bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilus Adhesin RrgA Interacts with Complement Receptor 3, Thereby Affecting Macrophage Function and Systemic Pneumococcal Disease
Authors: Orrskog Sofia , Rounioja Samuli , Spadafina Tiziana , Gallotta Marilena , Norman Martin , Hentrich Karina , Fälker Stefan , Ygberg-Eriksson Sofia , Hasenberg Mike , Johansson Björn , Uotila Liisa M. , Gahmberg Carl G. , Barocchi Michèle , Gunzer Matthias , Normark Staffan , Henriques-Normark Birgitta 
Published: December 2012

ABSTRACT

Pneumococcal pili have been shown to influence pneumococcal colonization, disease development, and the inflammatory response in mice. The role of the pilus-associated RrgA adhesin in pneumococcal interactions with murine and human macrophages was investigated. Expression of pili with RrgA enhanced the uptake of pneumococci by murine and human macrophages that was abolished by antibodies to complement receptor 3 (CR3) and not seen in CR3-deficient macrophages. Recombinant RrgA, but not pilus subunit RrgC, promoted CR3-mediated phagocytosis of coated beads by murine and human macrophages. Flow cytometry showed that purified CR3 binds pneumococcal cells expressing RrgA, and purified RrgA was shown to interact with CR3 and its I domain.
In vivo
, RrgA facilitated spread of pneumococci from the upper airways and peritoneal cavity to the bloodstream. Earlier onset of septicemia and more rapidly progressing disease was observed in wild-type mice compared to CR3-deficient mice challenged intranasally or intraperitoneally with pneumococci. Motility assays and time-lapse video microscopy showed that pneumococcal stimulation of macrophage motility required RrgA and CR3. These findings, together with the observed RrgA-dependent increase of intracellular survivors up to 10 h following macrophage infection, suggest that RrgA-CR3-mediated phagocytosis promotes systemic pneumococcal spread from local sites.

IMPORTANCE
Streptococcus pneumoniae
is a major contributor to morbidity and mortality in infectious diseases globally. Symptomatology is mainly due to pneumococcal interactions with host cells leading to an inflammatory response. However, we still need more knowledge on how pneumococci talk to immune cells and the importance of this interaction. Recently, a novel structure was identified on the pneumococcal surface, an adhesive pilus found in about 30% of clinical pneumococcal isolates. The pilus has been suggested to be important for successful spread of antibiotic-resistant pneumococcal clones globally. Here we sought to identify mechanisms for how the pneumococcal pilin subunit RrgA contributes to disease development by interacting with host immune cells. Our data suggest a new way for how pneumococci may cross talk with phagocytic cells and affect disease progression. An increased understanding of these processes may lead to better strategies for how to treat these common infections.
DESCENT AND C0-RIGIDITY OF SPECTRAL INVARIANTS ON MONOTONE SYMPLECTIC MANIFOLDS
Authors: SEYFADDINI SOBHAN 
Published: December 2012

We obtain estimates showing that on monotone symplectic manifolds (asymptotic) spectral invariants of Hamiltonians which vanish on a non-empty open set, U, descend from [Formula: see text] to Hamc(M\U). Furthermore, we show that these invariants are continuous with respect to the C0-topology on Hamc(M\U).We apply the above results to Hofer geometry and establish unboundedness of the Hofer diameter of Hamc(M\U) for stably displaceable U. We also answer a question of F. Le Roux about C0-continuity properties of the Hofer metric.
Remarks on the Pressure Regularity Criterion of the Micropolar Fluid Equations in Multiplier Spaces
Authors: Guo Fengjun 
Published: December 2012

This study is devoted to investigating the regularity criterion of weak solutions of the micropolar fluid equations in ℝ3. The weak solution of micropolar fluid equations is proved to be smooth on (0, T] when the pressure π(x, t) satisfies the following growth condition in the multiplier spaces	, . The previous results on Lorentz spaces and Morrey spaces are obviously improved.
FoxA1 Specifies Unique Androgen and Glucocorticoid Receptor Binding Events in Prostate Cancer Cells
Authors: Sahu Biswajyoti , Laakso Marko , Pihlajamaa Päivi , Ovaska Kristian , Sinielnikov Ievgenii , Hautaniemi Sampsa , Jänne Olli A. 
Published: December 2012

AbstractThe forkhead protein FoxA1 has functions other than a pioneer factor, in that its depletion brings about a significant redistribution in the androgen receptor (AR) and glucocorticoid receptor (GR) cistromes. In this study, we found a novel function for FoxA1 in defining the cell-type specificity of AR- and GR-binding events in a distinct fashion, namely, for AR in LNCaP-1F5 cells and for GR in VCaP cells. We also found different, cell-type and receptor-specific compilations of cis-elements enriched adjacent to the AR- and GR-binding sites. The AR pathway is central in prostate cancer biology, but the role of GR is poorly known. We find that AR and GR cistromes and transcription programs exhibit significant overlap, and GR regulates a large number of genes considered to be AR pathway-specific. This raises questions about the role of GR in maintaining the AR pathway under androgen-deprived conditions in castration-resistant prostate cancer patients. However, in the presence of androgen, ligand-occupied GR acts as a partial antiandrogen and attenuates the AR-dependent transcription program. Cancer Res; 73(5); 1570–80. ©2012 AACR.
Unconventional Role of the Inwardly Rectifying Potassium Channel Kir2.2 as a Constitutive Activator of RelA in Cancer
Authors: Lee Inkyoung , Lee Sook-Ja , Kang Tong Mook , Kang Won Ki , Park Chaehwa 
Published: December 2012

Abstract
The constitutive activation of NF-κB is a major event leading to the initiation, development, and progression of cancer. Recently, we showed that the size of preestablished tumors was reduced after the depletion of Kir2.2, an inwardly rectifying potassium channel. To determine the precise mechanism of action of Kir2.2 in the control of tumor growth, we searched for interacting proteins. Notably, NF-κB p65/RelA was identified as a binding partner of Kir2.2 in a yeast two-hybrid analysis. Further analyses revealed that Kir2.2 directly interacted with RelA in vitro and coimmunoprecipitated with RelA from cell lysates. Kir2.2 increased RelA phosphorylation at S536 and facilitated its translocation from the cytoplasm to the nucleus, thereby activating the transcription factor and increasing the expression level of NF-κB targets, including cyclin D1, matrix metalloproteinase (MMP)9, and VEGF. Kir2.2 was overexpressed in human cancer and the expression level was correlated with increased colony formation and tumor growth in mouse tumor models. On the basis of these findings, we propose an unconventional role for Kir2.2 as a constitutive RelA-activating protein, which is likely to contribute to tumor progression in vivo. Cancer Res; 73(3); 1056–62. ©2012 AACR.
Autoantibody Signatures Involving Glycolysis and Splicesome Proteins Precede a Diagnosis of Breast Cancer among Postmenopausal Women
Authors: Ladd Jon J. , Chao Timothy , Johnson Melissa M. , Qiu Ji , Chin Alice , Israel Rebecca , Pitteri Sharon J. , Mao Jianning , Wu Mei , Amon Lynn M. , McIntosh Martin , Li Christopher , Prentice Ross , Disis Nora , Hanash Samir 
Published: December 2012

AbstractWe assessed the autoantibody repertoire of a mouse model engineered to develop breast cancer and the repertoire of autoantibodies in human plasmas collected at a preclinical time point and at the time of clinical diagnosis of breast cancer. In seeking to identify common pathways, networks, and protein families associated with the humoral response, we elucidated the dynamic nature of tumor antigens and autoantibody interactions. Lysate proteins from an immortalized cell line from a MMTV-neu mouse model and from MCF7 human breast cancers were spotted onto nitrocellulose microarrays and hybridized with mouse and human plasma samples, respectively. Immunoglobulin-based plasma immunoreactivity against glycolysis and spliceosome proteins was a predominant feature observed both in tumor-bearing mice and in prediagnostic human samples. Interestingly, autoantibody reactivity was more pronounced further away than closer to diagnosis. We provide evidence for dynamic changes in autoantibody reactivity with tumor development and progression that may depend, in part, on the extent of antigen–antibody interactions. Cancer Res; 73(5); 1502–13. ©2012 AACR.
Epigenetic Regulator Smchd1 Functions as a Tumor Suppressor
Authors: Leong Huei San , Chen Kelan , Hu Yifang , Lee Stanley , Corbin Jason , Pakusch Miha , Murphy James M. , Majewski Ian J. , Smyth Gordon K. , Alexander Warren S. , Hilton Douglas J. , Blewitt Marnie E. 
Published: December 2012

AbstractSMCHD1 is an epigenetic modifier of gene expression that is critical to maintain X chromosome inactivation. Here, we show in mouse that genetic inactivation of Smchd1 accelerates tumorigenesis in male mice. Loss of Smchd1 in transformed mouse embryonic fibroblasts increased tumor growth upon transplantation into immunodeficient nude mice. In addition, loss of Smchd1 in Eμ-Myc transgenic mice that undergo lymphomagenesis reduced disease latency by 50% relative to control animals. In premalignant Eμ-Myc transgenic mice deficient in Smchd1, there was an increase in the number of pre-B cells in the periphery, likely accounting for the accelerated disease in these animals. Global gene expression profiling suggested that Smchd1 normally represses genes activated by MLL chimeric fusion proteins in leukemia, implying that Smchd1 loss may work through the same pathways as overexpressed MLL fusion proteins do in leukemia and lymphoma. Notably, we found that SMCHD1 is underexpressed in many types of human hematopoietic malignancy. Together, our observations collectively highlight a hitherto uncharacterized role for SMCHD1 as a candidate tumor suppressor gene in hematopoietic cancers. Cancer Res; 73(5); 1591–9. ©2012 AACR.
Current Preclinical Models for the Advancement of Translational Bladder Cancer Research
Authors: DeGraff David J. , Robinson Victoria L. , Shah Jay B. , Brandt William D. , Sonpavde Guru , Kang Yibin , Liebert Monica , Wu Xue-Ru , Taylor John A. 
Published: December 2012

AbstractBladder cancer is a common disease representing the fifth most diagnosed solid tumor in the United States. Despite this, advances in our understanding of the molecular etiology and treatment of bladder cancer have been relatively lacking. This is especially apparent when recent advances in other cancers, such as breast and prostate, are taken into consideration. The field of bladder cancer research is ready and poised for a series of paradigm-shifting discoveries that will greatly impact the way this disease is clinically managed. Future preclinical discoveries with translational potential will require investigators to take full advantage of recent advances in molecular and animal modeling methodologies. We present an overview of current preclinical models and their potential roles in advancing our understanding of this deadly disease and for advancing care. Mol Cancer Ther; 12(2); 121–30. ©2012 AACR.
Time-Varying Climate Sensitivity from Regional Feedbacks
Authors: Armour Kyle C. , Bitz Cecilia M. , Roe Gerard H. 
Published: December 2012

Abstract
The sensitivity of global climate with respect to forcing is generally described in terms of the global climate feedback—the global radiative response per degree of global annual mean surface temperature change. While the global climate feedback is often assumed to be constant, its value—diagnosed from global climate models—shows substantial time variation under transient warming. Here a reformulation of the global climate feedback in terms of its contributions from regional climate feedbacks is proposed, providing a clear physical insight into this behavior. Using (i) a state-of-the-art global climate model and (ii) a low-order energy balance model, it is shown that the global climate feedback is fundamentally linked to the geographic pattern of regional climate feedbacks and the geographic pattern of surface warming at any given time. Time variation of the global climate feedback arises naturally when the pattern of surface warming evolves, actuating feedbacks of different strengths in different regions. This result has substantial implications for the ability to constrain future climate changes from observations of past and present climate states. The regional climate feedbacks formulation also reveals fundamental biases in a widely used method for diagnosing climate sensitivity, feedbacks, and radiative forcing—the regression of the global top-of-atmosphere radiation flux on global surface temperature. Further, it suggests a clear mechanism for the “efficacies” of both ocean heat uptake and radiative forcing.
The Influence of Antenna Radome on Weather Radar Calibration and Its Real-Time Assessment
Authors: Gorgucci E. , Bechini R. , Baldini L. , Cremonini R. , Chandrasekar V. 
Published: December 2012

Abstract
Operational weather radars are usually equipped with a radome to reduce the wind load on the antenna and to allow continuous operation under bad weather conditions. The study is focused on quantifying the impact on radar polarimetric measurements due to the presence of a radome. Analysis refers to the transportable X-band polarimetric radar of the Agenzia Regionale per la Protezione Ambientale (ARPA) Piemonte (ARX), which uses a “bullet shaped” radome to provide environmental protection to the antenna and receiver apparatus system.
Radar calibration is performed using wet and dry radomes. Differential reflectivity calibration results are compared with those obtained using the sun as a radiation reference source. Estimates have comparable mean values, with their differences being within the standard deviation. The paper describes a method based on the self-consistency principle that takes into account the loss induced by radome wetting due to rain to adjust the absolute calibration of the radar in real time.
To verify how well this method overcomes the problem of excess attenuation caused by the presence of precipitation on the radome, two validation methods are presented. The first uses an empirical model to estimate the two-way wet radome losses for a qualitative comparison, with the corresponding losses obtained by the self-consistency principle. The second employs comparisons between radar and gauge rainfall accumulations with and without radome correction. This approach offers a clear understanding of the response of the correction, providing quantitative performance in a real case.
Contributions of Barotropic Energy Conversion to Northwest Pacific Tropical Cyclone Activity during ENSO
Authors: Ha Yao , Zhong Zhong , Zhu Yimin , Hu Yijia 
Published: December 2012

Abstract
The contribution of barotropic energy conversion to tropical cyclone (TC) activity over the western North Pacific (WNP) during warm and cold phases of El Niño–Southern Oscillation (ENSO) is investigated by separating TC vortices from reanalysis data and using a linearized eddy kinetic energy tendency equation. By comparing the characteristics of TC disturbances with synoptic-scale disturbances, it is found that the modulation of ENSO on the WNP TC intensity is presented more objectively by using TC kinetic energy (EKETC) than eddy kinetic energy (EKE). Barotropic energy conversion (KmKe) into TC disturbances (KmKeTC) is an effective indicator in detecting the barotropic energy source of low-level cyclone genesis and maintenance during the ENSO cycle. However, its dynamical processes play different roles. Shear in large-scale zonal wind and convergence in large-scale meridional wind provide direct barotropic energy source for TC genesis, but make effects in different regions of the WNP. In contrast, convergence in large-scale zonal and shear in large-scale meridional wind exert little influence on TC genesis during ENSO.
Between Silence and Speech
Authors: Tsalach Calanit 
Published: December 2012

In this article I wish to trace three everyday moments in which my Mizrahi Ethnic Identity intersects with the academic one, and then extract experiences of ethnic otherness that are built within those moments. Exploring these moments while considering Mizrahi identity construction, practices of otherness, and terms of silences enables a more nuanced understanding of the ways in which hegemonic practices work and oppress Mizrahi subjects, and how these subjects work against them. Throughout these described moments, Mizrahi ethnicity is marked as troublesome, inferior, or as an Other that is forced to struggle to find its place. It is constructed as opposed to, or as a threat to the academic. Throughout these described moments I remain silent. My voice is given back to me through this autoethnographic text. In this way, autoethnography is also a way to oppose otherness due to its power to see these moments of ethnic otherness and resist them.
A Computational model for compressed sensing RNAi cellular screening
Authors: Tan Hua , Fan Jing , Bao Jiguang , Dy Jennifer G , Zhou Xiaobo 
Published: December 2012

Abstract

Background
RNA interference (RNAi) becomes an increasingly important and effective genetic tool to study the function of target genes by suppressing specific genes of interest. This system approach helps identify signaling pathways and cellular phase types by tracking intensity and/or morphological changes of cells. The traditional RNAi screening scheme, in which one siRNA is designed to knockdown one specific mRNA target, needs a large library of siRNAs and turns out to be time-consuming and expensive.

Results
In this paper, we propose a conceptual model, called compressed sensing RNAi (csRNAi), which employs a unique combination of group of small interfering RNAs (siRNAs) to knockdown a much larger size of genes. This strategy is based on the fact that one gene can be partially bound with several small interfering RNAs (siRNAs) and conversely, one siRNA can bind to a few genes with distinct binding affinity. This model constructs a multi-to-multi correspondence between siRNAs and their targets, with siRNAs much fewer than mRNA targets, compared with the conventional scheme. Mathematically this problem involves an underdetermined system of equations (linear or nonlinear), which is ill-posed in general. However, the recently developed compressed sensing (CS) theory can solve this problem. We present a mathematical model to describe the csRNAi system based on both CS theory and biological concerns. To build this model, we first search nucleotide motifs in a target gene set. Then we propose a machine learning based method to find the effective siRNAs with novel features, such as image features and speech features to describe an siRNA sequence. Numerical simulations show that we can reduce the siRNA library to one third of that in the conventional scheme. In addition, the features to describe siRNAs outperform the existing ones substantially.

Conclusions
This csRNAi system is very promising in saving both time and cost for large-scale RNAi screening experiments which may benefit the biological research with respect to cellular processes and pathways.
Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb) in rat cardiac myocytes
Authors: Matsui Hiroki , Yokoyama Tomoyuki , Tanaka Chie , Sunaga Hiroaki , Koitabashi Norimichi , Takizawa Takako , Arai Masashi , Kurabayashi Masahiko 
Published: December 2012

Abstract

Background
Hyperleptinemia is known to participate in cardiac hypertrophy and hypertension, but the relationship between pressure overload and leptin is poorly understood. We therefore examined the expression of leptin (ob) and the leptin receptor (ob-R) in the pressure-overloaded rat heart. We also examined gene expressions in culture cardiac myocytes to clarify which hypertension-related stimulus induces these genes.

Results
Pressure overload was produced by ligation of the rat abdominal aorta, and ob and ob-R isoform mRNAs were measured using a real-time polymerase chain reaction (PCR). We also measured these gene expressions in neonatal rat cardiac myocytes treated with angiotensin II (ANGII), endothelin-1 (ET-1), or cyclic mechanical stretch. Leptin and the long form of the leptin receptor (ob-Rb) gene were significantly increased 4 weeks after banding, but expression of the short form of the leptin receptor (ob-Ra) was unchanged. ob-Rb protein expression was also detected by immunohistochemistry in hypertrophied cardiac myocytes after banding. Meanwhile, plasma leptin concentrations were not different between the control and banding groups. In cultured myocytes, ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb mRNA expression in a time-dependent manner, but ob-Ra mRNA was unchanged by any stress.

Conclusions
We first demonstrated that both pressure mediated hypertrophy and mechanical stretch up-regulate ob-Rb gene expression in heart and cardiac myocytes, which are thought to be important for leptin action in cardiac myocytes. These results suggest a new local mechanism by which leptin affects cardiac remodeling in pressure-overloaded hearts.
Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of miRNA related to lactation
Authors: Li Zhen , Liu Hongyun , Jin Xiaolu , Lo Lijan , Liu Jianxin 
Published: December 2012

Abstract

Background
MicroRNAs (miRNAs) have been implicated in the regulation of milk protein synthesis and development of the mammary gland (MG). However, the specific functions of miRNAs in these regulations are not clear. Therefore, the elucidation of miRNA expression profiles in the MG is an important step towards understanding the mechanisms of lactogenesis.

Results
Two miRNA libraries were constructed from MG tissues taken from a lactating and a non-lactating Holstein dairy cow, respectively, and the short RNA sequences (18–30 nt) in these libraries were sequenced by Solexa sequencing method. The libraries included 885 pre-miRNAs encoding for 921 miRNAs, of which 884 miRNAs were unique sequences and 544 (61.5%) were expressed in both periods. A custom-designed microarray assay was then performed to compare miRNA expression patterns in the MG of lactating and non-lactating dairy cows. A total of 56 miRNAs in the lactating MG showed significant differences in expression compared to non-lactating MG (P<0.05). Integrative miRNA target prediction and network analysis approaches were employed to construct an interaction network of lactation-related miRNAs and their putative targets. Using a cell-based model, six miRNAs (miR-125b, miR-141, miR-181a, miR-199b, miR-484 and miR-500) were studied to reveal their possible biological significance.

Conclusion
Our study provides a broad view of the bovine MG miRNA expression profile characteristics. Eight hundred and eighty-four miRNAs were identified in bovine MG. Differences in types and expression levels of miRNAs were observed between lactating and non-lactating bovine MG. Systematic predictions aided in the identification of lactation-related miRNAs, providing insight into the types of miRNAs and their possible mechanisms in regulating lactation.