bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer
Authors: Nilsson Maria , Adamo Hanibal , Bergh Anders , Halin Bergström Sofia 
Published: January 2016

AbstractLysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.
Glucose restriction induces transient G2 cell cycle arrest extending cellular chronological lifespan
Authors: Masuda Fumie , Ishii Mahiro , Mori Ayaka , Uehara Lisa , Yanagida Mitsuhiro , Takeda Kojiro , Saitoh Shigeaki 
Published: January 2016

AbstractWhile glucose is the fundamental source of energy in most eukaryotes, it is not always abundantly available in natural environments, including within the human body. Eukaryotic cells are therefore thought to possess adaptive mechanisms to survive glucose-limited conditions, which remain unclear. Here, we report a novel mechanism regulating cell cycle progression in response to abrupt changes in extracellular glucose concentration. Upon reduction of glucose in the medium, wild-type fission yeast cells undergo transient arrest specifically at G2 phase. This cell cycle arrest is dependent on the Wee1 tyrosine kinase inhibiting the key cell cycle regulator, CDK1/Cdc2. Mutant cells lacking Wee1 are not arrested at G2 upon glucose limitation and lose viability faster than the wild-type cells under glucose-depleted quiescent conditions, suggesting that this cell cycle arrest is required for extension of chronological lifespan. Our findings indicate the presence of a novel cell cycle checkpoint monitoring glucose availability, which may be a good molecular target for cancer therapy.
High early life mortality in free-ranging dogs is largely influenced by humans
Authors: Paul Manabi , Sen Majumder Sreejani , Sau Shubhra , Nandi Anjan K. , Bhadra Anindita 
Published: January 2016

AbstractFree-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex.
Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles
Authors: Harper Callista B. , Papadopulos Andreas , Martin Sally , Matthews Daniel R. , Morgan Garry P. , Nguyen Tam H. , Wang Tong , Nair Deepak , Choquet Daniel , Meunier Frederic A. 
Published: January 2016

AbstractNeuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo-BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran-containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles.
The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology and Influences Locomotor Activity in Drosophila Larvae
Authors: Ziegler Anna B. , Augustin Hrvoje , Clark Nathan L. , Berthelot-Grosjean Martine , Simonnet Mégane M. , Steinert Joern R. , Geillon Flore , Manière Gérard , Featherstone David E. , Grosjean Yael 
Published: January 2016

AbstractChanges in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. TheDrosophilalarval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes. Amino acids such as glutamate have been shown to regulateDrosophilaNMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. To identify amino acid transporters impacting glutmatergic signal transmission, we used Evolutionary Rate Covariation (ERC), a recently developed bioinformatic tool. Our screen identified ten proteins co-evolving with NMJ glutamate receptors. We selected one candidate transporter, the SLC7 (Solute Carrier) transporter family member JhI-21 (Juvenile hormone Inducible-21), which is expressed inDrosophilalarval motor neurons. We show that JhI-21 suppresses postsynaptic muscle glutamate receptor abundance and that JhI-21 expression in motor neurons regulates larval crawling behavior in a developmental stage-specific manner.
All-photonic drying and sintering process via flash white light combined with deep-UV and near-infrared irradiation for highly conductive copper nano-ink
Authors: Hwang Hyun-Jun , Oh Kyung-Hwan , Kim Hak-Sung 
Published: January 2016

AbstractWe developed an ultra-high speed photonic sintering method involving flash white light (FWL) combined with near infrared (NIR) and deep UV light irradiation to produce highly conductive copper nano-ink film. Flash white light irradiation energy and the power of NIR/deep UV were optimized to obtain high conductivity Cu films. Several microscopic and spectroscopic characterization techniques such as scanning electron microscopy (SEM), a x-ray diffraction (XRD) and Fourier-transform infrared (FT-IR) spectroscopy were employed to characterize the Cu nano-films. Optimally sintered Cu nano-ink films produced using a deep UV-assisted flash white light sintering technique had the lowest resistivity (7.62 μΩ·cm), which was only 4.5-fold higher than that of bulk Cu film (1.68 μΩ•cm).
AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis
Authors: Zhang Xiling , Yao Jian , Gao Kun , Chi Yuan , Mitsui Takahiko , Ihara Tatsuya , Sawada Norifumi , Kamiyama Manabu , Fan Jianglin , Takeda Masayuki 
Published: January 2016

AbstractBladder voiding dysfunction is closely related to local oxidation, inflammation and enhanced channel activities. Given that the AMP-activated protein kinase (AMPK) has anti-oxidative, anti-inflammatory and channel-inhibiting properties, we examined whether and how AMPK affected bladder activity. AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation. Downregulation of CREB with siRNA increased Cx43 expression. A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity. AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs. In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction. Further analysis comparing the responses of the wild-type (Cx43+/+) and heterozygous (Cx43+/−) Cx43 mice to cyclophosphamide revealed that the Cx43+/− mice retained a relatively normal micturition pattern compared to the Cx43+/+ mice. Taken together, our results indicate that AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction.
Loss of CAR promotes migration and proliferation of HaCaT cells and accelerates wound healing in rats via Src-p38 MAPK pathway
Authors: Su Linlin , Fu Lanqing , Li Xiaodong , Zhang Yue , Li Zhenzhen , Wu Xue , Li Yan , Bai Xiaozhi , Hu Dahai 
Published: January 2016

AbstractThe coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38 and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing.
Insights into cationic ordering in Re-based double perovskite oxides
Authors: Lim Tae-Won , Kim Sung-Dae , Sung Kil-Dong , Rhyim Young-Mok , Jeen Hyungjeen , Yun Jondo , Kim Kwang-Ho , Song Ki-Myung , Lee Seongsu , Chung Sung-Yoon , Choi Minseok , Choi Si-Young 
Published: January 2016

AbstractCationic ordering in Sr2FeReO6 (SFRO) and Sr2CrReO6 (SCRO) is investigated using magnetic property measurement, atomic-scale imaging and first-principles calculations. We find that the nature of cationic ordering strongly depends on the host oxides, although they have the same crystal symmetry and chemical formula. Firstly, adding Re is effective to enhance the cationic ordering in SFRO, but makes it worse in SCRO. Secondly, the microscopic structure of antisite (AS) defects, associated with the level of cationic ordering, is also distinguishable; the AS defects in SFRO are clustered in the form of an antiphase-boundary-like feature, while they are randomly scattered in SCRO. Interestingly, we observe that the clustered AS defects deteriorate the ferromagnetism more than the scattered defects. Our findings elevate the importance of the AS defect configuration as well as the amount of defects in terms of magnetic property.
Essential role of proteasomes in maintaining self-renewal in neural progenitor cells
Authors: Zhao Yunhe , Liu Xueqin , He Zebin , Niu Xiaojie , Shi Weijun , Ding Jian M. , Zhang Li , Yuan Tifei , Li Ang , Yang Wulin , Lu Li 
Published: January 2016

AbstractProtein turnover and homeostasis are regulated by the proteasomal system, which is critical for cell function and viability. Pluripotency of stem cells also relies on normal proteasomal activity that mitigates senescent phenotypes induced by intensive cell replications, as previously demonstrated in human bone marrow stromal cells. In this study, we investigated the role of proteasomes in self-renewal of neural progenitor cells (NPCs). Through bothin vivoandin vitroanalyses, we found that the expression of proteasomes was progressively decreased during aging. Likewise, proliferation and self-renewal of NPCs were also impaired in aged mice, suggesting that the down-regulation of proteasomes might be responsible for this senescent phenotype. Lowering proteasomal activity by loss-of-function manipulations mimicked the senescence of NPCs bothin vitroandin vivo; conversely, enhancing proteasomal activity restored and improved self-renewal in aged NPCs. These results collectively indicate that proteasomes work as a key regulator in promoting self-renewal of NPCs. This potentially provides a promising therapeutic target for age-dependent neurodegenerative diseases.
Phenotypic Characterization Analysis of Human Hepatocarcinoma by Urine Metabolomics Approach
Authors: Liang Qun , Liu Han , Wang Cong , Li Binbing 
Published: January 2016

AbstractHepatocarcinoma (HCC) is one of the deadliest cancers in the world and represents a significant disease burden. Better biomarkers are needed for early detection of HCC. Metabolomics was applied to urine samples obtained from HCC patients to discover noninvasive and reliable biomarkers for rapid diagnosis of HCC. Metabolic profiling was performed by LC-Q-TOF-MS in conjunction with multivariate data analysis, machine learning approaches, ingenuity pathway analysis and receiver-operating characteristic curves were used to select the metabolites which were used for the noninvasive diagnosis of HCC. Fifteen differential metabolites contributing to the complete separation of HCC patients from matched healthy controls were identified involving several key metabolic pathways. More importantly, five marker metabolites were effective for the diagnosis of human HCC, achieved a sensitivity of 96.5% and specificity of 83% respectively, could significantly increase the diagnostic performance of the metabolic biomarkers. Overall, these results illustrate the power of the metabolomics technology which has the potential as a non-invasive strategies and promising screening tool to evaluate the potential of the metabolites in the early diagnosis of HCC patients at high risk and provides new insight into pathophysiologic mechanisms.
Biofortified indica rice attains iron and zinc nutrition dietary targets in the field
Authors: Trijatmiko Kurniawan R. , Dueñas Conrado , Tsakirpaloglou Nikolaos , Torrizo Lina , Arines Felichi Mae , Adeva Cheryl , Balindong Jeanette , Oliva Norman , Sapasap Maria V. , Borrero Jaime , Rey Jessica , Francisco Perigio , Nelson Andy , Nakanishi Hiromi , Lombi Enzo , Tako Elad , Glahn Raymond P. , Stangoulis James , Chadha-Mohanty Prabhjit , Johnson Alexander A. T. , Tohme Joe , Barry Gerard , Slamet-Loedin Inez H. 
Published: January 2016

AbstractMore than two billion people are micronutrient deficient. Polished grains of popular rice varieties have concentration of approximately 2 μg g−1 iron (Fe) and 16 μg g−1 zinc (Zn). The HarvestPlus breeding programs for biofortified rice target 13 μg g−1 Fe and 28 μg g−1 Zn to reach approximately 30% of the estimated average requirement (EAR). Reports on engineering Fe content in rice have shown an increase up to 18 μg g−1 in glasshouse settings; in contrast, under field conditions, 4 μg g−1 was the highest reported concentration. Here, we report on selected transgenic events, field evaluated in two countries, showing 15 μg g−1 Fe and 45.7 μg g−1 Zn in polished grain. Rigorous selection was applied to 1,689 IR64 transgenic events for insert cleanliness and, trait and agronomic performances. Event NASFer-274 containing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes showed a single locus insertion without a yield penalty or altered grain quality. Endosperm Fe and Zn enrichment was visualized by X-ray fluorescence imaging. The Caco-2 cell assay indicated that Fe is bioavailable. No harmful heavy metals were detected in the grain. The trait remained stable in different genotype backgrounds.
A small molecule inhibitor of tropomyosin dissociates actin binding from tropomyosin-directed regulation of actin dynamics
Authors: Bonello Teresa T. , Janco Miro , Hook Jeff , Byun Alex , Appaduray Mark , Dedova Irina , Hitchcock-DeGregori Sarah , Hardeman Edna C. , Stehn Justine R. , Böcking Till , Gunning Peter W. 
Published: January 2016

AbstractThe tropomyosin family of proteins form end-to-end polymers along the actin filament. Tumour cells rely on specific tropomyosin-containing actin filament populations for growth and survival. To dissect out the role of tropomyosin in actin filament regulation we use the small molecule TR100 directed against the C terminus of the tropomyosin isoform Tpm3.1. TR100 nullifies the effect of Tpm3.1 on actin depolymerisation but surprisingly Tpm3.1 retains the capacity to bind F-actin in a cooperative manner. In vivo analysis also confirms that, in the presence of TR100, fluorescently tagged Tpm3.1 recovers normally into stress fibers. Assembling end-to-end along the actin filament is thereby not sufficient for tropomyosin to fulfil its function. Rather, regulation of F-actin stability by tropomyosin requires fidelity of information communicated at the barbed end of the actin filament. This distinction has significant implications for perturbing tropomyosin-dependent actin filament function in the context of anti-cancer drug development.
Blocking protein phosphatase 2A signaling prevents endothelial-to-mesenchymal transition and renal fibrosis: a peptide-based drug therapy
Authors: Deng Yuanjun , Guo Yanyan , Liu Ping , Zeng Rui , Ning Yong , Pei Guangchang , Li Yueqiang , Chen Meixue , Guo Shuiming , Li Xiaoqing , Han Min , Xu Gang 
Published: January 2016

AbstractEndothelial-to-mesenchymal transition (EndMT) contributes to the emergence of fibroblasts and plays a significant role in renal interstitial fibrosis. Protein phosphatase 2A (PP2A) is a major serine/threonine protein phosphatase in eukaryotic cells and regulates many signaling pathways. However, the significance of PP2A in EndMT is poorly understood. In present study, the role of PP2A in EndMT was evaluated. We demonstrated that PP2A activated in endothelial cells (EC) during their EndMT phenotype acquisition and in the mouse model of obstructive nephropathy (i.e., UUO). Inhibition of PP2A activity by its specific inhibitor prevented EC undergoing EndMT. Importantly, PP2A activation was dependent on tyrosine nitration at 127 in the catalytic subunit of PP2A (PP2Ac). Our renal-protective strategy was to block tyrosine127 nitration to inhibit PP2A activation by using a mimic peptide derived from PP2Ac conjugating a cell penetrating peptide (CPP: TAT), termed TAT-Y127WT. Pretreatment withTAT-Y127WT was able to prevent TGF-β1-induced EndMT. Administration of the peptide to UUO mice significantly ameliorated renal EndMT level, with preserved density of peritubular capillaries and reduction in extracellular matrix deposition. Taken together, these results suggest that inhibiting PP2Ac nitration using a mimic peptide is a potential preventive strategy for EndMT in renal fibrosis.
Direct fabrication of 3D graphene on nanoporous anodic alumina by plasma-enhanced chemical vapor deposition
Authors: Zhan Hualin , Garrett David J. , Apollo Nicholas V. , Ganesan Kumaravelu , Lau Desmond , Prawer Steven , Cervenka Jiri 
Published: January 2016

AbstractHigh surface area electrode materials are of interest for a wide range of potential applications such as super-capacitors and electrochemical cells. This paper describes a fabrication method of three-dimensional (3D) graphene conformally coated on nanoporous insulating substrate with uniform nanopore size. 3D graphene films were formed by controlled graphitization of diamond-like amorphous carbon precursor films, deposited by plasma-enhanced chemical vapour deposition (PECVD). Plasma-assisted graphitization was found to produce better quality graphene than a simple thermal graphitization process. The resulting 3D graphene/amorphous carbon/alumina structure has a very high surface area, good electrical conductivity and exhibits excellent chemically stability, providing a good material platform for electrochemical applications. Consequently very large electrochemical capacitance values, as high as 2.1 mF for a sample of 10 mm3, were achieved. The electrochemical capacitance of the material exhibits a dependence on bias voltage, a phenomenon observed by other groups when studying graphene quantum capacitance. The plasma-assisted graphitization, which dominates the graphitization process, is analyzed and discussed in detail.
Controlled growth of CH3NH3PbI3 nanowires in arrays of
open nanofluidic channels
Authors: Spina Massimo , Bonvin Eric , Sienkiewicz Andrzej , Náfrádi Bálint , Forró László , Horváth Endre 
Published: January 2016

AbstractSpatial positioning of nanocrystal building blocks on a solid surface is a
prerequisite for assembling individual nanoparticles into functional devices. Here,
we report on the graphoepitaxial liquid-solid growth of nanowires of the
photovoltaic compound CH3NH3PbI3 in open
nanofluidic channels. The guided growth, visualized in real-time with a simple
optical microscope, undergoes through a metastable solvatomorph formation in polar
aprotic solvents. The presently discovered crystallization leads to the fabrication
of mm2-sized surfaces composed of perovskite nanowires having
controlled sizes, cross-sectional shapes, aspect ratios and orientation which have
not been achieved thus far by other deposition methods. The automation of this
general strategy paves the way towards fabrication of wafer-scale perovskite
nanowire thin films well-suited for various optoelectronic devices, e.g. solar
cells, lasers, light-emitting diodes and photodetectors.