bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stat3 modulates chloride channel accessory protein expression in normal and neoplastic mammary tissue
Authors: Hughes Katherine , Blanck Maximilian , Pensa Sara , Watson Christine J 
Published: October 2016

AbstractMammary gland regression at the cessation of lactation (involution) is an exquisitely orchestrated process of cell death and tissue remodelling in which Stat3 signalling has an essential role. The involution microenvironment of the mammary gland is considered to be pro-tumourigenic and a proportion of cases of pregnancy-associated breast cancer are suggested to originate in tandem with involution. However, the apparent paradox that STAT3 is required for cell death in normal mammary gland, but is associated with breast cancer cell survival, has not been resolved. Herein, we investigate Stat3-mediated regulation of expression of members of the calcium-activated chloride channel regulator (CLCA) family of proteins during involution and mammary carcinogenesis. Using the conditionally immortal mammary epithelial cell line KIM-2, together with mice exhibiting mammary epithelial cell-specific deletion of Stat3 during lactation, we demonstrate that expression of mCLCA1 and mCLCA2 is elevated in concert with activation of Stat3. By contrast, murine CLCA5 (mCLCA5), the murine orthologue of human CLCA2, is significantly upregulated at 24, 72 and 96 h of involution in Stat3 knockout mice, suggesting a reciprocal regulation of these proteins by Stat3in vivo. Interestingly, orthotopic tumours arising from transplantation of 4T1 murine mammary tumour cells exhibit both phosphorylated Stat3 and mCLCA5 expression. However, we demonstrate that expression is highly compartmentalized to distinct subpopulations of cells, and that Stat3 retains a suppressive effect on mCLCA5 expression in 4T1 tumour cells. These findings enhance our understanding of the regulation of CLCA channel expression bothin vitroandin vivo, and in particular, demonstrate that expression of mCLCA1 and mCLCA2 during involution is profoundly dependent upon Stat3, whereas the relationship between mCLCA5 and Stat3 activity is reciprocal and restricted to different subpopulations of cells.
RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis
Authors: Ge Qiu-Lin , Liu San-Hong , Ai Zhi-Hong , Tao Min-Fang , Ma Li , Wen Shan-Yun , Dai Miao , Liu Fei , Liu Han-Shao , Jiang Rong-Zhen , Xue Zhuo-Wei , Jiang Yu-Hang , Sun Xiao-Hua , Hu Yi-Ming , Zhao Yong-Xu , Chen Xi , Tao Yu , Zhu Xiao-Lu , Ding Wen-Jing , Yang Bing-Qing , Liu Dan-Dan , Zhang Xiao-Ren , Teng Yin-Cheng 
Published: October 2016

AbstractDysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.
A distinct holoenzyme organization for two-subunit pyruvate carboxylase
Authors: Choi Philip H. , Jo Jeanyoung , Lin Yu-Cheng , Lin Min-Han , Chou Chi-Yuan , Dietrich Lars E. P. , Tong Liang 
Published: October 2016

AbstractPyruvate carboxylase (PC) has important roles in metabolism and is crucial for virulence for some pathogenic bacteria. PC contains biotin carboxylase (BC), carboxyltransferase (CT) and biotin carboxyl carrier protein (BCCP) components. It is a single-chain enzyme in eukaryotes and most bacteria, and functions as a 500 kD homo-tetramer. In contrast, PC is a two-subunit enzyme in a collection of Gram-negative bacteria, with the α subunit containing the BC and the β subunit the CT and BCCP domains, and it is believed that the holoenzyme has α4β4 stoichiometry. We report here the crystal structures of a two-subunit PC from Methylobacillus flagellatus. Surprisingly, our structures reveal an α2β4 stoichiometry, and the overall architecture of the holoenzyme is strikingly different from that of the homo-tetrameric PCs. Biochemical and mutagenesis studies confirm the stoichiometry and other structural observations. Our functional studies in Pseudomonas aeruginosa show that its two-subunit PC is important for colony morphogenesis.
ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation
Authors: Seo Ji Hae , Park Ji-Hyeon , Lee Eun Ji , Vo Tam Thuy Lu , Choi Hoon , Kim Jun Yong , Jang Jae Kyung , Wee Hee-Jun , Lee Hye Shin , Jang Se Hwan , Park Zee Yong , Jeong Jaeho , Lee Kong-Joo , Seok Seung-Hyeon , Park Jin Young , Lee Bong Jin , Lee Mi-Ni , Oh Goo Taeg , Kim Kyu-Won 
Published: October 2016

AbstractHeat shock protein (Hsp)70 is a molecular chaperone that maintains protein homoeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. However, the mechanisms by which Hsp70 balances these opposing functions under stress conditions remain unknown. Here, we demonstrate that Hsp70 preferentially facilitates protein refolding after stress, gradually switching to protein degradation via a mechanism dependent on ARD1-mediated Hsp70 acetylation. During the early stress response, Hsp70 is immediately acetylated by ARD1 at K77, and the acetylated Hsp70 binds to the co-chaperone Hop to allow protein refolding. Thereafter, Hsp70 is deacetylated and binds to the ubiquitin ligase protein CHIP to complete protein degradation during later stages. This switch is required for the maintenance of protein homoeostasis and ultimately rescues cells from stress-induced cell death in vitro and in vivo. Therefore, ARD1-mediated Hsp70 acetylation is a regulatory mechanism that temporally balances protein refolding/degradation in response to stress.
Spontaneous assembly of chemically encoded two-dimensional coacervate droplet arrays by acoustic wave patterning
Authors: Tian Liangfei , Martin Nicolas , Bassindale Philip G. , Patil Avinash J. , Li Mei , Barnes Adrian , Drinkwater Bruce W. , Mann Stephen 
Published: October 2016

AbstractThe spontaneous assembly of chemically encoded, molecularly crowded, water-rich micro-droplets into periodic defect-free two-dimensional arrays is achieved in aqueous media by a combination of an acoustic standing wave pressure field and in situ complex coacervation. Acoustically mediated coalescence of primary droplets generates single-droplet per node micro-arrays that exhibit variable surface-attachment properties, spontaneously uptake dyes, enzymes and particles, and display spatial and time-dependent fluorescence outputs when exposed to a reactant diffusion gradient. In addition, coacervate droplet arrays exhibiting dynamical behaviour and exchange of matter are prepared by inhibiting coalescence to produce acoustically trapped lattices of droplet clusters that display fast and reversible changes in shape and spatial configuration in direct response to modulations in the acoustic frequencies and fields. Our results offer a novel route to the design and construction of ‘water-in-water’ micro-droplet arrays with controllable spatial organization, programmable signalling pathways and higher order collective behaviour.
Nano-inspired fluidic interactivity for boiling heat transfer: impact and criteria
Authors: Kim Beom Seok , Choi Geehong , Shin Sangwoo , Gemming Thomas , Cho Hyung Hee 
Published: October 2016

AbstractThe enhancement of boiling heat transfer, the most powerful energy-transferring technology, will lead to milestones in the development of high-efficiency, next-generation energy systems. Perceiving nano-inspired interface functionalities from their rough morphologies, we demonstrate interface-induced liquid refreshing is essential to improve heat transfer by intrinsically avoiding Leidenfrost phenomenon. High liquid accessibility of hemi-wicking and catalytic nucleation, triggered by the morphological and hydrodynamic peculiarities of nano-inspired interfaces, contribute to the critical heat flux (CHF) and the heat transfer coefficient (HTC). Our experiments show CHF is a function of universal hydrodynamic characteristics involving interfacial liquid accessibility and HTC is improved with a higher probability of smaller nuclei with less superheat. Considering the interface-induced and bulk liquid accessibility at boiling, we discuss functionalizing the interactivity between an interface and a counteracting fluid seeking to create a novel interface, a so-called smart interface, for a breakthrough in boiling and its pragmatic application in energy systems.
Illusions of having small or large invisible bodies influence visual perception of object size
Authors: van der Hoort Björn , Ehrsson H. Henrik 
Published: October 2016

AbstractThe size of our body influences the perceived size of the world so that objects appear larger to children than to adults. The mechanisms underlying this effect remain unclear. It has been difficult to dissociate visual rescaling of the external environment based on an individual’s visible body from visual rescaling based on a central multisensory body representation. To differentiate these potential causal mechanisms, we manipulated body representation without a visible body by taking advantage of recent developments in body representation research. Participants experienced the illusion of having a small or large invisible body while object-size perception was tested. Our findings show that the perceived size of test-objects was determined by the size of the invisible body (inverse relation) and by the strength of the invisible body illusion. These findings demonstrate how central body representation directly influences visual size perception, without the need for a visible body, by rescaling the spatial representation of the environment.
Beatquency domain and machine learning improve prediction of cardiovascular death after acute coronary syndrome
Authors: Liu Yun , Scirica Benjamin M. , Stultz Collin M. , Guttag John V. 
Published: October 2016

AbstractFrequency domain measures of heart rate variability (HRV) are associated with adverse events after a myocardial infarction. However, patterns in the traditional frequency domain (measured in Hz, or cycles per second) may capture different cardiac phenomena at different heart rates. An alternative is to consider frequency with respect to heartbeats, or beatquency. We compared the use of frequency and beatquency domains to predict patient risk after an acute coronary syndrome. We then determined whether machine learning could further improve the predictive performance. We first evaluated the use of pre-defined frequency and beatquency bands in a clinical trial dataset (N = 2302) for the HRV risk measure LF/HF (the ratio of low frequency to high frequency power). Relative to frequency, beatquency improved the ability of LF/HF to predict cardiovascular death within one year (Area Under the Curve, or AUC, of 0.730 vs. 0.704, p < 0.001). Next, we used machine learning to learn frequency and beatquency bands with optimal predictive power, which further improved the AUC for beatquency to 0.753 (p < 0.001), but not for frequency. Results in additional validation datasets (N = 2255 and N = 765) were similar. Our results suggest that beatquency and machine learning provide valuable tools in physiological studies of HRV.
Steady flow and heat transfer analysis of Phan-Thein-Tanner fluid in double-layer optical fiber coating analysis with Slip Conditions
Authors: Khan Zeeshan , Shah Rehan Ali , Islam Saeed , Jan Bilal , Imran Muhammad , Tahir Farisa 
Published: October 2016

AbstractModern optical fibers require double-layer coating on the glass fiber to provide protection from signal attenuation and mechanical damage. The most important plastic resins used in wires and optical fibers are plastic polyvinyl chloride (PVC) and low-high density polyethylene (LDPE/HDPE), nylon and Polysulfone. In this paper, double-layer optical fiber coating is performed using melt polymer satisfying PTT fluid model in a pressure type die using wet-on-wet coating process. The assumption of fully developed flow of Phan-Thien-Tanner (PTT) fluid model, two-layer liquid flows of an immiscible fluid is modeled in an annular die, where the fiber is dragged at a higher speed. The equations characterizing the flow and heat transfer phenomena are solved exactly and the effects of emerging parameters (Deborah and slip parameters, characteristic velocity, radii ratio and Brinkman numbers on the axial velocity, flow rate, thickness of coated fiber optics, and temperature distribution) are reported in graphs. It is shown that an increase in the non-Newtonian parameters increase the velocity in the absence or presence of slip parameters which coincides with related work. The comparison is done with experimental work by taking λ → 0 (non-Newtonian parameter).
B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation
Authors: Bjarnadóttir Kristbjörg , Benkhoucha Mahdia , Merkler Doron , Weber Martin S. , Payne Natalie L. , Bernard Claude C. A. , Molnarfi Nicolas , Lalive Patrice H. 
Published: October 2016

AbstractStudies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B–TGF-β1−/−) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG). In this model, B–TGF-β1−/− mice showed an earlier onset of neurologic impairment compared to their littermate controls. Exacerbated EAE susceptibility in B–TGF-β1−/− mice was associated with augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-β1–deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity. Collectively our data suggest that B cells can down-regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings that may be relevant to B cell-targeted therapies.
Loss of Atg16 delays the alcohol-induced sedation response via regulation of Corazonin neuropeptide production in Drosophila
Authors: Varga Kata , Nagy Péter , Arsikin Csordás Katarina , Kovács Attila L. , Hegedűs Krisztina , Juhász Gábor 
Published: October 2016

AbstractAutophagy defects lead to the buildup of damaged proteins and organelles, reduced survival during starvation and infections, hypersensitivity to stress and toxic substances, and progressive neurodegeneration. Here we show that, surprisingly, Drosophila mutants lacking the core autophagy gene Atg16 are not only defective in autophagy but also exhibit increased resistance to the sedative effects of ethanol, unlike Atg7 or Atg3 null mutant flies. This mutant phenotype is rescued by the re-expression of Atg16 in Corazonin (Crz)-producing neurosecretory cells that are known to promote the sedation response during ethanol exposure, and RNAi knockdown of Atg16 specifically in these cells also delays the onset of ethanol-induced coma. We find that Atg16 and Crz colocalize within these neurosecretory cells, and both Crz protein and mRNA levels are decreased in Atg16 mutant flies. Thus, Atg16 promotes Crz production to ensure a proper organismal sedation response to ethanol.
Biotransformation of ferulic acid to vanillin in the packed bed-stirred fermentors
Authors: Yan Lei , Chen Peng , Zhang Shuang , Li Suyue , Yan Xiaojuan , Wang Ningbo , Liang Ning , Li Hongyu 
Published: October 2016

AbstractWe performed the biotransformation of ferulic acid to vanillin using Bacillus subtilis (B. subtilis) in the stirring packed-bed reactors filled with carbon fiber textiles (CFT). Scanning electron microscope (SEM), HPLC, qRT-PCR and ATP assay indicated that vanillin biotransformation is tightly related to cell growth, cellar activity and the extent of biofilm formation. The biotransformation was affected by hydraulic retention time (HRT), temperature, initial pH, stirring speed and ferulic acid concentration, and the maximum vanillin production was obtained at 20 h, 35 °C, 9.0, 200 rpm, 1.5 g/L, respectively. Repeated batch biotransformation performed under this optimized condition showed that the maximum productivity (0.047 g/L/h) and molar yield (60.43%) achieved in immobilized cell system were 1.84 and 3.61 folds higher than those achieved in free cell system. Therefore, the stirring reactor packed with CFT carrier biofilm formed by B. subtilis represented a valid biocatalytic system for the production of vanillin.
Structural and Functional Characterization of the VQ Protein Family and VQ Protein Variants from Soybean
Authors: Zhou Yuan , Yang Yan , Zhou Xinjian , Chi Yingjun , Fan Baofang , Chen Zhixiang 
Published: October 2016

AbstractProteins containing the FxxxVQxhTG or VQ motif interact with WRKY transcription factors. Although VQ proteins have been reported in several plants, knowledge about their structures, functions and evolution is still very limited. Here, we report structural and functional analysis of the VQ protein family from soybean. Like Arabidopsis homologues, soybean VQ proteins bind only Group I and IIc WRKY proteins and a substantial number of their genes are responsive to stress-associated phytohormones. Overexpression of some soybean VQ genes in Arabidopsis had strong effects on plant growth, development, disease resistance and heat tolerance. Phylogenetic analysis, sequence alignment and site-directed mutagenesis revealed that the region immediately upstream of the FxxxVQxhTG motif also affects binding to WRKY proteins. Consistent with a larger WRKY-binding VQ domain, soybean VQ22 protein from cultivated soybean contains a 4-amino acid deletion in the region preceding its VQ motif that completely abolishes its binding to WRKY proteins. By contrast, the 4-amino acid deletion is absent in the VQ22 protein from wild soybean species (Glycine soja). Overexpression of wild soybean VQ22 in cultivated soybean inhibited growth, particularly after cold treatment. Thus, the mutation of soybean VQ22 is associated with advantageous phenotypes and may have been positively selected during evolution.
Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58
Authors: Xu Wan-Xiang , Wang Jian , Tang Hai-Ping , He Ya-Ping , Zhu Qian-Xi , Gupta Satish K. , Gu Shao-Hua , Huang Qiang , Ji Chao-Neng , Liu Ling-Feng , Li Gui-Ling , Xu Cong-Jian , Xie Yi 
Published: October 2016

AbstractTo enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs.
A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms
Authors: Jones Alan M. , Westwood Isaac M. , Osborne James D. , Matthews Thomas P. , Cheeseman Matthew D. , Rowlands Martin G. , Jeganathan Fiona , Burke Rosemary , Lee Diane , Kadi Nadia , Liu Manjuan , Richards Meirion , McAndrew Craig , Yahya Norhakim , Dobson Sarah E. , Jones Keith , Workman Paul , Collins Ian , van Montfort Rob L. M. 
Published: October 2016

AbstractThe heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority have poor physicochemical properties and for many the exact mode of action is poorly understood, more detailed mechanistic and structural insight into ligand-binding to HSP70s is urgently needed. Here we describe the first comprehensive fragment-based inhibitor exploration of an HSP70 enzyme, which yielded an amino-quinazoline fragment that was elaborated to a novel ATP binding site ligand with different physicochemical properties to known adenosine-based HSP70 inhibitors. Crystal structures of amino-quinazoline ligands bound to the different conformational states of the HSP70 nucleotide binding domain highlighted the challenges of a fragment-based approach when applied to this particular flexible enzyme class with an ATP-binding site that changes shape and size during its catalytic cycle. In these studies we showed that Ser275 is a key residue in the selective binding of ATP. Additionally, the structural data revealed a potential functional role for the ATP ribose moiety in priming the protein for the formation of the ATP-bound pre-hydrolysis complex by influencing the conformation of one of the phosphate binding loops.
The detection accuracy of cone beam CT for osseous defects of the temporomandibular joint: a systematic review and meta-analysis
Authors: Ma Ruo-han , Yin Shuang , Li Gang 
Published: October 2016

AbstractThe purpose of this review was to evaluate whether cone-beam computed tomography (CBCT) is reliable for the detection of bone changes of the temporomandibular joint (TMJ). Studies collected from the PubMed, Web of Science, Cochrane Library, ScienceDirect, Embase, Wanfang and CNKI databases were searched, and the publishing time was limited from January 1990 to December 2015. Eight studies (23 experimental research groups) were eventually included for further analysis. The pooled sensitivity was 0.67 and the pooled specificity was 0.87, which leads to a relatively large area (0.84) under the Receiver Operating Characteristic (ROC) curve. The related pooled positive likelihood ratio (+LR) and the pooled negative likelihood ratio (−LR) were 5.2 and 0.38, respectively. The subgroup analysis was conducted for four subgroups categorized by voxel size (≤0.2; >0.2, ≤0.3; >0.3, ≤0.4; >0.4, and ≤0.5 (mm)), and the “>0.4, ≤0.5” subgroup had a higher pooled sensitivity and pooled specificity than the other groups. The present study demonstrates that CBCT has a relatively high diagnostic accuracy for TMJ bone changes, although its reliability is limited. Voxel size did not play a role in the accuracy of CBCT.