bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants
Authors: Pareja Fresia , Geyer Felipe C , Marchiò Caterina , Burke Kathleen A , Weigelt Britta , Reis-Filho Jorge S 
Published: November 2016

AbstractTriple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.
TUSC2(FUS1)-erlotinib Induced Vulnerabilities in Epidermal Growth Factor Receptor(EGFR) Wildtype Non-small Cell Lung Cancer(NSCLC) Targeted by the Repurposed Drug Auranofin
Authors: Xiaobo Cao , Majidi Mourad , Feng Meng , Shao Ruping , Wang Jing , Zhao Yang , Baladandayuthapani Veerabhadran , Song Juhee , Fang Bingliang , Ji Lin , Mehran Reza , Roth Jack A. 
Published: November 2016

AbstractExpression of the TUSC2/FUS1 tumor suppressor gene in TUSC2 deficient EGFR wildtype lung cancer cells increased sensitivity to erlotinib. Microarray mRNA expression analysis of TUSC2 inducible lung cancer cells treated with erlotinib uncovered defects in the response to oxidative stress suggesting that increasing reactive oxygen species (ROS) would enhance therapeutic efficacy. Addition of the thioredoxin reductase 1 inhibitor (TXNRD1) auranofin (AF) to NSCLC cells treated with combination of TUSC2 forced expression with erlotinib increased tumor cell apoptosis and inhibited colony formation. TXNRD1 overexpression rescued tumors from AF-TUSC2-erlotinib induced apoptosis. Neutralizing ROS with nordihydroguaiaretic acid (NDGA) abrogated cell death induced by AF-TUSC2-erlotinib, indicating a regulatory role for ROS in the efficacy of the three drug combination. Isobologram-based statistical analysis of this combination demonstrated superior synergism, compared with each individual treatment at lower concentrations. In NSCLC tumor xenografts, tumor growth was markedly inhibited and animal survival was prolonged over controls by AF-TUSC2-erlotinib. Microarray mRNA expression analysis uncovered oxidative stress and DNA damage gene signatures significantly upregulated by AF-TUSC2-erlotinib compared to TUSC2-erlotinib. Pathway analysis showed the highest positive z-score for the NRF2-mediated oxidative stress response. Taken together these findings show that the combination of TUSC2-erlotinib induces additional novel vulnerabilities that can be targeted with AF.
Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse
Authors: Jackson Isabel L. , Zhang Yuji , Bentzen Søren M. , Hu Jingping , Zhang Angel , Vujaskovic Zeljko 
Published: November 2016

AbstractDifferences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury.
Tunable graphene-based mid-infrared plasmonic wide-angle narrowband perfect absorber
Authors: Li Hongju , Wang Lingling , Zhai Xiang 
Published: November 2016

AbstractIn this paper, the periodic double-layer graphene ribbon arrays placed near a metallic ground plate coated by a dielectric layer are proposed and analyzed by the coupled-mode theory (CMT) to predict the perfect absorption response in the mid-infrared region. Numerical simulations of the finite-difference time-domain (FDTD) method confirm this effect and give the underlying physical origin. The anti-symmetric dipole-dipole coupling mode is supported by the double-layer graphene ribbons and acts as the electrical resonance to suppress the reflection, because of the impedance matching. The transmission from this system is restricted by the ultra-thick metallic ground plate. All incident electromagnetic energy is efficiently confined in the interlayer between graphene ribbons and the metallic plate, and the dramatic narrowband perfect absorption peak with the FWHM (full width at half maximums) of 300 nm hence is achieved. The spectral position of the absorption peak can be dynamically tuned by a small change in the chemical potential of graphene, in addition to varying geometrical parameters of the absorber. Meanwhile, this device exhibits good absorption stability over a wide angle range of incidence around ± 60° at least. Such absorber will benefit the fabrication of mid-infrared nano-photonic devices for optical filtering and storage.
Default Mode Network alterations in alexithymia: an EEG power spectra and connectivity study
Authors: Imperatori Claudio , Della Marca Giacomo , Brunetti Riccardo , Carbone Giuseppe Alessio , Massullo Chiara , Valenti Enrico Maria , Amoroso Noemi , Maestoso Giulia , Contardi Anna , Farina Benedetto 
Published: November 2016

AbstractRecent neuroimaging studies have shown that alexithymia is characterized by functional alterations in different brain areas [e.g., posterior cingulate cortex (PCC)], during emotional/social tasks. However, only few data are available about alexithymic cortical networking features during resting state (RS). We have investigated the modifications of electroencephalographic (EEG) power spectra and EEG functional connectivity in the default mode network (DMN) in subjects with alexithymia. Eighteen subjects with alexithymia and eighteen subjects without alexithymia matched for age and gender were enrolled. EEG was recorded during 5 min of RS. EEG analyses were conducted by means of the exact Low Resolution Electric Tomography software (eLORETA). Compared to controls, alexithymic subjects showed a decrease of alpha power in the right PCC. In the connectivity analysis, compared to controls, alexithymic subjects showed a decrease of alpha connectivity between: (i) right anterior cingulate cortex and right PCC, (ii) right frontal lobe and right PCC, and (iii) right parietal lobe and right temporal lobe. Finally, mediation models showed that the association between alexithymia and EEG connectivity values was directed and was not mediated by psychopathology severity. Taken together, our results could reflect the neurophysiological substrate of some core features of alexithymia, such as the impairment in emotional awareness.
Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano
Authors: Banskar Sunil , Bhute Shrikant S. , Suryavanshi Mangesh V. , Punekar Sachin , Shouche Yogesh S. 
Published: November 2016

AbstractBats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.
Enhancement of protein production via the strong DIT1 terminator and two RNA-binding proteins in Saccharomyces cerevisiae
Authors: Ito Yoichiro , Kitagawa Takao , Yamanishi Mamoru , Katahira Satoshi , Izawa Shingo , Irie Kenji , Furutani-Seiki Makoto , Matsuyama Takashi 
Published: November 2016

AbstractPost-transcriptional upregulation is an effective way to increase the expression of transgenes and thus maximize the yields of target chemicals from metabolically engineered organisms. Refractory elements in the 3′ untranslated region (UTR) that increase mRNA half-life might be available. In Saccharomyces cerevisiae, several terminator regions have shown activity in increasing the production of proteins by upstream coding genes; among these terminators the DIT1 terminator has the highest activity. Here, we found in Saccharomyces cerevisiae that two resident trans-acting RNA-binding proteins (Nab6p and Pap1p) enhance the activity of the DIT1 terminator through the cis element GUUCG/U within the 3′-UTR. These two RNA-binding proteins could upregulate a battery of cell-wall–related genes. Mutagenesis of the DIT1 terminator improved its activity by a maximum of 500% of that of the standard PGK1 terminator. Further understanding and improvement of this system will facilitate inexpensive and stable production of complicated organism-derived drugs worldwide.
Hypometabolism during Daily Torpor in Mice is Dominated by Reduction in the Sensitivity of the Thermoregulatory System
Authors: Sunagawa Genshiro A. , Takahashi Masayo 
Published: November 2016

AbstractSome mammals enter a hypometabolic state either daily torpor (minutes to hours in length) or hibernation (days to weeks), when reducing metabolism would benefit survival. Hibernators demonstrate deep torpor by reducing both the sensitivity (H) and the theoretical set-point temperature (TR) of the thermogenesis system, resulting in extreme hypothermia close to ambient temperature. However, these properties during daily torpor remain poorly understood due to the very short steady state of the hypometabolism and the large variation among species and individuals. To overcome these difficulties in observing and evaluating daily torpor, we developed a novel torpor-detection algorithm based on Bayesian estimation of the basal metabolism of individual mice. Applying this robust method, we evaluated fasting induced torpor in various ambient temperatures (TAs) and found that H decreased 91.5% during daily torpor while TR only decreased 3.79 °C in mice. These results indicate that thermogenesis during daily torpor shares a common property of sensitivity reduction with hibernation while it is distinct from hibernation by not lowering TR. Moreover, our findings support that mice are suitable model animals to investigate the regulation of the heat production during active hypometabolism, thus suggesting further study of mice may provide clues to regulating hypometabolism in mammals.
Quantitative analysis of upright standing in adults with late-onset Pompe disease
Authors: Valle Maria Stella , Casabona Antonino , Fiumara Agata , Castiglione Dora , Sorge Giovanni , Cioni Matteo 
Published: November 2016

AbstractPompe disease is a rare disorder producing muscle weakness and progressive impairments in performing daily motor activities, such as walking and standing. Most studies have focused on dysfunctions at cellular level, restricting the examination of gross motor functions to qualitative or subjective rating scales evaluations. With the aim of providing an instrumented quantification of upright standing in Pompe disease, we used a force platform to measure the center of pressure over three foot positions and with eyes open and closed. Amplitude and variability of body sway were measured to determine the level of postural stability, while power spectrum analysis and nonlinear computations were performed to explore the structure of the postural control. In comparison with healthy participants, patients with Pompe disease showed a reduced level of postural stability, but irrelevant variations in frequency content and spatio-temporal structure of the sway motion were detected. Changes in foot position did not increase the postural instability associated with Pompe disease, but prominent worsening occurred in the patients when they stand with eyes closed, particularly along the anterior-posterior direction. These results provide objective elements to monitor deficiencies of upright standing in Pompe disease, emphasizing the specific contributions of sway direction and sensory deficits.
How knowledge of the gastrointestinal absorption of elements could be used to predict transfer to milk
Authors: Howard Brenda J. , Wells Claire , Barnett Catherine L. , Sheppard Steve C. 
Published: November 2016

AbstractThe quality and quantity of data used to derive transfer parameter values for milk are variable and there are many data gaps for elements/radionuclides which may need to be considered for risk assessment of the agricultural foodchain. There has been a recent focus on critically evaluating current methods to fill data gaps and on identifying extrapolation methods to derive suitable values for the elements, and particularly radioisotopes, with no or sparse data. The relationship between fractional absorption of elements in the ruminant gastrointestinal tract and transfer to milk has been explored to determine whether knowledge of the former can be used to predict the latter. A relationship has been derived between fractional absorption of elements and two empirical ratios commonly used to quantify transfer to milk; transfer coefficients (element concentration in milk divided by element daily intake) and concentrations ratios (concentration in milk divided by concentration in feed). We propose that fractional absorption may be used to predict the order of magnitude of the transfer to milk of elements/radionuclides for which no relevant data have yet been identified or collated.
Alignment of Lyapunov Vectors: A Quantitative Criterion to Predict Catastrophes?
Authors: Beims Marcus W. , Gallas Jason A. C. 
Published: November 2016

AbstractWe argue that the alignment of Lyapunov vectors provides a quantitative criterion to predict catastrophes, i.e. the imminence of large-amplitude events in chaotic time-series of observables generated by sets of ordinary differential equations. Explicit predictions are reported for a Rössler oscillator and for a semiconductor laser with optoelectronic feedback.
Enhancement of interaction of L-929 cells with functionalized graphene via COOH+ ion implantation vs. chemical method
Authors: Zhao Meng-li , Liu Xiao-qi , Cao Ye , Li Xi-fei , Li De-jun , Sun Xue-liang , Gu Han-qing , Wan Rong-xin 
Published: November 2016

AbstractLow hydrophilicity of graphene is one of the major obstacles for biomaterials application. To create some hydrophilic groups on graphene is addressed this issue. Herein, COOH+ ion implantation modified graphene (COOH+/graphene) and COOH functionalized graphene were designed by physical ion implantation and chemical methods, respectively. The structure and surface properties of COOH+/graphene and COOH functionalized graphene were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Compared with graphene, COOH+/graphene and COOH functionalized graphene revealed improvement of cytocompatibility, including in vitro cell viability and morphology. More importantly, COOH+/graphene exhibited better improvement effects than functionalized graphene. For instance, COOH+/graphene with 1 × 1018 ions/cm2 showed the best cell-viability, proliferation and stretching. This study demonstrated that ion implantation can better improve the cytocompatibility of the graphene.
Chromatin associated SETD3 negatively regulates VEGF expression
Authors: Cohn Ofir , Feldman Michal , Weil Lital , Kublanovsky Margarita , Levy Dan 
Published: November 2016

AbstractSETD3 is a member of the protein lysine methyltransferase (PKMT) family, which catalyzes the addition of methyl group to lysine residues. Accumulating data suggest that PKMTs are involved in the regulation of a broad spectrum of biological processes by targeting histone and non-histone proteins. Using a proteomic approach, we have identified 172 new SETD3 interacting proteins. We show that SETD3 binds and methylates the transcription factor FoxM1, which has been previously shown to be associated with the regulation of VEGF expression. We further demonstrate that under hypoxic conditions SETD3 is down-regulated. Mechanistically, we find that under basal conditions, SETD3 and FoxM1 are enriched on the VEGF promoter. Dissociation of both SETD3 and FoxM1 from the VEGF promoter under hypoxia correlates with elevated expression of VEGF. Taken together, our data reveal a new SETD3-dependent methylation-based signaling pathway at chromatin that regulates VEGF expression under normoxic and hypoxic conditions.
Identification and molecular characterization of an IDA-like gene from litchi, LcIDL1, whose ectopic expression promotes floral organ abscission in Arabidopsis
Authors: Ying Peiyuan , Li Caiqin , Liu Xuncheng , Xia Rui , Zhao Minglei , Li Jianguo 
Published: November 2016

AbstractUnexpected abscission of flowers or fruits is a major limiting factor for crop productivity. Key genes controlling abscission in plants, especially in popular fruit trees, are largely unknown. Here we identified a litchi (Litchi chinensis Sonn.) IDA-like (INFLORESCENCE DEFICIENT IN ABSCISSION-like) gene LcIDL1 as a potential key regulator of abscission. LcIDL1 encodes a peptide that shows the closest homology to Arabidopsis IDA, and is localized in cell membrane and cytoplasm. Real-time PCR analysis showed that the expression level of LcIDL1 accumulated gradually following flower abscission, and it was obviously induced by fruit abscission-promoting treatments. Transgenic plants expressing LcIDL1 in Arabidopsis revealed a role of LcIDL1 similar to IDA in promoting floral organ abscission. Moreover, ectopic expression of LcIDL1 in Arabidopsis activated the expression of abscission-related genes. Taken together, our findings provide evidence that LcIDL1 may act as a key regulator in control of abscission.
Investigation of TbfA in Riemerella anatipestifer using plasmid-based methods for gene over-expression and knockdown
Authors: Liu MaFeng , Wang MengYi , Zhu DeKang , Wang MingShu , Jia RenYong , Chen Shun , Sun KunFeng , Yang Qiao , Wu Ying , Chen XiaoYue , Biville Francis , Cheng AnChun 
Published: November 2016

AbstractRiemerella anatipestifer is a duck pathogen that has caused serious economic losses to the duck industry worldwide. Despite this, there are few reported studies of the physiological and pathogenic mechanisms of Riemerella anatipestifer infection. In previous study, we have shown that TonB1 and TonB2 were involved in hemin uptake. TonB family protein (TbfA) was not investigated, since knockout of this gene was not successful at that time. Here, we used a plasmid based gene over-expression and knockdown to investigate its function. First, we constructed three Escherichia-Riemerella anatipestifer shuttle vectors containing three different native Riemerella anatipestifer promoters. The shuttle plasmids were introduced into Riemerella anatipestifer ATCC11845 by conjugation at an efficiency of 5 × 10−5 antibiotic-resistant transconjugants per recipient cell. Based on the high-expression shuttle vector pLMF03, a method for gene knockdown was established. Knockdown of TbfA in Riemerella anatipestifer ATCC11845 decreased the organism’s growth ability in TSB medium but did not affect its hemin utilization. In contrast, over-expression of TbfA in Riemerella anatipestifer ATCC11845ΔtonB1ΔtonB2. Significantly promoted the organism’s growth in TSB medium but significantly inhibited its hemin utilization. Collectively, these findings suggest that TbfA is not involved in hemin utilization by Riemerella anatipestifer.
Imaging Cytometry of Human Leukocytes with Third Harmonic Generation Microscopy
Authors: Wu Cheng-Ham , Wang Tzung-Dau , Hsieh Chia-Hung , Huang Shih-Hung , Lin Jong-Wei , Hsu Szu-Chun , Wu Hau-Tieng , Wu Yao-Ming , Liu Tzu-Ming 
Published: November 2016

AbstractBased on third-harmonic-generation (THG) microscopy and a k-means clustering algorithm, we developed a label-free imaging cytometry method to differentiate and determine the types of human leukocytes. According to the size and average intensity of cells in THG images, in a two-dimensional scatter plot, the neutrophils, monocytes, and lymphocytes in peripheral blood samples from healthy volunteers were clustered into three differentiable groups. Using these features in THG images, we could count the number of each of the three leukocyte types both in vitro and in vivo. The THG imaging-based counting results agreed well with conventional blood count results. In the future, we believe that the combination of this THG microscopy-based imaging cytometry approach with advanced texture analysis of sub-cellular features can differentiate and count more types of blood cells with smaller quantities of blood.