bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activin-A signaling promotes epithelial–mesenchymal transition, invasion, and metastatic growth of breast cancer
Authors: Bashir Mohsin , Damineni Surekha , Mukherjee Geetashree , Kondaiah Paturu 
Published: August 2015

Abstract
Background:
Activins belong to the transforming growth factor-β (TGF-β) superfamily of cytokines. Although the role of TGF-β in cancer progression has been highly advocated, the role of activin signaling in cancer is not well known. However, overexpression of activin-A has been observed in several cancers.

Aims:
The gene expression profile indicated higher expression of Activin-A in breast tumors. Hence the aim of this study was to evaluate the status and role of Activin signaling pathway in these tumors.

Methods:
Microarray analysis was performed to reveal gene expression changes in breast tumors. The results were validated by quantitative PCR and immunohistochemical analysis in two independent sets of normal and tumor samples. Further, correlation of activin expression with survival and distant metastasis was performed to evaluate its possible role in tumor progression. We used recombinant activin-A, inhibitors, overexpression, and knockdown strategies both in vitro and in vivo, to understand the mechanism underlying the protumorigenic role of this signaling pathway.

Results:
We report that activin-A signaling is hyperactivated in breast cancers as indicated by higher activin-A, phosphoSMAD2, and phosphoSMAD3 levels in advanced breast cancers. Bone morphogenetic proteins and molecules involved in this signaling pathway were downregulated, suggesting its suppression in breast cancers. Activin-A expression correlates inversely with survival and metastasis in advanced breast cancers. Further, activin-A promotes anchorage-independent growth, epithelial–mesenchymal transition, invasion, angiogenesis, and stemness of breast cancer cells. We show that activin-A-induced phenotype is mediated by SMAD signaling pathway. In addition, activin-A expression affects the tumor-forming ability and metastatic colonization of cancer cells in nude mice.

Conclusions:
These results suggest that activin-A has a critical role in breast cancer progression and, hence, targeting this pathway can be a valuable strategy in treating breast cancer patients.
A novel small molecule inhibitor of Candida albicans biofilm formation, filamentation and virulence with low potential for the development of resistance
Authors: Pierce Christopher G , Chaturvedi Ashok K , Lazzell Anna L , Powell Alexander T , Saville Stephen P , McHardy Stanton F , Lopez-Ribot Jose L 
Published: August 2015

Abstract
Background/Objectives:
Candida albicans is the principal causative agent of candidiasis, the most common fungal infection in humans. Candidiasis represents the third-to-fourth most frequent nosocomial infection worldwide, as this normal commensal of humans causes opportunistic infections in an expanding population of immune- and medically compromised patients. These infections are frequently associated with biofilm formation, which complicates treatment and contributes to unacceptably high mortality rates.

Methods:
To address the pressing need for new antifungals, we have performed a high-content screen of 20,000 small molecules in a chemical library (NOVACore) to identify compounds that inhibit C. albicans biofilm formation, and conducted a series of follow-up studies to examine the in vitro and in vivo activity of the identified compounds.

Results:
The screen identified a novel series of diazaspiro-decane structural analogs that were largely represented among the bioactive compounds. Characterization of the leading compound from this series indicated that it inhibits processes associated with C. albicans virulence, most notably biofilm formation and filamentation, without having an effect on overall growth or eliciting resistance. This compound demonstrated in vivo activity in clinically relevant murine models of both invasive and oral candidiasis and as such represents a promising lead for antifungal drug development. Furthermore, these results provide proof of concept for the implementation of antivirulence approaches against C. albicans and other fungal infections that would be less likely to foster the emergence of resistance.
Zipf’s law holds for phrases, not words
Authors: Ryland Williams Jake , Lessard Paul R. , Desu Suma , Clark Eric M. , Bagrow James P. , Danforth Christopher M. , Sheridan Dodds Peter 
Published: August 2015

AbstractWith Zipf’s law being originally and most famously observed for word frequency, it is surprisingly limited in its applicability to human language, holding over no more than three to four orders of magnitude before hitting a clear break in scaling. Here, building on the simple observation that phrases of one or more words comprise the most coherent units of meaning in language, we show empirically that Zipf’s law for phrases extends over as many as nine orders of rank magnitude. In doing so, we develop a principled and scalable statistical mechanical method of random text partitioning, which opens up a rich frontier of rigorous text analysis via a rank ordering of mixed length phrases.
Allogeneic mesenchymal stem cells inhibited T follicular helper cell generation in rheumatoid arthritis
Authors: Liu Rui , Li Xia , Zhang Zhuoya , Zhou Min , Sun Yue , Su Dinglei , Feng Xuebing , Gao Xiang , Shi Songtao , Chen Wanjun , Sun Lingyun 
Published: August 2015

AbstractT follicular helper (Tfh) cells provide help for antigen-specific B cells. We have previously shown that Tfh cell frequency was increased and associated with auto-antibodies in patients with rheumatoid arthritis (RA), suggesting a possible involvement of Tfh cells in its pathogenesis. Mesenchymal stem cells (MSCs) represent a promising alternative cell therapy for RA by modulating T and B cell activation and proliferation. However, it remains unknown whether MSCs have immunoregulation on Tfh cells. In this paper, we have demonstrated that allogeneic MSCs could suppress Tfh cell differentiation in RA patients partly via the production of indoleamine 2,3-dioxygenase (IDO). IFNγ generated from Tfh cell differentiation system induced IDO expression on MSCs. MSCs transplantation (MSCT) into collagen-induced arthritis (CIA) mice prevented arthritis progression by inhibiting both the number and function of Tfh cells in vivo. These findings reveal a novel suppressive function of MSCs in Tfh cells, which has implication in understanding the underlying mechanisms of the immunotherapeutic effects of MSCs on RA patients.
An advanced draft genome assembly of a desi type chickpea (Cicer arietinum L.)
Authors: Parween Sabiha , Nawaz Kashif , Roy Riti , Pole Anil K. , Venkata Suresh B. , Misra Gopal , Jain Mukesh , Yadav Gitanjali , Parida Swarup K. , Tyagi Akhilesh K. , Bhatia Sabhyata , Chattopadhyay Debasis 
Published: August 2015

AbstractChickpea (Cicer arietinum L.) is an important pulse legume crop. We previously reported a draft genome assembly of the desi chickpea cultivar ICC 4958. Here we report an advanced version of the ICC 4958 genome assembly (version 2.0) generated using additional sequence data and an improved genetic map. This resulted in 2.7-fold increase in the length of the pseudomolecules and substantial reduction of sequence gaps. The genome assembly covered more than 94% of the estimated gene space and predicted the presence of 30,257 protein-coding genes including 2230 and 133 genes encoding potential transcription factors (TF) and resistance gene homologs, respectively. Gene expression analysis identified several TF and chickpea-specific genes with tissue-specific expression and displayed functional diversification of the paralogous genes. Pairwise comparison of pseudomolecules in the desi (ICC 4958) and the earlier reported kabuli (CDC Frontier) chickpea assemblies showed an extensive local collinearity with incongruity in the placement of large sequence blocks along the linkage groups, apparently due to use of different genetic maps. Single nucleotide polymorphism (SNP)-based mining of intra-specific polymorphism identified more than four thousand SNPs differentiating a desi group and a kabuli group of chickpea genotypes.
UV-responsive nano-sponge for oil absorption and desorption
Authors: Kim Do Hyun , Jung Min Chan , Cho So-Hye , Kim Sang Hoon , Kim Ho-Young , Lee Heon Ju , Oh Kyu Hwan , Moon Myoung-Woon 
Published: August 2015

AbstractControlled surface wettability for oil has been intensively studied to remove industrial oil waste or oil spill pollution from seas or rivers. In particular, external stimuli-induced special wetting materials, such as photo-responsive TiO2, have attracted considerable attention for oil-water separation. In this study, a novel method is reported to fabricate a nano-sponge which is composed of hydrophobic hydrocarbon and hydrophilic TiO2 nanoparticles for oil absorption or desorption that are responsive to UV irradiation. The hydrocarbon in the nano-sponge could selectively absorb oil from water, whereas the absorbed oil is released into the water by TiO2 in response to UV irradiation. The nano-sponge functionalized porous polydimethylsiloxane released more than 98% of the absorbed crude oil with UV irradiation and air-bubbling. It could be continuously reused while maintaining a high absorption capacity and desorption efficiency without incurring secondary air or water pollution. This smart oil absorption/desorption methodology with excellent selectivity and recyclability with almost perfect removal of absorbed oil can be applied for oil-water separation, oil spill cleanup and reuse of spilled oil.
Effect of Support on the Activity of Ag-based Catalysts for Formaldehyde Oxidation
Authors: Zhang Jianghao , Li Yaobin , Zhang Yan , Chen Min , Wang Lian , Zhang Changbin , He Hong 
Published: August 2015

AbstractAg-based catalysts with different supports (TiO2, Al2O3 and CeO2) were prepared by impregnation method and subsequently tested for the catalytic oxidation of formaldehyde (HCHO) at low temperature. The Ag/TiO2 catalyst showed the distinctive catalytic performance, achieving the complete HCHO conversion at around 95 °C. In contrast, the Ag/Al2O3 and Ag/CeO2 catalysts displayed much lower activity and the 100% conversion was reached at 110 °C and higher than 125 °C, respectively. The Ag-based catalysts were next characterized by several methods. The characterization results revealed that supports have the dramatic influence on the Ag particle sizes and dispersion. Kinetic tests showed that the Ag based catalyst on the TiO2, Al2O3 or CeO2 supports have the similar apparent activation energy of 65 kJ mol−1, indicating that the catalytic mechanism keep immutability over these three catalysts. Therefore, Ag particle size and dispersion was confirmed to be the main factor affecting the catalytic performance for HCHO oxidation. The Ag/TiO2 catalyst has the highest Ag dispersion and the smallest Ag particle size, accordingly presenting the best catalytic performance for HCHO oxidation.
Automated biphasic morphological assessment of hepatitis B-related liver fibrosis using second harmonic generation microscopy
Authors: Wang Tong-Hong , Chen Tse-Ching , Teng Xiao , Liang Kung-Hao , Yeh Chau-Ting 
Published: August 2015

AbstractLiver fibrosis assessment by biopsy and conventional staining scores is based on histopathological criteria. Variations in sample preparation and the use of semi-quantitative histopathological methods commonly result in discrepancies between medical centers. Thus, minor changes in liver fibrosis might be overlooked in multi-center clinical trials, leading to statistically non-significant data. Here, we developed a computer-assisted, fully automated, staining-free method for hepatitis B-related liver fibrosis assessment. In total, 175 liver biopsies were divided into training (n = 105) and verification (n = 70) cohorts. Collagen was observed using second harmonic generation (SHG) microscopy without prior staining and hepatocyte morphology was recorded using two-photon excitation fluorescence (TPEF) microscopy. The training cohort was utilized to establish a quantification algorithm. Eleven of 19 computer-recognizable SHG/TPEF microscopic morphological features were significantly correlated with the ISHAK fibrosis stages (P < 0.001). A biphasic scoring method was applied, combining support vector machine and multivariate generalized linear models to assess the early and late stages of fibrosis, respectively, based on these parameters. The verification cohort was used to verify the scoring method and the area under the receiver operating characteristic curve was >0.82 for liver cirrhosis detection. Since no subjective gradings are needed, interobserver discrepancies could be avoided using this fully automated method.
Scale-dependency of the global mean surface temperature trend and its implication for the recent hiatus of global warming
Authors: Lin Yong , Franzke Christian L. E. 
Published: August 2015

AbstractStudies of the global mean surface temperature trend are typically conducted at a single (usually annual or decadal) time scale. The used scale does not necessarily correspond to the intrinsic scales of the natural temperature variability. This scale mismatch complicates the separation of externally forced temperature trends from natural temperature fluctuations. The hiatus of global warming since 1999 has been claimed to show that human activities play only a minor role in global warming. Most likely this claim is wrong due to the inadequate consideration of the scale-dependency in the global surface temperature (GST) evolution. Here we show that the variability and trend of the global mean surface temperature anomalies (GSTA) from January 1850 to December 2013, which incorporate both land and sea surface data, is scale-dependent and that the recent hiatus of global warming is mainly related to natural long-term oscillations. These results provide a possible explanation of the recent hiatus of global warming and suggest that the hiatus is only temporary.
Glutathione Decrement Drives Thermogenic Program In Adipose Cells
Authors: Lettieri Barbato Daniele , Tatulli Giuseppe , Maria Cannata Stefano , Bernardini Sergio , Aquilano Katia , Ciriolo Maria R. 
Published: August 2015

AbstractAdipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the “browning” effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes.
Key mechanisms involved in ionizing radiation-induced systemic effects. A current review
Authors: Mavragani Ifigeneia V. , Laskaratou Danae A. , Frey Benjamin , Candéias Serge M. , Gaipl Udo S. , Lumniczky Katalin , Georgakilas Alexandros G. 
Published: August 2015

AbstractOrganisms respond to physical, chemical and biological threats by a potent inflammatory response, aimed at preserving tissue integrity and restoring tissue homeostasis and function. Systemic effects in an organism refer to an effect or phenomenon which originates at a specific point and can spread throughout the body affecting a group of organs or tissues. Ionizing radiation (IR)-induced systemic effects arise usually from a local exposure of an organ or part of the body. This stress induces a variety of responses in the irradiated cells/tissues, initiated by the DNA damage response and DNA repair (DDR/R), apoptosis or immune response, including inflammation. Activation of this IR-response (IRR) system, especially at the organism level, consists of several subsystems and exerts a variety of targeted and non-targeted effects. Based on the above, we believe that in order to understand this complex response system better one should follow a ‘holistic’ approach including all possible mechanisms and at all organization levels. In this review, we describe the current status of knowledge on the topic, as well as the key molecules and main mechanisms involved in the ‘spreading’ of the message throughout the body or cells. Last but not least, we discuss the danger-signal mediated systemic immune effects of radiotherapy for the clinical setup.
Intracellular low molecular weight iron
Authors: DEIGHTON N. , HIDER R. C. 
Published: August 2015

Summary
A low molecular weight complex of an iron oligomer (Mr ~ 1000) has been isolated from rat liver and characterized physically and chemically. The h.p.l.c.-purified material contains the free amino acids glutamate and aspartate. Chemical techniques suggest the iron present in the factor is as iron(III) and is readily donated to high-affinity chelators such as the hydroxypyridinones and desferoxamine.
The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms
Authors: GEY K. FRED 
Published: August 2015

Summary
Plasma levels of major essential antioxidants were determined in representative random samples of middleaged men from 16 European study populations which differed up to 6-fold in age-specific mortality from ischaemic heart disease (IHD). In 12 study populations having total plasma cholesterol in the medium range (5.7–6.2 mmol/1) and usual blood pressure, both these classical risk factors lacked a significant correlation to IHD mortality, whereas the absolute level of vitamin E (α-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). On evaluation of all study populations, cholesterol and diastolic blood pressure had a moderate direct association with IHD, but their importance still remained inferior to that of vitamin E as an inversely associated, presumably protective factor. In stepwise regression and multiple regression analysis, the IHD mortality of the study populations was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and total cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol) and to 87% by all the above parameters plus diastolic blood pressure. In conclusion, in the present study the plasma status of vitamin E is the most important factor to explain cross-cultural differences of IHD mortality. This finding is consistent with the hypothesis of the prevention of arteriosclerosis by antioxidant protection against peroxidative lipoprotein modification, but does not exclude additional effects of antioxidant vitamins, e.g. on the cellular or immunological level.
Synchronizing the Neurospora crassa circadian clock with the rhythmic environment
Authors: Price-Lloyd N. , Elvin M. , Heintzen C. 
Published: August 2015

The metronomic predictability of the environment has elicited strong selection pressures for the evolution of endogenous circadian clocks. Circadian clocks drive molecular and behavioural rhythms that approximate the 24 h periodicity of our environment. Found almost ubiquitously among phyla, circadian clocks allow preadaptation to rhythms concomitant with the natural cycles of the Earth. Cycles in light intensity and temperature for example act as important cues that couple circadian clocks to the environment via a process called entrainment. This review summarizes our current understanding of the general and molecular principles of entrainment in the model organism Neurospora crassa, a simple eukaryote that has one of the best-studied circadian systems and light-signalling pathways.
ABC proteins and antibiotic drug resistance: is it all about transport?
Authors: Kerr I.D. , Reynolds E.D. , Cove J.H. 
Published: August 2015

The precise mechanism of antibiotic-resistance-conferring ABC (ATP-binding-cassette) proteins (termed NBD2) remains open to debate. Currently, two hypotheses are recognized. In one, the NBD2 proteins are envisaged to act at the ribosome to impair antibiotic access to the target site on the 23 S rRNA. In the other, NBD2 proteins are believed to act as the components of ATP driven efflux pumps by associating with membrane spanning proteins capable of binding and transporting antibiotics. Pertinent data in support of these two hypotheses are discussed in this paper.
Expression cloning of novel regulators of 92 kDa type IV collagenase expression
Authors: Nair R.R. , Boyd D.D. 
Published: August 2015

Overexpression of the 92 kDa type IV collagenase (MMP-9) contributes to cancer progression. However, to date, there are few known regulators of expression of this metalloproteinase. We employed an expression library comprising 500000 cDNA clones to screen for novel regulators of MMP-9 expression. HT1080 cells were transiently co-transfected with an MMP-9 promoter-luciferase reporter and pools of the cDNA expression library. Positive-scoring pools were subdivided in secondary and tertiary screens, after which the regulatory cDNAs were identified by DNA sequencing. This brief review illustrates the utility of expression cloning in identifying specific regulators of MMP-9 expression.
Regulation of acetyl-CoA carboxylase
Authors: Brownsey R.W. , Boone A.N. , Elliott J.E. , Kulpa J.E. , Lee W.M. 
Published: August 2015

Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530–560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.