bluuebunny/crossref_metadata_2025 huggingface dataset:
ColXα1 is a stromal component that colocalizes with elastin in the breast tumor extracellular matrix
Authors: Wang Yihong , Lu Shaolei , Xiong Jinjun , Singh Kamaljeet , Hui Yiang , Zhao Chaohui , Brodsky Alexander S , Yang Dongfang , Jolly Grant , Ouseph Madhu , Schorl Christoph , DeLellis Ronald A , Resnick Murray B
Published: September 2018

The tumor microenvironment regulates tissue development and homeostasis, and its dysregulation contributes to neoplastic progression. Increased expression of type X collagen α‐1 (ColXα1) in tumor‐associated stroma correlates with poor pathologic response to neoadjuvant chemotherapy in estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2)‐positive breast cancers. Evaluation of ColXα1 expression patterns suggests a potential connection with elastin fibers. To investigate the possible interaction between ColXα1 and elastin, we evaluated the expression of ColXα1 in relation to elastin fibers in normal breast tissue, ductal carcinoma in situ, and invasive breast carcinomas at cellular and subcellular levels. Our findings demonstrate that ColXα1 colocalizes with elastin in invasive breast cancer‐associated stroma by immunohistochemistry, immunofluorescence, and electron microscopy. In 212 invasive breast carcinomas, this complex was aberrantly and selectively expressed in tumor extracellular matrix in 79% of ER+/HER2−, 80% of ER+/HER2+, 76% of ER−/HER2+, and 58% of triple negative breast cancers. In contrast, ColXα1 was generally absent, while elastin was present perivascularly in normal breast tissue. ColXα1 and elastin were coexpressed in 58% of ductal carcinoma in situ (DCIS) in periductal areas. In mass‐forming DCIS with desmoplastic stroma, the complex was intensely expressed in periductal areas as well as within the tumor‐associated stroma in all cases. Our data suggest that the breast carcinoma neoplastic process may involve aberrant expression of ColXα1 and elastin in the tumor microenvironment emerging early at the DCIS stage. Enrichment of these complexes in tumor‐associated stroma may represent a stromal signature indicative of intrinsic differences between breast cancers. These findings shed light on investigation into the role of aberrant collagen complex expression in tumorigenesis and tumor progression which may be leveraged in therapeutic and theranostic applications.
Partial nephrectomy for T1b and T2 renal masses: A subtle paradigm shift and a new synthesis
Authors: Derweesh Ithaar H. , Ryan Stephen T. , Hamilton Zachary A.
Published: September 2018

Recent reports suggest oncologic equivalence between partial and radical nephrectomy for T1b and T2 renal cell carcinoma, with improved renal functional outcomes for partial nephrectomy. In this issue of Cancer, Ristau and colleagues provide further understanding of the limitations of nephron preservation in larger masses; and, ultimately, a randomized clinical trial may provide the most efficacious means of answering continued controversies and providing insight.

See also pages 3839‐48.
Synthesis and Investigation of 2,3,5,6‐Tetra‐(1H‐tetrazol‐5‐yl)pyrazine Based Energetic Materials
Authors: Witkowski Tomasz G. , Richardson Paul , Gabidullin Bulat , Hu Anguang , Murugesu Muralee
Published: September 2018

The structures and properties of several energetic compounds based on a high‐nitrogen‐content anion, namely 2,3,5,6‐tetra(1H‐tetrazol‐5‐yl)pyrazine (H4TTP) are reported here for the first time. These energetic salts were synthesized by reacting H4TTP with various alkali metal hydroxides (sodium, potassium, rubidium, caesium) and N‐based (ammonia, hydrazine, hydroxylamine, guanidine carbonate, aminoguanidine bicarbonate). The resulting materials were comprehensively characterized by multinuclear (1H, 13C) NMR spectroscopy, infrared spectroscopy, elemental analysis, DSC, as well as low‐temperature single‐crystal X‐ray diffraction. Heats of formation for the metal‐free species as well as detonation parameters were calculated. The presented energetic materials (EMs) show high thermal stability (207 °C≤Tdec≤300 °C), while the metal‐free ionic derivatives exhibit desirable properties such as detonation velocity (6873 m s−1≤VC‐J≤8364 m s−1), detonation pressure (14.3 GPa≤pC‐J≤24.9 GPa), and specific impulse (141.4≤Isp≤192.5 s).
Mutual coupling suppression of closely spaced microstrip antennas by ladder‐shaped conducting wall
Authors: Alsultan Raghad Ghalib , Yetkin Gölge Ögücü
Published: September 2018

To reduce the mutual coupling between two closely microstrip antennas (MSAs), a novel ladder‐shaped conducting wall structure (LSCW) has been proposed and presented in this paper. This structure consists of two ladder shaped strips of copper printed on an FR‐4 dielectric substrate. It is inserted between the MSAs, and also some part of LSCW surrounds a portion of each antenna. The developed compact multiple‐input multiple‐output system has a compact size of 50 × 25 mm2, and dual‐band design resonates at 4.45 or 10.3‐GHz frequencies depending on the dimensions of LSCW structure. It can be used in many wireless applications in C (4‐8 GHz) band or X (8‐12 GHz) band. The value of VSWR ≤1.5 for both resonant frequencies. Also, the diversity performance, such as the envelope correlation coefficient, the diversity gain, and the total efficiency are calculated and compared. A prototype is fabricated, and the measured mutual coupling shows that the isolation between the antenna ports has been enhanced about 50 dB at 4.45 GHz and 40 dB at 10.3 GHz.
Work effectively with BIT to assist student‐veterans
Authors: Hope Joan
Published: September 2018

When you work with student‐veterans as a disability services provider, you probably collaborate with other offices and groups on and off campus. The Veterans Affairs Administration and your institution's veteran support office are a few good resources. Your college or university's behavioral intervention team can also assist in helping student‐veterans adjust to campus life and meet the goals they set when they enrolled.
Understanding the population consequences of disturbance
Authors: Pirotta Enrico , Booth Cormac G. , Costa Daniel P. , Fleishman Erica , Kraus Scott D. , Lusseau David , Moretti David , New Leslie F. , Schick Robert S. , Schwarz Lisa K. , Simmons Samantha E. , Thomas Len , Tyack Peter L. , Weise Michael J. , Wells Randall S. , Harwood John
Published: September 2018

Managing the nonlethal effects of disturbance on wildlife populations has been a long‐term goal for decision makers, managers, and ecologists, and assessment of these effects is currently required by European Union and United States legislation. However, robust assessment of these effects is challenging. The management of human activities that have nonlethal effects on wildlife is a specific example of a fundamental ecological problem: how to understand the population‐level consequences of changes in the behavior or physiology of individual animals that are caused by external stressors. In this study, we review recent applications of a conceptual framework for assessing and predicting these consequences for marine mammal populations. We explore the range of models that can be used to formalize the approach and we identify critical research gaps. We also provide a decision tree that can be used to select the most appropriate model structure given the available data. Synthesis and applications: The implementation of this framework has moved the focus of discussion of the management of nonlethal disturbances on marine mammal populations away from a rhetorical debate about defining negligible impact and toward a quantitative understanding of long‐term population‐level effects. Here we demonstrate the framework's general applicability to other marine and terrestrial systems and show how it can support integrated modeling of the proximate and ultimate mechanisms that regulate trait‐mediated, indirect interactions in ecological communities, that is, the nonconsumptive effects of a predator or stressor on a species' behavior, physiology, or life history.
Variation in the vital rates of an Antarctic marine predator: the role of individual heterogeneity
Authors: Paterson J. Terrill , Rotella Jay. J. , Link William A. , Garrott Robert
Published: September 2018

Variation in life‐history traits such as lifespan and lifetime reproductive output is thought to arise, in part, due to among‐individual differences in the underlying probabilities of survival and reproduction. However, the stochastic nature of demographic processes can also generate considerable variation in fitness‐related traits among otherwise‐identical individuals. An improved understanding of life‐history evolution and population dynamics therefore depends on evaluating the relative role of each of these processes. Here, we used a 33‐yr data set with reproductive histories for 1,274 female Weddell seals from Erebus Bay, Antarctica, to assess the strength of evidence for among‐individual heterogeneity in the probabilities of survival and reproduction, while accounting for multiple other sources of variation in vital rates. Our analysis used recent advances in Bayesian model selection techniques and diagnostics to directly compare model fit and predictive power between models that included individual effects on survival and reproduction to those that did not. We found strong evidence for costs of reproduction to both survival and future reproduction, with breeders having rates of survival and subsequent reproduction that were 3% and 6% lower than rates for non‐breeders. We detected age‐related changes in the rates of survival and reproduction, but the patterns differed for the two rates. Survival rates steadily declined from 0.92 at age 7 to 0.56 at the maximal age of 31 yr. In contrast, reproductive rates increased from 0.68 at age 7 to 0.79 at age 16 and then steadily declined to 0.37 for the oldest females. Models that included individual effects explained more variation in observed life histories and had better estimated predictive power than those that did not, indicating their importance in understanding sources of variation among individuals in life‐history traits. We found that among‐individual heterogeneity in survival was small relative to that for reproduction. Our study, which found patterns of variation in vital rates that are consistent with a series of predictions from life‐history theory, is the first to provide a thorough assessment of variation in important vital rates for a long‐lived, high‐latitude marine mammal while taking full advantage of recent developments in model evaluation.
A fluorescence toolbox: A review of investigation of electrophoretic separations, process, and interfaces
Authors: Thompson S. , Pappas Dimitri
Published: September 2018

This review focuses on fluorescence spectroscopy techniques for the investigation of electrophoretic separations. Fluorescence has been used as a sensitive detector for capillary, gel, and microchip electrophoresis for decades. However, advanced fluorescence methods can be used to study transport, interfacial phenomena, intermolecular and affinity interactions, and other processes that occur during separation. This so‐called spectroscopic toolkit can be implemented to understand fundamental behavior in electrophoresis and electrokinetic chromatography. Techniques such as fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and fluorescence anisotropy are discussed in relation to electrophoretic separations. Newer methods such as super‐resolution microscope are also introduced.
Hydro‐geomorphic behavior of contrasting tropical landscapes and critical zone response to changing climate
Authors: Dialynas Yannis G. , Bras Rafael L.
Published: September 2018

The potentially important influence of climate change on landscape evolution and on critical zone processes is not sufficiently understood. The relative contribution of hydro‐climatic factors on hillslope erosion rates may significantly vary with topography at the watershed scale. The objective of this study is to quantify the hydro‐geomorphic behavior of two contrasting landscapes in response to different climate change scenarios in the Luquillo Critical Zone Observatory, a site of particular geomorphological interest, in terms of hillslope erosion and rainfall‐triggered landslides. We investigate the extent to which hillslope erosion and landslide occurrence remain relatively invariant with future hydro‐climatic perturbations. The adjacent Mameyes and Icacos watersheds are studied, which are underlain by contrasting lithologies. A high resolution coupled hydro‐geomorphic model based on tRIBS (Triangulated Irregular Network‐based Real‐time Integrated Basin Simulator) is used. Observations of landslide activity and hillslope erosion are used to evaluate the model performance. The process‐based model quantifies feedbacks among different hydrologic processes, landslide occurrence, and topsoil erosion and deposition. Simulations suggest that the propensity for landslide occurrence in the Luquillo Mountains is controlled by tropical storms, subsurface water flow, and by non‐climatic factors, and is expected to remain significant through 2099. The Icacos watershed, which is underlain by quartz diorite, is dominated by relatively large landslides. The relative frequency of smaller landslides is higher at the Mameyes watershed, which is underlain by volcaniclastic rock. While projections of precipitation decrease at the study site may lead to moderate decline in hillslope erosion rates, the simulated erosional potential of the two diverse landscapes likely remains significant. © 2018 John Wiley & Sons, Ltd.
Screening for gum‐producing Lactic acid bacteria in Oil palm (Elaeis guineensis) and raphia palm (Raphia regalis) sap from South‐West Nigeria
Authors: Adamu‐Governor Oniovosa Leonard , Shittu Taofik A. , Afolabi Oluwatoyin Rebecca , Uzochukwu Sylvia Veronica Ajagugha
Published: September 2018

Lactic acid bacteria have wide applications in food processing. Lactic acid bacteria produced exopolysaccharides (EPS) which could be used as possible replacer for commercial stabilizer and thickeners produced by nonfood grade bacteria. Seventy‐two samples of Oil and Raphia palm sap were collected in eighteen locations across South‐Western Nigeria and screened for exopolysaccharide production in 6% sucrose agar using streaked plate method. Four hundred EPS‐producing bacteria (EPB) isolated were clustered based on morphological characteristics into two broad groups and preliminary screened for EPS‐producing capacity. Twenty representative of EPB were selected from the broad groups for tentative identification by API 50CHL and 10 high yielding EPB were selected for large‐scale EPS production. Each strain was inoculated into 6% sucrose broth with 3% (v/v) preculture grown overnight in a 1.5 ml flask and incubated at 37°C for 72 hr. The EPSs were purified and freeze‐dried prior to quantification of yields. EPS‐producing bacteria were identified as Leuconostoc lactis, Lactobacillus fermentum, Lactobacillus delbrueckii ssp. lactis, L. delbrueckii ssp. delbrueckii, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus crispatus, and Leuconostoc mesenteroides ssp. mesenteroides/dextranicum. EPS yield ranged from 132–810.75 mg/L and EPS‐producing potential of lactic acid bacteria (LAB) strains ranged; 36% (132–245 mg/L), 36% (250–460 mg/L), and 28% (461–820 mg/L). L. plantarum had the highest EPS yield of 810.75 mg/L whereas L. crispatus had the least yield 242.5 mg/L. These results suggest that majority of LAB in palm wine saps are gum‐producing bacteria. Leuconostoc and Lactobacillus were the most abundant LAB found in this study while L. plantarum could have applications as potential starter cultures for the production of exopolysaccharides (EPS) at industrial level.
Physicochemical characterization and antioxidant activity of Palestinian honey samples
Authors: Imtara Hamada , Elamine Youssef , Lyoussi Badiâa
Published: September 2018

Physicochemical characteristics, main minerals, and antioxidant activity were determined for Palestinian honey samples belonging to different floral and geographical origins. The features of the analyzed samples were within the established international standards for honey quality control. One clear exception was the hydroxymethylfurfural (HMF) of the Ziziphus sample purchased from the Jericho region, which is the lowest city in the word characterized by a hot desert climate. The observed HMF value was 81.86 ± 2.64 mg/kg being two folds the maximum allowed in honey samples (40 mg/kg). As a second objective of the present work, the parameters were divided into two groups with different discriminatory power. The assessed physicochemical parameters, and the antioxidant activities, specific to the botanical origin discrimination, were used to run the first PCA. A strong correlation could be seen between the bioactive compounds and the antioxidant activities despite the geographical origin of the samples. Thyme and Ziziphus samples were the best samples, while citrus sample presented the lowest activity. Regarding the geographical discrimination, Ash and mineral contents in addition to the electrical conductivity were used. The output PCA conserved high represent ability of the data in the two‐first components being 82.72% and 9.60%. A little discrimination between the samples produced in the north and those produced in the south of the country, but it was not perfect. The intervention of the botanical variability could be the reason.
CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons
Authors: Fülle Lorenz , Offermann Nina , Hansen Jan Niklas , Breithausen Björn , Erazo Anna Belen , Schanz Oliver , Radau Luca , Gondorf Fabian , Knöpper Konrad , Alferink Judith , Abdullah Zeinab , Neumann Harald , Weighardt Heike , Henneberger Christian , Halle Annett , Förster Irmgard
Published: September 2018

Chemokines are important signaling molecules in the immune and nervous system. Using a fluorescence reporter mouse model, we demonstrate that the chemokine CCL17, a ligand of the chemokine receptor CCR4, is produced in the murine brain, particularly in a subset of hippocampal CA1 neurons. We found that basal expression of Ccl17 in hippocampal neurons was strongly enhanced by peripheral challenge with lipopolysaccharide (LPS). LPS‐mediated induction of Ccl17 in the hippocampus was dependent on local tumor necrosis factor (TNF) signaling, whereas upregulation of Ccl22 required granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). CCL17 deficiency resulted in a diminished microglia density under homeostatic and inflammatory conditions. Further, microglia from naïve Ccl17‐deficient mice possessed a reduced cellular volume and a more polarized process tree as assessed by computer‐assisted imaging analysis. Regarding the overall branching, cell surface area, and total tree length, the morphology of microglia from naïve Ccl17‐deficient mice resembled that of microglia from wild‐type mice after LPS stimulation. In line, electrophysiological recordings indicated that CCL17 downmodulates basal synaptic transmission at CA3–CA1 Schaffer collaterals in acute slices from naïve but not LPS‐treated animals. Taken together, our data identify CCL17 as a homeostatic and inducible neuromodulatory chemokine affecting the presence and morphology of microglia and synaptic transmission in the hippocampus.
Alkali endohedrals of C24(BN)12 heterofullerenes: A DFT aqueous phase study
Authors: Karachi Nima , Boshra Asadollah
Published: September 2018

Results achieved by density functional theory have been reported in terms of the energetic, electronic, vibrational frequencies, and thermochemical functions related to alkali metal endohedral derivatives of C24(BN)12 heterofullerenes in gas and aqueous phases. The endohedral heterofullerene cations are regarded as highly polar structures in both gas and aqueous phases. They indicate thermochemically approved solvation in the aqueous phase. The inclusion reactions are exothermic and spontaneous in the aqueous solution except for K+ cation. The calculated standard reduction potentials of alkali cation endohedral derivatives suggest them as potent oxidizing agents.
Determinants of patient participation for safer care: A qualitative study of physicians' experiences and perceptions
Authors: Schildmeijer Kristina , Nilsen Per , Ericsson Carin , Broström Anders , Skagerström Janna
Published: September 2018

Objective

There is a paucity of research on physicians' perspectives on involving patients to achieve safer care. This study aims to explore determinants of patient participation for safer care, according to physicians in Swedish health care.

Methods

We used a deductive descriptive design, applying qualitative content analysis based on the Capability‐Opportunity‐Motivation‐Behaviour framework. Semi‐structured interviews were conducted with 13 physicians in different types of health care units, to achieve a heterogeneous sample. The main outcome measure was barriers and facilitators to patient participation of potential relevance for patient safety.

Results

Analysis of the data yielded 14 determinants (ie, subcategories) functioning as barriers and/or facilitators to patient participation of potential relevance for patient safety. These determinants were mapped to five categories: physicians' capability to involve patients in their care; patients' capability to become involved in their care, as perceived by the physicians; physicians' opportunity to achieve patient participation in their care; physicians' motivation to involve patients in their care; and patients' motivation to become involved in their care, as perceived by the physicians.

Conclusion

There are many barriers to patient participation to achieve safer care. There are also facilitators, but these tend to depend on initiatives of individual physicians and patients, because organizational‐level support may be lacking. Many of the determinants are interdependent, with physicians' perceived time constraints influencing other barriers.
Sex differences in personality are larger in gender equal countries: Replicating and extending a surprising finding
Authors: Mac Giolla Erik , Kajonius Petri J.
Published: September 2018

Sex differences in personality have been shown to be larger in more gender equal countries. We advance this research by using an extensive personality measure, the IPIP‐NEO‐120, with large country samples (N > 1000), from 22 countries. Furthermore, to capture the multidimensionality of personality we measure sex differences with a multivariate effect size (Mahalanobis distance D). Results indicate that past research, using univariate measures of effect size, have underestimated the size of between‐country sex differences in personality. Confirming past research, there was a strong correlation (r = .69) between a country's sex differences in personality and their Gender Equality Index. Additional analyses showed that women typically score higher than men on all five trait factors (Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness), and that these relative differences are larger in more gender equal countries. We speculate that as gender equality increases both men and women gravitate towards their traditional gender roles.
Aiming for Authenticity: Successes and Struggles of an Attempt to Increase Authenticity in Writing
Authors: Behizadeh Nadia
Published: September 2018

The author analyzed an attempt to increase authenticity of writing in a middle school English language arts classroom. Drawing on a grounded theory of authenticity developed based on stated needs of a diverse group of students, the author and classroom teacher designed curriculum that sought to help students choose a valued topic, emphasize meaning making while developing writing skills and strategies, and have an impact on an audience. Students were also provided with opportunities to share in‐process and final work with others. Curricular attempts to enact these proposed factors of authentic writing in a personal narrative project are detailed, along with successes and struggles with implementing each factor. Findings highlight the importance of students writing for an actual, intended audience instead of an imagined one. Additionally, the author discusses how social justice education may provide a unifying curricular framework that strengthens students’ sense of audience and purpose.
Bioactive composites based on double network approach with tailored mechanical, physico‐chemical, and biological features
Authors: D'Amora Ugo , Ronca Alfredo , Raucci Maria Grazia , Lin Hai , Soriente Alessandra , Fan Yujiang , Zhang Xingdong , Ambrosio Luigi
Published: September 2018

Hyaluronic acid (HA)‐based hydrogels are one of the most promising naturally derived biomaterials for tissue engineering applications, as they can play an important role in many key cellular processes. In this study, HA was chemically functionalized with photo‐cross‐linkable motifs by reacting with methacrylic anhydride (MA) to obtain methacrylated hyaluronic acid (MeHA). A range of MA/HA molar ratios was used to obtain different degrees of substitution (DS) ranging from 3.5% to 74.5%, as showed by nuclear magnetic resonance and attenuated total reflection spectroscopy. By fine tuning the DS, the chemical reaction parameters, and the polymer concentration, it was demonstrated the possibility to tailor their mechanical features. Double network (DN) hydrogels were prepared through the synergic use of MeHA and polyethylene glycole diacrylate (PEGDA). To improve the biological properties of DN hydrogels, bioactive solid signals such as hydroxyapatite nanoparticles (HAp) prepared by sol–gel approach were used in combination with DN hydrogels to obtain an advanced composite material with dual function in terms of mechanical and biological support for soft/hard tissue formation. The results highlighted that composite‐DN hydrogels showed a 10‐time increase of the storage modulus, if compared to neat MeHA, and an early alkaline phosphatase expression from human mesenchymal stem cells in basal medium. This work can be considered a first systematic approach for the designing of photo‐cross‐linkable hydrogels, based on a combination of natural/synthetic polymers and HAp, that could be applied in three‐dimensional additive manufacturing techniques such as stereolithography. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3079–3089, 2018.
A 3D in vitro model of the dermoepidermal junction amenable to mechanical testing
Authors: Jung Jangwook P. , Lin Wei‐Han , Riddle Megan J. , Tolar Jakub , Ogle Brenda M.
Published: September 2018

Recessive dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in collagen‐type VII gene critical for the dermoepidermal junction (DEJ) formation. Neither tissues of animal models nor currently available in vitro models are amenable to the quantitative assessment of mechanical adhesion between dermal and epidermal layers. Here, we created a 3D in vitro DEJ model using extracellular matrix (ECM) proteins of the DEJ anchored to a poly(ethylene glycol)‐based slab (termed ECM composites) and seeded with human keratinocytes and dermal fibroblasts. Keratinocytes and fibroblasts of healthy individuals were well maintained in the ECM composite and showed the expression of collagen type VII over a 2‐week period. The ECM composites with healthy keratinocytes and fibroblasts exhibited yield stress associated with the separation of the model DEJ at 0.268 ± 0.057 kPa. When we benchmarked this measure of adhesive strength with that of the model DEJ fabricated with cells of individuals with RDEB, the yield stress was significantly lower (0.153 ± 0.064 kPa) consistent with our current mechanistic understanding of RDEB. In summary, a 3D in vitro model DEJ was developed for quantification of mechanical adhesion between epidermal‐ and dermal‐mimicking layers, which can be utilized for assessment of mechanical adhesion of the model DEJ applicable for Epidermolysis Bullosa‐associated therapeutics. © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3231–3238, 2018.
Retracted: Effects of RNA interference–mediated E‐selectin gene silencing on cell adhesion molecule expression and cell‐cell adhesion in vascular endothelial cells in mice with immunologic contact urticaria
Authors: Meng Zu‐Dong , Wang Xiao‐Lan , Du Tian‐Ping , Wang Yu , Qin Gui‐Fang , Zhao Hong‐Bo , Chen Yu‐Jie , Tian Bo
Published: September 2018

Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent. Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of RNA interference–mediated E‐selectin (
SELE) gene silencing on cell adhesion molecule expression and on cell‐cell adhesion in vascular endothelial cells (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the successful establishment of mouse models of ICU induced by antidinitrophenol immunoglobulin E (IgE) combining 2,4‐dinitrofluorobenzene challenge, enzyme‐linked immunosorbent assay and immunohistochemistry were used to measure the levels of IgE, interleukin 4 (IL‐4), interferon‐γ (IFN‐γ), and histamine as well as the positive expression rate of SELE, respectively. The siRNA‐
SELE vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse‐transcription polymerase chain reaction and Western blot assay to determine the relative expression of SELE, eosinophil cationic protein (ECP), intercellular adhesion molecule 1 (ICAM‐1), L‐selectin (CD62L), and the alpha chain of leukocyte function–associated antigen‐1 (CD11a). Adhesion assay was then performed to assess the cell adhesion ability in VECs. Elevated levels of IgE, IL‐4, IFN‐γ, and histamine and increased positive expression rate of SELE were indicative of successful establishment of mouse models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM‐1, CD62L, and CD11a were highest in the OE‐
SELE group. Besides, cell adhesion ability of VECs was notably promoted. Collectively, the current study define the potential role of
SELE silencing as an inhibitor to ICU development by inhibiting cell adhesion ability of VECs.
Expression of exosomal microRNAs during chondrogenic differentiation of human bone mesenchymal stem cells
Authors: Sun Hao , Hu Shu , Zhang Ziji , Lun Jiayong , Liao Weiming , Zhang Zhiqi
Published: September 2018

The aim of the current study was to compare the expression of microRNAs (miRNAs) in exosomes derived from human bone mesenchymal stem cells (hBMSCs) with and without chondrogenic induction. Exosomes derived from hBMSCs were isolated and identified. Microarray analysis was performed to compare miRNA expression between exosomes derived from hBMSCs with and without chondrogenic induction, and quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to verify the differentially expressed miRNAs. hBMSCs were transfected with miRNA mimic to extract miRNA‐overexpressed exosomes. The results showed that most exosomes exhibited a cup‐shaped or round‐shaped morphology with a diameter of approximately 50‐200 nm and expressed CD9 and CD63. We detected 141 miRNAs that were differentially expressed with and without chondrogenic induction by over a twofold change, including 35 upregulated miRNAs, such as miR‐1246, miR‐1290, miR‐193a‐5p, miR‐320c, and miR‐92a, and 106 downregulated miRNAs, such as miR‐377‐3p and miR‐6891‐5p. qRT‐PCR analysis validated these results. Exosomes derived from hBMSCs overexpressing miR‐320c were more efficient than normal exosomes derived from control hBMSCs at promoting osteoarthritis chondrocyte proliferation, down‐regulated matrix metallopeptidase 13 and up‐regulated (sex determining region Y)‐box 9 expression during hBMSC chondrogenic differentiation. In conclusion, we identified a group of upregulated miRNAs in exosomes derived from hBMSCs with chondrogenic induction that may play an important role in mesenchymal stem cell‐derived exosomes in cartilage regeneration and, ultimately, the treatment of arthritis. We demonstrated the potential of these modified exosomes in the development of novel therapeutic strategies.
Silencing of microRNA‐375 affects immune function in mice with liver failure by upregulating astrocyte elevated gene‐1 through reducing apoptosis of Kupffer cells
Authors: Ke Qing‐Hong , Chen Hai‐Yong , He Zeng‐Lei , Lv Zhen , Xu Xiao‐Feng , Qian Yi‐Gang , Zheng Shu‐Sen
Published: September 2018

This study aims to investigate how microRNA‐375 (miR‐375) improves immune function by regulating liver macrophages (Kupffer cells) in mice with liver failure. Forty mice were divided into ConA‐1h, ConA‐3h, ConA‐6h, and control groups, with 10 mice in each group. Mice models of liver failure were established by injecting concanavalin A (ConA) solution via the tail veins of mice, and then primary Kupffer cells were isolated and cultured. Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme‐linked immunosorbent assay were conducted to examine the expressions of miR‐375, astrocyte elevated gene‐1 (AEG‐1), interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and IL‐1β in Kupffer cells of mice with liver failure as well as after silencing of miR‐375. Flow cytometry was used to determine cell apoptosis. During the liver failure process, miR‐375, IL‐6, TNF‐α, and IL‐1β expressions were increased over time, while AEG‐1 expression decreased over time in the control, ConA‐1h, ConA‐3h, and ConA‐6h groups. Opposite alternations were observed after silencing of miR‐375. Dual‐luciferase reporter gene assay showed that AEG‐1 was a target gene of miR‐375. Flow cytometry determination showed that the ratio of apoptotic Kupffer cells decreased after silencing of miR‐375. Overexpression of AEG‐1 could rescue the suppression of IL‐6, TNF‐α, and IL‐1β expressions in Kupffer cells after the short‐term induction of ConA and further inhibit cell apoptosis. Our study provides evidence that miR‐375 could regulate Kupffer cells to improve immune function in mice with liver failure.
Functional characterization of the Sox2, c‐Myc, and Oct4 promoters
Authors: Chen Hao , Jin Kai , Song Jiuzhou , Zuo Qisheng , Yang Huilin , Zhang Yani , Li Bichun
Published: September 2018

To better understand the mechanisms in transcriptional regulation, we analyzed the promoters of the reprogramming key genes Sox2,
c‐Myc, and
Oct4. Here, we cloned different 5′ deletions of the goat
Sox2,
c‐Myc, and
Oct4 promoters, and evaluated their functions by green fluorescent protein reporter system and dual‐luciferase reporter system. Site‐directed mugagenesis and epigenetic modifiers were used to explore the influence of transcription binding sites and epigenetic status on the promoters. The results suggested that the basal promoters were located in the − 109 to 49, − 147 to 1, and − 96 to 30 bp regions of the
Sox2,
c‐Myc, and
Oct4 promoters. The transcription factors that identified to influence the
Sox2,
c‐Myc, and
Oct4 promoter activities were Elf‐1 and activating protein 2 (AP‐2), C/EBP and Sp1, and Mzf1 and Sp1, respectively. The epigenetic alternation of the
Sox2,
c‐Myc, and
Oct4 promoters by 5‐aza‐2′‐deoxycytidine or/and trichostatin A significantly increased the promoter activities. In conclusion, the result determined the core promoter areas of the
Sox2,
c‐Myc, and
Oct4 genes, and identified the transcription factors that influence their promoter activities. We also verified that the
Sox2,
c‐Myc, and
Oct4 promoters were hypermethylated and hypoacetylated.
Acute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice
Authors: Gaspar Rafael Calais , Muñoz Vitor Rosetto , Kuga Gabriel Keine , Nakandakari Susana Castelo Branco Ramos , Minuzzi Luciele Guerra , Botezelli José Diego , da Silva Adelino S.R. , Cintra Dennys Esper , de Moura Leandro Pereira , Ropelle Eduardo Rochete , Pauli José Rodrigo
Published: September 2018

The obesity is a result of energy imbalance and the increase in thermogenesis seems an interesting alternative for the treatment of this disease. The mechanism of energy expenditure through thermogenesis is tightly articulated in the hypothalamus by leptin. The hypothalamic extracellular signal‐regulated kinase‐1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and mediates the sympathetic signal to the brown adipose tissue (BAT). In this context, physical exercise is one of the main interventions for the treatment of obesity. Thus, this study aimed to verify the effects of acute physical exercise on leptin‐induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese mice. Here we showed that acute physical exercise reduced the fasting glucose of obese mice and increased leptin‐induced hypothalamic p‐ERK1/2 and uncoupling protein 1 (UCP1) content in BAT (
P < 0.05). These molecular changes are accompanied by an increased oxygen uptake (VO
2) and heat production in obese exercised mice (
P < 0.05). The increased energy expenditure in the obese exercised animals occurred independently of changes in spontaneous activity. Thus, this is the first study demonstrating that acute physical exercise can increase leptin‐induced hypothalamic ERK1/2 phosphorylation and energy expenditure of obese mice.
Inhibiting role of rosiglitazone in the regulation of inflammatory response and protective effects for severe acute pancreatitis in mice
Authors: Nie Shen , Cui Xiaoya , Guo Jinping , Ma Xiaohua , Zhi Haijun , Li Shilei , Li Yong
Published: September 2018

Objectives

Our study aimed to probe the effects of rosiglitazone treatment on a severe acute pancreatitis (SAP) model induced by caerulein and investigate the underlying mechanism.

Methods

Differentially expressed messenger RNAs (mRNAs) in the mice of a SAP group were screened out by microarray analysis. The inflammatory response pathway was obtained from the online website DAVID Bioinformatics Resources 6.8. The interactions of caerulein and its target proteins were shown by search tool for interactions of chemicals (STITCH). Functional interactions of the genes associated with pancreatitis and the target proteins of caerulein were obtained with search tool for interactions of chemicals (STRING). SAP mice were established by hourly intraperitoneal injection of caerulein. Rosiglitazone was used as treatment drug, and pancreatic inflammation was assessed. The expression of Socs3 was studied by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot analysis. The expression of interleukin (IL)‐6, IL‐1b, and Egr1 were studied by RT‐PCR and Western blot analysis.

Results

The GSE77983 data were analyzed, and the results showed that Socs3 was overexpressed in SAP tissues. The inflammation response pathway in pancreas was selected by DAVID, STITCH, and STRING. After injection of rosiglitazone in mice, the serum levels of amylase and lipase were decreased. Furthermore, the mRNA and protein levels of Socs3 and inflammatory cytokines in pancreatic tissues were downregulated.

Conclusions

Rosiglitazone could protect mice with SAP from injury by downregulating Socs3 and inhibiting the inflammatory response pathway.
New N‐benzhydrylpiperazine/1,3,4‐oxadiazoles conjugates inhibit the proliferation, migration, and induce apoptosis in HeLa cancer cells via oxidative stress–mediated mitochondrial pathway
Authors: khanam Rashmin , kumar Raj , Hejazi Iram Iqbal , Shahabuddin Syed , Meena Ramovatar , Rajamani Paulraj , Yadav Nitin , Bhat Asif Iqbal , Athar Fareeda
Published: September 2018

N‐benzhydrylpiperazine and 1,3,4‐oxadiazoles are pharmacologically active scaffolds which exhibits significant inhibitory growth effects against various cancer cells, however, antiproliferation effects and the underlying mechanism for inducing apoptosis for aforementioned scaffolds addressing HeLa cancer cells remains uncertain. In this study,
N‐benzhydrylpiperazine clubbed with 1,3,4‐oxadiazoles (4a–4h) were synthesized, subsequently characterized using high resolution spectroscopic techniques and eventually evaluated for their antiproliferation potential by inducing apoptosis in HeLa cancer cells. The MTT assay screening results revealed that among all, compound
4d (
N‐benzhydryl‐4‐((5‐(4‐aminophenyl)‐1,3,4‐oxadiazol‐2‐yl)methyl)piperazine) in particular, exhibited IC
50 value of 28.13 ± 0.21 μg/mL and significantly inhibited the proliferation of HeLa cancer cells in concentration‐dependent manner. The in vitro anticancer assays for treated HeLa cells resulted in alterations in the cell morphology, reduction in colony formation, and inhibition of cell migration in concentration‐dependent treatment. Furthermore, G2/M phase arrest, variations in the nuclear morphology, degradation of chromosomal DNA confirmed the ongoing apoptosis in treated HeLa cells. Increase in the expression of cytochrome
C and caspase‐3 confirmed the involvement of intrinsic mitochondrial pathway regulating the cell death. Also, elevation in reactive oxygen species level and loss of mitochondrial membrane potential signified that compound
4d induced apoptosis in HeLa cells by generating the oxidative stress. Therefore, compound
4d may act as a potent chemotherapeutic agent against human cervical cancer.
Comparison of large‐scale deletions of the sperm mitochondrial DNA in normozoospermic and asthenoteratozoospermic men
Authors: Gholinezhad Maryam , Yousefnia‐pasha Yousefreza , Hosseinzadeh Colagar Abasalt , Mohammadoo‐Khorasani Milad , Bidmeshkipour Ali
Published: September 2018

Background and objective

Mitochondria play a crucial role in energy metabolism for the survival and motility of sperm during fertilization. The aim of this study was to determine the association of large‐scale mitochondrial DNA deletions with abnormal sperm motility and morphology in asthenoteratozoospermic patients.

Materials and methods

In this case‐control study, 41 semen samples were collected from 18 normozoospermic healthy men and 23 asthenoteratozoospermic patients, according to the WHO guidelines. The swim‐up technique was used for separation of spermatozoa on the basis of their motility. Long‐range polymerase chain reaction (PCR) was used for screening of mitochondrial DNA (mtDNA) large‐scale deletions, and primer shift PCR was used for confirmation of deletions.

Results

The mean sperm motility, normal morphology, and progressive motility in asthenoteratozoospermic patients were significantly lower than in the normozoospermic group (P < 0.0001). There was a positive significant correlation between motility and normal sperm morphology (
P < 0.0001,
r = 0.741). The results of long‐range PCR revealed the existence of 4866‐bp deletion along with the two common 4977‐bp and 7436‐bp deleted mtDNA in both groups. However, the frequency of multiple mtDNA deletions in the asthenoteratozoospermic group (15/23, 65.22%) was significantly higher than that in the normozoospermic group (7/18, 38.89%). Direct sequencing of the 534‐bp PCR product revealed that it was amplified from the mtDNA with a 4866‐bp deletion flanked by a seven‐nucleotide direct repeat (5′‐ACCCCCT‐3′).

Conclusions

Our findings suggested that these large‐scale deletions of mtDNA may be genetic risk factors for poor sperm quality in asthenoteratozoospermia‐induced male infertility. Thus, it is necessary to understand the mechanisms behind the generation of these deletions.
Focal adhesion kinase, RhoA, and p38 mitogen‐activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors
Authors: Manzur María J. , Aguilera Milton O. , Kotler Mónica L. , Berón Walter , Ciuffo Gladys M.
Published: September 2018

Apoptosis plays an important role in cellular processes such as development, differentiation, and homeostasis. Although the participation of angiotensin II (Ang II) AT2 receptors (AT
2R) in cellular apoptosis is well accepted, the signaling pathway involved in this process is not well established. We evaluated the participation of signaling proteins focal adhesion kinase (FAK), RhoA, and p38 mitogen‐activated protein kinase (p38MAPK) in apoptosis induced by Ang II via AT
2R overexpressed in HeLa cells. Following a short stimulation time (120 to 240 minutes) with Ang II, HeLa‐AT
2 cells showed nuclear condensation, stress fibers disassembly and membrane blebbing. FAK, classically involved in cytoskeleton reorganization, has been postulated as an early marker of cellular apoptosis. Thus, we evaluated FAK cleavage, detected at early stimulation times (15 to 30 minutes). Apoptosis was confirmed by increased caspase‐3 cleavage and enzymatic activity of caspase‐3/7. Participation of RhoA was evaluated. HeLa‐AT
2 cells overexpressing RhoA wild‐type (WT) or their mutants, RhoA V14 (constitutively active form) or RhoA N19 (dominant‐negative form) were used to explore RhoA participation. HeLa‐AT
2 cells expressing the constitutively active variant RhoA V14 showed enhanced apoptotic features at earlier times as compared with cells expressing the WT variant. RhoA N19 expression prevented nuclear condensation/caspase activation. Inhibition of p38MAPK caused an increase in nuclear condensation and caspase‐3/7 activation, suggesting a protective role of p38MAPK. Our results clearly demonstrated that stimulation of AT
2R induce apoptosis with participation of FAK and RhoA while p38MAPK seems to play a prosurvival role.
Distal‐less homeobox 3, a negative regulator of myogenesis, is downregulated by microRNA‐133
Authors: Qadir Abdul S. , Lee Jeeyong , Lee Yun‐Sil , Woo Kyung Mi , Ryoo Hyun‐Mo , Baek Jeong‐Hwa
Published: September 2018

Distal‐less homeobox 3 (Dlx3), a member of the Dlx family of homeobox proteins, is a transcriptional activator of runt‐related transcription factor 2 (Runx2) during osteogenic differentiation. It has been demonstrated that forced expression of Runx2 induces an osteogenic program and ectopic calcification in muscles. Therefore, it would be reasonable to predict that Dlx3 also affects myogenic differentiation. The relationship between Dlx3 and myogenesis, however, remains poorly understood. Therefore, in this study, the role and regulation of Dlx3 during myogenic differentiation were investigated. Expression level of Dlx3 was downregulated in human mesenchymal stem cells (MSCs), mouse MSCs, and C2C12 cells cultured in myogenic medium. Dlx3 level was inversely correlated with myogenic differentiation 1 and the muscle‐specific microRNA, microRNA‐133 (miR‐133). The expression level of Runx2 was closely regulated by Dlx3 even under myogenic conditions. Overexpression of Dlx3 markedly downregulated expression levels of myogenic transcription factors and myotube formation in C2C12 cells, whereas Dlx3 knockdown enhanced myogenic differentiation. The Dlx3 3′‐untranslated region (3′‐UTR) has two potential binding sites for miR‐133. Luciferase reporter assays demonstrated that Dlx3 is a direct target of miR‐133a and miR‐133b, and that the two target sites are redundantly active. Taken together, these results suggest that Dlx3 is a negative regulator of myogenic differentiation and that miR‐133a and miR‐133b enhance myogenic differentiation, partly through inhibition of Dlx3 expression via direct targeting of the Dlx3 3′‐UTR.