Ning 
Published: March 2015

AbstractBRAF mutations can be found in various solid tumors. But accurate and reliable screening for BRAF mutation that is compatible for clinical application is not yet available. In this study, we used an automated immunohistochemistry (IHC) staining coupled with mouse monoclonal anti-BRAF V600E (VE1) primary antibody to screen the BRAF V600E mutation in 779 tumor cases, including 611 colorectal carcinomas (CRC), 127 papillary thyroid carcinomas (PTC) and 41 malignant melanomas. Among the 779 cases, 150 cases were positive for BRAF (V600E) staining, including 38 (of 611, 6%) CRCs, 102 (of 127, 80%) PTCs and 10 (of 41, 24%) malignant melanomas. Sanger sequencing and real-time PCR confirmed the sensitivity and specificity of IHC staining for the V600E mutation are 100% and 99%, respectively. Therefore, our study demonstrates that the fully automated IHC is a reliable tool to determine BRAF mutation status in CRC, PTC and melanoma and can be used for routine clinical screen.
Increased plant productivity and decreased microbial respiratory C loss by plant growth-promoting rhizobacteria under elevated CO2
Authors: Nie Ming , Bell Colin , Wallenstein Matthew D. , Pendall Elise 
Published: March 2015

AbstractIncreased plant productivity and decreased microbial respiratory C loss can potentially mitigate increasing atmospheric CO2, but we currently lack effective means to achieve these goals. Soil microbes may play critical roles in mediating plant productivity and soil C/N dynamics under future climate scenarios of elevated CO2(eCO2) through optimizing functioning of the root-soil interface. By using a labeling technique with13C and15N, we examined the effects of plant growth-promotingPseudomonas fluorescenson C and N cycling in the rhizosphere of a common grass species under eCO2. These microbial inoculants were shown to increase plant productivity. Although strong competition for N between the plant and soil microbes was observed, the plant can increase its capacity to store more biomass C per unit of N underP. fluorescensaddition. Unlike eCO2effects,P. fluorescensinoculants did not change mass-specific microbial respiration and accelerate soil decomposition related to N cycling, suggesting these microbial inoculants mitigated positive feedbacks of soil microbial decomposition to eCO2. The potential to mitigate climate change by optimizing soil microbial functioning by plant growth-promotingPseudomonas fluorescensis a prospect for ecosystem management.
Isotopic Resonance Hypothesis: Experimental Verification by Escherichia coli Growth Measurements
Authors: Xie Xueshu , Zubarev Roman A. 
Published: March 2015

AbstractIsotopic composition of reactants affects the rates of chemical and biochemical reactions. As a rule, enrichment of heavy stable isotopes leads to progressively slower reactions. But the recent isotopic resonance hypothesis suggests that the dependence of the reaction rate upon the enrichment degree is not monotonous. Instead, at some “resonance” isotopic compositions, the kinetics increases, while at “off-resonance” compositions the same reactions progress slower. To test the predictions of this hypothesis for the elements C, H, N and O, we designed a precise (standard error ±0.05%) experiment that measures the parameters of bacterial growth in minimal media with varying isotopic composition. A number of predicted resonance conditions were tested, with significant enhancements in kinetics discovered at these conditions. The combined statistics extremely strongly supports the validity of the isotopic resonance phenomenon (p ≪ 10−15). This phenomenon has numerous implications for the origin of life studies and astrobiology and possible applications in agriculture, biotechnology, medicine, chemistry and other areas.
Sensitization of Gram-negative bacteria to rifampin and OAK combinations
Authors: Jammal Joanna , Zaknoon Fadia , Kaneti Galoz , Goldberg Keren , Mor Amram 
Published: March 2015

AbstractWhile individually inefficient against Gram-negative bacteria, in-vitro combinations of rifampin and OAK were mutually synergistic since sub-minimal inhibitory concentrations of one compound have potentiated the other by 2–4 orders of magnitude. Synergy persisted in-vivo as single-dose systemic treatment of Klebsiella infected mice resulted in 10–20% versus 60% survival, respectively accomplished by individual and combined compounds. This outcome was achieved without drug formulation, rather, pharmacokinetic considerations have inspired the therapeutic regimen.
Macaques Exhibit a Naturally-Occurring Depression Similar to Humans
Authors: Xu Fan , Wu Qingyuan , Xie Liang , Gong Wei , Zhang Jianguo , Zheng Peng , Zhou Qinmin , Ji Yongjia , Wang Tao , Li Xin , Fang Liang , Li Qi , Yang Deyu , Li Juan , Melgiri Narayan D. , Shively Carol , Xie Peng 
Published: March 2015

AbstractRodent models have dominated preclinical investigations into the mechanisms of depression. However, these models-which rely on subjecting individual rodents to physical stressors - do not realistically resemble the etiopathological development of depression, which occurs naturally in a social context. A non-human primate model that better reflects the social ethological aspects of depression would be more advantageous to investigating pathophysiological mechanisms and developing antidepressant therapeutics. Here, we describe and model a naturally-occurring depressive state in a non-human primate species, the cynomolgus monkey (Macaca fascicularis), in a realistic social ethological context and associate the depressed behavioral phenotype with significant serum metabolic perturbations. One to two subjects per stable social colony (17–22 subjects) manifested a depressive phenotype that may be attributed to psychosocial stress. In accordance with rodent and human studies, the serum metabolic phenotype of depressed and healthy subjects significantly differed, supporting the model's face validity. However, application of the fast-acting antidepressant ketamine failed to demonstrate predictive validity. This study proposes a non-human primate depression model in a realistic social ethological context that can better approximate the psychosocial stressors underlying depression.
IP-10 measured by Dry Plasma Spots as biomarker for therapy responses in Mycobacterium Tuberculosis infection
Authors: Tonby Kristian , Ruhwald Morten , Kvale Dag , Dyrhol-Riise Anne Ma 
Published: March 2015

AbstractTuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapid TB diagnosis and ensure treatment initiation and cure are needed, especially in regions with high prevalence of multi-drug resistant TB. Soluble interferon gamma inducible protein 10 (IP-10) analyzed from dry plasma spots (DPS) has potential as an immunodiagnostic marker in TB infection. We analyzed IP-10 levels in plasma directly and extracted from DPS in parallel by ELISA from 34 clinically well characterized patients with TB disease before and throughout 24 weeks of effective anti-TB chemotherapy. We detected a significant decline of IP-10 levels in both plasma and DPS already after two weeks of therapy with good correlation between the tests. This was observed both in pulmonary and extrapulmonary TB. In conclusion, plasma IP-10 may serve as an early biomarker for anti-TB chemotherapy responses and the IP-10 DPS method has potential to be developed into a point-of care test for use in resource-limited settings. Further studies must be performed to validate the use of IP-10 DPS in TB high endemic countries.
Hydrogen-Bonding-Supported Self-Healing Antifogging Thin Films
Authors: Zhang Xiaojie , He Junhui 
Published: March 2015

AbstractInspired by the repair of DNA through efficient reformation of hydrogen bonds (H-bonds), herein we report a facile one-step approach to construction of self-healing antifogging thin films on the basis of partly cross-linked poly(vinyl alcohol)(PVA) and poly(acrylic acid)(PAA). By designing the molar ratio of hydroxyl groups to carboxyl groups, the cross-linked polymer thin films maintain abundant free hydroxyl groups to present excellent antifogging property, which is derived from the hydrophilicity and hygroscopicity of the thin films. The thin films showed smart intrinsic self-healing characteristics towards wounds caused by external forces, which is attributed to sufficient free hydroxyl groups at the scratched interfaces to reform H-bonds across the interfaces and a sufficient chain mobility that is indispensable for chain diffusion across the interfaces and hydroxyl groups association to form H-bonds. No synthetic surfaces reported so far possess all the unique characteristics of the polymer thin films: intrinsic self-healing, long-term antifogging, excellent mechanical property, high transmittance and large-scale feasibility.
Structure based aggregation studies reveal the presence of helix-rich intermediate during α-Synuclein aggregation
Authors: Ghosh Dhiman , Singh Pradeep K. , Sahay Shruti , Jha Narendra Nath , Jacob Reeba S. , Sen Shamik , Kumar Ashutosh , Riek Roland , Maji Samir K. 
Published: March 2015

AbstractMechanistic understanding of nucleation dependent polymerization by α-synuclein (α-Syn) into toxic oligomers and amyloids is important for the drug development against Parkinson's disease. However the structural and morphological characterization during nucleation and subsequent fibrillation process of α-Syn is not clearly understood. Using a variety of complementary biophysical techniques monitoring entire pathway of nine different synucleins, we found that transition of unstructured conformation into β-sheet rich fibril formation involves helix-rich intermediates. These intermediates are common for all aggregating synucleins, contain high solvent-exposed hydrophobic surfaces, are cytotoxic to SHSY-5Y cells and accelerate α-Syn aggregation efficiently. A multidimensional NMR study characterizing the intermediate accompanied with site-specific fluorescence study suggests that the N-terminal and central portions mainly participate in the helix-rich intermediate formation while the C-terminus remained in an extended conformation. However, significant conformational transitions occur at the middle and at the C-terminus during helix to β-sheet transition as evident from Trp fluorescence study. Since partial helix-rich intermediates were also observed for other amyloidogenic proteins such as Aβ and IAPP, we hypothesize that this class of intermediates may be one of the important intermediates for amyloid formation pathway by many natively unstructured protein/peptides and represent a potential target for drug development against amyloid diseases.
Vortex Chain in a Resonantly Pumped Polariton Superfluid
Authors: Boulier T. , Terças H. , Solnyshkov D. D. , Glorieux Q. , Giacobino E. , Malpuech G. , Bramati A. 
Published: March 2015

AbstractExciton-polaritons are light-matter mixed states interacting via their exciton fraction. They can be excited, manipulated and detected using all the versatile techniques of modern optics. An exciton-polariton gas is therefore a unique platform to study out-of-equilibrium interacting quantum fluids. In this work, we report the formation of a ring-shaped array of same sign vortices after injection of angular momentum in a polariton superfluid. The angular momentum is injected by a ℓ = 8 Laguerre-Gauss beam. In the linear regime, a spiral interference pattern containing phase defects is visible. In the nonlinear (superfluid) regime, the interference disappears and eight vortices appear, minimizing the energy while conserving the quantized angular momentum. The radial position of the vortices evolves in the region between the two pumps as a function of the density. Hydrodynamic instabilities resulting in the spontaneous nucleation of vortex-antivortex pairs when the system size is sufficiently large confirm that the vortices are not constrained by interference when nonlinearities dominate the system.
Differentiation of human induced pluripotent stem cells to mature functional Purkinje neurons
Authors: Wang Shuyan , Wang Bin , Pan Na , Fu Linlin , Wang Chaodong , Song Gongru , An Jing , Liu Zhongfeng , Zhu Wanwan , Guan Yunqian , Xu Zhi-Qing David , Chan Piu , Chen Zhiguo , Zhang Y. Alex 
Published: March 2015

AbstractIt remains a challenge to differentiate human induced pluripotent stem cells (iPSCs) or embryonic stem (ES) cells to Purkinje cells. In this study, we derived iPSCs from human fibroblasts and directed the specification of iPSCs first to Purkinje progenitors, by adding Fgf2 and insulin to the embryoid bodies (EBs) in a time-sensitive manner, which activates the endogenous production of Wnt1 and Fgf8 from EBs that further patterned the cells towards a midbrain-hindbrain-boundary tissue identity. Neph3-positive human Purkinje progenitors were sorted out by using flow cytometry and cultured either alone or with granule cell precursors, in a 2-dimensional or 3-dimensional environment. However, Purkinje progenitors failed to mature further under above conditions. By co-culturing human Purkinje progenitors with rat cerebellar slices, we observed mature Purkinje-like cells with right morphology and marker expression patterns, which yet showed no appropriate membrane properties. Co-culture with human fetal cerebellar slices drove the progenitors to not only morphologically correct but also electrophysiologically functional Purkinje neurons. Neph3-posotive human cells could also survive transplantation into the cerebellum of newborn immunodeficient mice and differentiate to L7- and Calbindin-positive neurons. Obtaining mature human Purkinje cells in vitro has significant implications in studying the mechanisms of spinocerebellar ataxias and other cerebellar diseases.
Whole-exome sequencing identifies OR2W3 mutation as a cause of autosomal dominant retinitis pigmentosa
Authors: Ma Xiangyu , Guan Liping , Wu Wei , Zhang Yao , Zheng Wei , Gao Yu-Tang , Long Jirong , Wu Na , Wu Long , Xiang Ying , Xu Bin , Shen Miaozhong , Chen Yanhua , Wang Yuewen , Yin Ye , Li Yingrui , Xu Haiwei , Xu Xun , Li Yafei 
Published: March 2015

AbstractRetinitis pigmentosa (RP), a heterogeneous group of inherited ocular diseases, is a genetic condition that causes retinal degeneration and eventual vision loss. Though some genes have been identified to be associated with RP, still a large part of the clinical cases could not be explained. Here we reported a four-generation Chinese family with RP, during which 6 from 9 members of the second generation affected the disease. To identify the genetic defect in this family, whole-exome sequencing together with validation analysis by Sanger sequencing were performed to find possible pathogenic mutations. After a pipeline of database filtering, including public databases and in-house databases, a novel missense mutation, c. 424 C > T transition (p.R142W) in OR2W3 gene, was identified as a potentially causative mutation for autosomal dominant RP. The mutation co-segregated with the disease phenotype over four generations. This mutation was validated in another independent three-generation family. RT-PCR analysis also identified that OR2W3 gene was expressed in HESC-RPE cell line. The results will not only enhance our current understanding of the genetic basis of RP, but also provide helpful clues for designing future studies to further investigate genetic factors for familial RP.
The Secretion Process of Liquid Silk with Nanopillar Structures from Stenopsyche marmorata (Trichoptera: Stenopsychidae)
Authors: Hatano Tomohiro , Nagashima Takayuki 
Published: March 2015

AbstractStenopsyche marmorata larvae spin underwater adhesive silk for constructing nests and capture nets. The silk can be divided into fiber and adhesive regions, according to their function. The silk fiber region has a two-layer structure: a core layer situated at the center of the fiber and S. marmorata fibroin, the major component of the silk. In the anterior part of the anterior silk gland, the morphological characteristics suggest that the silk insolubilization leading to fibrillation occurs by luminal pH neutralization. The adhesive region is composed of three layers: the outermost (OM), B and C layers. On the B layer, coated with the OM layer, numerous nano-order pillar structures (nanopillar structures) are located at regular intervals. A nanopillar structure is approximately 40 nm in diameter and 125 nm in length. The precursor materials of the nanopillar structure are electron-dense globules of approximately 25 nm in diameter that are located in the A layer of the lumen of the middle silk gland. The precursor globules autonomously connect to one another on the B layer when the liquid silk is transported to the lumen of the bulbous region. The nanopillar structures probably contribute to the strong underwater adhesion of S. marmorata silk.
Effect of Electric Field Gradient on Sub-nanometer Spatial Resolution of Tip-enhanced Raman Spectroscopy
Authors: Meng Lingyan , Yang Zhilin , Chen Jianing , Sun Mengtao 
Published: March 2015

AbstractTip-enhanced Raman spectroscopy (TERS) with sub-nanometer spatial resolution has been recently demonstrated experimentally. However, the physical mechanism underlying is still under discussion. Here we theoretically investigate the electric field gradient of a coupled tip-substrate system. Our calculations suggest that the ultra-high spatial resolution of TERS can be partially attributed to the electric field gradient effect owning to its tighter spatial confinement and sensitivity to the infrared (IR)-active of molecules. Particularly, in the case of TERS of flat-lying H2TBPP molecules,we find the electric field gradient enhancement is the dominating factor for the high spatial resolution, which qualitatively coincides with previous experimental report. Our theoretical study offers a new paradigm for understanding the mechanisms of the ultra-high spatial resolution demonstrated in tip-enhanced spectroscopy which is of importance but neglected.