bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fruit and seed traits of the elephant-dispersed African savanna plantBalanites maughamii
Authors: Midgley J. J. , Kruger L. M. , Viljoen S. , Bijl A. , Steenhuisen S.-L. 
Published: August 2015

Abstract:Balanites maughamiiappears to be an obligate elephant-dispersed species. Its fruits are strongly scented and produce a large range of volatiles, particularly aliphatic acids such as hexanoic and isovaleric acid. The seed coat can resist a compression force of >1.5 kN. Seeds removed from the seed coat, and those from compressed seeds or from elephant dung, have better germination than seeds enclosed by undamaged seed-coats, which largely failed to germinate over a 2-mo period. Mastication by elephants may be necessary to split the seed coat to allow germination and the germinant to emerge from the seed coat. We identify four traits of elephant-dispersed fruits; they are dull-coloured, presented on the ground, strongly scented and have exceptionally strong seed coats.
Clarifying the anatomy of hearts with concordant ventriculo-arterial connections but abnormally related arterial trunks
Authors: Gupta Saurabh K. , Ramakrishnan Sivasubramanian , Gulati Gurpreet S. , Henry G. William , Spicer Diane E. , Backer Carl L. , Anderson Robert H. 
Published: August 2015

AbstractHearts in which the arterial trunks arise from the morphologically appropriate ventricles, but in a parallel manner, rather than the usual spiralling arrangement, have long fascinated anatomists. These rare entities, for quite some time, were considered embryological impossibilities, but ongoing experience has shown that they can be found in various segmental combinations. Problems still exist about how best to describe them, as the different variants are often described with esoteric terms, such as anatomically corrected malposition or isolated ventricular inversion. In this review, based on our combined clinical and morphological experience, we demonstrate that the essential feature of all hearts described in this manner is a parallel arrangement of the arterial trunks as they exit from the ventricular mass. We show that the relationship of the arterial roots needs to be described in terms of the underlying ventricular topology, rather than according to the arrangement of the atrial chambers. We then discuss the importance of determining atrial arrangement on the basis of the morphology of the appendages, following the precepts as set out in the so-called “morphological method” and distinguished according to the extent of the pectinate muscles relative to the atrioventricular junctions as opposed to basing diagnosis on the venoatrial connections. We show that, when approached in this manner, the various combinations can be readily diagnosed in the clinical setting and described in straightforward way.
HMGB1 in the pathogenesis of ultraviolet-induced ocular surface inflammation
Authors: Han S J , Min H J , Yoon S C , Ko E A , Park S J , Yoon J-H , Shin J-S , Seo K Y 
Published: August 2015

AbstractHigh-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein as well as a crucial cytokine that regulates inflammation. This study demonstrated that secretion of HMGB1 due to ultraviolet (UV) radiation inducing ocular surface inflammation-mediated reactive oxygen species (ROS) production. After treating conjunctival epithelial cells with UV radiation, HMGB1 was translocated from the nucleus to the cytoplasm and then eventually to the extracellular space. HMGB1 played a crucial role in UV-induced conjunctival neutrophil infiltration, which subsided when mice were pretreated with the HMGB1 inhibitors soluble receptor for advanced glycation endproducts (sRAGEs) and HMGB1 A box protein. In case of using ROS quencher, there was decrease in UV-induced HMGB1 secretion in conjunctival epithelial cells and mice. Considering that UV-induced chronic inflammation causes ocular surface change as pterygium, we have confirmed high HMGB1 translocation and ROS expression in human pterygium. Our findings therefore revealed a previously unknown mechanism of UV-induced ocular inflammation related to ROS and HMGB1 suggesting a new medical therapeutic target.
The novel protective role of P27 in MLN4924-treated gastric cancer cells
Authors: Zhang Q , Hou D , Luo Z , Chen P , Lv B , Wu L , Ma Y , Chu Y , Liu H , Liu F , Yu S , Zhang J , Yang D , Liu J 
Published: August 2015

AbstractThe tumor-suppressor gene cyclin-dependent kinase inhibitor 1B (P27) is downregulated in gastric cancer cells mainly through proteolytic degradation mediated by the SKP-Cullin1-F-Box (SCF) complex. But the correlation between its downregulation and gastric cancer prognosis still remains indefinite. MLN4924, an anti-tumor agent, which suppresses the SCF complex by inhibiting Cullin1 neddylation, emerges as a promising tool to elucidate its functions in gastric cancer cells. In this study, MLN4924 induced significant growth inhibition of gastric cancer cells in a dose-dependent manner, along with the simultaneous accumulation of P27 and cell cycle abnormalities such as G2/M arrest. Importantly, we found that P27 silencing in MLN4924-treated cells resulted in an enhancement of growth inhibition both in vitro and in vivo. Mechanism analysis revealed the antagonism effects of antioxidants to this excess apoptosis, suggesting reactive oxygen species (ROS) overproduction especially in the mitochondria was the principal cause of the augmentation. Moreover, the robust ROS attacked the mitochondria to initiate collapse of the mitochondrial membrane permeability and the exportation of apoptosis-inducing factor (AIF), IAP-binding mitochondrial protein (SMAC/DIABLO) and cytochrome c. Finally, we also found that P27 knockdown affected the expression profile of several critical BH3 family members to amplify the mitochondrial dysfunction and apoptosis. In summary, our findings unveiled a protective role of P27 by maintaining mitochondrial membrane permeability in MLN4924-treated gastric cancer cells, and therefore highlighted the potential combination of MLN4924 with P27 inhibition to improve its therapeutic efficacy.
CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells
Authors: Qiu X , Klausen C , Cheng J-C , Leung P C K 
Published: August 2015

AbstractOvarian high-grade serous carcinomas (HGSCs) and invasive low-grade serous carcinomas (LGSCs) are considered to be distinct entities. In particular, LGSCs are thought to arise from non-invasive serous borderline ovarian tumors (SBOTs) and show poor responsiveness to conventional chemotherapy. The pro-apoptotic effects of CD40 ligand (CD40L) have been demonstrated in HGSC, though the underlying mechanisms are not fully understood. Conversely, the therapeutic potential of the CD40L-CD40 system has yet to be evaluated in LGSC. We now show that CD40 protein is focally expressed on tumor cells in two of five primary LGSCs compared with no expression in eight primary SBOTs. Treatment with CD40L or agonistic CD40 antibody decreased the viability of LGSC-derived MPSC1 and VOA1312 cells, but not SBOT3.1 cells. Small interfering RNA (siRNA) targeting CD40 was used to show that it is required for these reductions in cell viability. CD40L treatment increased cleaved caspase-3 levels in MPSC1 cells though, surprisingly, neither pan-caspase inhibitor nor caspase-3 siRNA reversed or even attenuated CD40L-induced cell death. In addition, CD40-induced cell death was not affected by knockdown of the mitochondrial proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG). Interestingly, CD40L-induced cell death was blocked by necrostatin-1, an inhibitor of receptor-interacting protein 1 (RIP1), and attenuated by inhibitors of RIP3 (GSK’872) or MLKL (mixed lineage kinase domain-like; necrosulfonamide). Our results indicate that the upregulation of CD40 may be relatively common in LGSC and that CD40 activation induces RIP1-dependent, necroptosis-like cell death in LGSC cells.
Transglutaminase 2—a novel inhibitor of adipogenesis
Authors: Myneni V D , Melino G , Kaartinen M T 
Published: August 2015

AbstractDifferentiation of preadipocytes to lipid storing adipocytes involves extracellular signaling pathways, matrix remodeling and cytoskeletal changes. A number of factors have been implicated in maintaining the preadipocyte state and preventing their differentiation to adipocytes. We have previously reported that a multifunctional and protein crosslinking enzyme, transglutaminase 2 (TG2) is present in white adipose tissue. In this study, we have investigated TG2 function during adipocyte differentiation. We show that TG2 deficient mouse embryonic fibroblasts (Tgm2−/− MEFs) display increased and accelerated lipid accumulation due to increased expression of major adipogenic transcription factors, PPARγ and C/EBPα. Examination of Pref-1/Dlk1, an early negative regulator of adipogenesis, showed that the Pref-1/Dlk1 protein was completely absent in Tgm2−/− MEFs during early differentiation. Similarly, Tgm2−/− MEFs displayed defective canonical Wnt/β-catenin signaling with reduced β-catenin nuclear translocation. TG2 deficiency also resulted in reduced ROCK kinase activity, actin stress fiber formation and increased Akt phosphorylation in MEFs, but did not alter fibronectin matrix levels or solubility. TG2 protein levels were unaltered during adipogenic differentiation, and was found predominantly in the extracellular compartment of MEFs and mouse WAT. Addition of exogenous TG2 to Tgm2+/+ and Tgm2−/− MEFs significantly inhibited lipid accumulation, reduced expression of PPARγ and C/EBPα, promoted the nuclear accumulation of β-catenin, and recovered Pref-1/Dlk1 protein levels. Our study identifies TG2 as a novel negative regulator of adipogenesis.
Lipid-bilayer-assisted two-dimensional self-assembly of DNA origami nanostructures
Authors: Suzuki Yuki , Endo Masayuki , Sugiyama Hiroshi 
Published: August 2015

AbstractSelf-assembly is a ubiquitous approach to the design and fabrication of novel supermolecular architectures. Here we report a strategy termed ‘lipid-bilayer-assisted self-assembly’ that is used to assemble DNA origami nanostructures into two-dimensional lattices. DNA origami structures are electrostatically adsorbed onto a mica-supported zwitterionic lipid bilayer in the presence of divalent cations. We demonstrate that the bilayer-adsorbed origami units are mobile on the surface and self-assembled into large micrometre-sized lattices in their lateral dimensions. Using high-speed atomic force microscopy imaging, a variety of dynamic processes involved in the formation of the lattice, such as fusion, reorganization and defect filling, are successfully visualized. The surface modifiability of the assembled lattice is also demonstrated by in situ decoration with streptavidin molecules. Our approach provides a new strategy for preparing versatile scaffolds for nanofabrication and paves the way for organizing functional nanodevices in a micrometer space.
Optical control of NMDA receptors with a diffusible photoswitch
Authors: Laprell Laura , Repak Emilienne , Franckevicius Vilius , Hartrampf Felix , Terhag Jan , Hollmann Michael , Sumser Martin , Rebola Nelson , DiGregorio David A. , Trauner Dirk 
Published: August 2015

AbstractN-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity, learning and memory, and are implicated in various neuronal disorders. We synthesized a diffusible photochromic glutamate analogue, azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions as a photoswitchable agonist. ATG is inactive in its dark-adapted trans-isoform, but can be converted into its active cis-isoform using one-photon (near UV) or two-photon (740 nm) excitation. Irradiation with violet light photo-inactivates ATG within milliseconds, allowing agonist removal on the timescale of NMDAR deactivation. ATG is compatible with Ca2+ imaging and can be used to optically mimic synaptic coincidence detection protocols. Thus, ATG can be used like traditional caged glutamate compounds, but with the added advantages of NMDAR specificity, low antagonism of GABAR-mediated currents, and precise temporal control of agonist delivery.
PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus
Authors: Xu Daqian , Wang Zheng , Zhang Yuxue , Jiang Wei , Pan Yi , Song Bao-Liang , Chen Yan 
Published: August 2015

AbstractCholesterol biosynthesis is regulated by transcription factors SREBPs and their escort protein Scap. On sterol depletion, Scap/SREBP complex is transported from endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. Under cholesterol sufficient condition, Insigs act as anchor proteins to retain Scap/SREBP in the ER. However, the anchor protein of Scap/SREBP in the Golgi is unknown. Here we report that a Golgi-localized membrane protein progestin and adipoQ receptors 3 (PAQR3) interacts with Scap and SREBP and tethers them to the Golgi. PAQR3 promotes Scap/SREBP complex formation, potentiates SREBP processing and enhances lipid synthesis. The mutually exclusive interaction between Scap and PAQR3 or Insig-1 is regulated by cholesterol level. PAQR3 knockdown in liver blunts SREBP pathway and decreases hepatic cholesterol content. Disrupting the interaction of PAQR3 with Scap/SREBP by a synthetic peptide inhibits SREBP processing and activation. Thus, PAQR3 regulates cholesterol homeostasis by anchoring Scap/SREBP to the Golgi and disruption of such function reduces cholesterol biosynthesis.
Fracture Mechanism and Toughness Optimization of Macroscopic Thick Graphene Oxide Film
Authors: Ye Shibing , Chen Bin , Feng Jiachun 
Published: August 2015

AbstractCombined high strength and toughness of film materials are rather important for their industrial applications. As a new class of films, graphene oxide films (GOFs) attract intense attention in many applications but are frequently divergent, inconsistent and poorly reproducible in their mechanical properties. In this study, we first demonstrate that different chemical compositions and assembly structures probably are responsible for the difference in elongations between cast GOFs and filtration GOFs. Comprehensive analysis of the morphologies and mechanical properties indicates that the enhanced elongation of the thick cast GOFs is mainly attributed to the presence of a unique skin-wrinkles-skin structure, which more easily forms in cast GOFs than in filtration counterparts. On the basis of this finding, we attempt to optimize the strength-toughness performance of the cast GOFs by adjusting their structures. With an appropriate thickness of 12.5 μm, the GOFs can achieve an ultrahigh toughness up to 4.37 MJ m−3, which is even comparable to the polymer-toughening graphene/GO-based paper-like materials. Such an optimization of the mechanical properties from the perspective of skin-wrinkles-skin structure appears to be a universal approach that could be extended to a variety of other film materials.
Overexpression Of Hepatocyte Nuclear Factor-1beta Predicting Poor Prognosis Is Associated With Biliary Phenotype In Patients With Hepatocellular Carcinoma
Authors: Yu Dan-Dan , Jing Ying-Ying , Guo Shi-Wei , Ye Fei , Lu Wen , Li Quan , Dong Yu-Long , Gao Lu , Yang Yu-Ting , Yang Yang , Wu Meng-Chao , Wei Li-Xin 
Published: August 2015

AbstractHepatocyte nuclear factor-1beta (HNF-1B) is involved in the hepatobiliary specification of hepatoblasts to cholangiocytes during liver development and is strongly expressed throughout adult biliary epithelium. The aim of this study was to examine the expression of HNF-1B in different pathologic subtypes of primary liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (ICC) and the relationship between HNF-1B expression, clinicopathological features and prognosis. We retrospectively investigated 2 cohorts of patients, including 183 HCCs and 69 ICCs. The expression of HNF-1B was examined by immunohistochemistry. We found that HNF-1B expression was associated with pathological subtype of primary tumor and HNF-1B expression in HCC tissue may be associated with the change of phenotype on recurrence. The HNF-1B expression was positively correlated with biliary/HPC (hepatic progenitor cell) markers expression. Further, multivariable analysis showed that HNF-1B expression was an independent prognostic factor for both overall survival and disease-free survival of HCC patients. However, no correlation between HNF-1B expression and survival was found in ICC patients. In summary, HCC with high HNF-1B expression displayed biliary phenotype and tended to show poorer prognosis. HNF-1B-positive malignant cells could be bipotential cells and give rise to both hepatocytic and cholangiocytic lineages during tumorigenesis.
An equation to estimate the difference between theoretically predicted and SDS PAGE-displayed molecular weights for an acidic peptide
Authors: Guan Yihong , Zhu Qinfang , Huang Delai , Zhao Shuyi , Jan Lo Li , Peng Jinrong 
Published: August 2015

AbstractThe molecular weight (MW) of a protein can be predicted based on its amino acids (AA) composition. However, in many cases a non-chemically modified protein shows an SDS PAGE-displayed MW larger than its predicted size. Some reports linked this fact to high content of acidic AA in the protein. However, the exact relationship between the acidic AA composition and the SDS PAGE-displayed MW is not established. Zebrafish nucleolar protein Def is composed of 753 AA and shows an SDS PAGE-displayed MW approximately 13 kDa larger than its predicted MW. The first 188 AA in Def is defined by a glutamate-rich region containing ~35.6% of acidic AA. In this report, we analyzed the relationship between the SDS PAGE-displayed MW of thirteen peptides derived from Def and the AA composition in each peptide. We found that the difference between the predicted and SDS PAGE-displayed MW showed a linear correlation with the percentage of acidic AA that fits the equation y = 276.5x − 31.33 (x represents the percentage of acidic AA, 11.4% ≤ x ≤ 51.1%; y represents the average ΔMW per AA). We demonstrated that this equation could be applied to predict the SDS PAGE-displayed MW for thirteen different natural acidic proteins.
A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation
Authors: Kleikers Pamela WM. , Hooijmans Carlijn , Göb Eva , Langhauser Friederike , Rewell Sarah SJ. , Radermacher Kim , Ritskes-Hoitinga Merel , Howells David W. , Kleinschnitz Christoph , HHW Schmidt Harald 
Published: August 2015

AbstractBiomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2-/y studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.
Decreased Na+ influx lowers hippocampal neuronal excitability in a mouse model of neonatal influenza infection
Authors: Park Hoyong , Eun Yu Ji , Kim Sungmin , Nahm Sang-Soep , Chung ChiHye 
Published: August 2015

AbstractInfluenza virus infection is one of common infectious diseases occurring worldwide. The human influenza virus can infect the central nervous system and cause brain dysfunctions affecting cognition and spatial memory. It has been previously shown that infection with the influenza viral protein within the hippocampus decreases Ca2+ influx and reduces excitatory postsynaptic currents. However, the neuronal properties of animals surviving neonatal infection have not been investigated. Using a mouse model of neonatal influenza infection, we performed thorough electrophysiological analyses of hippocampal neurotransmission. We found that animals surviving the infection exhibited reduced spontaneous transmission with no significant defects in evoked neurotransmission. Interestingly, the hippocampus of the infected group conducted synaptic transmission with less fidelity upon repeated stimulations and failed to generate action potentials faithfully upon step current injections primarily due to reduced Na+ influx. The reversal potential for the Na+ current was hyperpolarized and the activation of Na+ channels was slower in the infected group while the inactivation process was minimally disturbed. Taken together, our observations suggest that neonatally infected offsprings exhibit noticeable deficits at rest and severe failures when higher activity is required. This study provides insight into understanding the cellular mechanisms of influenza infection-associated functional changes in the brain.
Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting
Authors: Zilbermintz Leeor , Leonardi William , Jeong Sun-Young , Sjodt Megan , McComb Ryan , Ho Chi-Lee C. , Retterer Cary , Gharaibeh Dima , Zamani Rouzbeh , Soloveva Veronica , Bavari Sina , Levitin Anastasia , West Joel , Bradley Kenneth A. , Clubb Robert T. , Cohen Stanley N. , Gupta Vivek , Martchenko Mikhail 
Published: August 2015

AbstractA longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.
Selective Connexin43 Inhibition Prevents Isoproterenol-Induced Arrhythmias and Lethality in Muscular Dystrophy Mice
Authors: Gonzalez J. Patrick , Ramachandran Jayalakshmi , Xie Lai-Hua , Contreras Jorge E. , Fraidenraich Diego 
Published: August 2015

AbstractDuchenne muscular dystrophy (DMD) is caused by an X-linked mutation that leads to the absence of dystrophin, resulting in life-threatening arrhythmogenesis and associated heart failure. We targeted the gap junction protein connexin43 (Cx43) responsible for maintaining cardiac conduction. In mild mdx and severe mdx:utr mouse models of DMD and human DMD tissues, Cx43 was found to be pathologically mislocalized to lateral sides of cardiomyocytes. In addition, overall Cx43 protein levels were markedly increased in mouse and human DMD heart tissues examined. Electrocardiography on isoproterenol challenged mice showed that both models developed arrhythmias and died within 24 hours, while wild-type mice were free of pathology. Administering peptide mimetics to inhibit lateralized Cx43 function prior to challenge protected mdx mice from arrhythmogenesis and death, while mdx:utr mice displayed markedly improved ECG scores. These findings suggest that Cx43 lateralization contributes significantly to DMD arrhythmogenesis and that selective inhibition may provide substantial benefit.