Publication date: Available online 13 April 2017
Source:Human Pathology
Author(s): Eliane Tabea Taube, Carsten Denkert, Jalid Sehouli, Ulrike Unger, Catarina Alisa Kunze, Jan Budczies, Manfred Dietel, Elena Braicu, Silvia Darb-Esfahani
High-grade serous ovarian carcinoma remains one of the most lethal malignancies in females. For histopathological differentiation from mesothelioma cytokeratin, 5/6 immunohistochemistry is widely used. Another preferred marker for differential diagnosis to mesothelioma is ER-α. In this study, we determined the rate of cytokeratin 5/6 positive cells in primary high-grade serous carcinoma. A cohort of 215 patients with high-grade serous ovarian carcinoma was evaluated immunohistochemically for the protein expression of cytokeratin 5/6. The majority of tumors demonstrated, at least partly positive for cytokeratin 5/6 (n=148, 68.3%), showing different staining patterns from scattered stained cells to a diffuse staining, at times with a distinctive tumor-stroma border motif. 67 (31%) were entirely negative. No correlation of cytokeratin IRS with conventional staging parameters could be demonstrated. From the different IRS values for cytokeratin, 5/6 IRS=12 (n=6, 2.9%) seemed to indicate a worse prognosis, albeit not statistically significant. An association with ER-α expression could not be detected but the combination of CK5/6 IRS=12 and ER-α negativity resulted in a significant negative prognostic marker (overall survival P=.003 und progression free survival P<.0001). We substantiate cytokeratin 5/6 protein expression as a frequent feature of high-grade serous ovarian carcinoma with various staining patterns, an important fact for the routine differential diagnosis with mesothelioma. Furthermore, cytokeratin 5/6 in combination with ER-α proved to be a negative prognostic marker, wherefore we suggest further investigation of its biological significance and possible manifestation of a basal differentiation.
http://ift.tt/2otOSNU
Παρασκευή 14 Απριλίου 2017
Cytokeratin 5/6 expression, prognosis and association with ER-α in high-grade serous ovarian carcinoma
Rituximab treatment circumvents the prognostic impact of tumor infiltrating T-cells in follicular lymphoma patients
Publication date: Available online 13 April 2017
Source:Human Pathology
Author(s): Luc Xerri, Sarah Huet, Jeffrey M. Venstrom, Edith Szafer-Glusman, Bettina Fabiani, Danielle Canioni, Catherine Chassagne-Clément, Peggy Dartigues-Cuilléres, Fréderic Charlotte, Camille Laurent, Benedicte Gelas-Dore, Christopher R. Bolen, Elizabeth Punnoose, Reda Bouabdallah, Pauline Brice, Franck Morschhauser, Guillaume Cartron, Daniel Olive, Gilles Salles
Previous immunohistochemical (IHC) studies showed controversial data about the prognostic value of tumor infiltrating lymphocytes (TIL) in follicular lymphoma (FL). In order to clarify this issue, a large series of FL samples from rituximab-treated patients enrolled in the randomized PRIMA trial were examined. IHC was quantified using automated image analysis in 417, 287, 418, 406, 379, and 369 patients for CD3, CD4, CD8, PD1, ICOS, and FOXP3; respectively. RNAseq analysis was used to quantify TIL–related mRNA transcripts from 148 patients. When each IHC marker was used as a continuous variable in the whole cohort, high CD3 counts were associated with better progression free survival (PFS) (P=.025). When an optimal IHC cut-point was applied to the whole patient population, high CD3 counts and high PD1 counts were associated with better PFS (P=.011 and P=.044, respectively), whereas none of the other TIL markers had any significant correlation with outcome. When a stringent analysis was performed by dividing the whole cohort into a training set and a validation set, none of the TIL markers showed a prognostic significance in both groups. RNAseq analysis showed a significant correlation between high levels of CD3 and CD8 transcripts and better PFS (P=.001 and P=.037, respectively). No prognostic correlation was found as to the level of other immune gene transcripts. These results suggest that the IHC prognostic value of TILs is circumvented by rituximab treatment, although there is a trend for high numbers of CD3+ TILs to correlate with better PFS.
http://ift.tt/2nMaAPP
Juvenile myelomonocytic leukemia with prominent CD141 myeloid dendritic cell differentiation
Publication date: Available online 13 April 2017
Source:Human Pathology
Author(s): Howard Meyerson, Amad Awadallah, Georgetta Blidaru, Ebenezer Osei, June Schlegelmilch, Rachel Egler, Rolla Abu-Arja, Hilda Ding
Myeloid malignancies showing CD141(+) myeloid dendritic cell (MDC) differentiation have not been documented. Here, we describe a patient with juvenile myelomonocytic leukemia (JMML) in which a prominent CD141(+) cell population was identified most consistent with CD141(+) MDCs based on phenotypic similarity with normal CD141(+) MDCs. Molecular studies demonstrated a KRAS mutation. The findings from the spleen and bone marrow are described. This is the first well-documented demonstration of CD141(+) MDC differentiation of a hematopoietic neoplasm.
http://ift.tt/2otBQjt
Scholar : These new articles for Corrections are available online
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Scholar : These new articles for Addiction Research & Theory are available online
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Scholar : These new articles for Annals of Leisure Research are available online
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Scholar : Canadian Society of Forensic Science Journal, Volume 50, Issue 2, June 2017 is now available online on Taylor & Francis Online
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Scholar : Canadian Water Resources Journal / Revue canadienne des ressources hydriques, Volume 42, Issue 2, June 2017 is now available online on Taylor & Francis Online
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Scholar : Journal of Heritage Tourism, Volume 12, Issue 3, July 2017 is now available online on Taylor & Francis Online
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Scholar : Atlantic Studies, Volume 14, Issue 2, June 2017 is now available online on Taylor & Francis 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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Scholar : These new articles for International Journal of Heritage Studies are available online
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Scholar : Aging & Mental Health, Volume 21, Issue 4, April 2017 is now available online on Taylor & Francis Online
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Equilibrium, thermodynamic and kinetic investigations for biosorption of uranium with green algae (Cladophora hutchinsiae)
Source:Journal of Environmental Radioactivity, Volumes 175–176
Author(s): Esra Bağda, Mustafa Tuzen, Ahmet Sarı
Removal of toxic chemicals from environmental samples with low-cost methods and materials are very useful approach for especially large-scale applications. Green algae are highly abundant biomaterials which are employed as useful biosorbents in many studies. In the present study, an interesting type of green algae, Cladophora hutchinsiae (C. hutchinsiae) was used for removal of highly toxic chemical such as uranium. The pH, biosorbent concentration, contact time and temperature were optimized as 5.0, 12 g/L, 60 min and 20 °C, respectively. For the equilibrium calculations, three well known isotherm models (Langmuir, Freundlich and Dubinin-Radushkevich) were employed. The maximum biosorption capacity of the biosorbent was calculated as about 152 mg/g under the optimum batch conditions. The mean energy of biosorption was calculated as 8.39 kJ/mol from the D–R biosorption isotherm. The thermodynamic and kinetic characteristics of biosorption were also investigated to explain the nature of the process. The kinetic data best fits the pseudo-second-order kinetic model with a regression coefficient of >0.99 for all studied temperatures. The calculated ΔH° and ΔG° values showed that the biosorption process is exothermic and spontaneous for temperatures between 293 and 333 K. Furthermore, after seven cycling process, the sorption and desorption efficiencies of the biosorbent were found to be 70, and 58%, respectively meaning that the biosorbent had sufficiently high reusability performance as a clean-up tool.
http://ift.tt/2nLUoOE
Thoron Mitigation System based on charcoal bed for applications in thorium fuel cycle facilities (part 2): Development, characterization, and performance evaluation
Source:Journal of Environmental Radioactivity, Volume 172
Author(s): K. Sudeep Kumara, B.K. Sahoo, J.J. Gaware, B.K. Sapra, Y.S. Mayya, N. Karunakara
Exposure due to thoron (220Rn) gas and its decay products in a thorium fuel cycle facility handling thorium or 232U/233U mixture compounds is an important issue of radiological concern requiring control and mitigation. Adsorption in a flow-through charcoal bed offers an excellent method of alleviating the release of 220Rn into occupational and public domain. In this paper, we present the design, development, and characterization of a Thoron Mitigation System (TMS) for industrial application. Systematic experiments were conducted in the TMS for examining the 220Rn mitigation characteristics with respect to a host of parameters such as flow rate, pressure drop, charcoal grain size, charcoal mass and bed depth, water content, and heat of the carrier gas. An analysis of the experimental data shows that 220Rn attenuation in a flow through charcoal bed is not exponential with respect to the residence time, L/Ua (L: bed depth; Ua: superficial velocity), but follows a power law behaviour, which can be attributed to the occurrence of large voids due to wall channeling in a flow through bed. The study demonstrates the regeneration of charcoal adsorption capacity degraded due to moisture adsorption, by hot air blowing technique. It is found that the mitigation factor (MF), which is the ratio of the inlet 220Rn concentration (Cin) to the outlet 220Rn concentration (Cout), of more than 104 for the TMS is easily achievable during continuous operation (>1000 h) at a flow rate of 40 L min−1 with negligible (<1 cm of water column) pressure drop. The Thoron Mitigation System based on adsorption on charcoal bed offers a compact and effective device to remove 220Rn from affluent air streams in a space constrained domain. The prototype system has been installed in a thorium fuel cycle facility where it is being evaluated for its long-term performance and overall effectiveness in mitigating 220Rn levels in the workplace.
http://ift.tt/2otq0Wu
Metabolic reprograming of anti-tumor immunity
Source:Current Opinion in Immunology, Volume 46
Author(s): Madhusudhanan Sukumar, Rigel J Kishton, Nicholas P Restifo
Immunotherapies designed to trigger T cell destruction of tumor cells can result in sustained and complete responses in patients whose cancers were resistant to available treatment options. Evidence suggests that powering the T cell response – how T cells generate energy – plays an important role in their effectiveness. Furthermore the metabolism of T cells can be modulated to improve their anti-cancer activities. In this review, we will discuss the key metabolic properties of anti-cancer T cells, along with potential strategies to enhance immunotherapy through the modulation of T cell metabolism.
http://ift.tt/2pge6PI
Classification Systems in Gestational Trophoblastic Neoplasia - Sentiment or Evidenced Based?
Source:Cancer Treatment Reviews
Author(s): V.L. Parker, A.A. Pacey, J.E. Palmer, J.A. Tidy, M.C. Winter, B.W. Hancock
The classification system for Gestational Trophoblastic Neoplasia (GTN) has proved a controversial topic for over 100 years. Numerous systems simultaneously existed in different countries, with three main rival classifications gaining popularity, namely histological, anatomical and clinical prognostic systems.Until 2000, prior to the combination of the FIGO and WHO classifications, there was no worldwide consensus on the optimal classification system, largely due to a lack of high quality data proving the merit of one system over another. Remarkably, a validated, prospectively tested classification system is yet to be conducted.Over time, increasing criticisms have emerged regarding the currently adopted combined FIGO/WHO classification system, and its ability to identify patients most likely to develop primary chemotherapy resistance or disease relapse. This is particularly pertinent for patients with low-risk disease, whereby one in three patients are resistant to first line therapy, rising to four out of five women who score 5 or 6.This review aims to examine the historical basis of the GTN classification systems and critically appraise the evidence on which they were based. This culminates in a critique of the current FIGO/WHO prognostic system and discussion surrounding clinical preference versus evidence based practice.
http://ift.tt/2pdGiFE
Scholar : These new articles for AIDS Care are available online
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Corrigendum to “3D aerosol climatology over East Asia derived from CALIOP observations” [Atmos. Environ. 152 (2017) 503–518]
Source:Atmospheric Environment, Volume 158
Author(s): Yongbo Zhou, Xuejin Sun, Chuanliang Zhang, Riwei Zhang, Yan Li, Haoran Li
http://ift.tt/2oxTqEr
Editorial board
Source:Atmospheric Environment, Volume 158
http://ift.tt/2osJNFo
Real-time chemical characterization of atmospheric particulate matter in China: A review
Source:Atmospheric Environment, Volume 158
Author(s): Yong Jie Li, Yele Sun, Qi Zhang, Xue Li, Mei Li, Zhen Zhou, Chak K. Chan
Atmospheric particulate matter (PM) pollution has become a major health threat accompanying the rapid economic development in China. For decades, filter-based offline chemical analyses have been the most widely adopted means to investigate PM and have provided much information for understanding this type of pollution in China. However, offline analyses have low time resolutions and the chemical information thus obtained fail to reflect the dynamic nature of the sources and the rapid processes leading to the severe PM pollution in China. In recent years, advances in real-time PM chemical characterization have created a new paradigm for PM studies in China. In this review, we summarize those advances, focusing on the most widely used mass spectrometric and ion chromatographic techniques. We describe the findings from those studies in terms of spatiotemporal variabilities, degree of neutralization and oxygenation, source apportionment, secondary formation, as well as collocated measurements of the chemical and physical (hygroscopic and optical) properties of PM. We also highlight the new insights gained from those findings and suggest future directions for further advancing our understanding of PM pollution in China via real-time chemical characterization.
http://ift.tt/2oxJXNn
Deep Inspiration Breath-hold for Left-sided Breast Cancer Patients with Unfavorable Cardiac Anatomy Requiring Internal Mammary Nodal Irradiation
Publication date: Available online 13 April 2017
Source:Practical Radiation Oncology
Author(s): Osama Mohamad, Jean Shiao, Bo Zhao, Karen Roach, Ezequiel Ramirez, Dat Vo, Kimberly Thomas, Xuejun Gu, Ann Spangler, Kevin Albuquerque, Asal Rahimi
PurposeTo evaluate the utility of moderate deep inspiration breath-hold (mDIBH) in reducing heart exposure in left breast cancer patients who have unfavorable cardiac anatomy and need internal mammary nodal (IMLN) irradiation (RT).Material and MethodsWe used maximum heart distance (MHD), defined as maximum distance of heart within the treatment field, >1cm as a surrogate for unfavorable cardiac anatomy. Twenty-two left breast cancer patients with unfavorable cardiac anatomy requiring IMLN-RT underwent free-breathing (FB) and mDIBH CT simulation and planning. 3D–partially wide tangents (3D–PWT) and IMRT plans were generated. Dose-volume histograms were used to compare heart and lung dosimetric parameters. Duration of treatment delivery was recorded for all fractions.ResultsMHD decreased significantly in mDIBH scans. mDIBH significantly reduced mean heart dose (222.7 vs. 578.4cGy; p<0.0001) and left lung V20Gy (31.93 vs. 38.41%; p=0.0006) in both 3D–PWT and IMRT plans. ΔMHD(FB-BH), defined as the change in MHD after breath-hold, reliably predicted mean heart dose reduction after mDIBH. Radiation was effectively delivered in 11.31±3.40min with an average of 10.06±2.74 breath-holds per fraction.ConclusionsmDIBH is efficient and can effectively decrease mean heart dose in patients with unfavorable cardiac anatomy who need IMLN-RT thus simplifying planning and delivery for them. The reduction in mean heart dose is proportional to the reduction in maximum heart distance.
http://ift.tt/2pfSOSo
The Healing Influence of Nature
Publication date: Available online 13 April 2017
Source:Practical Radiation Oncology
Author(s): Kathryn McConnell Greven
http://ift.tt/2pfRiQ0
Volumetric-modulated Dynamic WaveArc therapy reduces the dose to the hippocampus in patients with pituitary adenomas and craniopharyngiomas
Publication date: Available online 13 April 2017
Source:Practical Radiation Oncology
Author(s): Megumi Uto, Takashi Mizowaki, Kengo Ogura, Yuki Miyabe, Mitsuhiro Nakamura, Nobutaka Mukumoto, Hideaki Hirashima, Masahiro Hiraoka
PurposeReducing the radiation dose to the hippocampus is important in patients with brain tumors in order to preserve cognitive function. The Vero4DRT system can realize a new irradiation technique, termed volumetric-modulated Dynamic WaveArc therapy (VMDWAT), which allows the safe use of sequential noncoplanar volumetric-modulated beams without couch rotation. Since VMDWAT appears to reduce the hippocampus dose in patients with pituitary adenomas and craniopharyngiomas, we performed a planning study to compare the dose distribution of volumetric-modulated arc therapy using only a coplanar arc (coVMAT) and VMDWAT.Methods and materials.CoVMAT and VMDWAT plans were created for 30 patients with pituitary adenomas and craniopharyngiomas. The prescription dose was 52.2Gy in 29 fractions, with 99% of each planning target volume covered by 90% of the prescribed dose. Optimization was performed for maximal reduction of the dose to the hippocampus. Treatment time was defined as the beam-on time.ResultsThe mean equivalent dose in 2-Gy fractions to 40% of the volume of the bilateral hippocampus (EQD40%) for coVMAT/VMDWAT were 9.90/5.31Gy, respectively (p<0.001). The mean EQD40% in VMDWAT was less than 7.3Gy, which is the threshold for predicting cognitive impairment. While the volume of normal brain receiving 5Gy (V5) was significantly larger in VMDWAT, compared to coVMAT, the normal brain volume receiving 10, 15, 20, 25, 30, 35, 40, 45, and 50Gy (V10–50) was significantly smaller in VMDWAT. The conformity and homogeneity indices were significantly better in VMDWAT. The mean VMDWAT treatment time was longer compared to coVMAT (70.1 vs. 67.1seconds, respectively).ConclusionsWhile VMDWAT increased brain V5 and the treatment time compared with coVMAT, it significantly reduced the dose to the hippocampus and brain V10–50 and improved target conformity and homogeneity. VMDWAT could be a promising treatment technique for pituitary adenomas and craniopharyngiomas.
http://ift.tt/2pdyNyC
Sinoatrial Node Toxicity after Stereotactic Ablative Radiotherapy to Lung Tumors
Publication date: Available online 13 April 2017
Source:Practical Radiation Oncology
Author(s): Yushen Qian, Han Zhu, Erqi L. Pollom, Ben Y. Durkee, Aadel A. Chaudhuri, Michael Gensheimer, Maximilian Diehn, David B. Shultz, Billy W. Loo
PurposeStereotactic ablative radiotherapy (SABR) is an established treatment for selected lung tumors. Sinoatrial node (SAN) toxicity after thoracic SABR has not been reported in the literature. We sought to understand the risk of SAN toxicity owing to incidental dose to the SAN from SABR.Materials and MethodsWe conducted a retrospective review of patients with early-stage lung cancer or limited pulmonary metastases who underwent thoracic SABR to a right-sided central lung tumor (within 2cm of the mainstem bronchus or other mediastinal structures) between January 2008 and December 2014, analyzed a subset whose treatment imparted dose to the SAN exceeding 10% of the prescription dose, and examined patient and treatment dosimetric characteristics. Mean follow-up interval was 28months. Time to toxicity was defined from start of SABR.ResultsOf 47 patients with central tumors in the right lung treated with SABR reviewed, 13 met our study criteria. A contouring atlas of regional cardiac anatomy was created. One patient treated with SABR for non-small cell lung cancer at the right hilum developed symptomatic sick sinus syndrome, requiring pacemaker placement 6months after treatment. Her acute presentation and short interval between SABR and onset of symptoms suggest that SAN toxicity was likely due to radiation induced injury. Both her age and mean dose to her SAN were the third highest in our cohort. She remained free from cancer progression at 24months follow-up. Twelve additional patients who received significant dose to the SAN from SABR did not develop toxicity.ConclusionWhile uncommon, SAN toxicity from SABR to right sided central thoracic tumors should be recognized and followed in future studies.SummaryIn this first-time clinical case series of 13 patients who received modest incidental radiation to the sinoatrial node (SAN) from SABR for lung tumors, one patient developed symptomatic sick sinus syndrome, requiring pacemaker placement 6months after treatment. Both her age and mean dose to her SAN were the third highest in our cohort. While uncommon, SAN toxicity from SABR to right sided central thoracic tumors should be recognized and followed in future studies.
http://ift.tt/2pfN0Z5
Tri-phasic contrast enhanced CT simulation with bolus tracking for pancreas SBRT target delineation
Publication date: Available online 13 April 2017
Source:Practical Radiation Oncology
Author(s): Devon J Godfrey, Bhavik N Patel, Justus D Adamson, Ergys Subashi, Joseph K Salama, Manisha Palta
PurposeBolus-tracked multi-phasic contrast CT is often employed in diagnostic radiology to enhance the visibility of pancreas tumors, but is uncommon in radiotherapy pancreas CT simulation, and its impact on GTV delineation is unknown. This study evaluates the lesion conspicuity and consistency of pancreas SBRT GTVs contoured in the different contrast phases of tri-phasic CT simulation scans.Methods and MaterialsTri-phasic, bolus-tracked planning CT simulation scans of ten consecutive pancreas SBRT patients were acquired, yielding images of the pancreas during the late arterial (LA), portal venous (PV), and either the early arterial (EA) or delayed phase (DP). GTVs were contoured on each phase by a GI-specialized radiation oncologist and reviewed by a fellowship-trained abdominal radiologist who specializes in pancreatic imaging. The volumes of the registered GTVs, their overlap ratio, and the 3-dimensional margin expansions necessary for each GTV to fully encompass GTVs from the other phases were calculated. The contrast difference between tumor and normal pancreas was measured, and two radiation oncologists rank ordered the phases according to their value for the lesion contouring task.ResultsTumor-to-pancreas enhancement was on average much larger for the LA and PV than the DP or EA phases and the LA and PV phases were also consistently preferred by the radiation oncologists. Enhancement differences amongst the phases resulted in highly variable GTV volumes with no observed trends. Overlap ratios ranged from 18-75% across all three phases, improving to 43-91% when considering only the preferred LA and PV phases. GTV expansions necessary to encompass all GTVs ranged from 0.3–1.8cm for all three phases, improving slightly to 0.1–1.4cm when considering just the LA and PV phases.ConclusionsFor pancreas SBRT, we recommend combining the GTVs from a multi-phasic CT simulation with bolus-tracking, including, at a minimum, a Boolean "OR" of the LA and PV phases.
http://ift.tt/2pdwdsb
Surfactant-free high solids content polymer dispersions
Publication date: 19 May 2017
Source:Polymer, Volume 117
Author(s): Sevilay Bilgin, Radmila Tomovska, José M. Asua
Surfactant-free high solids waterborne polymer dispersions were produced under industrial-like semicontinuous conditions by substituting traditional emulsifiers with stabilizing moieties in situ production from a pH and temperature insensitive ionic monomer (sodium styrene sulfonate, NaSS). Copolymerization between NaSS and comonomers occurred through a mechanism that involves solution polymerization in the aqueous phase and compartmentalized polymerization in a shell created around the particles. This knowledge allowed the development of a polymerization strategy that led to high incorporation of NaSS (up to 83.5%). Solids contents over 60 wt% were achieved with modest concentrations of NaSS (1.35 wt%) and a variety of monomers (acrylates, methacrylates, styrene) can be efficiently polymerized. These latexes presented superior salt and freeze-thaw stability without compromising the water sensitivity of the films.
Graphical abstract
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Syntheses and characterizations of high refractive index and low birefringence polyimides containing spirobifluorene in the side chain
Publication date: 19 May 2017
Source:Polymer, Volume 117
Author(s): Pushan Wen, Rui He, Xiang-Dan Li, Myong-Hoon Lee
Two new diamine monomers having a spirobifluorene structure were synthesized through four steps, and polymerized with three different dianhydrides (PMDA, CBDA and 6FDA) to obtain six polyimides with spirobifluorene structure in the side chain. All the resulting polyimides displayed excellent thermal stability and high glass transition temperature. These polyimides synthesized from CBDA and 6FDA showed good solubility in typical organic solvents such as NMP, DMF and DMSO. Transparent and flexible cast films can be obtained from soluble polyimides or poly(amic acid) solution. The transmittance of polyimide films was higher than 90% in the visible wavelength range (higher than 80% in case of polyimide containing PMDA). The refractive indices of the result polyimides were found to be in the range from 1.6343 to 1.7007, which is higher than that of normal polymers. In addition, the optical birefringences of these polyimides were extremely low (0.0005–0.0014). The high refractive index and low birefringence of these polyimides as well as other descent physical and thermal properties would offer them possible applications in high performance optical materials such as flexible substrates.
Graphical abstract
http://ift.tt/2obloTL
Crystallization kinetics and morphology of biodegradable Poly(ε-caprolactone) with chain-like distribution of ferroferric oxide nanoparticles: Toward mechanical enhancements
Publication date: 19 May 2017
Source:Polymer, Volume 117
Author(s): Kai Zhang, Gen-Hui Li, Yu-Dong Shi, Yi-Fu Chen, Jian-Bing Zeng, Ming Wang
Distribution of nanoparticles in nanocomposites is one of the most important roles to design unique morphologies and properties; however, up to now, it is still very difficult to control distribution of nanoparticles in polymer matrix. Here we show a simple approach to fabricate ferroferric oxide (Fe3O4) nanoparticles with controllable chain-like distribution in poly(ε-caprolactone) (PCL) by a magnetic self-organization. Randomly distributed Fe3O4 nanoparticles can be polarized and the interparticle dipole-dipole attraction drives their assembly into linear chains in an external magnetic field. The accelerated PCL crystallization happens at low Fe3O4 loadings, while the retardation to crystallization happens at high Fe3O4 loadings, especially for the samples with chain-like structures. Furthermore, PCL spherulites are also arranged into chain-like structures by the Fe3O4 nanoparticle chains. As a result, the PCL/Fe3O4 nanocomposites with chain-like structures exhibit higher storage modulus, Young's modulus and tensile strength than that of the corresponding nanocomposites with random distribution of Fe3O4 nanoparticles, indicating mechanical enhancements.
Graphical abstract
http://ift.tt/2obp7k8
Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans
Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108
Author(s): Dylan J. Dues, Claire E. Schaar, Benjamin K. Johnson, Megan J. Bowman, Mary E. Winn, Megan M. Senchuk, Jeremy M. Van Raamsdonk
Mutations affecting components of the mitochondrial electron transport chain have been shown to increase lifespan in multiple species including the worm Caenorhabditis elegans. While it was originally proposed that decreased generation of reactive oxygen species (ROS) resulting from lower rates of electron transport could account for the observed increase in lifespan, recent evidence indicates that ROS levels are increased in at least some of these long-lived mitochondrial mutants. Here, we show that the long-lived mitochondrial mutant isp-1 worms have increased resistance to oxidative stress. Our results suggest that elevated ROS levels in isp-1 worms cause the activation of multiple stress-response pathways including the mitochondrial unfolded protein response, the SKN-1-mediated stress response, and the hypoxia response. In addition, these worms have increased expression of specific antioxidant enzymes, including a marked upregulation of the inducible superoxide dismutase genes sod-3 and sod-5. Examining the contribution of sod-3 and sod-5 to the oxidative stress resistance in isp-1 worms revealed that loss of either of these genes increased resistance to oxidative stress, but not other forms of stress. Deletion of sod-3 or sod-5 decreased the lifespan of isp-1 worms and further exacerbated their slow physiologic rates. Thus, while deletion of sod-3 and sod-5 genes has little impact on stress resistance, physiologic rates or lifespan in wild-type worms, these genes are required for the longevity of isp-1 worms. Overall, this work shows that the increased resistance to oxidative stress in isp-1 worms does not account for their longevity, and that resistance to oxidative stress can be experimentally dissociated from lifespan.
Graphical abstract
http://ift.tt/2nLsDWp
Sirt3 confers protection against neuronal ischemia by inducing autophagy: Involvement of the AMPK-mTOR pathway
Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108
Author(s): Shu-Hui Dai, Tao Chen, Xia Li, Kang-Yi Yue, Peng Luo, Li-Kun Yang, Jie Zhu, Yu-Hai Wang, Zhou Fei, Xiao-Fan Jiang
Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP generation and reactive oxygen species (ROS) production. Our previous study showed that Sirt3 exerts protective effects against oxidative stress in neuronal cells. In this study, we investigated the role of Sirt3 in neuronal ischemia using an oxygen and glucose deprivation (OGD) model. Sirt3 was up-regulated by OGD and overexpression of Sirt3 through lentivirus transfection significantly reduced OGD-induced lactate dehydrogenase (LDH) release and neuronal apoptosis. These effects were accompanied by reduced hydrogen dioxide (H2O2) production, enhanced ATP generation and preserved mitochondrial membrane potential (MMP). The results of immunocytochemistry and electron microscopy showed that Sirt3 increased autophagy in OGD-injured neurons, which was also confirmed by the increased expression of Beclin-1 as well as LC3-I to LC3-II conversion. In addition, the autophagy inhibitor 3-MA and bafilomycin A1 partially prevented the effects of Sirt3 on LDH release and apoptosis after OGD. The results of western blotting showed that overexpression of Sirt3 in cortical neurons markedly increased the phosphorylation of AMPK, whereas the phosphor-mTOR (p-mTOR) levels decreased both in the presence and absence of OGD insult. Furthermore, pre-treatment with the AMPK inhibitor compound C partially reversed the protective effects of Sirt3. Taken together, these findings demonstrate that Sirt3 protects against OGD insult by inducing autophagy through regulation of the AMPK-mTOR pathway and that Sirt3 may have therapeutic value for protecting neurons from cerebral ischemia.
Graphical abstract
http://ift.tt/2nLFWpK
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
