bluuebunny/crossref_metadata_2025_split huggingface dataset:
An estrogen‐induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations
Authors: Yang Chieh‐Hsiang , Almomen Aliyah , Wee Yin Shen , Jarboe Elke A. , Peterson C. Matthew , Janát‐Amsbury Margit M. 
Published: March 2015

AbstractEndometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone‐induced EH mouse model was developed using a subcutaneous estradiol (E2)‐sustained releasing pellet, which elevates the serum E2 level in mice, closely mimicking the effect known as estrogen dominance with underlying, pathological E2 levels in patients. The onset and progression of EH generated within this model recapitulate a clinically relevant, pathological transformation, beginning with disordered proliferation developing to simple EH, advancing to atypical EH, and then progressing to precancerous stages, all following a chronologic manner. Although a general increase in nuclear progesterone receptor (PR) expression occurred after E2 expression, a total loss in PR was noted in some endometrial glands as disease advanced to simple EH. Furthermore, estrogen receptor (ER) expression in the nucleus of endometrial cells was reduced in disordered proliferation and increased when EH progressed to atypical EH and precancerous stages. This EH model also resembles other pathological patterns found in human disease such as leukocytic infiltration, genetic aberrations in β‐catenin, and joint phosphatase and tensin homolog/paired box gene 2 (PTEN/PAX2) silencing. In summary, this new and comprehensively characterized EH model is cost‐effective, easily reproducible, and may serve as a tool for preclinical testing of therapeutic agents and facilitate further investigation of EH.
Signaling pathways and mechanisms of hypoxia‐induced autophagy in the animal cells
Authors: Fang Yungyun , Tan Jin , Zhang Qiang 
Published: March 2015

AbstractHypoxia occurs in a series of supraphysiological circumstances, for instance, sleep disorders, myocardial infarction and cerebral stroke, that can induce a systematic inflammatory response. Such a response may then lead to a widespread dysfunction and cell injury. Autophagy, a cellular homeostatic process that governs the turnover of damaged organelles and proteins, can be triggered by multiple forms of extra‐ and intracellular stress, for example, hypoxia, nutrient deprivation and reactive oxygen specie. Central to this process is the formation of double‐membrane vesicles, thereby autophagosomes sequester portions of cytosol and deliver them to the lysosomes for a breakdown. In recent years, several distinct oxygen‐sensing pathways that regulate the cellular response to autophagy have been defined. For instance, hypoxia influences autophagy in part through the activation of the hypoxia‐inducible factor (HIF)‐dependent pathways. In chronic and moderate hypoxia, autophagy plays a protective role by mediating the removal of the damaged organelles and protein. Moreover, three additional oxygen‐sensitive signaling pathways are also associated with the activation of autophagy. These include mammalian target of rapamycin (mTOR) kinase, unfolded protein response (UPR)‐ and PKCδ‐JNK1‐dependent pathways. Contrary to the protective effects of autophagy, during rapid and severe oxygen fluctuations, autophagy may be detrimental and induce cell death. In this review, we highlight a serious of recent advances on how autophagy is regulated at the molecular level and on final consequences of cell under different hypoxic environment.
Primary nodular lymphocyte‐predominant Hodgkin lymphoma of uterine cervix mimicking leiomyoma
Authors: Li Wan‐Shan , Wang Ren‐Ching , Wang John , Chang Kung‐Chao 
Published: March 2015

Key Clinical MessageNodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) accounts for about 5% of all Hodgkin lymphomas and predominantly involves peripheral lymph nodes. Primary NLPHL of uterine cervix is very rare. Here, we report cervical NLPHL with CD21 expression in a 43‐year‐old woman, who presented with abnormal vaginal bleeding for 1 year.
Super‐resolved calibration‐free flow cytometric characterization of platelets and cell‐derived microparticles in platelet‐rich plasma
Authors: Konokhova Anastasiya I. , Chernova Darya N. , Moskalensky Alexander E. , Strokotov Dmitry I. , Yurkin Maxim A. , Chernyshev Andrei V. , Maltsev Valeri P. 
Published: March 2015

AbstractImportance of microparticles (MPs), also regarded as extracellular vesicles, in many physiological processes and clinical conditions motivates one to use the most informative and precise methods for their characterization. Methods based on individual particle analysis provide statistically reliable distributions of MP population over characteristics. Although flow cytometry is one of the most powerful technologies of this type, the standard forward‐versus‐side‐scattering plots of MPs and platelets (PLTs) overlap considerably because of similarity of their morphological characteristics. Moreover, ordinary flow cytometry is not capable of measurement of size and refractive index (RI) of MPs. In this study, we 1) employed the potential of the scanning flow cytometer (SFC) for identification and characterization of MPs from light scattering; 2) suggested the reference method to characterize MP morphology (size and RI) with high precision; and 3) determined the lowest size of a MP that can be characterized from light scattering with the SFC. We equipped the SFC with 405 and 488 nm lasers to measure the light‐scattering profiles and side scattering from MPs, respectively. The developed two‐stage method allowed accurate separation of PLTs and MPs in platelet‐rich plasma. We used two optical models for MPs, a sphere and a bisphere, in the solution of the inverse light‐scattering problem. This solution provides unprecedented precision in determination of size and RI of individual spherical MPs—median uncertainties (standard deviations) were 6 nm and 0.003, respectively. The developed method provides instrument‐independent quantitative information on MPs, which can be used in studies of various factors affecting MP population. © 2015 International Society for Advancement of Cytometry
Visualization of pulmonary clearance mechanisms via noninvasive optical imaging validated by near‐infrared flow cytometry
Authors: Zhou Haiying , Gunsten Sean P. , Zhegalova Natalia G. , Bloch Sharon , Achilefu Samuel , Christopher Holley J. , Schweppe Daniel , Akers Walter , Brody Steven L. , Eades William C. , Berezin Mikhail Y. 
Published: March 2015

AbstractIn vivo optical imaging with near‐infrared (NIR) probes is an established method of diagnostics in preclinical and clinical studies. However, the specificities of these probes are difficult to validate ex vivo due to the lack of NIR flow cytometry. To address this limitation, we modified a flow cytometer to include an additional NIR channel using a 752 nm laser line. The flow cytometry system was tested using NIR microspheres and cell lines labeled with a combination of visible range and NIR fluorescent dyes. The approach was verified in vivo in mice evaluated for immune response in lungs after intratracheal delivery of the NIR contrast agent. Flow cytometry of cells obtained from the lung bronchoalveolar lavage demonstrated that the NIR dye was taken up by pulmonary macrophages as early as 4‐h post‐injection. This combination of optical imaging with NIR flow cytometry extends the capability of imaging and enables complementation of in vivo imaging with cell‐specific studies. © 2015 International Society for Advancement of Cytometry
Light depolarization measurements in malaria: A new job for an old friend
Authors: Rebelo Maria , Tempera Carolina , Bispo Claudia , Andrade Claudia , Gardner Rui , Shapiro Howard M. , Hänscheid Thomas 
Published: March 2015

AbstractThe use of flow cytometry in malaria research has increased over the last decade. Most approaches use nucleic acid stains to detect parasite DNA and RNA and require complex multi‐color, multi‐parameter analysis to reliably detect infected red blood cells (iRBCs). We recently described a novel and simpler approach to parasite detection based on flow cytometric measurement of scattered light depolarization caused by hemozoin (Hz), a pigment formed by parasite digestion of hemoglobin in iRBCs. Depolarization measurement by flow cytometry was described in 1987; however, patent issues restricted its use to a single manufacturer's hematology analyzers until 2009. Although we recently demonstrated that depolarization measurement of Hz, easily implemented on a bench top flow cytometer (Cyflow), provided useful information for malaria work, doubts regarding its application and utility remain in both the flow cytometry and malaria communities, at least in part because instrument manufacturers do not offer the option of measuring depolarized scatter. Under such circumstances, providing other researchers with guidance as to how to do this seemed to offer the most expeditious way to resolve the issue. We accordingly examined how several commercially available flow cytometers (CyFlow SL, MoFLo, Attune and Accuri C6) could be modified to detect depolarization due to the presence of free Hz on solution, or of Hz in leukocytes or erythrocytes from rodent or human blood. All were readily adapted, with substantially equivalent results obtained with lasers emitting over a wide wavelength range. Other instruments now available may also be modifiable for Hz measurement. Cytometric detection of Hz using depolarization is useful to study different aspects of malaria. Adding additional parameters, such as DNA content and base composition and RNA content, can demonstrably provide improved accuracy and sensitivity of parasite detection and characterization, allowing malaria researchers and eventually clinicians to benefit from cytometric technology. © 2015 International Society for Advancement of Cytometry
A Cre‐inducible fluorescent reporter for observing apical membrane dynamics
Authors: Pan Xinchao , Schnell Ulrike , Karner Courtney M. , Small Erin V. , Carroll Thomas J. 
Published: March 2015

SummaryThe ability to image living tissues with fluorescent proteins has revolutionized the fields of cell and developmental biology. Fusions between fluorescent proteins and various polypeptides are allowing scientists to image tissues with sub‐cellular resolution. Here, we describe the generation and activity of a genetically engineered mouse line expressing a fusion between the green fluorescent protein (GFP) and the apically localized protein Crumbs3 (Crb3). This reporter drives Cre‐inducible expression of Crb3–GFP under control of the EF1a regulatory domains. The fusion protein is broadly expressed in embryonic and adult tissues and shows apical restriction in the majority of epithelial cell types. It displays a variably penetrant gain of function activity in the neural tube. However, in several cell types, over‐expression of Crb3 does not appear to have any effect on normal development or maintenance. Detailed analysis of kidneys expressing this reporter indicates normal morphology and function highlighting the utility for live imaging. Thus, the EF1aCrb3–GFP mouse line will be of broad use for studying membrane and/or tissue dynamics in living tissues. genesis 53:285–293, 2015. © 2015 Wiley Periodicals, Inc.
Genetic structure in insular and mainland populations of house sparrows (Passer domesticus) and their hemosporidian parasites
Authors: Bichet Coraline , Moodley Yoshan , Penn Dustin J. , Sorci Gabriele , Garnier Stéphane 
Published: March 2015

AbstractSmall and isolated populations usually exhibit low levels of genetic variability, and thus, they are expected to have a lower capacity to adapt to changes in environmental conditions, such as exposure to pathogens and parasites. Comparing the genetic variability of selectively neutral versus functional loci allows one to assess the evolutionary history of populations and their future evolutionary potential. The genes of the major histocompatibility complex (MHC) control immune recognition of parasites, and their unusually high diversity is genes which is likely driven by parasite‐mediated balancing selection. Here, we examined diversity and differentiation of neutral microsatellite loci and functionalMHCclass I genes in house sparrows (Passer domesticus), living in six insular and six mainland populations, and we aimed to determine whether their diversity or differentiation correlates with the diversity and the prevalence of infection of hemosporidian parasites. We found that island bird populations tended to have lower neutral genetic variability, whereasMHCvariability gene was similar between island and mainland populations. Similarly, island populations tended to show greater genetic differentiation than mainland populations, especially at microsatellite markers. The maintenance ofMHCgenetic diversity and its less marked structure in the island populations could be attributed to balancing‐selection. The greaterMHCdifferentiation among populations was negatively correlated with similarity in blood parasites (prevalence and diversity of parasite strains) between populations. Even at low prevalence and small geographical scale, haemosporidian parasites might contribute to structure the variability of immune genes among populations of hosts.
Relationships between climate and growth of Gymnocypris selincuoensis in the Tibetan Plateau
Authors: Tao Juan , Chen Yifeng , He Dekui , Ding Chengzhi 
Published: March 2015

AbstractThe consequences of climate change are becoming increasingly evident in the Tibetan Plateau, represented by glaciers retreating and lakes expanding, but the biological response to climate change by plateau–lake ecosystems is poorly known. In this study, we applied dendrochronology methods to develop a growth index chronology with otolith increment widths of Selincuo naked carp (Gymnocypris selincuoensis), which is an endemic species in Lake Selincuo (4530 m), and investigated the relationships between fish growth and climate variables (regional and global) in the last three decades. A correlation analysis and principle component regression analysis between regional climate factors and the growth index chronology indicated that the growth of G. selincuoensis was significantly and positively correlated with length of the growing season and temperature‐related variables, particularly during the growing season. Most of global climate variables, which are relevant to the Asian monsoon and the midlatitude westerlies, such as El Nino Southern Oscillation Index, the Arctic Oscillation, North Atlantic Oscillation, and North America Pattern, showed negative but not significant correlations with the annual growth of Selincuo naked carp. This may have resulted from the high elevation of the Tibetan Plateau and the high mountains surrounding this area. In comparison, the Pacific Decade Oscillation (PDO) negatively affected the growth of G. selincuoensis. The reason maybe that enhancement of the PDO can lead to cold conditions in this area. Taken together, the results indicate that the Tibetan Plateau fish has been affected by global climate change, particularly during the growing season, and global climate change likely has important effects on productivity of aquatic ecosystems in this area.
The relationship between back pain and mortality in older adults varies with disability and gender: Results from the Cambridge City over‐75s Cohort (CC75C) study
Authors: Docking R.E. , Fleming J. , Brayne C. , Zhao J. , Macfarlane G.J. , Jones G.T. ,   Cambridge City over‐75s Cohort (CC75C) study collaboration
Published: March 2015

AbstractBackgroundThis study aims to determine whether older adults reporting back pain (BP) are at increased risk of premature mortality, specifically, to examine the association with disabling/non‐disabling pain separately.MethodsParticipants aged ≥75 years were recruited to the Cambridge City over‐75s Cohort (CC75C) study. Participants answered interviewer‐administered questions on BP and were followed up until death. The relationship between BP and mortality was examined using Cox regression, adjusted for potential confounding factors. Separate models were computed for men and women.ResultsFrom 1174 individuals with BP data, the date of death was known for 1158 (99%). A significant association was found between disabling BP and mortality (hazard ratio: 1.4; 95% confidence interval: 1.1–1.8) and this remained, albeit of borderline significance, following adjustment for socio‐demographic variables and potential disease markers (1.3; 0.99–1.7). Further, this association was found to vary with sex: women experienced a 40% increase in the risk of mortality associated with disabling BP (1.4; 1.1–1.9), whereas no such increase was observed for men (1.0; 0.5–1.9). Participants with non‐disabling BP were not at increased risk of mortality.ConclusionsThis study confirmed previous findings regarding the relationship between pain and excess mortality. Further, we have shown that, among older adults, this association is specific to disabling pain and to women. Clinicians should be aware not only of the short‐term implications of disabling BP but also the longer‐term effects. Future research should attempt to understand the mechanisms underpinning this relationship to avoid excess mortality and should aim to determine why the relationship differs in men and women.
Aluminium, gallium, and molybdenum toxicity to the tropical marine microalga Isochrysis galbana
Authors: Trenfield Melanie A. , van Dam Joost W. , Harford Andrew J. , Parry David , Streten Claire , Gibb Karen , van Dam Rick A. 
Published: March 2015

Abstract

There is a shortage of established chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms. The authors tested the suitability of the tropical microalga Isochrysis galbana for use in routine ecotoxicology and assessed the effects of 72-h exposures to copper (Cu, a reference toxicant), aluminium (Al), gallium (Ga), and molybdenum (Mo), key metals of alumina refinery discharge, on the growth of I. galbana at 3 temperatures: 24 °C, 28 °C, and 31 °C. The sensitivity of both I. galbana and the test method was validated by the response to Cu exposure, with 10% and 50% effect concentrations (EC10 and EC50) of 2.5 μg/L and 18 μg/L, respectively. The EC10 and EC50 values for total Al at 28 °C were 640 μg/L and 3045 μg/L, respectively. The toxicity of both Cu and Al at 24 °C and 31 °C was similar to that at 28 °C. There was no measurable toxicity from dissolved Ga exposures of up to 6000 μg/L or exposures to dissolved Mo of up to 9500 μg/L. Solubility limits at 28 °C for the dissolved fractions (&lt;10 kDa) of Al, Ga, and Mo were approximately 650 μg/L Al, &gt;7000 μg/L Ga, and &gt;6000 μg/L Mo. In test solutions containing &gt;650 μg/L total Al, dissolved and precipitated forms of Al were present, with precipitated Al becoming more dominant as total Al increased. The test method proved suitable for routine ecotoxicology, with I. galbana showing sensitivity to Cu but Al, Ga, and Mo exhibiting little to no toxicity to this species. Environ Toxicol Chem 2015;34:1833–1840. © 2015 SETAC
A hybrid implicit scheme for solving Navier–Stokes equations
Authors: Wang Gang , Mian Haris Hameed , Liu Yi , Ye Zhengyin 
Published: March 2015

SummaryA hybrid implicit scheme is developed in this study to solve 3D compressible Navier–Stokes equations on a hybrid unstructured mesh. An approximate evaluation technique for the residual term at a new time level is presented according to the analysis of the main physical mechanism introduced by the lower–upper symmetric Gauss–Seidel (LU‐SGS) relaxation‐based backward Euler implicit method. The residual evaluation method is computationally inexpensive because it does not require flux calculations for every cell surface. The approximated new time residual can be obtained without considerable computational effort; thus, a point‐implicit scheme with a multigrid property is designed to march a further time step after the previous LU‐SGS‐based backward Euler stage. This step leads to the principal ingredient of the presented two‐stage hybrid implicit scheme.To investigate the convergence behavior and performance of the two‐stage hybrid implicit scheme, 2D and 3D viscous flows around the NACA0012 airfoil, NHLP 2D multi‐airfoil, and DLR‐F6 wing–body–pylon–nacelle configuration are simulated by using different grid types. The convergence histories of the single LU‐SGS‐based backward Euler scheme and the presented two‐stage hybrid implicit scheme are analyzed and compared for each test case. The test results show that the hybrid implicit scheme is more efficient and robust than the single‐stage LU‐SGS scheme. Copyright © 2015 John Wiley & Sons, Ltd.
Adaptive Evolutionary Neural Networks for Forecasting and Trading without a Data‐Snooping Bias
Authors: Sermpinis Georgios , Verousis Thanos , Theofilatos Konstantinos 
Published: March 2015

AbstractIn this paper, we present two neural‐network‐based techniques: an adaptive evolutionary multilayer perceptron (aDEMLP) and an adaptive evolutionary wavelet neural network (aDEWNN). The two models are applied to the task of forecasting and trading the SPDR Dow Jones Industrial Average (DIA), the iShares NYSE Composite Index Fund (NYC) and the SPDR S&P 500 (SPY) exchange‐traded funds (ETFs). We benchmark their performance against two traditional MLP and WNN architectures, a smooth transition autoregressive model (STAR), a moving average convergence/divergence model (MACD) and a random walk model. We show that the proposed architectures present superior forecasting and trading performance compared to the benchmarks and are free from the limitations of the traditional neural networks such as the data‐snooping bias and the time‐consuming and biased processes involved in optimizing their parameters. Copyright © 2015 John Wiley & Sons, Ltd.