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Τρίτη 28 Μαρτίου 2017
Scholar : These new articles for The American Journal of Drug and Alcohol Abuse are available online
Scholar : These new articles for The Aging Male are available online
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Influencia de la cirugía mamaria previa en la biopsia selectiva del ganglio centinela en pacientes con cáncer de mama
Publication date: Available online 27 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): V. López-Prior, R. Díaz-Expósito, I. Casáns Tormo
ObjetivoRevisar la aplicabilidad de la biopsia selectiva del ganglio centinela en pacientes con cáncer de mama y antecedente de cirugía mamaria previa, y examinar los factores que podrían influir en la detección del ganglio centinela.Material y métodosRevisamos retrospectivamente la biopsia selectiva del ganglio centinela en 91 pacientes con cáncer de mama dividiéndolas en 2 grupos según el antecedente quirúrgico de la mama: cirugía estética en 30 (grupo I) y conservadora en 61 (grupo II). Se realizó linfogammagrafía prequirúrgica tras inyección intratumoral en 21 casos y periareolar en 70. Se analizaron los patrones de drenaje linfático y la detección global del ganglio centinela según características clínicas, patológicas y quirúrgicas.ResultadosLa detección global del ganglio centinela en la linfogammagrafía fue del 92,3%, con un 7,7% de drenajes extraaxilares. La detección fue similar en el grupo I (93,3%) y grupo II (91,8%). En 2 pacientes (2,2%) detectamos ganglios centinelas en la axila contralateral, estando afectados en el estudio anatomopatológico. El porcentaje de no detección del ganglio centinela en la gammagrafía fue del 7,7%. Se encontró una proporción de no detección significativamente mayor en tumores con mayor grado histológico (28,6% grado III, 4,5% grado I y 3,6% grado II).ConclusiónSe puede realizar la biopsia selectiva del ganglio centinela en pacientes con antecedente de cirugía mamaria previa, pero serían necesarios más estudios para valorar la influencia en la detección del ganglio centinela de diferentes aspectos en este escenario clínico. Un elevado grado histológico se relaciona significativamente con una menor detección.AimThe aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection.Material and methodsA retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables.ResultsThe overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II).ConclusionSentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection.
http://ift.tt/2o2OuIn
Editorial Board/Title Page
Source:Cortex, Volume 89
http://ift.tt/2nryaht
Avoiding boredom: Caudate and insula activity reflects boredom-elicited purchase bias
Source:Cortex
Author(s): Dennis E. Dal Mas, Bianca C. Wittmann
People show a strong tendency to avoid boring situations, but the neural systems mediating this behavioural bias are yet unknown. We used fMRI to investigate how the anticipation of a boring task influences decisions to purchase entertainment. Participants accepted higher prices to avoid boredom compared to control tasks, and individual differences in boredom experience predicted the increase in price. This behavioural bias was associated with higher activity in the caudate nucleus during music purchases driven by boredom avoidance. Insula activation was increased during performance of the boring task and subsequently associated with individual differences in boredom-related decision making. These results identify a mechanism that drives decisions to avoid boring situations and potentially underlies consumer decisions.
http://ift.tt/2nrtl7M
Protective factors against disordered eating in family systems: a systematic review of research
Abstract
Objective
This systematic review aims to identify and evaluate the literature investigating protective factors and eating disorders (EDs), to establish what is known about factors in family systems that could be considered protective against the development of ED/disordered eating.
Methods
A systematic review of the literature was conducted on five databases, using search terms related to ED/disordered eating and protective factors. Studies were systematically screened and included if they made reference to a protective factor within the family system and explored associations with a quantitative measure of ED/disordered eating behaviours. All included studies were evaluated for study quality.
Results
Twenty-five studies met criteria for inclusion. Ten papers made use of longitudinal or prospective designs appropriate to identify factors potentially protecting against the development of disordered eating difficulties, while a further 15 papers report cross-sectional associations between family factors and disordered eating outcomes. Studies looked at aspects of family relationships and family practices around food or eating. There was a particular research focus on the potential protective role of regular family meals.
Conclusions and Implications
Many of the potential protective factors identified, such as family support and connectedness, may be non-specific to eating difficulties, promoting general adaptive development and a range of positive development outcomes. Factors in the family environment around food, eating and weight, such as frequent family meals and avoiding comments about weight, may be more specific to ED and disordered eating. Issues with the methodologies used severely impact on the ability to draw conclusions about whether factors are 'protective'.
http://ift.tt/2ndUgST
Scholar : These new articles for Addiction Research & Theory are available online
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“On-Off-On” fluorescence sensor based on g-C3N4 nanosheets for selective and sequential detection of Ag+ and S2-
Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Shan Wang, Qian Lu, Xu Yan, Mingming Yang, Ranfeng Ye, Dan Du, Yuehe Lin
Detection of silver (Ag+) and sulfide (S2−) ions is important because their presence in large amounts can cause many diseases. In this study, a novel, simple, "on-off-on" fluorescence sensor based on g-C3N4 nanosheets for sequential detection of Ag+ and S2- was designed. The fluorescence signal of the g-C3N4 nanosheets is quenched because Ag+ chelates with the N of the g-C3N4 nanosheets, leading to photoinduced electron transfer from the sheets to Ag+. After adding S2−, the fluorescence of the g-C3N4 nanosheets is recovered due to formation of Ag2S, which activates the fluorescence of the g-C3N4 nanosheets. The recovery efficiency was found to increase with increasing concentrations of S2-, with linear calibration ranging from 0nmol/L to 30nmol/L. Other potentially interfering species, such as SO42−, PO43−, HPO42−, H2PO4−, CO32−, NO3−, Ac−, and HCO3−, presented negligible effects on S2− detection. Moreover, the proposed sensor exhibited several advantages, including low cost, easy preparation, rapid detection, excellent biocompatibility, and a switchable fluorescence response. These attributes make this fluorescent sensor a promising tool for environmental applications.
Graphical abstract
http://ift.tt/2ocYYSy
Scholar : These new articles for Comedy Studies are available online
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Scholar : These new articles for Asian Englishes are available online
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Sensitive determination of malondialdehyde in exhaled breath condensate and biological fluids by capillary electrophoresis with laser induced fluorescence detection
Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Júlia Lačná, František Foret, Petr Kubáň
In this work, a sensitive capillary electrophoresis method with laser induced fluorescence detection for determination of malondialdehyde in various biological fluids was developed. Malondialdehyde reacts with thiobarbituric acid under optimized conditions of pH=2, reaction time of 60min and temperature of 90°C, yielding an adduct that can be separated in a 50mM sodium borate background electrolyte at pH 9. The separation of the formed adduct was accomplished in less than 6min with limit of detection of 1.1nM due to the use of 532nm laser module, exactly matching the maximum excitation wavelength of the formed adduct. The developed method offers unprecedented sensitivity and was for the first time used for analysis of malondialdehyde in exhaled breath condensate. The method proved to be also applicable to other samples of biological fluids, such as blood plasma and saliva.
Graphical abstract
http://ift.tt/2od1AA1
Development of reusable magnetic chitosan microspheres adsorbent for selective extraction of trace level silver nanoparticles in environmental waters prior to ICP-MS analysis
Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Tesfaye Tolessa, Xiao-Xia Zhou, Meseret Amde, Jing-Fu Liu
Solid-phase extraction (SPE) based on reusable magnetic chitosan microspheres was coupled with ICP-MS for separation and quantification of silver nanoparticles (AgNPs) in the presence of silver ions in environmental water samples. The monodisperse magnetic chitosan microspheres with an average size of 2µm were engineered using suspension cross-linking technique, and characterized and investigated for its application as SPE adsorbent. Parameters affecting the SPE were optimized, and the best performance was achieved by extracting a 20mL sample (pH 4.5) with 10mg adsorbent for 90min, followed by elution with 1mL 1% (w/v) thiourea in 10% (v/v) nitric acid for 10min. The detection limit, calculated as 3s (s, standard deviation for 11 blank readings), for three AgNPs coated with polyvinyl pyrrolidone (PVP), citrate and polyvinyl alcohol (PVA) and sizes of 31, 40, 46nm, respectively, were in the range of 0.016‒0.023μg/L. The repeatability and reproducibility (RSD, n=7) at a spiking level of 0.1μg/L AgNPs were 4.2% and 8.1%, respectively. The developed method has been applied in the analysis of AgNPs in river, lake and wastewater samples, with excellent extraction efficiencies (84.9‒98.8%) for AgNPs at spiking levels of 0.86 and 8.70μg/L. The cationic chitosan microspheres showed good species selectivity and reusability for extraction of AgNPs in the presence of Ag+, and hence the proposed method is simple, cost effective and environmentally friendly.
Graphical abstract
http://ift.tt/2odeQVf
Rapid and efficient separation of glycoprotein using pH double-responsive imprinted magnetic microsphere
Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Jingfan Xie, Guanqun Zhong, Changqun Cai, Chunyan Chen, Xiaoming Chen
As biomarkers of many diseases, glycoproteins are of great significance to clinical diagnostics. However, the determination of low abundant glycoproteins in complex biological samples without any pretreatment process is still a problem. In this study, a rapid and convenient separation method for highly efficient enrichment of glycoproteins is reported, based on pH double-responsive imprinted magnetic microspheres. Thin imprinted polymer shells were fabricated onto the surface of magnetic microspheres by free radical polymerization, using 2-(Dimethylamino) ethyl methacrylate as pH-sensitive monomer, 4-vinylphenylbronic acid as boronate affinity monomer, and ovalbumin (OVA) as template molecule. Combining the advantages of pH-sensitive monomer and boronate affinity monomer, rapidly capture-release of OVA could be modulated by changing solution pH. Moreover, high absorption ability (81.2mg/g) was achieved within about 10min. This study provided responsible way to imprint glycoproteins and showed great potential for glycoprotein detection in clinical diagnostic.
Graphical abstract
http://ift.tt/2odptqX
Polyelectrolyte mediated nano hybrid particle as a nano-sensor with outstandingly amplified specificity and sensitivity for enzyme free estimation of cholesterol
Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Mazhar Chebl, Zeinab Moussa, Markus Peurla, Digambara Patra
As a proof of concept, here it is established that curcumin integrated chitosan oligosaccharide lactate (COL) self-assembles on silica nanoparticle surface to form nano hybrid particles (NHPs). These NHPs have size in the ranges of 25–35nm with silica nanoparticle as its core and curcumin-COL as outer layer having thickness of 4–8nm. The fluorescence intensity of these NHPs are found to be quenched and emission maximum is ~50nm red shifted compared to free curcumin implying inner filter effect and/or homo-FRET between curcumin molecules present on the surface of individual nano hybrid particle. Although fluorescence of free curcumin is remarkably quenched by Hg2+/Cu2+ ions due to chelation through keto-enol form, the fluorescence of NHPs is unaffected by Hg2+/Cu2+ ion that boosts analytical selectivity. The fluorescence intensity is outstandingly enhanced in the presence of cholesterol but is not influenced by ascorbic acid, uric acid, glucose, albumin, lipid and other potential interfering substances that either obstruct during enzymatic reaction or affect fluorescence of free curcumin. Thus, NHPs outstandingly improve analytical specificity, selectivity and sensitivity during cholesterol estimation compared to free curcumin. The interaction between cholesterol and NHPs is found to be a combination of ground state electrostatic interaction through the free hydroxyl group of cholesterol along with hydrophobic interaction between NHPs and cholesterol and excited state interaction. The proposed cholesterol biosensor illustrates a wider linear dynamic range, 0.002–10mmolL−1, (upper limit is due to lack of solubility of cholesterol) needed for biomedical application and better than reported values during enzymatic reaction. In addition, the NHPs are found to be photo-stable potentially making it suitable for simple, quick and cost-effective cholesterol estimation and opening an alternative approach other than enzymatic reaction using nano hybrid structure to tune analytical specificity, selectivity and sensitivity of probe molecule.
Graphical abstract
http://ift.tt/2od1ybn
Selective detection of ZnO nanoparticles in aqueous suspension by capillary electrophoresis analysis using dithiothreitol and L-cysteine adsorbates
Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Samar Alsudir, Edward P.C. Lai
The UV detection sensitivity of ZnO nanoparticles in capillary electrophoresis (CE) analysis was selectively enhanced, by 27 or 19 folds, after adsorption of dithiothreitol (DTT) or cysteine (Cys) in 10mM sodium phosphate buffer. Adsorption equilibrium was reached within 90min for DTT but only 10min for Cys. The adsorption process was best modeled by the Langmuir isotherm, indicating the formation of a monolayer of DTT or Cys on the surface of ZnO nanoparticles. The selectivity of DTT and Cys towards ZnO nanoparticles was tested using alumina (Al2O3), ceria (CeO2), silica (SiO2) and titania (TiO2) nanoparticles. No changes in the CE-UV peak area of either adsorbates or nanoparticles were observed, indicating a lack of adsorption. Dynamic light scattering (DLS) provided similar evidence of the selectivity of both adsorbates towards ZnO. Cys also improved the colloidal stability of ZnO nanoparticles by breaking down the aggregates, as evidenced by a reduction of their average hydrodynamic diameter. This new analytical approach provides a simple and rapid methodology to detect ZnO nanoparticles selectively by CE-UV analysis with enhanced sensitivity.
Graphical abstract
http://ift.tt/2odcdTi
Quantification of copper content with laser induced breakdown spectroscopy as a potential indicator of offal adulteration in beef
Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Maria P. Casado-Gavalda, Yash Dixit, David Geulen, Raquel Cama-Moncunill, Xavier Cama-Moncunill, Maria Markiewicz-Keszycka, Patrick J. Cullen, Carl Sullivan
Laser induced breakdown spectroscopy (LIBS) is an emerging technique in the field of food analysis which provides various advantages such as minimal sample preparation, chemical free, rapid detection, provision of spatial information and portability. In this study, LIBS was employed for quantitative analysis of copper content in minced beef samples spiked with beef liver over three independent batches. Copper content was determined with graphite furnace atomic absorption spectroscopy (GFAAS) in order to obtain reference values for modelling. Partial least square regression (PLSR) was performed to build a calibration and validation model. A calibration model with a high Rcv2 of 0.85 and a RMSECV of 43.5ppm was obtained, confirming a good fit for the model. The validation model showed a good prediction accuracy with a high Rp2 of 0.85 and RMSEP of 36.8ppm. Moreover, on a further study to evaluate the spatial capabilities, LIBS was able to successfully map copper content within a pellet, indicating the suitability of LIBS to provide spatial information and therefore potential use on heterogeneous samples. Overall, it can be concluded that LIBS combined with chemometrics demonstrates potential as a quality monitoring tool for the meat processing industry.
Graphical abstract
http://ift.tt/2od661q
Automatic segmentation of liver tumors from multiphase contrast-enhanced CT images based on FCNs
Source:Artificial Intelligence in Medicine
Author(s): Changjian Sun, Shuxu Guo, Huimao Zhang, Jing Li, Meimei Chen, Shuzhi Ma, Lanyi Jin, Xiaoming Liu, Xueyan Li, Xiaohua Qian
This paper presents a novel, fully automatic approach based on a fully convolutional network (FCN) for segmenting liver tumors from CT images. Specifically, we designed a multi-channel fully convolutional network (MC-FCN) to segment liver tumors from multiphase contrast-enhanced CT images. Because each phase of contrast-enhanced data provides distinct information on pathological features, we trained one network for each phase of the CT images and fused their high-layer features together. The proposed approach was validated on CT images taken from two databases: 3Dircadb and JDRD. In the case of 3Dircadb, using the FCN, the mean ratios of the volumetric overlap error (VOE), relative volume difference (RVD), average symmetric surface distance (ASD), root mean square symmetric surface distance (RMSD) and maximum symmetric surface distance (MSSD) were 15.6±4.3%, 5.8±3.5%, 2.0±0.9%, 2.9±1.5mm, 7.1±6.2mm, respectively. For JDRD, using the MC-FCN, the mean ratios of VOE, RVD, ASD, RMSD, and MSSD were 8.1±4.5%, 1.7±1.0%, 1.5±0.7%, 2.0±1.2mm, 5.2±6.4mm, respectively. The test results demonstrate that the MC-FCN model provides greater accuracy and robustness than previous methods.
http://ift.tt/2nwC7D8
Protein fold recognition based on sparse representation based classification
Source:Artificial Intelligence in Medicine
Author(s): Ke Yan, Yong Xu, Xiaozhao Fang, Chunhou Zheng, Bin Liu
Knowledge of protein fold type is critical for determining the protein structure and function. Because of its importance, several computational methods for fold recognition have been proposed. Most of them are based on well-known machine learning techniques, such as Support Vector Machines (SVMs), Artificial Neural Network (ANN), etc. Although these machine learning methods play a role in stimulating the development of this important area, new techniques are still needed to further improve the predictive performance for fold recognition. Sparse Representation based Classification (SRC) has been widely used in image processing, and shows better performance than other related machine learning methods. In this study, we apply the SRC to solve the protein fold recognition problem. Experimental results on a widely used benchmark dataset show that the proposed method is able to improve the performance of some basic classifiers and three state-of-the-art methods to feature selection, including autocross-covariance (ACC) fold, D-D, and Bi-gram. Finally, we propose a novel computational predictor called MF-SRC for fold recognition by combining these three features into the framework of SRC to achieve further performance improvement. Compared with other computational methods in this field on DD dataset, EDD dataset and TG dataset, the proposed method achieves stable performance by reducing the influence of the noise in the dataset. It is anticipated that the proposed predictor may become a useful high throughput tool for large-scale fold recognition or at least, play a complementary role to the existing predictors in this regard.
http://ift.tt/2od3CQE
N-(aroyl)-N-(arylmethyloxy)-α-alanines: selective inhibitors of aldose reductase
Publication date: Available online 28 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Susanna Nencetti, Concettina La Motta, Armando Rossello, Stefania Sartini, Elisa Nuti, Lidia Ciccone, Elisabetta Orlandini
Aldose reductase (ALR2), a NADPH-dependent reductase, is the first and rate-limiting enzyme of the polyol pathway of glucose metabolism and is implicated in the pathogenesis of secondary diabetic complications. In the last decades, this enzyme has been targeted for inhibition but despite the numerous efforts made to identify potent and safe ALR2 inhibitors, many clinical candidates have been a failure. For this reason the research of new ALR2 inhibitors highly effective, selective and with suitable pharmacokinetic properties is still of great interest. In this paper some new N-(aroyl)-N-(arylmethyloxy)alanines have been synthesized and tested for their ability to inhibit ALR2. Some of the synthesized compounds exhibit IC50 in the low micromolar range and all have proved to be highly selective towards ALR2. The N-(aroyl)-N-(arylmethyloxy)-α-alanines are a promising starting point for the development of new ALR2 selective drugs with the aim of delaying the onset of diabetic complications.
Graphical abstract
http://ift.tt/2nIfmN9
Effect of 1,2,3-Triazole salts, non-classical bioisosteres of miltefosine, on Leishmania amazonensis.
Publication date: Available online 28 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Pedro H.F. Stroppa, Luciana M.R. Antinarelli, Arturene M.L. Carmo, Jacy Gameiro, Elaine S. Coimbra, Adilson D. da Silva
Here, we report the effect of new non-classical bioisoteres of miltefosine on Leishmania amazonensis. Fifteen compounds were synthesized and the compound dhmtAc, containing an acetate anion, a side chain of 10 carbon atoms linked to N-1 and a methyl group linked to N-3, showed high and selective biological activity against L. amazonensis. On the intracellular amastigotes, stages of the parasite related to human disease, the IC50 values were near or similar to the 1.0 μM (0.9, 0.8 and 1.0 μM on L. amazonensis-WT, and two transgenic L. amazonensis expressing GFP and RFP, respectively), being more active than miltefosine. Furthermore, dhmtAc did not show toxic effects on human erythrocytes and macrophages (CC50 = 115.9 μM) being more destructive to the intracellular parasites (selectivity index > 115). Promastigotes and intramacrophage amastigotes treated with dhmtAc showed low capacity for reversion of the effect of the compound. A study of the mechanism of action of this compound showed some features of metazoan apoptosis, including cell volume decreases, loss of mitochondrial membrane potential, ROS production, an increase in the intracellular lipid bodies, in situ labeling of DNA fragments by TUNEL labeling and phosphatidylserine exposure to the outerleaflet of the plasma membrane. In addition, the plasma membrane disruption, revealed by PI labeling, suggests cell death by necrosis. No increase in autophagic vacuoles formation in treated promastigotes was observed. Taken together, the data indicate that the bioisotere of miltefosine, dhmtAc, has promising antileishmanial activity that is mediated via apoptosis and necrosis.
Graphical abstract
http://ift.tt/2nIyWc1
STRUCTURE, GENETICS AND FUNCTION OF THE PULMONARY ASSOCIATED SURFACTANT PROTEINS A AND D: THE EXTRA-PULMONARY ROLE OF THESE C TYPE LECTINS
Publication date: Available online 27 March 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Frederico Vieira, Johannes W. Kung, Faizah Bhatti
The collectins family encompasses several collagenous Ca2+-dependent defense lectins that are described as pathogen recognition molecules. They play an important role in both adaptive and innate immunity. Surfactant protein A and D are two of these proteins which were initially discovered in association with surfactant in the pulmonary system. The structure, immune and inflammatory functions, and genetic variations have been well described in relation to their roles, function and pathophysiology in the pulmonary system. Subsequently, these proteins have been discovered in a wide range of other organs and organ systems. The role of these proteins outside the pulmonary system is currently an active area of research. This review intends to provide a current overview of the genetics, structure and extra-pulmonary functions of the surfactant collectin proteins.
http://ift.tt/2nwzvoI
Exosomes and Exosomal microRNAs in Prostate Cancer Radiotherapy
Publication date: Available online 27 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bijaya Malla, Kathrin Zaugg, Erik Vassella, Daniel M. Aebersold, Alan Dal Pra
Despite current risk stratification systems based on traditional clinico-pathological factors, many localized and locally advanced prostate cancers fail radical treatments (i.e. radical prostatectomy, radiotherapy with or without androgen deprivation therapy). Therefore, there is a pressing need for enhanced methods of disease stratification through novel prognostic and predictive tools that could reliably be applied in clinical practice. Exosomes are 50 nm – 150 nm small vesicles released by cancer cells that reflect genetic and non-genetic materials of parent cancer cells. Cancer cells might contain distinct sets of microRNA profiles, the expression of which might change due to stress such as radiation therapy. These alterations or distinctions in contents allow exosomes to be used as prognostic/predictive biomarkers as well as for monitoring of treatment response in cancer. Additionally, microRNAs have been shown to influence multiple processes in prostate tumorigenesis, including cell proliferation, induction of apoptosis, migration, oncogene inhibition, and radio-resistance. Thus, comparative exosomal microRNA profiling at different levels could help portray tumor aggressiveness and response to radiotherapy. Although technical challenges persist in exosome isolation and characterization, recent improvements in microRNA profiling have evolved towards in-depth analyses of the exosomal cargo and its functions. Herein, we review the role of exosomes and exosomal microRNAs in biological processes of prostate cancer progression and radiotherapy response with particular focus on the development of clinical assays for treatment personalization.
http://ift.tt/2nqWxfq
Dosimetric predictors of patient reported xerostomia and dysphagia with de-intensified chemoradiotherapy for HPV-associated oropharyngeal squamous cell carcinoma
Publication date: Available online 27 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bhishamjit S. Chera, David Fried, Alex Price, Robert J. Amdur, William Mendenhall, Chiray Lu, Shiva Das, Nathan Sheets, Lawrence Marks, Panayiotis Mavroidis
Purpose/Objective(s): To estimate the association between different dose/volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of de-intensified chemoradiotherapy (CRT).Methods and MaterialsForty-five patients were treated on a phase II study assessing the efficacy of de-intensified CRT for favorable risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiotherapy with concurrent weekly cisplatin (30 mg/m2), and reported severity of their xerostomia/dysphagia (pre- and post-treatment) using the patient reported outcome version of the CTCAE (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥ 2 was considered clinically meaningful. Associations between dose/volume metrics and patient outcomes were assessed with Receiver Operating Characteristic (ROC) curve and logistic regression model.ResultsSix months post CRT, patients reporting < 2 change in xerostomia severity (N=14) had an average Dmean = 22 ± 9 Gy to the sum of the contralateral glands (parotid+submandibular) compared to the patients reporting ≥ 2 change (N=21), who had an average Dmean = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (AUC = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30% and Dmean = 21Gy. 6 months post CRT, patients reporting < 2 change in dysphagia severity (N=26) had an average V55 = 76±13 (%) to the superior pharyngeal constrictor compared to the patients reporting ≥ 2 change in severity (N=9), who had average V55 = 89±13 (%). V55 - V60 had the strongest association with dysphagia (AUC = 0.70-0.75). Based on the regression analysis, a 20% risk of toxicity was associated with V55 = 78%, V60 = 40%. The findings at 12 months were similar.ConclusionsFollowing de-intensified CRT, the rate of patient reported xerostomia/dysphagia appears to be associated with the V15 of the combined contralateral salivary glands and V55 to V60 of the superior pharyngeal constrictors.
Teaser
The association of different dose/volume metrics of the salivary glands and pharyngeal constrictors to patient reported xerostomia/dysphagia was performed for patients treated with a de-intensified chemoradiotherapy regimen. In the setting of de-intensified chemoradiotherapy, the rate of patient reported xerostomia/dysphagia appears to associated with the V15 of the combined contralateral parotid and submandibular glands (a more stringent metric than what has been used with conventional doses) and V55 to V60 of superior pharyngeal constrictors.http://ift.tt/2o2eMdN
Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients
Publication date: Available online 27 March 2017
Source:Free Radical Biology and Medicine
Author(s): Susana Rovira-Llopis, Celia Bañuls, Aranzazu M de Marañon, Noelia Diaz-Morales, Ana Jover, Sandra Garzon, Milagros Rocha, Victor M. Victor, Antonio Hernandez-Mijares
IntroductionLow testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients.Materials and methodsThe study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesion molecules and leukocyte-endothelium cell interactions were evaluated.ResultsTestosterone levels were lower in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFα, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabetic patients, while rolling velocity was reduced. Testosterone levels correlated negatively with glucose, HOMA-IR, HbA1c, triglycerides, nonHDL-c, ApoB, hs-CRP and AIP, and positively with HDL-c and ApoA1. The multivariable regression model showed that HDL-c, HOMA-IR and age were independently associated with testosterone. Furthermore, testosterone levels correlated positively with membrane potential and rolling velocity and negatively with ROS production, VCAM-1, rolling flux and adhesion.ConclusionsOur data highlight that low testosterone levels in diabetic men are related to impaired metabolic profile and mitochondrial function and enhanced inflammation and leukocyte-endothelium cell interaction, which leaves said patients at risk of cardiovascular events.
Graphical abstract
http://ift.tt/2nIbCvh
Cigarette smoke extract induced exosome release is mediated by depletion of exofacial thiols and can be inhibited by thiol-antioxidants
Publication date: Available online 28 March 2017
Source:Free Radical Biology and Medicine
Author(s): Birke J. Benedikter, Charlotte Volgers, Pascalle H. van Eijck, Emiel F.M. Wouters, Paul H.M. Savelkoul, Niki L. Reynaert, Guido R.M.M. Haenen, Gernot G.U. Rohde, Antje R. Weseler, Frank R.M. Stassen
IntroductionAirway epithelial cells have been described to release extracellular vesicles (EVs) with pathological properties when exposed to cigarette smoke extract (CSE). As CSE causes oxidative stress, we investigated whether its oxidative components are responsible for inducing EV release and whether this could be prevented using the thiol antioxidants N-acetyl-L-cysteine (NAC) or glutathione (GSH).MethodsBEAS-2B cells were exposed for 24h to CSE, H2O2, acrolein, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), bacitracin, rutin or the anti-protein disulfide isomerase (PDI) antibody clone RL90; with or without NAC or GSH. EVs in media were measured using CD63+CD81+ bead-coupled flow cytometry or tunable resistive pulse sensing (TRPS). For characterization by Western Blotting, cryo-transmission electron microscopy and TRPS, EVs were isolated using ultracentrifugation. Glutathione disulfide and GSH in cells were assessed by a GSH reductase cycling assay, and exofacial thiols using Flow cytometry.ResultsCSE augmented the release of the EV subtype exosomes, which could be prevented by scavenging thiol-reactive components using NAC or GSH. Among thiol-reactive CSE components, H2O2 had no effect on exosome release, whereas acrolein imitated the NAC-reversible exosome induction. The exosome induction by CSE and acrolein was paralleled by depletion of cell surface thiols. Membrane impermeable thiol blocking agents, but not specific inhibitors of the exofacially located thiol-dependent enzyme PDI, stimulated exosome release.Summary/conclusionThiol-reactive compounds like acrolein account for CSE-induced exosome release by reacting with cell surface thiols. As acrolein is produced endogenously during inflammation, it may influence exosome release not only in smokers, but also in ex-smokers with chronic obstructive pulmonary disease. NAC and GSH prevent acrolein- and CSE-induced exosome release, which may contribute to the clinical benefits of NAC treatment.
Graphical abstract
http://ift.tt/2nIc1gV
Activation-induced deoxycytidine deaminase: Structural basis favoring WRC hot motif specificities unique among APOBEC family members
Source:DNA Repair
Author(s): Phuong Pham, Samir A. Afif, Mayuko Shimoda, Kazuhiko Maeda, Nobuo Sakaguchi, Lars C. Pedersen, Myron F. Goodman
http://ift.tt/2nI657A
A novel small molecule compound possesses immunomodulatory properties on bone marrow-derived dendritic cells via TLR7 signaling pathway and alleviates the development of SLE
Publication date: June 2017
Source:International Immunopharmacology, Volume 47
Author(s): Sheng Gao, Linbo Yuan, Cunyu Li, Liping Han, Chunyan Hua
Dendritic cells (DCs) play an important role in the development and maintenance of immune tolerance. Activation of TLR7, which is expressed in DCs, is thought to contribute to the complex pathophysiology of systemic lupus erythematosus (SLE). In this study, we analyzed the in vitro and in vivo function of a novel small-molecule compound, FC-99, which was previously reported to have immunomodulatory functions. We found that FC-99 inhibited the expression of CD40 and inflammatory mediators (IL-6, IL-12, and CXCL-10), as well as R848-induced phosphorylation of IκB-α. We also present evidence that FC-99 is remarkably efficacious in the treatment of murine lupus. Interestingly, FC-99 affected the maturation and percentage of DCs in lupus-prone mice. Therefore, FC-99 may serve as a potential drug candidate for treatment of SLE.
http://ift.tt/2nwjUpg
Platycodin D protects against cigarette smoke-induced lung inflammation in mice
Publication date: June 2017
Source:International Immunopharmacology, Volume 47
Author(s): Wei Gao, Ying Guo, Hongxia Yang
Cigarette smoke is the one of the major factors that leads to chronic obstructive pulmonary disease (COPD). Inflammation and oxidant stress have been known to play critical roles in the development of COPD. Platycodin D (PLD) has been reported to have anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the protective effects of PLD on cigarette smoke (CS)-induced lung inflammation in mice. PLD was adminstrated i.p. to mice 2h before CS exposure daily for five consecutive days. The production of inflammatory cytokines TNF-α and IL-1β were measured by ELISA. The levels of malonaldehyde (MDA) and nitric oxide (NO) were also detected in this study. The expression of nuclear factor-erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NF-κB, and IκBα were detected by western blot analysis. The results showed that PLD significantly attenuated CS-induced lung pathological changes, inflammatory cells infiltration, as well as TNF-α and IL-1β production. CS-induced MDA and NO production were also inhibited by treatment of PLD. Western blot analysis showed that PLD significantly suppressed CS-induced NF-κB activation. In addition, PLD was found to increase the expression of Nrf2 and HO-1. Taken together, these results indicated that PLD protected against CS-induced lung inflammation by inhibiting inflammatory and oxidative response through activating Nrf2 signaling pathway. PLD might be an effective treatment for CS-induced lung inflammation.
http://ift.tt/2ocPFCl
Removal of sulfamethoxazole (SMX) and sulfapyridine (SPY) from aqueous solutions by biochars derived from anaerobically digested bagasse
Abstract
This study explored the sorption of sulfamethoxazole (SMX) and sulfapyridine (SPY) onto biochars produced from raw and anaerobically digested bagasse. Initial evaluation of six bagasse biochars showed that digested bagasse biochar prepared at 600 °C (DBG600) was the best adsorbent to remove SMX and SPY. Further laboratory batch sorption experiments showed that DBG600 adsorbed SMX and SPY from aqueous solution with maximum adsorption capacity of 54.38 and 8.60 mg g−1, respectively. Solution pH showed strong effect on the sorption ability of DBG600 to the two antibiotics, and the sorption decreased with increasing of solution pH. Experimental and model results suggested that adsorption of SMX and SPY onto DBG600 might be controlled by the π–π interaction.
http://ift.tt/2mMrYUl
The geochemical release feature of Tl in Tl-rich pyrite mine wastes: a long-term leaching test
Abstract
Identifying and revealing the geochemical behaviour of Tl during mine waste weathering are very important to assess the potential environmental impact of Thallium (Tl) from open mine-waste piles. Herein, two methods including the modified BCR sequential extraction and the long-term humidity cell tests (HCT) were employed to understand the Tl chemical fractions and to stimulate intense chemical weathering process, respectively. The results from BCR sequential extraction showed that the Tl concentration in the studied sample was 18.78 mg/kg, containing 1.878 mg/kg oxidisable, 0.282 mg/kg acid exchangeable and 1.596 mg/kg reducible Tl. The acid exchangeable fraction contributed to a particular potential risk to the aquatic marine life in the early stages and the Fe/Mn oxidisable fraction posed a potential risk being dissolved into solution at low pH (i.e. acidic conditions). The variations of Tl concentration in leachates were classified as two period as the pH values decrease. In the first period, the Tl concentrations decreased positively with pH value with poor correlation between pH value and SO42− concentration in leachates. Drastic release of Tl was observed in the early period once the material was exposed to air and water, being ascribe to the acid exchangeable fraction bound to carbonate as dissolved by acid. During the second period, three increased peaks of Tl concentration (11.02, 16.03, 43.15 μg/L) and four increased peaks of SO42− concentration (315, 390, 899.61 and 2670 mg/L) were observed. A good correlation (R 2 = 0.8384) between the concentrations of Tl and SO42− was observed, indicating the Tl was mainly released from the oxidation of sulphide.
http://ift.tt/2oufygj
Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases
Conditions: Malignant Neoplasm of Bone and Articular Cartilage; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasm of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasm of Respiratory and Intrathoracic Organ Carcinoma; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Melanoma and Other Malignant Neoplasms of Skin
Intervention: Drug: Gemcitabine
Sponsors: M.D. Anderson Cancer Center; James B. and Lois R. Archer Charitable Foundation; Gateway for Cancer Research
Not yet recruiting - verified March 2017
http://ift.tt/2nqUY0Q
Intervention: Drug: Gemcitabine
Sponsors: M.D. Anderson Cancer Center; James B. and Lois R. Archer Charitable Foundation; Gateway for Cancer Research
Not yet recruiting - verified March 2017
http://ift.tt/2nqUY0Q
Varicella seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection
Source:Vaccine
Author(s): Joshua R. Duncan, Catherine T. Witkop, Bryant J. Webber, Amy A. Costello
Background/ObjectivesInfection with varicella zoster virus (VZV) produces lifelong immunity, but duration of post-vaccination immunity has not been established. The purpose of this study is to determine if a difference exists in the long-term seropositivity of anti-VZV antibodies in a cohort of young adults who were vaccinated against varicella as compared to a similar cohort with a history of chickenpox disease, and to determine which variables best predict waning seropositivity following varicella vaccination.MethodsThis retrospective cohort study captures immunization and serology data from approximately 10,000 recruits who entered basic military training between January 1, 2008, and December 31, 2015, and who have childhood immunization records in the Air Force Aeromedical Services Information Management System. Varicella vaccine immunogenicity was determined relative to the immunogenicity of chickenpox disease, as measured by multiplex flow immunoassay. Among vaccine recipients, waning seroimmunity was modeled and adjusted for several important covariates.ResultsBasic military trainees who received varicella vaccine in childhood were 24% less likely to be seropositive to VZV than trainees who were exempt from vaccine due to a history of chickenpox disease. There was no significant difference in seropositivity between male and female trainees. The odds of a vaccinated trainee being seropositive to VZV decreased by 8% with each year elapsed since vaccination. Seroprevalence declined below estimated herd immunity thresholds in vaccinated trainees born after 1994, and in the cohort as a whole for trainees born after 1995.ConclusionDespite prior vaccination, seroimmunity in a large cohort of young adults unexposed to wild-type VZV failed to meet the estimated threshold for herd immunity. If vaccination in accordance with the current US VZV vaccination schedule is inadequate to maintain herd immunity, young adults not previously exposed to wild-type VZV may be at increased risk for varicella outbreaks.
http://ift.tt/2nwfr68
Measuring Patient-Reported Adverse Events in Oncology Practice Improves Quality of Life in Nasopharyngeal Carcinoma
Condition: Nasopharyngeal Neoplasms
Interventions: Other: adverse events using patient-reported outcomes version of common terminology criteria for adverse events (PRO-CTCAE) questionaire; Other: do not report adverse events through patient-reported outcomes version of common terminology criteria for adverse events (PRO-CTCAE) questionaire
Sponsor: Sun Yat-sen University
Not yet recruiting - verified March 2017
http://ift.tt/2nHRCca
Interventions: Other: adverse events using patient-reported outcomes version of common terminology criteria for adverse events (PRO-CTCAE) questionaire; Other: do not report adverse events through patient-reported outcomes version of common terminology criteria for adverse events (PRO-CTCAE) questionaire
Sponsor: Sun Yat-sen University
Not yet recruiting - verified March 2017
http://ift.tt/2nHRCca
Lower vaccine uptake amongst older individuals living alone: A systematic review and meta-analysis of social determinants of vaccine uptake
Publication date: Available online 27 March 2017
Source:Vaccine
Author(s): Anu Jain, A.J. van Hoek, Delia Boccia, Sara L. Thomas
IntroductionVaccination is a key intervention to reduce infectious disease mortality and morbidity amongst older individuals. Identifying social factors for vaccine uptake enables targeted interventions to reduce health inequalities.ObjectiveTo systematically appraise and quantify social factors associated with vaccine uptake amongst individuals aged ≥60years from Europe.MethodsWe searched Medline and Embase from inception to 24/02/2016. The association of vaccine uptake was examined for social factors relevant at an individual level, to provide insight into individuals' environment and enable development of targeted interventions by healthcare providers to deliver equitable healthcare. Factors included: living alone, marital status, education, income, vaccination costs, area-level deprivation, social class, urban versus rural residence, immigration status and religion. Between-study heterogeneity for each factor was identified using I2-statistics and Q-statistics, and investigated by stratification and meta-regression analysis. Meta-analysis was conducted, when appropriate, using fixed- or random-effects models.ResultsFrom 11,754 titles, 35 eligible studies were identified (uptake of: seasonal influenza vaccine (SIV) only (n=27) or including pneumococcal vaccine (PV) (n=5); herpes zoster vaccine (n=1); pandemic influenza vaccine (n=1); PV only (n=1)). Higher SIV uptake was reported for individuals not living alone (summary odds ratios (OR)=1.39 (95% confidence interval (CI): 1.16–1.68). Lower SIV uptake was observed in immigrants and in more deprived areas: summary OR=0.57 (95%CI: 0.47–0.68) and risk ratio=0.93 (95%CI: 0.92–0.94) respectively. Higher SIV uptake was associated with higher income (OR=1.26 (95%CI: 1.08–1.47)) and higher education (OR=1.05 (95%CI: 1–1.11)) in adequately adjusted studies. Between-study heterogeneity did not appear to result from variation in categorisation of social factors, but for education was partly explained by varying vaccination costs (meta-regression analysis p=<0.0001); individuals with higher education had higher vaccine uptake in countries without free vaccination.ConclusionsQuantification of associations between social factors and lower vaccine uptake, and notably living alone (an overlooked factor in vaccination programmes), should enable health professionals target specific social groups to tackle vaccine-related inequalities.
http://ift.tt/2ocE6en
Study Assessing the Effects of Chemotherapy in Advanced Esophagogastric Adenocarcinoma
Conditions: Esophageal Neoplasms; Stomach Neoplasms
Interventions: Drug: Carboplatin; Drug: Docetaxel; Drug: Capecitabine; Drug: Epirubicin; Drug: Oxaliplatin
Sponsor: Rigshospitalet, Denmark
Recruiting - verified March 2017
http://ift.tt/2nqRrQ4
Interventions: Drug: Carboplatin; Drug: Docetaxel; Drug: Capecitabine; Drug: Epirubicin; Drug: Oxaliplatin
Sponsor: Rigshospitalet, Denmark
Recruiting - verified March 2017
http://ift.tt/2nqRrQ4
Predictors of influenza vaccination in the U.S. among children 9–13years of age
Source:Vaccine
Author(s): Teresa M. Imburgia, Kristin S. Hendrix, Kelly L. Donahue, Lynne A. Sturm, Gregory D. Zimet
Background and objectivesU.S. estimates of seasonal influenza (flu) vaccine uptake in 2014–2015 were 62% for 5–12year olds, dropping to 47% for 13–17year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9–13year old children.MethodsAn online U.S. survey of mothers of children aged 9–13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status.ResultsThere were 2363 respondents (Mean age=38years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p=n.s.).ConclusionsThis sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites.
http://ift.tt/2nw03H0
Pertussis vaccination in pregnancy: State of the art
Source:Vaccine
Author(s): Elke Leuridan
Pertussis vaccination in pregnancy has been introduced by several national advisory bodies, mostly in industrialized countries, as a means to protect young infants from disease by high titers of maternal antibodies. Most recommendations derive from epidemiological needs, but many knowledge gaps remained after implementation. This report aims to overview the solved and unsolved aspects of prenatal vaccination with a pertussis containing vaccine.
http://ift.tt/2ocM7Qk
Adjuvanticity of a CTLA-4 3′ UTR complementary oligonucleotide for emulsion formulated recombinant subunit and inactivated vaccines
Source:Vaccine
Author(s): Xin Li, Lei Yang, Peiyan Zhao, Yun Yao, Fangjie Lu, Liqun Tu, Jiwei Liu, Zhiqin Li, Yongli Yu, Liying Wang
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is recognized as a critical inhibitory regulator of T-cell proliferation and activation, opposing the action of CD28-mediated co-stimulation. Interfering or blocking CTLA-4 can result in continuous T-cell activation required for the full immune response to pathogenic microbes and vaccines. To test if nucleic acid-based CTLA-4 inhibitors could be developed into a novel adjuvant, we designed two oligonucleotides, CMD-1 and CMD-2, with the sequences complementary to the conserve regions identical between human and mouse CTLA-4 mRNA 3′ untranslated region (3′ UTR), and tested their in vitro effects on CTLA-4 production and their adjuvanticity for vaccines in mice. We found that CMD-1 inhibited the antigen-induced CTLA-4 up-regulation on the CD4+ T cells by interfering its mRNA expression, maintained higher levels of CD80 and CD86 on the CD11c+ cells and promoted the recalled proliferation of the CD4+ T cells and CD19+ B cells, and that the CMD-1 enhanced the antibody response against recombinant PCV2b capsid protein or inactivated foot-and-mouth disease virus in both ICR and BALB/c mice. These data suggest that the CMD-1 could be used as a novel vaccine adjuvant capable of inhibiting inhibitory signals rather than inducing stimulatory signals of immune cells.
http://ift.tt/2nwawSs
The Rehabilitation Effectiveness for Activities for Life (REAL) study: a national programme of research into NHS inpatient mental health rehabilitation services across England.
NHS inpatient mental health rehabilitation services successfully support the recovery of service users with complex needs, but more effective interventions are needed to improve service users' skills for successful community living.
http://ift.tt/2ocL6YI
MicroRNAs Make a Difference in Cardiovascular Robustness
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Rachael Bakker, Richard W. Carthew
Invertebrate microRNAs (miRNAs) can suppress developmental variability that is caused by environmental and genetic variation. In this issue of Developmental Cell, Kasper et al. (2017) show that zebrafish miRNAs suppress variability in cardiovascular development during embryogenesis, providing insight into the conserved link between miRNAs and robustness.
Teaser
Invertebrate microRNAs (miRNAs) can suppress developmental variability that is caused by environmental and genetic variation. In this issue of Developmental Cell, Kasper et al. (2017) show that zebrafish miRNAs suppress variability in cardiovascular development during embryogenesis, providing insight into the conserved link between miRNAs and robustness.http://ift.tt/2nI2BSF
Pushing Yap into the Nucleus with Shear Force
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Jason Kuan Han Lai, Didier Y.R. Stainier
Endothelial cells line blood vessels and experience shear stress from blood flow. In this issue of Developmental Cell, Nakajima and colleagues (2017) show that in zebrafish Yap responds to blood flow by translocating into the nucleus, where it drives a genetic program to maintain vascular stability.
Teaser
Endothelial cells line blood vessels and experience shear stress from blood flow. In this issue of Developmental Cell, Nakajima and colleagues (2017) show that in zebrafish Yap responds to blood flow by translocating into the nucleus, where it drives a genetic program to maintain vascular stability.http://ift.tt/2ocFsG1
Autophagy: It’s in Your Blood
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Sergei Doulatov, George Q. Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
Teaser
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.http://ift.tt/2nHSrSd
Macrophages Help Cells Connect to Pattern Zebrafish Stripes
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Thomas B. Kornberg
Mechanisms that disseminate the proteins that orchestrate organ and tissue development have been a major focus of cell and developmental biology. Reporting in Science, Eom and Parichy (2017) characterize the role that macrophages play in facilitating long-distance signaling between the cells that make stripes in the adult zebrafish.
Teaser
Mechanisms that disseminate the proteins that orchestrate organ and tissue development have been a major focus of cell and developmental biology. Reporting in Science, Eom and Parichy (2017) characterize the role that macrophages play in facilitating long-distance signaling between the cells that make stripes in the adult zebrafish.http://ift.tt/2ocUJ9G
Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Hiroyuki Nakajima, Kimiko Yamamoto, Sobhika Agarwala, Kenta Terai, Hajime Fukui, Shigetomo Fukuhara, Koji Ando, Takahiro Miyazaki, Yasuhiro Yokota, Etienne Schmelzer, Heinz-Georg Belting, Markus Affolter, Virginie Lecaudey, Naoki Mochizuki
Endothelial cells (ECs) line the inside of blood vessels and respond to mechanical cues generated by blood flow. Mechanical stimuli regulate the localization of YAP by reorganizing the actin cytoskeleton. Here we demonstrate blood-flow-mediated regulation of endothelial YAP in vivo. We indirectly monitored transcriptional activity of Yap1 (zebrafish YAP) and its spatiotemporal localization in living zebrafish and found that Yap1 entered the nucleus and promoted transcription in response to blood flow. In cultured human ECs, laminar shear stress induced nuclear import of YAP and its transcriptional activity in a manner independent of Hippo signaling. We uncovered a molecular mechanism by which flow induced the nuclear translocation of YAP through the regulation of filamentous actin and angiomotin. Yap1 mutant zebrafish showed a defect in vascular stability, indicating an essential role for Yap1 in blood vessels. Our data imply that endothelial Yap1 functions in response to flow to maintain blood vessels.
Graphical abstract
Teaser
Nakajima et al. monitor the spatiotemporal localization and transcriptional activity of Yap1 in ECs of living zebrafish and reveal that blood flow regulates localization of Yap1 through mechanotransduction signaling.http://ift.tt/2nHJW9N
Asymmetric Notch Amplification to Secure Stem Cell Identity
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Anthony M. Rossi, Claude Desplan
Stem cells self-renew and produce progenitors with limited proliferative potential. Reporting in Developmental Cell, Liu et al. (2017) demonstrate that in some neural stem cells, Notch activity is asymmetrically amplified by a positive feedback loop with the super elongation complex (SEC) to quickly differentiate between stem cells and progenitors.
Teaser
Stem cells self-renew and produce progenitors with limited proliferative potential. Reporting in Developmental Cell, Liu et al. (2017) demonstrate that in some neural stem cells, Notch activity is asymmetrically amplified by a positive feedback loop with the super elongation complex (SEC) to quickly differentiate between stem cells and progenitors.http://ift.tt/2nHKj45
The Super Elongation Complex Drives Neural Stem Cell Fate Commitment
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Kun Liu, Dan Shen, Jingwen Shen, Shihong M. Gao, Bo Li, Chouin Wong, Weidong Feng, Yan Song
Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription. HES in turn upregulates SEC activity, forming an unexpected self-reinforcing feedback loop with SEC. SEC inactivation leads to neuroblast loss, whereas its forced activation results in neural progenitor dedifferentiation and tumorigenesis. Our studies unveil an SEC-mediated intracellular amplifier mechanism in ensuring robustness and precision in stem cell fate commitment and provide mechanistic explanation for the highly frequent association of SEC overactivation with human cancers.
Graphical abstract
Teaser
Liu et al. implicate the super elongation complex (SEC), best known for transcription elongation checkpoint control, in driving Drosophila neural stem cell (NSC) fate commitment. SEC is highly expressed in NSCs, where it interacts directly with the Notch signaling pathway in a self-reinforcing feedback loop for timely stem cell fate lock-in.http://ift.tt/2ocMomg
MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Dionna M. Kasper, Albertomaria Moro, Emma Ristori, Anand Narayanan, Guillermina Hill-Teran, Elizabeth Fleming, Miguel Moreno-Mateos, Charles E. Vejnar, Jing Zhang, Donghoon Lee, Mengting Gu, Mark Gerstein, Antonio Giraldez, Stefania Nicoli
Proper functioning of an organism requires cells and tissues to behave in uniform, well-organized ways. How this optimum of phenotypes is achieved during the development of vertebrates is unclear. Here, we carried out a multi-faceted and single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single and multi-gene microRNA (miRNA) families. We found that embryos lacking particular miRNA-dependent signaling pathways develop a vascular trait similar to wild-type, but with a profound increase in phenotypic heterogeneity. Aberrant trait variance in miRNA mutant embryos uniquely sensitizes their vascular system to environmental perturbations. We discovered a previously unrecognized role for specific vertebrate miRNAs to protect tissue development against phenotypic variability. This discovery marks an important advance in our comprehension of how miRNAs function in the development of higher organisms.
Graphical abstract
Teaser
Phenotypic diversity must be controlled to ensure balance between trait functionality and trait adaptability to changing environments. Kasper et al. establish that specific miRNAs limit phenotypic variation of the vascular system in a vertebrate embryo. Altered phenotypic variability resulting from miRNA loss sensitizes blood vessels to diverse environmental stresses.http://ift.tt/2ocF1Ly
miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Haibo Wang, Ana Lis Moyano, Zhangyan Ma, Yaqi Deng, Yifeng Lin, Chuntao Zhao, Liguo Zhang, Minqing Jiang, Xuelian He, Zhixing Ma, Fanghui Lu, Mei Xin, Wenhao Zhou, Sung Ok Yoon, Ernesto R. Bongarzone, Q. Richard Lu
A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice. Integrated transcriptome profiling and biotin-affinity miRNA pull-down approaches reveal stage-specific miR-219 targets in oligodendrocytes and further uncover a novel network for miR-219 targeting of differentiation inhibitors including Lingo1 and Etv5. Inhibition of Lingo1 and Etv5 partially rescues differentiation defects of miR-219-deficient oligodendrocyte precursors. Furthermore, miR-219 mimics enhance myelin restoration following lysolecithin-induced demyelination as well as experimental autoimmune encephalomyelitis, principal animal models of multiple sclerosis. Together, our findings identify context-specific miRNA-regulated checkpoints that control myelinogenesis and a therapeutic role for miR-219 in CNS myelin repair.
Graphical abstract
Teaser
Wang et al. show that miR-219 collaborates with miR-338 and is required for proper oligodendrocyte differentiation and myelination in the mammalian CNS by targeting a network of stage-specific differentiation inhibitors, including Lingo1 and Etv5. Therapeutic delivery of miR-219 also enhances myelin repair in animal models of multiple sclerosis.http://ift.tt/2ocx09w
The Putative Drp1 Inhibitor mdivi-1 Is a Reversible Mitochondrial Complex I Inhibitor that Modulates Reactive Oxygen Species
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Evan A. Bordt, Pascaline Clerc, Brian A. Roelofs, Andrew J. Saladino, László Tretter, Vera Adam-Vizi, Edward Cherok, Ahmed Khalil, Nagendra Yadava, Shealinna X. Ge, T. Chase Francis, Nolan W. Kennedy, Lora K. Picton, Tanya Kumar, Sruti Uppuluri, Alexandrea M. Miller, Kie Itoh, Mariusz Karbowski, Hiromi Sesaki, R. Blake Hill, Brian M. Polster
Mitochondrial fission mediated by the GTPase dynamin-related protein 1 (Drp1) is an attractive drug target in numerous maladies that range from heart disease to neurodegenerative disorders. The compound mdivi-1 is widely reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate brain injury. Here, we show that mdivi-1 reversibly inhibits mitochondrial complex I-dependent O2 consumption and reverse electron transfer-mediated reactive oxygen species (ROS) production at concentrations (e.g., 50 μM) used to target mitochondrial fission. Respiratory inhibition is rescued by bypassing complex I using yeast NADH dehydrogenase Ndi1. Unexpectedly, respiratory impairment by mdivi-1 occurs without mitochondrial elongation, is not mimicked by Drp1 deletion, and is observed in Drp1-deficient fibroblasts. In addition, mdivi-1 poorly inhibits recombinant Drp1 GTPase activity (Ki > 1.2 mM). Overall, these results suggest that mdivi-1 is not a specific Drp1 inhibitor. The ability of mdivi-1 to reversibly inhibit complex I and modify mitochondrial ROS production may contribute to effects observed in disease models.
Graphical abstract
Teaser
Bordt, Clerc et al. show that the putative Drp1 inhibitor mdivi-1 reversibly inhibits mitochondrial complex I without impairing Drp1 GTPase activity or lengthening mitochondria. mdivi-1 attenuates mitochondrial reactive oxygen species production under conditions relevant to ischemia/reperfusion injury. These mechanisms may provide an alternative explanation for some of mdivi-1's in vivo effects.http://ift.tt/2ocDSng
Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration
Publication date: 27 March 2017
Source:Developmental Cell, Volume 40, Issue 6
Author(s): Ines Wagner, Heng Wang, Philipp M. Weissert, Werner L. Straube, Anna Shevchenko, Marc Gentzel, Goncalo Brito, Akira Tazaki, Catarina Oliveira, Takuji Sugiura, Andrej Shevchenko, András Simon, David N. Drechsel, Elly M. Tanaka
Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell cycle entry by dedifferentiating newt muscle cells. Protease-activated BMP4/7 heterodimers that are present in serum strongly induced myotube cell cycle re-entry with protease cleavage yielding a 30-fold potency increase of BMP4/7 compared with canonical BMP4/7. Inhibition of BMP signaling via muscle-specific dominant-negative receptor expression reduced cell cycle entry in vitro and in vivo. In vivo inhibition of serine protease activity depressed cell cycle re-entry, which in turn was rescued by cleaved-mimic BMP. This work identifies a mechanism of BMP activation that generates blastema cells from differentiated muscle.
Teaser
In the newt, limb regeneration starts with local blood clotting and requires myofibers to dedifferentiate and re-enter the cell cycle to make proliferative myogenic precursors. Wagner et al. show that blood clotting proteases cleave and activate blood-derived BMPs to promote BMP signaling-dependent cell cycle re-entry for myofiber dedifferentiation.http://ift.tt/2ocEbi8
Editorial Board
Publication date: April 2017
Source:Pathology - Research and Practice, Volume 213, Issue 4
http://ift.tt/2otYQgP
Scholar : These new articles for Annals of GIS are available online
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Scholar : These new articles for Acta Agriculturae Scandinavica, Section B — Soil & Plant Science are available online
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