bluuebunny/crossref_metadata_2025_split huggingface dataset:
RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
Authors: Wang Z , Zhou Y , Hu X , Chen W , Lin X , Sun L , Xu X , Hong W , Wang T 
Published: October 2015

AbstractRILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investigated. In this study, we showed that overexpression of RILP in breast cancer cells inhibits the migration and invasion, whereas the depletion of RILP by RNAi-mediated knockdown promotes the migration and invasion. We identified RalGDS (Ral guanine nucleotide dissociation stimulator) as a novel interacting partner for RILP, and truncation analysis revealed the N-terminal region of RILP is responsible for interacting with the guanine nucleotide exchange factor (GEF) domain of RalGDS. Immunofluorescence microscopy revealed that RalGDS can be recruited to the late endosomal compartments by RILP. Further investigations indicated that the overexpression of RILP inhibits the activity of RalA, a downstream target of RalGDS. Our data suggest that RILP suppresses the invasion of breast cancer cells by interacting with RalGDS to inhibit its GEF activity for RalA.
A bacterial metabolite induces glutathione-tractable proteostatic damage, proteasomal disturbances, and PINK1-dependent autophagy in C. elegans
Authors: Martinez B A , Kim H , Ray A , Caldwell G A , Caldwell K A 
Published: October 2015

AbstractGene-by-environment interactions are thought to underlie the majority of idiopathic cases of neurodegenerative disease. Recently, we reported that an environmental metabolite extracted from Streptomyces venezuelae increases ROS and damages mitochondria, leading to eventual neurodegeneration of C. elegans dopaminergic neurons. Here we link those data to idiopathic disease models that predict loss of protein handling as a component of disorder progression. We demonstrate that the bacterial metabolite leads to proteostatic disruption in multiple protein-misfolding models and has the potential to synergistically enhance the toxicity of aggregate-prone proteins. Genetically, this metabolite is epistatically regulated by loss-of-function to pink-1, the C. elegans PARK6 homolog responsible for mitochondrial maintenance and autophagy in other animal systems. In addition, the metabolite works through a genetic pathway analogous to loss-of-function in the ubiquitin proteasome system (UPS), which we find is also epistatically regulated by loss of PINK-1 homeostasis. To determine remitting counter agents, we investigated several established antioxidants and found that glutathione (GSH) can significantly protect against metabolite-induced proteostasis disruption. In addition, GSH protects against the toxicity of MG132 and can compensate for the combined loss of both pink-1 and the E3 ligase pdr-1, a Parkin homolog. In assessing the impact of this metabolite on mitochondrial maintenance, we observe that it causes fragmentation of mitochondria that is attenuated by GSH and an initial surge in PINK-1-dependent autophagy. These studies mechanistically advance our understanding of a putative environmental contributor to neurodegeneration and factors influencing in vivo neurotoxicity.
Liquid exfoliation of solvent-stabilized few-layer black phosphorus for applications beyond electronics
Authors: Hanlon Damien , Backes Claudia , Doherty Evie , Cucinotta Clotilde S. , Berner Nina C. , Boland Conor , Lee Kangho , Harvey Andrew , Lynch Peter , Gholamvand Zahra , Zhang Saifeng , Wang Kangpeng , Moynihan Glenn , Pokle Anuj , Ramasse Quentin M. , McEvoy Niall , Blau Werner J. , Wang Jun , Abellan Gonzalo , Hauke Frank , Hirsch Andreas , Sanvito Stefano , O’Regan David D. , Duesberg Georg S. , Nicolosi Valeria , Coleman Jonathan N. 
Published: October 2015

AbstractFew-layer black phosphorus (BP) is a new two-dimensional material which is of great interest for applications, mainly in electronics. However, its lack of environmental stability severely limits its synthesis and processing. Here we demonstrate that high-quality, few-layer BP nanosheets, with controllable size and observable photoluminescence, can be produced in large quantities by liquid phase exfoliation under ambient conditions in solvents such as N-cyclohexyl-2-pyrrolidone (CHP). Nanosheets are surprisingly stable in CHP, probably due to the solvation shell protecting the nanosheets from reacting with water or oxygen. Experiments, supported by simulations, show reactions to occur only at the nanosheet edge, with the rate and extent of the reaction dependent on the water/oxygen content. We demonstrate that liquid-exfoliated BP nanosheets are potentially useful in a range of applications from ultrafast saturable absorbers to gas sensors to fillers for composite reinforcement.
The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis
Authors: Nakasaki Manando , Hwang Yongsung , Xie Yun , Kataria Sunny , Gund Rupali , Hajam Edries Y. , Samuel Rekha , George Renu , Danda Debashish , M.J. Paul , Nakamura Tomoyuki , Shen Zhouxin , Briggs Steve , Varghese Shyni , Jamora Colin 
Published: October 2015

AbstractFibrosis is a pervasive disease in which the excessive deposition of extracellular matrix (ECM) compromises tissue function. Although the underlying mechanisms are mostly unknown, matrix stiffness is increasingly appreciated as a contributor to fibrosis rather than merely a manifestation of the disease. Here we show that the loss of Fibulin-5, an elastic fibre component, not only decreases tissue stiffness, but also diminishes the inflammatory response and abrogates the fibrotic phenotype in a mouse model of cutaneous fibrosis. Increasing matrix stiffness raises the inflammatory response above a threshold level, independent of TGF-β, to stimulate further ECM secretion from fibroblasts and advance the progression of fibrosis. These results suggest that Fibulin-5 may be a therapeutic target to short-circuit this profibrotic feedback loop.
Antroquinonol Lowers Brain Amyloid-β Levels and Improves Spatial Learning and Memory in a Transgenic Mouse Model of Alzheimer’s Disease
Authors: Chang Wen-Han , Chen Miles C. , Cheng Irene H. 
Published: October 2015

AbstractAlzheimer’s disease (AD) is the most common form of dementia. The deposition of brain amyloid-β peptides (Aβ), which are cleaved from amyloid precursor protein (APP), is one of the pathological hallmarks of AD. Aβ-induced oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Antroquinonol, a ubiquinone derivative isolated from Antrodia camphorata, has been shown to reduce oxidative stress and inflammatory cytokines via activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2) pathway, which is downregulated in AD. Therefore, we examined whether antroquinonol could improve AD-like pathological and behavioral deficits in the APP transgenic mouse model. We found that antroquinonol was able to cross the blood-brain barrier and had no adverse effects via oral intake. Two months of antroquinonol consumption improved learning and memory in the Morris water maze test, reduced hippocampal Aβ levels and reduced the degree of astrogliosis. These effects may be mediated through the increase of Nrf2 and the decrease of histone deacetylase 2 (HDAC2) levels. These findings suggest that antroquinonol could have beneficial effects on AD-like deficits in APP transgenic mouse.
Crystal structural basis for Rv0315, an immunostimulatory antigen and inactive beta-1,3-glucanase of Mycobacterium tuberculosis
Authors: Dong Wanyu , Huang Junhua , Li Yanan , Tan Yubei , Shen Zhou , Song Yunfeng , Wang Dang , Xiao Shaobo , Chen Huanchun , Fu Zhen F. , Peng Guiqing 
Published: October 2015

AbstractMycobacterium tuberculosis (Mtb) remains a leading cause of morbidity and mortality worldwide, as two billion people are latently infected with Mtb. To address Mtb drug resistance and the limitations of current vaccines, the characteristics of candidate Mtb vaccines need to be explored. Here, we report the three-dimensional structure of Rv0315 at 1.70 Å resolution, a novel immunostimulatory antigen of Mtb and demonstrate that Rv0315 is an inactive β-1,3-glucanase of the glycoside hydrolase 16 (GH16) family. Our study further elaborates the molecular basis for the lack of glucan recognition by Rv0315. Rv0315 has a large open groove and this particular topology cannot bind oligosaccharide chains in solution, thus explaining the lack of detectable hydrolytic activity towards its substrate. Additionally, we identified Glu-176, a conserved catalytic residue in GH16 endo-β-1,3-glucanases, as essential for Rv0315 to induce immunological responses. These results indicate that Rv0315 likely diverged from a broad-specificity ancestral GH16 glucanase and this inactive member of the GH16 family offers new insights into the GH16 glucanase. Together, our findings suggest that an inactive β-1,3-glucanase in Mtb drives T-helper 1 (Th1) immune responses, which may help develop more effective vaccines against Mtb infection.
Divergent endometrial inflammatory cytokine expression at peri-implantation period and after the stimulation by copper intrauterine device
Authors: Chou Chia-Hung , Chen Shee-Uan , Shun Chia-Tung , Tsao Po-Nien , Yang Yu-Shih , Yang Jehn-Hsiahn 
Published: October 2015

AbstractEndometrial inflammation has contradictory effects. The one occurring at peri-implantation period is favourable for embryo implantation, whereas the other occurring after the stimulation by copper intrauterine device (Cu-IUD) prevents from embryo implantation. In this study, 8 week female ICR mice were used to investigate the endometrial inflammation, in which they were at proestrus stage (Group 1), at peri-implantation period (Group 2) and had a copper wire implanted into right uterine horn (Group 3). Cytokine array revealed that two cytokines were highly expressed in Group 2 and Group 3 as compared with Group 1 and seven cytokines, including tumour necrosis factor α (TNF-α), had selectively strong expression in Group 3. Immunohistochemistry demonstrated prominent TNF-α staining on the endometrium after Cu-IUD stimulation and in vitro culture of human endometrial glandular cells with Cu induced TNF-α secretion. The increased TNF-α concentration enhanced in vitro THP-1 cells chemotaxis and reduced embryo implantation rates. These results suggest that inflammatory cytokine profiles of endometrium are different between those at peri-implantation period and after Cu-IUD stimulation and TNF-α is the one with selectively strong expression in the latter. It might account for the contradictory biological effects of endometrial inflammation.
Using AIE Luminogen for Long-term and Low-background Three-Photon Microscopic Functional Bioimaging
Authors: Zhu Zhenfeng , Leung Chris W. T. , Zhao Xinyuan , Wang Yalun , Qian Jun , Tang Ben Zhong , He Sailing 
Published: October 2015

AbstractFluorescent probes are one of the most popularly used bioimaging markers to monitor metabolic processes of living cells. However, long-term light excitation always leads to photobleaching of fluorescent probes, unavoidable autofluorescence as well as photodamage of cells. To overcome these limitations, we synthesized a type of photostable luminogen named TPE-TPP with an aggregation induced emission (AIE) characteristic and achieved its three-photon imaging with femtosecond laser excitation of 1020 nm. By using TPE-TPP as fluorescent probes, three-photon microscopy under 1020 nm excitation showed little photo-damage, as well as low autofluorescence to HeLa cells. Due to the AIE effect, the TPE-TPP nanoaggregates uptaken by cells were resistant to photobleaching under three-photon excitation for an extended period of time. Furthermore, we demonstrated that for the present TPE-TPP AIE the three-photon microscopy (with 1020 nm excitation) had a better signal to noise ratio than the two-photon microscopy (with 810 nm excitation) in tissue imaging.
The effect of enamel proteins on erosion
Authors: Baumann T. , Carvalho T. S. , Lussi A. 
Published: October 2015

AbstractEnamel proteins form a scaffold for growing hydroxyapatite crystals during enamel formation. They are then almost completely degraded during enamel maturation, resulting in a protein content of only 1% (w/v) in mature enamel. Nevertheless, this small amount of remaining proteins has important effects on the mechanical and structural properties of enamel and on the electrostatic properties of its surface. To analyze how enamel proteins affect tooth erosion, human enamel specimens were deproteinated. Surface microhardness (SMH), surface reflection intensity (SRI) and calcium release of both deproteinated and control specimens were monitored while continuously eroding them. The deproteination itself already reduced the initial SMH and SRI of the enamel significantly (p < 0.001 and p < 0.01). During the course of erosion, the progression of all three evaluated parameters differed significantly between the two groups (p < 0.001 for each). The deproteinated enamel lost its SMH and SRI faster and released more calcium than the control group, but these differences were only significant at later stages of erosion, where not only surface softening but surface loss can be observed. We conclude that enamel proteins have a significant effect on erosion, protecting the enamel and slowing down the progression of erosion when irreversible surface loss starts to occur.
Levels of polyunsaturated fatty acids correlate with growth rate in plant cell cultures
Authors: Meï Coline , Michaud Morgane , Cussac Mathilde , Albrieux Catherine , Gros Valérie , Maréchal Eric , Block Maryse A. , Jouhet Juliette , Rébeillé Fabrice 
Published: October 2015

AbstractIn higher plants, fatty acids (FAs) with 18 carbons (18C) represent about 70% of total FAs, the most abundant species being 18:2 and 18:3. These two polyunsaturated FAs (PUFAs) represent about 55% of total FAs in Arabidopsis cell suspension cultures, whereas 18:1 represents about 10%. The level of PUFAs may vary, depending on ill-defined factors. Here, we compared various sets of plant cell cultures and noticed a correlation between the growth rate of a cell population and the level of unsaturation of 18C FAs. These observations suggest that the final level of PUFAs might depend in part on the rate of cell division and that FAD2 and FAD3 desaturases, which are respectively responsible for the formation of 18:2 and 18:3 on phospholipids, have limiting activities in fast-growing cultures. In plant cell culture, phosphate (Pi) deprivation is known to impair cell division and to trigger lipid remodeling. We observed that Pi starvation had no effect on the expression of FAD genes and that the level of PUFAs in this situation was also correlated with the growth rate. Thus, the level of PUFAs appears as a hallmark in determining cell maturity and aging.
Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection
Authors: Maji Abhijit , Misra Richa , Kumar Mondal Anupam , Kumar Dhirendra , Bajaj Divya , Singhal Anshika , Arora Gunjan , Bhaduri Asani , Sajid Andaleeb , Bhatia Sugandha , Singh Sompal , Singh Harshvardhan , Rao Vivek , Dash Debasis , Baby Shalini E , Sarojini Michael Joy , Chaudhary Anil , Gokhale Rajesh S. , Singh Yogendra 
Published: October 2015

AbstractExtrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.
Identification of disulfide cross-linked tau dimer responsible for tau propagation
Authors: Kim Dohee , Lim Sungsu , Haque Md. Mamunul , Ryoo Nayeon , Hong Hyun Seok , Rhim Hyewhon , Lee Dong-Eun , Chang Young-Tae , Lee Jun-Seok , Cheong Eunji , Kim Dong Jin , Kim Yun Kyung 
Published: October 2015

AbstractRecent evidence suggests that tau aggregates are not only neurotoxic, but also propagate in neurons acting as a seed for native tau aggregation. Prion-like tau transmission is now considered as an important pathogenic mechanism driving the progression of tau pathology in the brain. However, prion-like tau species have not been clearly characterized. To identify infectious tau conformers, here we prepared diverse tau aggregates and evaluated the effect on inducing intracellular tau-aggregation. Among tested, tau dimer containing P301L-mutation is identified as the most infectious form to induce tau pathology. Biochemical analysis reveals that P301L-tau dimer is covalently cross-linked with a disulfide bond. The relatively small and covalently cross-linked tau dimer induced tau pathology efficiently in primary neurons and also in tau-transgenic mice. So far, the importance of tau disulfide cross-linking has been overlooked in the study of tau pathology. Here our results suggested that tau disulfide cross-linking might play critical role in tau propagation by producing structurally stable and small tau conformers.
High Elastic Moduli of a 54Al2O3-46Ta2O5 Glass Fabricated via Containerless Processing
Authors: Rosales-Sosa Gustavo A. , Masuno Atsunobu , Higo Yuji , Inoue Hiroyuki , Yanaba Yutaka , Mizoguchi Teruyasu , Umada Takumi , Okamura Kohei , Kato Katsuyoshi , Watanabe Yasuhiro 
Published: October 2015

AbstractGlasses with high elastic moduli have been in demand for many years because the thickness of such glasses can be reduced while maintaining its strength. Moreover, thinner and lighter glasses are desired for the fabrication of windows in buildings and cars, cover glasses for smart-phones and substrates in Thin-Film Transistor (TFT) displays. In this work, we report a 54Al2O3-46Ta2O5glass fabricated by aerodynamic levitation which possesses one of the highest elastic moduli and hardness for oxide glasses also displaying excellent optical properties. The glass was colorless and transparent in the visible region and its refractive indexndwas as high as 1.94. The measured Young’s modulus and Vickers hardness were 158.3 GPa and 9.1 GPa, respectively, which are comparable to the previously reported highest values for oxide glasses. Analysis made using27Al Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) spectroscopy revealed the presence of a significantly large fraction of high-coordinated Al in addition to four-coordinated Al in the glass. The high elastic modulus and hardness are attributed to both the large cationic field strength of Ta5+ions and the large dissociation energies per unit volume of Al2O3and Ta2O5.
Simultaneous excitation and emission enhancements in upconversion luminescence using plasmonic double-resonant gold nanorods
Authors: Liu Xin , Yuan Lei Dang 
Published: October 2015

AbstractThe geometry and dimension of a gold nanorod (GNR) are optimally designed to enhance the fluorescence intensity of a lanthanide-doped upconversion nanocrystal placed in close proximity to the GNR. A systematic study of the electromagnetic interaction between the upconversion emitter of three energy levels and the GNR shows that the enhancement effect arising from localized electric field-induced absorption can be balanced by the negative effect of electronic transition from an intermediate state to the ground state of the emitter. The dependence of fluorescence enhancement on the emitter-GNR separation is investigated and the results demonstrate a maximum enhancement factor of 120 folds and 160 folds at emission wavelengths 650 and 540 nm, respectively. This is achieved at the emitter-GNR separation ranging from 5 to 15 nm, depending on the initial quantum efficiency of the emitter. The modified upconversion luminescence behavior by adjusting the aspect ratio of the GNR and the relative position of the emitter indicates the dominate role of excitation process in the total fluorescence enhancement. These findings are of great importance for rationally designing composite nanostructures of metal nanoparticles and upconversion nanocrystals with maximized plasmonic enhancement for bioimaging and sensing applications.
An in vitro assessment of liposomal topotecan simulating metronomic chemotherapy in combination with radiation in tumor-endothelial spheroids
Authors: Jyoti Amar , Fugit Kyle D. , Sethi Pallavi , McGarry Ronald C. , Anderson Bradley D. , Upreti Meenakshi 
Published: October 2015

AbstractLow dose metronomic chemotherapy (LDMC) refers to prolonged administration of low dose chemotherapy designed to minimize toxicity and target the tumor endothelium, causing tumor growth inhibition. Topotecan (TPT) when administered at its maximum tolerated dose (MTD) is often associated with systemic hematological toxicities. Liposomal encapsulation of TPT enhances efficacy by shielding it from systemic clearance, allowing greater uptake and extended tissue exposure in tumors. Extended release of TPT from liposomal formulations also has the potential to mimic metronomic therapies with fewer treatments. Here we investigate potential toxicities of equivalent doses of free and actively loaded liposomal TPT (LTPT) and compare them to a fractionated low dose regimen of free TPT in tumor-endothelial spheroids (TES) with/without radiation exposure for a prolonged period of 10 days. Using confocal microscopy, TPT fluorescence was monitored to determine the accumulation of drug within TES. These studies showed TES, being more reflective of the in vivo tumor microenvironment, were more sensitive to LTPT in comparison to free TPT with radiation. More importantly, the response of TES to low-dose metronomic TPT with radiation was comparable to similar treatment with LTPT. This TES study suggests nanoparticle formulations designed for extended release of drug can simulate LDMC in vivo.