Scholar : Scholar Alert - [ intitle:laryngeal ]

Scholar Alert: [ intitle:laryngeal ]

[HTML] The primary growth of laryngeal squamous cell carcinoma cells in vitro is effectively supported by paired cancer-associated fibroblasts alone

M Wang, C Wu, Y Guo, X Cao, W Zheng, GK Fan - Tumor Biology, 2017

Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in
vitro and have a low survival rate. However, in our previous work to establish a laryngeal
squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts

Diagnostic accuracy of surface coil MRI in assessing cartilaginous invasion in laryngeal tumours: Do we need contrast-agent administration?

L Preda, G Conte, L Bonello, C Giannitto, E Tagliabue… - European Radiology, 2017

Objectives To assess the diagnostic accuracy of MRI performed using surface coils, with and
without contrast medium, in predicting thyroid and cricoid cartilage infiltration in laryngeal
tumours, and to investigate whether the radiologist's experience influences diagnostic

[HTML] Laryngeal evidence for the first and second passaggio in professionally trained sopranos

M Echternach, F Burk, M Köberlein, A Selamtzis… - PloS one, 2017

Results In both the first and the second passaggio, variations of vocal fold vibration patterns
were found. Four distinct patterns emerged: smooth transitions with either increasing or
decreasing durations of glottal closure, abrupt register transitions, and intermediate loss of

Conservative Surgical and Non-surgical Options in Management of T3 Laryngeal Cancer

C Piazza, A Paderno - Current Otorhinolaryngology Reports, 2017

Abstract Purpose of Review We herein address the most up-to-date findings in the literature
in relation to surgical and non-surgical organ preservation strategies aimed at treatment of
T3 laryngeal cancer. Recent Findings T3 laryngeal cancer represents an advanced stage of

Expression of Cell Cycle-related Proteins p16, p27 and Ki-67 Proliferating Marker in Laryngeal Squamous Cell Carcinomas and in Laryngeal Papillomas

U CIESIELSKA, T ZATONSKI, K NOWINSKA… - Anticancer Research, 2017

Background: The deregulation of the cell cycle is crucial for the processes of carcinogenesis
and tumor progression. The cell cycle is under the control of cyclin-dependent kinases
(CDKs) and their inhibitors (CDKIs). Proteins p16 and p27 are CDKIs, and their altered

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Scholar : Ειδοποίηση Μελετητή - [ Laryngomal

Ειδοποίηση Μελετητή:[ Laryngomalacia ]

[HTML] Predictors of failure of DISE-directed adenotonsillectomy in children with sleep disordered breathing

N Alsufyani, A Isaac, M Witmans, P Major, H El-Hakim - Journal of Otolaryngology- …, 2017

... On bivariate analysis, neuropsychiatric diagnosis (r = 0.286, p = 0.042), history of sleepwalking
or enuresis (r = 0.103, p = 0.044), MOS (r = 0.123, p = 0.033), presence of DNS (r = 0.107, p =
0.036), and presence of laryngomalacia (r = 0.122, p = 0.017) all positively correlated ...

ACPA 2017 ORAL PRESENTATION

A Johns, JG McComb, M Urata - The Cleft Palate–Craniofacial Journal, 2017

Page 1. ACPA 2017 ORAL PRESENTATION ABSTRACTS The peer-reviewed
abstracts presented at the 74th Annual Meeting of the ACPA are published as
submitted by the authors. For financial conflict of interest disclosure ...

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Scholar : Ειδοποίηση Μελετητή - [ ΦΩΝΗ ]

Ειδοποίηση Μελετητή:[ ΦΩΝΗ ]

[HTML] An Unheard, Inhuman Music: Narrative Voice and the Question of the Animal in Kafka's "Josephine, the Singer or the Mouse Folk"

K Driscoll - Humanities, 2017

... Within this schema, ie, within the logic of carnophallogocentrism, the narrative voice would be
the embodiment of λόγος (logos), on the side of the Father and the Law, while Josephine,
embodying φωνή (phōné), would be on the side of the animal, excluded from political life ...

[PDF] Ο ρόλος των γυναικών στην αναβάθμιση της δημόσιας διοίκησης καθώς και η συνδρομή τους, στην οικονομική και κοινωνική αναπτυξιακή διαδικασία μέσα από δράσεις …

Α Αγγέλου - 2017

Page 1. ΠΡΟΓΡΑΜΜΑ ΜΕΤΑΠΤΥΧΙΑΚΩΝ ΣΠΟΥΔΩΝ ΤΜΗΜΑΤΟΣ ΔΙΕΘΝΩΝ
ΕΥΡΩΠΑΙΚΩΝ ΣΠΟΥΔΩΝ ΣΤΗΝ « ΕΥΡΩΠΑΙΚΗ ΟΛΟΚΛΗΡΩΣΗ ΚΑΙ ΔΙΑΚΥΒΕΡΝΗΣΗ
» ♦♦♦ ΜΕΤΑΠΤΥΧΙΑΚΗ ΔΙΠΛΩΜΑΤΙΚΗ ΕΡΓΑΣΙΑ « Ο ρόλος ...

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Ειδοποίηση Μελετητή:[ ΣΤΡΕΠΤΟΚΟΚΚΟΣ ]

[PDF] Συνδυαστική ανάλυση δεδομένων μεταβολομικής και πρωτεομικής από δείγματα ασθενών με χρόνια νεφρική ανεπάρκεια

Π Τζανή-Τζανοπούλου - 2017

... Οι συστημικές λοιμώξεις εμφανίζονται κυρίως στις αναπτυσσόμενες χώρες και μπορεί να
προκαλούνται από βακτήρια (φυματίωση σε Ινδία και Μέση Ανατολή, στρεπτόκοκκος στην Αφρική),
ιούς (Ηπατίτιδα B και C, AIDS στην Αφρική) και πρωτόζωα (ελονοσία στην ...

[PDF] Συνδυασμός πρωτεϊνικών και πεπτιδικών δεδομένων με σκοπό την ταυτοποίηση νεφρικών πρωτεασών που εμπλέκονται στην επιδείνωση της χρόνιας νεφρικής …

Γ Καπέτσης - 2017

... λοιμώξεις μπορεί να οφείλονται σε βακτήρια (φυματίωση σε Ινδία και Μέση Ανατολή,
στρεπτόκοκκος στην Αφρική), ιούς (HIV, ηπατίτιδα B και C στην Αφρική) και παράσιτα
(λεϊσμανίαση στην Αφρική και στην Ασία και ελονοσία στην Αφρική) [10]. ...

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3 Tesla 23Na Magnetic Resonance Imaging During Acute Kidney Injury

Publication date: Available online 8 May 2017
Source:Academic Radiology
Author(s): Matthias Hammon, Susan Grossmann, Peter Linz, Hannes Seuss, Rebecca Hammon, Daniela Rosenhauer, Rolf Janka, Alexander Cavallaro, Friedrich C. Luft, Jens Titze, Michael Uder, Anke Dahlmann
Rationale and ObjectivesSodium and proton magnetic resonance imaging (²³Na/¹H-MRI) have shown that muscle and skin can store Na⁺ without water. In chronic renal failure and in heart failure, Na⁺ mobilization occurs, but is variable depending on age, dialysis vintage, and other features. Na⁺ storage depots have not been studied in patients with acute kidney injury (AKI).Materials and MethodsWe studied 7 patients with AKI (mean age: 51.7 years; range: 25–84) and 14 age-matched and gender-matched healthy controls. All underwent ²³Na/¹H-MRI at the calf. Patients were studied before and after acute hemodialysis therapy within 5–6 days. The ²³Na-MRI produced grayscale images containing Na⁺ phantoms, which served to quantify Na⁺ contents. A fat-suppressed inversion recovery sequence was used to quantify H2O content.ResultsPlasma Na⁺ levels did not change. Mean Na⁺ contents in muscle and skin did not significantly change following four to five cycles of hemodialysis treatment (before therapy: 32.7 ± 6.9 and 44.2 ± 13.5 mmol/L, respectively; after dialysis: 31.7 ± 10.2 and 42.8 ± 11.8 mmol/L, respectively; P > .05). Water content measurements did not differ significantly before and after hemodialysis in muscle and skin (P > .05). Na⁺ contents in calf muscle and skin of patients before hemodialysis were significantly higher than in healthy subjects (16.6 ± 2.1 and 17.9 ± 3.2) and remained significantly elevated after hemodialysis.ConclusionsNa⁺ in muscle and skin accumulates in patients with AKI and, in contrast to patients receiving chronic hemodialysis and those with acute heart failure, is not mobilized with hemodialysis within 5–6 days.



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Breast Density Legislation in New England

Publication date: Available online 8 May 2017
Source:Academic Radiology
Author(s): Ana P. Lourenco, Roberta M. DiFlorio-Alexander, Priscilla J. Slanetz
Rationale and ObjectivesThis study aimed to assess radiologists' knowledge about breast density legislation as well as perceived practice changes resulting from the enactment of breast density legislation.Materials and MethodsThis is an institutional review board-exempt anonymous email survey of 523 members of the New England Roentgen Ray Society. In addition to radiologist demographics, survey questions addressed radiologist knowledge of breast density legislation, knowledge of breast density as a risk factor for breast cancer, recommendations for supplemental screening, and perceived practice changes resulting from density notification legislation.ResultsOf the 523 members, 96 responded, yielding an 18% response rate. Seventy-three percent of respondents practiced in a state with breast density legislation. Sixty-nine percent felt that breast density notification increased patient anxiety about breast cancer, but also increased patient (74%) and provider (66%) understanding of the effect of breast density on mammographic sensitivity. Radiologist knowledge of the relative risk of breast cancer when comparing breasts of different density was variable.ConclusionsConsiderable confusion and controversy regarding breast density persists, even among practicing radiologists.



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Quantification of Mouse Renal Perfusion Using Arterial Spin Labeled MRI at 1 T

Publication date: Available online 8 May 2017
Source:Academic Radiology
Author(s): Quyen N. Do, Ananth J. Madhuranthakam, Peter Bendel, Robert E. Lenkinski
Rationale and ObjectivesQuantitative measurement of renal perfusion in murine models provides important information on the organ physiology and disease states. The 1-T desktop magnetic resonance imaging has a small footprint and a self-contained fringe field. This resultant flexibility in siting makes the system ideal for preclinical imaging research. Our objective was to evaluate the capability of the 1-T desktop magnetic resonance imaging to measure mouse renal perfusion without the administration of exogenous contrast agents.Materials and MethodsWe implemented a flow-sensitive alternating inversion recovery (FAIR)-based arterial spin labeling sequence with a mouse volume coil on a 1-T desktop magnetic resonance scanner. The validity of the implementation was tested by comparing obtained renal perfusion results with literature values for normal mice and challenging the technique with mice treated with furosemide, a blood vessel vasoconstrictor drug.ResultsThe measured cortical and medullary perfusions were quantified to be 402 ± 95 and 184 ± 52 mL/100 g/min, respectively, in agreement with literature values. The ratio of cortical to medullary renal blood flow was between 2 and 3 and was independent of the mouse weight. As expected, upon furosemide injection, a decrease (~50%) in cortical perfusion was observed in the mice population, at 1 hour post injection compared to baseline (P < 0.0001), which returned to baseline after 24 hours (P = 0.68).ConclusionsWe reported the successful application of FAIR-based arterial spin labeling for noncontrast perfusion measurement of mouse kidneys using a 1-T desktop scanner. The easy implementation of FAIR sequence on a 1-T desktop scanner offers the potential for longitudinal perfusion studies in limited access areas such as behind the barrier in mouse facilities and in multimodality preclinical imaging laboratories without the administration of exogenous contrast agents.



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Maximum Aortic Valve Opening Phase for Annulus Sizing in Pre-TAVR CTA

Publication date: Available online 8 May 2017
Source:Academic Radiology
Author(s): Nam Ju Lee, Saurabh Jha, Bong Ju Lee, Harold Litt
Rationale and ObjectivesThe optimal phase for the measurement of the aortic annular area for transcatheter aortic valve replacement (TAVR) is not standardized, although most agree that systolic measurements are preferred, when the annulus is larger. We hypothesized that the maximum annular area occurs at the cardiac phase of the maximum aortic valve opening (MAVO) and that this phase can be accurately and reproducibly assessed by visual inspection only.Materials and MethodsThe aortic valve opening area was inspected visually by two readers to determine the MAVO phase. The annular area was measured at the MAVO phase and the typical systolic phase (35% of the R-R interval). Differences in the annular area that would change valve sizing for prostheses were noted.ResultsFifty patients (mean age 81) were studied. Ninety percent had the MAVO at the 15%–25% R-R interval. There was high interobserver correlation (0.89) for determining the MAVO phase by visual inspection. For 49 out of 50 patients, the annular area was maximal at the MAVO phase. The mean difference in the annular area between the MAVO phase and 35% was 22.3 (±4.57) mm². In 12% of the patients, the difference in the annular area changed the recommended size of a self-expanding prosthesis and would have altered the procedure in 32% for balloon-expandable prostheses.ConclusionsVisually assessed MAVO occurs in early systole for most patients and is almost always the cardiac phase of the maximal aortic annular area. This method allows rapid and reproducible determination of the appropriate phase for TAVR planning measurements. Consideration should be given to optimizing pre-TAVR computed tomography acquisitions for early systolic reconstruction and visual determination of the MAVO.



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Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell-of-Origin Sarcoma Models

Publication date: June 2017
Source:Neoplasia, Volume 19, Issue 6
Author(s): Lucia Martinez-Cruzado, Juan Tornin, Aida Rodriguez, Laura Santos, Eva Allonca, Maria Teresa Fernandez-Garcia, Aurora Astudillo, Juana Maria Garcia-Pedrero, Rene Rodriguez
Trabectedin has been approved for second-line treatment of soft tissue sarcomas. However, its efficacy to target sarcoma initiating cells has not been addressed yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and undifferentiated pleomorphic sarcoma (UPS) developed from transformed human mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in the cell type responsible for initiating sarcomagenesis and their derived cancer stem cells (CSC) subpopulations. We found that low nanomolar concentrations of trabectedin efficiently inhibited the growth of sarcoma-initiating cells, induced cell cycle arrest, DNA damage and apoptosis. Interestingly, trabectedin treatment repressed the expression of multiple genes responsible for the development of the CSC phenotype, including pluripotency factors, CSC markers and related signaling pathways. Accordingly, trabectedin induced apoptosis and reduced the survival of CSC-enriched tumorsphere cultures with the same efficiency that inhibits the growth of bulk tumor population. In vivo, trabectedin significantly reduced the mitotic index of MRCLS xenografts and inhibited tumor growth at a similar extent to that observed in doxorubicin-treated tumors. Combination of trabectedin with campthotecin (CPT), a chemotherapeutic drug that shows a robust anti-tumor activity when combined with alkylating agents, resulted in a very strong synergistic inhibition of tumor cell growth and highly increased DNA damage and apoptosis induction. Importantly, the enhanced anti-tumor activity of this combination was also observed in CSC subpopulations. These data suggest that trabectedin and CPT combination may constitute a novel strategy to effectively target both the cell-of-origin and CSC subpopulations in sarcoma.



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The effect of ALA-PDT under normoxia and cobalt chloride (CoCl2)-induced hypoxia on adhesion molecules (ICAM-1, VCAM-1) secretion by colorectal cancer cells

Publication date: Available online 8 May 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Aleksandra Kawczyk-Krupka, Zenon Czuba, Beata Kwiatek, Sebastian Kwiatek, Magdalena Krupka, Karolina Sieroń
BACKGROUNDThe most fundamental problem in cancer biology research is to understand the mechanisms of cancer cell resistance to oncological therapies. Literature reports emphasize the important role of adhesion molecules: intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (ICAM-1 and VCAM-1) in cancer progression and resistance to treatment. Photodynamic therapy (PDT) could become the component of a personalized approach to colorectal cancer, therefore we examined the effects of ALA (δ-aminolevulinic) acid PDT in normoxia and under cobalt chloride (CoCl2)-induced hypoxia on ICAM-1 and VCAM-1 secretion by colorectal cancer cells.METHODSHuman colorectal cancer cells of different malignant potential SW480 and SW620 were used in the experiment. Cell lines were treated ALA, in order to achieve conditions comparable to in vivo hypoxia, CoCl2 was added, then cells were irradiated both in normoxia and in hypoxia-like conditions. Cell viability was assessed using the LDH and MTT assays and apoptosis. ICAM-1 and VCAM-1 concentrations were determined with the Bio − Plex ProTM Assay and System.RESULTSThe experiment revealed that ALA PDT under normoxia and CoCl2-induced hypoxia had no significant effect on ICAM-1 and VCAM-1-dependent adhesion of colorectal cancer cells. The secretion of ICAM-1 by SW480 ell line was more pronounced compared to ICAM-1 secretion by SW620 cells.CONCLUSIONDetermination of tumor marker levels and especially adhesion molecules involved in metastatic spread is necessary. Our experiment reveals, that ALA PDT in normoxia and CoCl2-induced hypoxia has no effect on adhesion molecules secretion by colon cancer cells in vitro.



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An Update on Memory Reconsolidation Updating

Publication date: Available online 8 May 2017
Source:Trends in Cognitive Sciences
Author(s): Jonathan L.C. Lee, Karim Nader, Daniela Schiller
The reactivation of a stored memory in the brain can make the memory transiently labile. During the time it takes for the memory to restabilize (reconsolidate) the memory can either be reduced by an amnesic agent or enhanced by memory enhancers. The change in memory expression is related to changes in the brain correlates of long-term memory. Many have suggested that such retrieval-induced plasticity is ideally placed to enable memories to be updated with new information. This hypothesis has been tested experimentally, with a translational perspective, by attempts to update maladaptive memories to reduce their problematic impact. We review here progress on reconsolidation updating studies, highlighting their translational exploitation and addressing recent challenges to the reconsolidation field.



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Intramyocardial fate and effect of iron nanoparticles co-injected with MACS® purified stem cell products

Publication date: August 2017
Source:Biomaterials, Volume 135
Author(s): Paula Müller, Ralf Gaebel, Heiko Lemcke, Frank Wiekhorst, Frauke Hausburg, Cajetan Lang, Nicole Zarniko, Bernd Westphal, Gustav Steinhoff, Robert David
BackgroundMagnetic activated cell sorting (MACS^®) is routinely used to isolate stem cell subpopulations intended for the treatment of cardiovascular diseases. In strong contrast, studies examining the amount, effect and intramyocardial distribution of iron nanoparticles used for magnetic cell labelling are missing, although iron excess can cause functional disorders in the heart.Methods and resultsCD133⁺ haematopoietic and CD271⁺ mesenchymal stem cells were purified from bone marrow using automatically and manually MACS^® based systems. Flow cytometric measurements demonstrated a rapid loss of MACS^® MicroBeads from cells under culture conditions, while storage under hypothermic conditions decelerated their detachment. Moreover, an average loading of ∼11 fg iron/cell caused by magnetic labelling was determined in magnetic particle spectroscopy. Importantly, hemodynamic measurements as well as histological examinations using a myocardial ischemia/reperfusion mouse model showed no influence of MACS^® MicroBeads on cardiac regeneration, while the transplantation of stem cells caused a significant improvement. Furthermore, immunostainings demonstrated the clearance of co-injected iron nanoparticles from stem cells and the surrounding heart tissue within 48 h post transplantation.ConclusionsOur results indicate that iron amounts typically co-injected with MACS^® purified stem cells do not harm cardiac functions and are cleared from heart tissue within a few hours. Therefore, we conclude that MACS^® MicroBeads exhibit a good compatibility in the cardiac environment.



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High yield, scalable and remotely drug-loaded neutrophil-derived extracellular vesicles (EVs) for anti-inflammation therapy

Publication date: August 2017
Source:Biomaterials, Volume 135
Author(s): Jin Gao, Sihan Wang, Zhenjia Wang
Extracellular vesicles (EVs) are nanoscale membrane-formed compartments naturally secreted from cells, which are intercellular mediators regulating physiology and pathogenesis, therefore they could be a novel therapeutic carrier for targeted delivery. However, the translation of EVs is hindered by the heterogeneous composition, low yield, inefficient drug loading and unlikely scalability. Here we report a strategy to generate EVs using nitrogen cavitation (NC-EVs) that instantly disrupts neutrophils to form nanosized membrane vesicles. NC-EVs are similar to naturally secreted EVs (NS-EVs), but contain less subcellular organelles and nuclear acids. The production of NC-EVs was increased by 16 folds and is easy to scale up for clinical use compared to NS-EVs. To examine the usefulness of NC-EVs as a drug delivery platform, piceatannol (an anti-inflammation drug) was remotely loaded in NC-EVs via the pH gradient. We found that piceatannol-loaded NC-EVs dramatically alleviated acute lung inflammation/injury and sepsis induced by lipopolysaccharide (LPS). Our studies reveal that nitrogen cavitation is a novel approach to efficiently generate EVs from any cell type and could be exploited for personalized nanomedicine.



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Editorial board

Publication date: July 2017
Source:Biomaterials, Volume 134





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Natural healing-inspired collagen-targeting surgical protein glue for accelerated scarless skin regeneration

Publication date: July 2017
Source:Biomaterials, Volume 134
Author(s): Eun Young Jeon, Bong-Hyuk Choi, Dooyup Jung, Byeong Hee Hwang, Hyung Joon Cha
Skin scarring after deep dermal injuries is a major clinical problem due to the current therapies limited to established scars with poor understanding of healing mechanisms. From investigation of aberrations within the extracellular matrix involved in pathophysiologic scarring, it was revealed that one of the main factors responsible for impaired healing is abnormal collagen reorganization. Here, inspired by the fundamental roles of decorin, a collagen-targeting proteoglycan, in collagen remodeling, we created a scar-preventive collagen-targeting glue consisting of a newly designed collagen-binding mussel adhesive protein and a specific glycosaminoglycan. The collagen-targeting glue specifically bound to type I collagen in a dose-dependent manner and regulated the rate and the degree of fibrillogenesis. In a rat skin excisional model, the collagen-targeting glue successfully accelerated initial wound regeneration as defined by effective reepithelialization, neovascularization, and rapid collagen synthesis. Moreover, the improved dermal collagen architecture was demonstrated by uniform size of collagen fibrils, their regular packing, and a restoration of healthy tissue component. Collectively, our natural healing-inspired collagen-targeting glue may be a promising therapeutic option for improving the healing rate with high-quality and effective scar inhibition.



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Co and terpolymer reactivity ratios of chemically amplified resists

Publication date: 2 June 2017
Source:Polymer, Volume 118
Author(s): Narahari S. Pujari, Mingxing Wang, Kenneth E. Gonsalves
Resists are important multicomponent system require in microelectronic industry for fabrication of integrated circuit (IC) devices. The current high end IC (integrated circuit) technology node in manufacturing is 20 nm and looking toward 16 and 10 nm nodes to fulfil market demand. A series of chemically amplified resists (CARs) based on co and terpolymers of 4-hydroxystyrene (HOST), 2-ethyl-2-adamantyl methacrylate (EAMA) and/or a monomer-bound anionic photoacid generator (PAG) were prepared and characterized. Specifically, Triphenylsulfonium salt 4-(methacryloxy)-2,3,5,6-tetrafluorobenzenesulfonate (F4 PAG) was incorporated into the main chain to get PAG bound polymer microstructure.The aim of the study was to investigate interplay of individual monomers in co and terpolymer systems. This was achieved by understanding the reactivity ratios and monomer sequence distribution in the polymer. Analysis was conducted by using a software PROCOP version2.3. The co/terpolymer compositions were determined by quantitative ¹H NMR spectra. The copolymer reactivity ratio of each monomer was determined with Fineman–Ross, Kelen–Tüdös, and nonlinear least-squares curve- fitting methods. It was observed that EAMA is not polymerizable under given reaction conditions and copolymerization of EAMA-PAG was also not possible. HOST-EAMA system yielded reactivity ratios near zero indicating that they form quasi alternating structures. HOST-PAG system yielded copolymers rich in PAG. On the basis of the reactivity ratios determined from the binary copolymers, Alfrey–Goldfinger equations were used to estimate the compositions of the terpolymers. In terpolymer system, where two monomers were non homopolymerizable, both PAG and EAMA competed to add up to the HOST radical. All six reactivity values were less then unity indicating preferred cross propagation of radicals. PAG was the most reactive monomer. Monomer sequence distribution of copolymer and terpolymer was established to get an idea of detailed microstructure of the chain. Copolymers confirmed 84% of dyads formation of each monomer while terpolymer analysis revealed dominance of HOST centered triads. In addition to this, kinetics of terpolymerization reaction was performed to validate the theory. Findings from the study can be used to tailor make CAR synthesis for optimum EUV (extreme ultraviolet) lithography performance.

Graphical abstract

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Controlled cationic polymer particles prepared by dispersion polymerizations using poly(l-lysine) macromonomers as a stabilizer

Publication date: 2 June 2017
Source:Polymer, Volume 118
Author(s): Tomomichi Itoh, Shingo Okada, Katsuaki Kojima, Hironori Asano, Hiroaki Shimomoto, Eiji Ihara
A novel poly(l-lysine) macromonomer was successfully prepared via a click reaction between vinyl benzyl azide and propargyl-terminated poly(l-lysine), and it was used as a functional stabilizer for the dispersion polymerization of styrene; narrowly distributed polystyrene particles were produced as a result, onto which cationic poly(l-lysine) chains were grafted. The resulting particles exhibited a pH-responsive dispersion behavior in aqueous solutions due to the properties of the poly(l-lysine) chains at the particle surface. It was found that the particle size and the surface density of the resultant particles could be varied by tuning the concentrations of the macromonomer, styrene, and initiator used in the initial solution of the dispersion polymerization. The poly(l-lysine) macromonomer was also found to be effective when used as a stabilizer for the dispersion polymerization of both methyl methacrylate and a styrene/acrylonitrile mixture.

Graphical abstract

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PELP1 - A Key Mediator of Estrogen Signaling and Actions in the Brain

Abstract

Proline-, Glutamic acid-, and Leucine-rich Protein 1 (PELP1) is an estrogen receptor (ER) coregulator protein identified by our collaborative group. Work from our lab and others has shown that PELP1 is a scaffold protein that interacts with ERs, kinase signaling factors, as well as proteins involved in chromatin remodeling and DNA repair. Its role in mediating 17β-Estradiol (E2) signaling and actions has been heavily studied in cancer cells, but only recently has attention turned to its role in the brain. In this review, we discuss the tissue, cellular and subcellular localization of PELP1 in the brain. We also discuss recent evidence from PELP1 forebrain-specific knockout mice that demonstrate a critical role of PELP1 in mediating both extranuclear and nuclear ER signaling in the brain, as well as E2-induced neuroprotection, anti-inflammatory effects, and regulation of cognitive function. Finally, the PELP1 interactome and unique gene network regulated by PELP1 in the brain is discussed, especially as it provides new insights into PELP1 biology, protein interactions, and mechanisms of action in the brain. As a whole, the findings discussed in this review indicate that PELP1 functions as a critical ER coregulator in the brain to mediate E2 signaling and actions.

This article is protected by copyright. All rights reserved.

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Y5 receptor signalling counteracts the anorectic effects of PYY3-36 in diet induced obese mice

Abstract

Peptide YY 3-36 (PYY3-36) is known as a critical satiety factor reducing food intake both in rodents and humans. While the anorexic effect of PYY3-36 is thought to be mediated mainly by the Y2 receptor, the involvement of other Y-receptors in this process has never been conclusively resolved. Amongst them the Y5 receptor (Y5R) is the most likely candidate to also be a target for PYY3-36 which is thought to counteract the anorectic effects of Y2R activation. Here we show that short term treatment of diet induced obese WT and Y5R knockout mice (Y5KO) with PYY3-36 leads to significantly reduced food intake in both genotypes, which is more pronounced in Y5R KO mice. Interestingly, chronic PYY3-36 infusion via minipumps to WT mice causes increased cumulative food intake, which is associated with increased body weight gain. In contrast, lack of Y5R reversed this effect. Consistent with the observed increased body weight and fat mass in WT treated mice, glucose tolerance was also impaired by chronic PYY3-36 treatment. Again this was less affected in Y5KO mice suggestive of a role of Y5R's in the regulation of glucose homeostasis. Taken together, our data suggests that PYY3-36 mediated signalling via Y5 receptors may counteract the anorectic effects that it mediates via the Y2 receptor (Y2R) consequently lowering bodyweight in the absence of Y5 signalling. These findings open the potential of combination therapy using PYY3-36 and Y5R antagonists to enhance PYY3-36′s food intake reducing effects.

This article is protected by copyright. All rights reserved.

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Severity strata for EASI, mEASI, oSCORAD, SCORAD, ADSI and BSA in adolescents and adults with atopic dermatitis

Abstract

Background

Scoring systems for assessing the signs of atopic dermatitis (AD) are complex and difficult to interpret. Severity strata are helpful to properly interpret these assessments. We sought to confirm previously reported strata for Eczema Area and Severity Index (EASI), Scoring AD (SCORAD) and objective component of SCORAD (oSCORAD) and develop strata for the modified EASI (mEASI), Atopic Dermatitis Severity Index (ADSI) and body surface (BSA) for use in adults with AD.

Methods

Skin-examination was performed in 673 adolescents and adults (age ≥13 years) with diagnosed AD in a dermatology practice setting. Strata were selected using an anchoring approach based on a 4-point Investigator's Global Assessment of severity (clear of active skin lesions, mild, moderate or severe disease).

Results

We determined potential severity strata for EASI (0=clear, 0.1-5.9=mild, 6.0-22.9=moderate, 23.0-72=severe; kappa=0.694), mEASI (0-0.9=clear, 1-8.9=mild, 9.0-29.9=moderate, 30.0-90=severe; kappa=0.71), oSCORAD (0-7.9=clear, 8.0-23.9=mild, 24.0-37.9=moderate, 38.0-83=severe; kappa=0.70), SCORAD (0-9.9=clear, 10.0-28.9=mild, 29.0-48.9=moderate, 49.0-103=severe; kappa=0.68), ADSI (0-1.9=clear, 2-5.9=mild, 6.0-8.9=moderate and 9.0-15=severe; kappa=0.55), and BSA (0=clear, 0.1-15.9=mild, 16.0-39.9=moderate, 40.0-100=severe; kappa=0.656). oSCORAD >0 were found in clear skin due to the presence of xerosis, which is scored in oSCORAD. Similarly, SCORAD >0 were found in clear skin due to the scoring of xerosis, pruritus and sleeplessness. Similarly, mEASI and ADSI scores >0 occurred in patients with clear skin due to scoring of pruritus.

Conclusions

We recommend using these strata for interpretation of their respective measures in clinical trials of AD. There are important differences between the 5 assessments, which profoundly impact the interpretation of their scores.

This article is protected by copyright. All rights reserved.

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Sirolimus therapy for children with problematic Kaposiform haemangioendothelioma and tufted angioma

Abstract

Kaposiform haemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumours that typically present during infancy or childhood. Originally regarded as distinct lesions, they are now considered as part of a spectrum. Presentation is usually as an enlarging, tender, blue or red mass. Both KHE and TA may be associated with Kasabach-Merritt Phenomenon (KMP), a severe haemorrhagic state arising from intralesional platelet trapping, microangiopathic haemolytic anaemia, and consumptive coagulopathy.

This article is protected by copyright. All rights reserved.

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Treatment satisfaction and need for shared decision-making in patients with psoriasis from Peru

Abstract

psoriasis is reported by the World Health Organization as a chronic skin disease with an elevated physical, emotional and socioeconomic burden. However, this burden is underestimated in developing countries, such as Peru, due the lack of epidemiological research in dermatology. This uncertainty hinders the development of appropriate patient-centered health care that prevent patients from unnecessary suffering.

This article is protected by copyright. All rights reserved.

http://ift.tt/2q1EkGw

The adaptor protein ARA55 and the nuclear kinase HIPK1 assist c-Myb in recruiting p300 to chromatin

Publication date: Available online 8 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Mads Bengtsen, Linda Sørensen, Linn Aabel, Marit Ledsaak, Vilborg Matre, Odd Stokke Gabrielsen
LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs, have been shown to play diverse roles in several cellular processes. A common theme is that they mediate important protein-protein interactions that are key to their function. Androgen receptor-associated protein 55 (ARA55) belongs to this family of bridging proteins containing four C-terminal LIM domains. It has a dual role with functions both at focal adhesions and in the nucleus, apparently shuttling between the two compartments. In the present work, we have expanded our understanding of its nuclear functions by showing that it interacts with three nuclear regulators not previously linked to ARA55. We first identified ARA55 as a novel interaction partner of the nuclear kinase HIPK1 and found that ARA55, like HIPK1, also interacts with the transcription factor c-Myb. In search of a function for these associations, we observed that the coactivator p300 not only binds to c-Myb, but to ARA55 as well. When combined, c-Myb, p300, HIPK1 and ARA55 caused strong synergistic activation of a chromatinized reporter gene. In parallel, all partners, including p300, were efficiently recruited to chromatin at the c-Myb-bound promoter. Consistent with this cooperation, we found that c-Myb and ARA55 share a common set of target genes in an osteosarcoma cellular context. We propose that ARA55 and HIPK1 assist c-Myb in recruiting the coactivator and acetyltransferase p300 to chromatin.



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I strongly recommend that all practicing physicians consider such a list, and review it occasionally. I wish for the judgement to know what is best for my patients and to weigh the merits of interventions; surgically, medically, and radiotherapeutically. I wish that I can master the complexities of the practice of medicine and be worthwhile as a physician. I wish for the honesty and integrity to objectively assess my competencies and fallibilities. I wish for the intellectual drive to maintain currency of knowledge. I wish for the wisdom to assess and maintain appropriate costs for medical care. I wish for the integrity to avoid marketing my skills and accomplishments unrealistically and erroneously. I wish for the compassion that allows me to separate my personal problems from the needs of the patients that I serve. I wish for the courage to challenge the wisdom of those that create policies and regulations that fail to consider the full dimension and scope of medical care. Please p

Brazilian Journal of Otorhinolaryngology

Print version ISSN 1808-8694

On-line version ISSN 1808-8686

Braz. j. otorhinolaryngol. vol.83 no.2 São Paulo 

http://dx.doi.org/10.1016/j.bjorl.2017.01.001 

EDITORIAL

Ethics in the twenty first century otolaryngology☆

Charles W. Cummings1 

1Johns Hopkins University, Baltimore, USA. E-mail: ccumming@jhmi.edu

In the United States, the climate of the practice of Medicine is in transition and under siege by policy revisionists and governmental/political opportunists. Regulatory and legislative hubris has enshrouded the medical arena through formulaic dictums and onerous regulations oft times constructed by individuals who have no clinical experience or knowledge. The art of Medicine is being dismantled by emphasis on outcomes based solely on statistical evidence, with no concern for the human variables. Objective analysis is not inherently bad provided the personal and social factors are properly emphasized in the analysis. Freedom to make clinical decisions MUST be preserved for optimal care.

This phenomenon exerts undue pressure on the clinician leading to professional frustration and anemia of job satisfaction. Also, the environment which enables the best of care is further challenged and compromised.

Never the less, we, as physicians, must continue to acknowledge our calling and respond to the gifts of our profession. It seems appropriate to review the commitments that we have made to ourselves and our patients. Over the years, I have created a wish list concerning the way I want to conduct myself to satisfy my professional goals. What follows are those wishes. I strongly recommend that all practicing physicians consider such a list, and review it occasionally.

I wish for the judgement to know what is best for my patients and to weigh the merits of interventions; surgically, medically, and radiotherapeutically.

I wish that I can master the complexities of the practice of medicine and be worthwhile as a physician.

I wish for the honesty and integrity to objectively assess my competencies and fallibilities.

I wish for the intellectual drive to maintain currency of knowledge.

I wish for the wisdom to assess and maintain appropriate costs for medical care.

I wish for the integrity to avoid marketing my skills and accomplishments unrealistically and erroneously.

I wish for the compassion that allows me to separate my personal problems from the needs of the patients that I serve.

I wish for the courage to challenge the wisdom of those that create policies and regulations that fail to consider the full dimension and scope of medical care.

Please preserve the art of Medicine. We must steward our wonderful calling.

☆Please cite this article as: Cummings CW. Ethics in the twenty first century otolaryngology. Braz J Otorhinolaryngol. 2017;83:119.2

Conflicts of interest

The author declares no conflicts of interest.

© 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda.

 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 

Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial

Av. Indianópolia, 1287

04063-002 São Paulo/SP Brasil

Tel.: (0xx11) 5053-7500

Fax: (0xx11) 5053-7512

revista@aborlccf.org.br

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Preparation and characterization of tunable oil-encapsulated alginate microfibers

Publication date: 15 August 2017
Source:Materials & Design, Volume 128
Author(s): A.S. Chaurasia, F. Jahanzad, S. Sajjadi
A single-step microfluidic approach was developed which allowed a wide range of oil-loaded calcium-alginate microfibers to be fabricated at the same compositions but with different morphologies. A framework for characterization of wavy fibers was developed which linked the fiber morphology and tensile strength to the encapsulation type and geometry. The geometry of oil encapsulates as well as the fibers surface morphology were conveniently tuned via the gelation reaction dynamics and phase flow rates. A 2D mathematical reconstruction of the fiber's surface revealed that fibers having spherical and ellipsoid encapsulates enjoyed the highest surface roughness. Tubular fibers endured the highest tensile force before failure, compared to fibers with other encapsulate geometries at a fixed alginate phase ratio (ϕalg). Fibers with increased ϕalg withstood a higher tensile force. However, the strength of fibers reduced if the increase in ϕalg altered the encapsulate geometry from tubular to discrete oil segments. Tubular fibers also underwent maximum elastic and plastic deformation prior to failure, among all fibers.

Graphical abstract

http://ift.tt/2ptHMZ9

Direct measurement of residual strains in CFRP-tungsten hybrids using embedded strain gauges

Publication date: 5 August 2017
Source:Materials & Design, Volume 127
Author(s): M. Kanerva, P. Antunes, E. Sarlin, O. Orell, J. Jokinen, M. Wallin, T. Brander, J. Vuorinen
In this work, the implementation of fully embedded electrical resistance strain gauges was studied for a hybrid material system. The samples were laminated using carbon-fiber-reinforced plastic (CFRP) and tungsten. The raw materials and the adhesive used for bonding strain sensors were characterized to understand the overlapping sources of non-linearity and error. Test-specific correction functions for a thermal output were determined for the strain gauge measurement and comparative fiber Bragg grating (FBG) measurement. The strain accumulation in the fiber direction during the cool-down phase for different cure cycles was analyzed using a finite element simulation. According to the results, embedded electrical resistance strain gauges can be used to determine the thermal expansion of a hybrid laminate with acceptable accuracy when thermal output is compensated for using case-specific correction functions accounting for measurement setup, the stiffness of the gauge bonding adhesive, and embedding.

Graphical abstract

http://ift.tt/2ptEXYp

Mechanical performance of piezoelectric fiber composites and electroelastic field concentration near the electrode edges

Publication date: 15 August 2017
Source:Materials & Design, Volume 128
Author(s): Xi Yuan, Song Zhu, Xianfang Li, Chao Chen, Kechao Zhou, Dou Zhang
As important smart materials, piezoelectric fiber composites (PFCs) have shown excellent performance in many areas. However, the electric field strength concentration at the edge of the interdigital electrode may lead to crack propagation and eventual actuating failure of PFCs. In this paper, a novel analytical solution on the electroelastic response of PFCs is proposed to characterize the mechanical performance and obtain optimal structure parameters. The problem is converted to a singular integral equation with logarithmic kernel. By solving the resulting equation, the distributions of electric potential, electric displacement, electric field strength, and strain of PFCs fiber are obtained. The finite element method (FEM) is employed to confirm the results. The results demonstrate that the electric displacement and strain of PFCs are dramatically affected by the permittivity properties and piezoelectric constant of materials. The PFCs made by PZT-5H have higher surface electric displacement than PZT-5A and PZT-4. For a ratio of W/L=1/4, both the electric field and strain obtained the minimal value at the electrode edges, which is better for the mechanical performance of PFCs. Moreover, when the thickness of fibers decreases, the actuating performance of PFCs improves and the probability of fracture failure lessens.

Graphical abstract

http://ift.tt/2qLyWdu

Effects of arsenic on adipocyte metabolism: Is arsenic an obesogen?

Publication date: Available online 8 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): Zeltzin A. Ceja-Galicia, Alberto Daniel, Ana María Salazar, Pablo Pánico, Patricia Ostrosky-Wegman, Andrea Díaz-Villaseñor
The environmental obesogen model proposes that in addition to a high-calorie diet and diminished physical activity, other factors such as environmental pollutants and chemicals are involved in the development of obesity. Although arsenic has been recognized as a risk factor for Type 2 Diabetes with a specific mechanism, it is still uncertain whether arsenic is also an obesogen. The impairment of white adipose tissue (WAT) metabolism is crucial in the onset of obesity, and distinct studies have evaluated the effects of arsenic on it, however only in some of them for obesity-related purposes. Thus, the known effects of arsenic on WAT/adipocytes were integrated based on the diverse metabolic and physiological processes that occur in WAT and are altered in obesity, specifically: adipocyte growth, adipokine secretion, lipid metabolism, and glucose metabolism. The currently available information suggests that arsenic can negatively affect WAT metabolism, resulting in arsenic being a potential obesogen.

Graphical abstract

http://ift.tt/2pWdcdC

Crosstalk between STAT5 activation and PI3K/AKT functions in normal and transformed mammary epithelial cells

Publication date: Available online 8 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): Patrick D. Rädler, Barbara L. Wehde, Kay-Uwe Wagner
Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to function downstream of several peptide hormones and cytokines that are required for postnatal development and secretory function of the mammary gland. As part of an extended network, these signal transducers can engage in crosstalk with other pathways to facilitate synergistic, and sometimes antagonistic, actions of different growth factors. Specifically, signaling through the JAK2/STAT5 cascade has been demonstrated to be indispensable for the specification, proliferation, differentiation, and survival of secretory mammary epithelial cells. Following a concise description of major cellular programs in mammary gland development and the role of growth factors that rely on JAK/STAT signaling to orchestrate these programs, this review highlights the significance of active STAT5 and its crosstalk with the PI3 kinase and AKT1 for mediating the proliferation of alveolar progenitors and survival of their functionally differentiated descendants in the mammary gland. Based on its ability to provide self-sufficiency in growth signals that are also capable of overriding intrinsic cell death programs, persistently active STAT5 can serve as a potent oncoprotein that contributes to the genesis of breast cancer. Recent experimental evidence demonstrated that, similar to normal developmental programs, oncogenic functions of STAT5 rely on molecular crosstalk with PI3K/AKT signaling for the initiation, and in some instances the progression, of breast cancer. The multitude by which STATs can interact with individual mediators of the PI3K/AKT signaling cascade may provide novel avenues for targeting signaling nodes within molecular networks that are crucial for the survival of cancer cells.



http://ift.tt/2pWeTrs

Luminescent properties of heterotrinuclear 3d–4f complexes constructed from a naphthalenediol-based acyclic bis(salamo)-type ligand

Publication date: 5 September 2017
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 184
Author(s): Wen-Kui Dong, Shan-Shan Zheng, Jin-Tong Zhang, Yang Zhang, Yin-Xia Sun
Heterotrinuclear 3d–4f complexes with a naphthalenediol-based acyclic bis(salamo)-type ligand have been synthesized and structurally characterized. Spectral titrations clearly show that the heterotrinuclear complexes [Zn2(L)La(OAc)3] (1), [Zn2(L)Ce(OAc)3] (2) and [Zn2(L)Dy(OAc)3(CH3OH)]·CH2Cl2 (3) are acquired by the substitution reaction of the obtained homotrinuclear Zn(II) complex with 1 equiv. of Ln(NO3)3 (Ln³⁺=La³⁺, Ce³⁺ and Dy³⁺). Two Zn(II) ions are penta- and hexa-coordinated with geometries of distorted tetragonal pyramid and octahedron. La(III) ion is deca-coordinated, adopting a distorted bicapped square antiprism geometry. Ce(III) ion is nona-coordinated with geometry of distorted capped square antiprism as well as Dy(III) ion. The different coordination modes of acetate ions in complexes 1, 2 and 3 lead to different coordination numbers of the lanthanide(III) ions. Furthermore, the structures and fluorescence properties have been discussed.

Graphical abstract

http://ift.tt/2pWlodF

Trace element levels in an area impacted by old mining operations and their relationship with beehive products

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 599–600
Author(s): E. Álvarez-Ayuso, P. Abad-Valle
The environmental status of an area impacted by Roman mining activities was assessed in order to establish the current risks posed by such old mine emplacements. For this purpose, soil samples were collected throughout the mining area and analysed for their total, mobile and mobilizable trace element (As, Cd, Mo, Sb and Zn) contents. Additionally, beehive products (honey and pollen) were also sampled and evaluated for their use as environmental indicators of the area. The results obtained were compared with those from a control non-polluted area. The mine soils presented slightly increased levels of Cd and Sb (about 2- to -3-fold their normal soil concentrations), whereas the enrichment of As reached considerable levels, with concentrations almost ten-fold of those considered the threshold for causing toxicity. Leachable As contents exhibited very high values (1.2–21.9mgkg⁻¹), indicating the need for risk attenuation measures. All trace elements were mainly partitioned in the soil residual fraction, especially Mo (76–99%) and Sb (61–91%). Significant partitioning levels were also found in the reducible fraction of As (up to 35%) and Cd (up to 38%), and in the oxidizable fraction of Mo (up to 23%). The reducible pool of As was particularly relevant due to the eventual mobilization of this element under reducing conditions. Among the beehive products tested, honey proved not to be useful as an environmental indicator, whereas pollen showed great potential as an indicator when the contamination levels were moderate to high.

Graphical abstract

http://ift.tt/2pWlkKX

A screen-printed voltammetric electronic tongue for the analysis of complex mixtures of metal ions

Publication date: October 2017
Source:Sensors and Actuators B: Chemical, Volume 250
Author(s): Clara Pérez-Ràfols, Núria Serrano, José Manuel Díaz-Cruz, Cristina Ariño, Miquel Esteban
A voltammetric electronic tongue was constituted by four screen-printed modified electrodes: a carbon nanofiber modified electrode, an ex-situ antimony film electrode prepared from carbon nanofiber modified electrode, and two carbon nanofiber electrodes chemically modified with Cys and GSH. The tongue was successfully applied to the analysis of a complex mixture of metal ions (4 analytes and 2 interferences) by differential pulse anodic stripping voltammetry. Each sensor was firstly studied for the determination of each metal separately confirming that all electrodes showed differentiated response for the metals. The obtained voltammetric signals provided by the sensor array were processed by Partial Least Squares regression (PLS) to resolve the overlapped nature of the obtained multimetal stripping measurements. This PLS model was built considering a hierarchical model in order to reduce the large amount of data. The method was applied to synthetic mixtures of Cd(II), Pb(II), Tl(I), and Bi(III) in the presence of Zn(II) and In(III) at the levels of μg L⁻¹ and successfully validated with correlation coefficients of both calibration and prediction higher than 0.9 obtained from predicted vs. expected concentration graphs. Moreover, the simultaneous determination of Cd(II), Pb(II), Tl(I), and Bi(III) in the presence of Zn(II) and In(III) in a spiked tap water was also satisfactory achieved, providing comparable results to those obtained by ICP-MS.

Graphical abstract

http://ift.tt/2pWiS7t

Heavy metals translocation and accumulation from the rhizosphere soils to the edible parts of the medicinal plant Fengdan (Paeonia ostii) grown on a metal mining area, China

Publication date: September 2017
Source:Ecotoxicology and Environmental Safety, Volume 143
Author(s): Zhang Jun Shen, De Cong Xu, Yan Song Chen, Zhen Zhang
Fengdan (Paeonia ostii) is one of Chinese 34 famous medicinal materials. This study investigated the concentrations of Arsenic (As), Chromium (Cr), Cadmium (Cd), Copper (Cu), Lead (Pb), Iron (Fe), Manganese (Mn), and Zinc (Zn) in rhizosphere soils, cortex mouton and seeds of Fengdan planted in a metal mining area, China. The mean concentrations of As, Cd, Cu, and Zn in the rhizosphere soils were above the limits set by the Chinese Soil Environmental Quality Standard (GB 15618-1995). The contamination factor (CF) of Cd was >5, while it was >2for As, Cu, Pb, and Zn in all the soils. The integrated pollution index for all the soils was >3 and ˂ 5. Metal concentrations in the edible parts of Fengdan were in the following decreasing order: Mn>Fe>Zn>Cu>Pb>As>Cr≥Cd. The transfer factor mean values for As, Cu, Cd and Fe in the cortex moutan of old Fengdan (over 6 years) were significantly higher than in young Fengdan. Available metal concentrations, pH and soil organic matter content influenced the metal concentrations of the cortex moutan. The results indicated that mining and smelting operations have led to heavy metals contamination of soils and medicinal parts of Fengdan. The major metal pollutants were elemental Cd, Cu, Pb, and Zn. Heavy metals mainly accumulated in the cortex moutan of Fengdan. The mean concentrations of Cd, Cu, and Pb in the old cortex moutan (over 6 years) were above those of the Chinese Green Trade Standards for Medicinal Plants and Preparations in Foreign Trade (WM/T2-2004).

Graphical abstract

http://ift.tt/2pWpfHP

Fate of inorganic elements during fast pyrolysis of biomass in a cyclone reactor

Publication date: 1 September 2017
Source:Fuel, Volume 203
Author(s): Henrik Wiinikka, Ann-Christine Johansson, Linda Sandström, Olov G.W. Öhrman
In order to reduce ash related operational problem and particle emissions during pyrolysis oil combustion it is important to produce pyrolysis oil with very low concentration of inorganics. In this paper, the distribution of all major inorganic elements (S, Si, Al, Ca, Fe, K, Mg, Mn, Na, P, Ti and Zn) in the pyrolysis products (solid residue and two fractions of pyrolysis oil) was investigated during pyrolysis of stem wood, bark, forest residue, salix and reed canary grass. The raw materials were pyrolysed in a cyclone reactor and the produced pyrolysis oils were recovered as two oil fractions, a condensed fraction and an aerosol fraction. The inorganic composition of the ingoing raw material, the solid residue and the two pyrolysis oil fractions were analysed with inductively coupled plasma spectrometry techniques.All major inorganic elements, except sulphur, were concentrated in the solid residue. A significant amount of sulphur was released to the gas phase during pyrolysis. For zinc, potassium and iron about 1–10wt% of the ingoing amount, depending on the raw material, was found in the pyrolysis oil. For the rest of the inorganics, generally less than 1wt% of the ingoing amount was found in the pyrolysis oil. There were also differences in distribution of inorganics between the condensed and the aerosol oil fractions. The easily volatilized inorganic elements such as sulphur and potassium were found to a larger extent in the aerosol fraction, whereas the refractory elements were found to a larger extent in the condensed fraction. This implies that oil fractionation can be a method to produce oil fractions with different inorganic concentrations which thereafter can be used in different technical applications depending on their demand on the inorganic composition of the pyrolysis oil.



http://ift.tt/2pWdTDt

Cardiovascular Outcome Trials in Patients With Advanced Kidney Disease: Time for Action.

Author: Zannad, Faiez MD, PhD; Rossignol, Patrick MD, PhD

Page: 1769-1771

http://ift.tt/2pYBUKA

Public Reporting II: State of the Art-Current Public Reporting in Cardiovascular Medicine.

Author: Weintraub, William S. MD; Garratt, Kirk N. MD

Page: 1772-1774

http://ift.tt/2q0pksn

Sources of Sodium in US Adults From 3 Geographic Regions.

Author: Harnack, Lisa J. DrPH; Cogswell, Mary E. DrPH; Shikany, James M. PhD; Gardner, Christopher D. PhD; Gillespie, Cathleen MS; Loria, Catherine M. PhD; Zhou, Xia MS; Yuan, Keming MS; Steffen, Lyn M. PhD

Page: 1775-1783

http://ift.tt/2pYufvW

Sources of Dietary Sodium: Implications for Patients, Physicians, and Policy.

Author: Appel, Lawrence J. MD, MPH; Foti, Kathryn MPH

Page: 1784-1787

http://ift.tt/2q0K96O

Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]).

Author: Parkash, Ratika MD, MS; Wells, George A. PhD; Sapp, John L. MD; Healey, Jeffrey S. MD; Tardif, Jean-Claude MD; Greiss, Isabelle MD; Rivard, Lena MD, MSc; Roux, Jean-Francois MD; Gula, Lorne MD; Nault, Isabelle MD; Novak, Paul MD; Birnie, David MD; Ha, Andrew MD; Wilton, Stephen B. MD, MSc; Mangat, Iqwal MD; Gray, Christopher MD; Gardner, Martin MD; Tang, Anthony S.L. MD

Page: 1788-1798

http://ift.tt/2pYqOoX

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Author: Freedman, Ben MBBS, PhD *; Camm, John MD *; Calkins, Hugh MD *; Healey, Jeffrey S. MD, MSc *; Rosenqvist, Marten MD, PhD *; Wang, Jiguang MD, PhD *; Albert, Christine M. MD, MPH; Anderson, Craig S. PhD; Antoniou, Sotiris BPharm(Hons), MSc; Benjamin, Emelia J. MD, ScM; Boriani, Giuseppe MD, PhD; Brachmann, Johannes MD, PhD; Brandes, Axel MD, DMSc; Chao, Tze-Fan MD, PhD; Conen, David MD, MPH; Engdahl, Johan MD, PhD; Fauchier, Laurent MD, PhD; Fitzmaurice, David A. MD; Friberg, Leif MD, PhD; Gersh, Bernard J. MB, ChB, DPhil; Gladstone, David J. MD, PhD; Glotzer, Taya V. MD; Gwynne, Kylie MA; Hankey, Graeme J. MD; Harbison, Joseph MD; Hillis, Graham S. MBChB, PhD; Hills, Mellanie T. BSc; Kamel, Hooman MD; Kirchhof, Paulus MD; Kowey, Peter R. MD; Krieger, Derk MD, PhD; Lee, Vivian W. Y. BSc, PharmD; Levin, Lars-Ake PhD; Lip, Gregory Y. H. MD; Lobban, Trudie; Lowres, Nicole PhD; Mairesse, Georges H. MD; Martinez, Carlos MD, MSc; Neubeck, Lis BA(Hons), PhD; Orchard, Jessica BEc/LLB, MPH; Piccini, Jonathan P. MD, MHS; Poppe, Katrina PhD; Potpara, Tatjana S. MD, PhD; Puererfellner, Helmut MD; Rienstra, Michiel MD, PhD; Sandhu, Roopinder K. MD, MPH; Schnabel, Renate B. MD, MSc *; Siu, Chung-Wah MD; Steinhubl, Steven MD; Svendsen, Jesper H. MD, DMSc; Svennberg, Emma MD, PhD; Themistoclakis, Sakis MD; Tieleman, Robert G. MD, PhD; Turakhia, Mintu P. MD, MAS; Tveit, Arnljot MD, PhD; Uittenbogaart, Steven B. MD, MSc; Van Gelder, Isabelle C. MD, PhD; Verma, Atul MD; Wachter, Rolf MD; Yan, Bryan P. MBBS.

Page: 1851-1867

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Transcatheter Treatment of Severe Tricuspid Regurgitation With the Edge-to-Edge MitraClip Technique.

Author: Nickenig, Georg MD; Kowalski, Marek MD; Hausleiter, Jorg MD; Braun, Daniel MD; Schofer, Joachim MD; Yzeiraj, Ermela MD; Rudolph, Volker MD; Friedrichs, Kai MD; Maisano, Francesco MD; Taramasso, Maurizio MD; Fam, Neil MD; Bianchi, Giovanni MD; Bedogni, Francesco MD; Denti, Paolo MD; Alfieri, Ottavio MD; Latib, Azeem MD; Colombo, Antonio MD; Hammerstingl, Christoph MD; Schueler, Robert MD

Page: 1802-1814

http://ift.tt/2pYGPLx

Blood Pressure Control in Atrial Fibrillation: One of Many Critical Components in Risk Factor Modification.

Author: Lau, Dennis H. MBBS, PhD; Hendriks, Jeroen PhD; Kalman, Jonathan M. MBBS, PhD; Sanders, Prashanthan MBBS, PhD

Page: 1799-1801

http://ift.tt/2q0Jtyj

Percutaneous Therapy for Tricuspid Regurgitation: A New Frontier for Interventional Cardiology.

Author: Kapadia, Samir MD; Krishnaswamy, Amar MD; Tuzcu, E. Murat MD

Page: 1815-1818

http://ift.tt/2q0K8Qi

Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies.

Author: Toth, Peter P. MD, PhD; Descamps, Olivier MD, PhD; Genest, Jacques MD; Sattar, Naveed MD, PhD; Preiss, David MD, PhD; Dent, Ricardo MD; Djedjos, Constantine MD; Wu, Yuna PhD; Geller, Michelle MD; Uhart, Magdalena MD; Somaratne, Ransi MD; Wasserman, Scott M. MD; for the PROFICIO Investigators

Page: 1819-1831

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Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

Author: Tiburcy, Malte MD; Hudson, James E. PhD; Balfanz, Paul; Schlick, Susanne MS; Meyer, Tim PhD; Chang Liao, Mei-Ling PhD; Levent, Elif PhD; Raad, Farah PhD; Zeidler, Sebastian PhD; Wingender, Edgar PhD; Riegler, Johannes PhD; Wang, Mouer MD; Gold, Joseph D. PhD; Kehat, Izhak MD, PhD; Wettwer, Erich PhD; Ravens, Ursula MD, PhD; Dierickx, Pieterjan PhD; van Laake, Linda W. MD, PhD; Goumans, Marie Jose PhD; Khadjeh, Sara PhD; Toischer, Karl MD; Hasenfuss, Gerd MD; Couture, Larry A. PhD; Unger, Andreas PhD; Linke, Wolfgang A. PhD; Araki, Toshiyuki PhD; Neel, Benjamin MD, PhD; Keller, Gordon PhD; Gepstein, Lior MD, PhD; Wu, Joseph C. MD, PhD; Zimmermann, Wolfram-Hubertus MD

Page: 1832-1847

http://ift.tt/2q0BEcf

One Stride Forward: Maturation and Scalable Production of Engineered Human Myocardium.

Author: Yang, Xiulan PhD; Murry, Charles E. MD, PhD

Page: 1848-1850

http://ift.tt/2pYxMKR

Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association.

Author: Vos, Miriam B. MD, MSPH, FAHA; Chair; Kaar, Jill L. PhD; Welsh, Jean A. PhD, MPH, RN; Van Horn, Linda V. PhD, RD, FAHA; Feig, Daniel I. MD, PhD; Anderson, Cheryl A.M. PhD, MPH, MS, FAHA; Patel, Mahesh J. MD; Cruz Munos, Jessica MD; Krebs, Nancy F. MD, MS; Xanthakos, Stavra A. MD, MS; Johnson, Rachel K. PhD, MPH, RD, FAHA; On behalf of the American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Functional Genomics and Translational Biology; and Council on Hypertension

Page: e1017-e1034

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Highlights of the American College of Cardiology Annual Scientific Sessions 2017.

Author: Kuvin, Jeffrey T. MD; Kates, Andrew M. MD

Page: 1868-1869

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Wide QRS Complex Tachycardia: What Is the Diagnosis?.

Author: Wang, Gaopin; Liu, Renguang; Chang, Qinghua MD

Page: 1870-1872

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Impact of Structural Cerebral Damage in Adults With Tetralogy of Fallot.

Author: Sluman, Maayke A. MD; Richard, Edo MD, PhD; Bouma, Berto J. MD, PhD; van Dalen, Jan Willem MSc; van Wanrooij, Lennard L. MSc; Groenink, Maarten MD, PhD; Caan, Matthan W. A. PhD; Nederveen, Aart J. PhD; Mutsaerts, Henk-Jan M. M. MD, PhD; Majoie, Charles B. L. M. MD, PhD; Schmand, Ben A. PhD; Mulder, Barbara J. M. MD, PhD

Page: 1873-1875

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Letter by Damen et al Regarding Article, "A Critical Appraisal of Aspirin in Secondary Prevention: Is Less More?".

Author: Damen, Sander A. J. MD; Brouwer, Marc A. MD, PhD; Verheugt, Freek W. A. MD, PhD

Page: e1035-e1036

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Response by Valgimigli and Gargiulo to Letter Regarding Article, "A Critical Appraisal of Aspirin in Secondary Prevention: Is Less More?".

Author: Valgimigli, Marco MD, PhD; Gargiulo, Giuseppe MD

Page: e1037-e1038

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Letter by Puri et al Regarding Article, "Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control".

Author: Puri, Raman DM; Puri, Sonam MD; Rajani, Anil MD

Page: e1039-e1040

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Correction to: Percutaneous Therapy for Tricuspid Regurgitation: A New Frontier for Interventional Cardiology.

Author:

Page: e1041

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β Cell Renewal versus Differentiation: Slow and Steady Wins the Race

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Ondine Cleaver
Pancreatic endocrine progenitor cells proliferate and transiently express the bHLH transcription factor Ngn3. In recent issues of Developmental Cell, Azzarelli et al. (2017) and Krentz et al. (2017) demonstrate how CDK phosphorylation of Ngn3 governs the switch between their renewal and differentiation. Lengthening the cell cycle allows Ngn3 accumulation, outpacing phosphorylation-induced degradation.

Teaser

Pancreatic endocrine progenitor cells proliferate and transiently express the bHLH transcription factor Ngn3. In recent issues of Developmental Cell, Azzarelli et al. (2017) and Krentz et al. (2017) demonstrate how CDK phosphorylation of Ngn3 governs the switch between their renewal and differentiation. Lengthening the cell cycle allows Ngn3 accumulation, outpacing phosphorylation-induced degradation.


http://ift.tt/2q12BMU

A Geometric Model of Stripe Refinement

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Eric D. Siggia
Organizing data about patterning and morphogenesis into a coherent framework remains a challenge in developmental biology. Reporting in Science, Corson et al. (2017) apply innovative analysis to an old problem of bristle patterns in Drosophila, reducing the nonlinear interactions among tens of cells to a succinct model with quantitative predictions.

Teaser

Organizing data about patterning and morphogenesis into a coherent framework remains a challenge in developmental biology. Reporting in Science, Corson et al. (2017) apply innovative analysis to an old problem of bristle patterns in Drosophila, reducing the nonlinear interactions among tens of cells to a succinct model with quantitative predictions.


http://ift.tt/2pYfoS8

The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Rhett A. Kovall, Brian Gebelein, David Sprinzak, Raphael Kopan
The Notch signaling pathway relies on a proteolytic cascade to release its transcriptionally active intracellular domain, on force to unfold a protective domain and permit proteolysis, on extracellular domain glycosylation to tune the forces exerted by endocytosed ligands, and on a motley crew of nuclear proteins, chromatin modifiers, ubiquitin ligases, and a few kinases to regulate activity and half-life. Herein we provide a review of recent molecular insights into how Notch signals are triggered and how cell shape affects these events, and we use the new insights to illuminate a few perplexing observations.

Teaser

In this review, Kovall et al. describe structure-based insights into Notch receptor/ligand interactions, the proteins involved in receptor modifications and cleavage, details on what forces are required to activate Notch, how cell shape might affect this process, and how the active NICD molecule mediates changes in gene expression.


http://ift.tt/2q0Igaq

Gastric Acid Secretion from Parietal Cells Is Mediated by a Ca2+ Efflux Channel in the Tubulovesicle

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Nirakar Sahoo, Mingxue Gu, Xiaoli Zhang, Neel Raval, Junsheng Yang, Michael Bekier, Raul Calvo, Samarjit Patnaik, Wuyang Wang, Greyson King, Mohammad Samie, Qiong Gao, Sasmita Sahoo, Sinju Sundaresan, Theresa M. Keeley, Yanzhuang Wang, Juan Marugan, Marc Ferrer, Linda C. Samuelson, Juanita L. Merchant, Haoxing Xu
Gastric acid secretion by parietal cells requires trafficking and exocytosis of H/K-ATPase-rich tubulovesicles (TVs) toward apical membranes in response to histamine stimulation via cyclic AMP elevation. Here, we found that TRPML1 (ML1), a protein that is mutated in type IV mucolipidosis (ML-IV), is a tubulovesicular channel essential for TV exocytosis and acid secretion. Whereas ML-IV patients are reportedly achlorhydric, transgenic overexpression of ML1 in mouse parietal cells induced constitutive acid secretion. Gastric acid secretion was blocked and stimulated by ML1 inhibitors and agonists, respectively. Organelle-targeted Ca²⁺ imaging and direct patch-clamping of apical vacuolar membranes revealed that ML1 mediates a PKA-activated conductance on TV membranes that is required for histamine-induced Ca²⁺ release from TV stores. Hence, we demonstrated that ML1, acting as a Ca²⁺ channel in TVs, links transmitter-initiated cyclic nucleotide signaling with Ca²⁺-dependent TV exocytosis in parietal cells, providing a regulatory mechanism that could be targeted to manage acid-related gastric diseases.

Graphical abstract

Teaser

Acid secretion from the parietal cells of the stomach is essential for food digestion. Sahoo et al. identified TRPML1 as a histamine-activated Ca²⁺ channel in the tubulovesicles required for gastric acid secretion. Synthetic agonists and inhibitors of TRPML1 may be developed to control acid secretion and treat acid-related gastric diseases.


http://ift.tt/2pYycRa

More Cytoplasm, More Problems

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Predrag Jevtić, Daniel L. Levy
In this issue of Developmental Cell, Kyogoku and Kitajima (2017) investigate the effect of cytoplasmic volume on the fidelity of chromosome segregation during meiosis in mouse oocytes. The authors find that large cytoplasmic volume affects spindle pole morphology, chromosome alignment, and stringency of checkpoint signaling, resulting in error-prone chromosome segregation.

Teaser

In this issue of Developmental Cell, Kyogoku and Kitajima (2017) investigate the effect of cytoplasmic volume on the fidelity of chromosome segregation during meiosis in mouse oocytes. The authors find that large cytoplasmic volume affects spindle pole morphology, chromosome alignment, and stringency of checkpoint signaling, resulting in error-prone chromosome segregation.


http://ift.tt/2pYl3rk

Large Cytoplasm Is Linked to the Error-Prone Nature of Oocytes

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Hirohisa Kyogoku, Tomoya S. Kitajima
Chromosome segregation during meiosis in oocytes is error prone. The uniquely large cytoplasmic size of oocytes, which provides support for embryogenesis after fertilization, might be a predisposing factor for meiotic errors. However, this hypothesis remains unproven. Here, we show that cytoplasmic size affects the functionality of the acentrosomal spindle. Artificially decreasing the cytoplasmic size in mouse oocytes allows the acentrosomal spindle poles to have a better-focused distribution of microtubule-organizing centers and to biorient chromosomes more efficiently, whereas enlargement of the cytoplasmic size has the opposite effects. Moreover, we found that the cytoplasmic size-dependent dilution of nuclear factors, including anaphase inhibitors that are preformed at the nuclear membrane, limits the spindle's capacity to prevent anaphase entry with misaligned chromosomes. The present study defines a large cytoplasmic volume as a cell-intrinsic feature linked to the error-prone nature of oocytes. This may represent a trade-off between meiotic fidelity and post-fertilization developmental competence.

Graphical abstract

Teaser

Kyogoku and Kitajima show that cytoplasmic size affects the functionality of the acentrosomal spindle and the stringency of the spindle checkpoint in mouse oocytes, thus providing evidence that the large cytoplasmic size of oocytes is linked to error-prone chromosome segregation during female meiosis, which is a leading cause of aneuploidy.


http://ift.tt/2q0DXMf

The PomXYZ Proteins Self-Organize on the Bacterial Nucleoid to Stimulate Cell Division

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Dominik Schumacher, Silke Bergeler, Andrea Harms, Janet Vonck, Sabrina Huneke-Vogt, Erwin Frey, Lotte Søgaard-Andersen
Cell division site positioning is precisely regulated to generate correctly sized and shaped daughters. We uncover the strategy used by the social bacterium Myxococcus xanthus to position the FtsZ cytokinetic ring at midcell. PomX, PomY, and the nucleoid-binding ParA/MinD ATPase PomZ self-assemble forming a large nucleoid-associated complex that localizes at the division site before FtsZ to directly guide and stimulate division. PomXYZ localization is generated through self-organized biased random motion on the nucleoid toward midcell and constrained motion at midcell. Experiments and theory show that PomXYZ motion is produced by diffusive PomZ fluxes on the nucleoid into the complex. Flux differences scale with the intracellular asymmetry of the complex and are converted into a local PomZ concentration gradient across the complex with translocation toward the higher PomZ concentration. At midcell, fluxes equalize resulting in constrained motion. Flux-based mechanisms may represent a general paradigm for positioning of macromolecular structures in bacteria.

Teaser

Schumacher et al. find that the PomXYZ complex self-organizes on the bacterial nucleoid and promotes positioning of the cytokinetic ring. Diffusive fluxes of PomZ into the complex scale with intracellular asymmetry and are converted into a local PomZ concentration gradient that promotes biased motion toward and constrained motion at midcell.


http://ift.tt/2q0l5gr

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Charlotte H. Durkin, Flavia Leite, João V. Cordeiro, Yutaka Handa, Yoshiki Arakawa, Ferran Valderrama, Michael Way
RhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.

Graphical abstract

Teaser

Many different viral infections induce cell contraction and blebbing. Durkin, Leite, et al. show that during vaccinia infection, RhoC and not RhoA regulates this ROCK-mediated cytopathic effect of cell contraction. They delineate a pathway for RhoC regulation, in which the viral protein F11 blocks RhoC antagonism by RhoD-recruited Pak6.


http://ift.tt/2pYyQOS

Abl Regulates Planar Polarized Junctional Dynamics through β-Catenin Tyrosine Phosphorylation

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Masako Tamada, Dene L. Farrell, Jennifer A. Zallen




http://ift.tt/2pYpCC5

The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization

Publication date: 30 June 2017
Source:Behavioural Brain Research, Volume 329
Author(s): Akihiro Mouri, Yukihiro Noda, Minae Niwa, Yurie Matsumoto, Takayoshi Mamiya, Atsumi Nitta, Kiyofumi Yamada, Shoei Furukawa, Tatsunori Iwamura, Toshitaka Nabeshima
3,4-Methylenedioxymethamphetamine (MDMA) is known to induce dependence and psychosis in humans. Brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity and neurotrophy in midbrain dopaminergic neurons. This study aimed to investigate the role of BDNF in MDMA-induced dependence and psychosis. A single dose of MDMA (10mg/kg) induced BDNF mRNA expression in the prefrontal cortex, nucleus accumbens, and amygdala, but not in the striatum or the hippocampus. However, repeated MDMA administration for 7 days induced BDNF mRNA expression in the striatum and hippocampus. Both precursor and mature BDNF protein expression increased in the nucleus accumbens, mainly in the neurons. Additionally, rapidly increased extracellular serotonin levels and gradually and modestly increased extracellular dopamine levels were noted within the nucleus accumbens of mice after repeated MDMA administration. Dopamine receptor antagonists attenuated the effect of repeated MDMA administration on BDNF mRNA expression in the nucleus accumbens. To examine the role of endogenous BDNF in the behavioral and neurochemical effects of MDMA, we used mice with heterozygous deletions of the BDNF gene. MDMA-induced place preference, behavioral sensitization, and an increase in the levels of extracellular serotonin and dopamine within the nucleus accumbens, were attenuated in BDNF heterozygous knockout mice. These results suggest that BDNF is implicated in MDMA-induced dependence and psychosis by activating the midbrain serotonergic and dopaminergic neurons.



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Antidepressant-like effect of valproic acid—Possible involvement of PI3K/Akt/mTOR pathway

Publication date: 30 June 2017
Source:Behavioural Brain Research, Volume 329
Author(s): Isabel Vieira de Assis Lima, Ana Flávia Almeida-Santos, Talita Hélen Ferreira-Vieira, Daniele Cristina Aguiar, Fabíola Mara Ribeiro, Alline Cristina Campos, Antônio Carlos Pinheiro de Oliveira
RationaleFew studies suggest that antidepressants exert their effects by activating some signaling pathways, including the phosphatidylinositol 3-kinase (PI3K). Moreover, valproic acid (VPA) activates the PI3K pathway. Thus, here we investigated the antidepressant-like effect of VPA and if its effect is related to PI3K/Akt/mTOR activation.MethodsC57Bl/6 (WT) and PI3Kγ^−/− mice received VPA injections (30, 100 or 300mg/kg, i.p.) and 30min after they were submitted to the forced swimming (FS), tail suspension (TS) and open field (OF) tests. Another group was pretreated with rapamycin (5mg/kg, i.p.) 150min before VPA administration. Akt phosphorylation levels were measured by Western blotting.ResultsIn WT mice, VPA (30mg/kg) reduced the immobility time in both FS and TS tests. However, VPA (300mg/kg) increased the immobility time in FS test. All doses of VPA did not alter locomotor activity. In PI3Kγ^−/− mice, none of the doses revealed antidepressant-like effect. However, in the OF test, the lower dose of VPA increased the travelled distance in comparison with vehicle group. An increase in Akt phosphorylation levels was observed in WT, but not in PI3Kγ^−/− mice. Finally, the pretreatment of WT mice with rapamycin abolished the antidepressant-like effect of VPA (30mg/kg) in FS test.ConclusionThese data suggest that the antidepressant-like effects of VPA might depend on PI3K and mTOR activation. Thus, more studies are necessary to investigate the mechanisms involved in the antidepressant-like effect induced by VPA in order to investigate novel therapeutic targets for the treatment of depression.



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Semantic memory deficits are associated with pica in individuals with acquired brain injury

Publication date: 30 June 2017
Source:Behavioural Brain Research, Volume 329
Author(s): Michitaka Funayama, Taro Muramatsu, Akihiro Koreki, Motoichiro Kato, Masaru Mimura, Yoshitaka Nakagawa
Although pica is one of the most prominent signs in individuals with severe cognitive impairment, the mechanisms and neural basis for pica have not been well elucidated. To address this issue, patients with acquired brain injury who showed pica and hyperorality were investigated. Eleven patients with pica, i.e., individuals who eat non-food items, and eight patients with hyperorality but who never eat non-food items were recruited. The cognitive and behavioral assessments and neural substrates of the two groups were compared. For basic cognitive and behavioral functions, two kinds of mental state examination—the mini-mental state examination and the new clinical scale for rating of mental states of the elderly—were administered. For pica-related behavioral features, frontal release signs, semantic memory deficits, and changes in eating behaviors were compared. Compared with the hyperorality group, the pica group had more severe semantic memory deficits and fewer frontal release signs, whereas there was no significant difference in changes in eating behaviors. Individuals in the pica group always had a lesion in the posterior part of the middle temporal gyrus. These findings suggest that semantic memory deficits following temporal lobe damage are associated with pica.



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A new construct of antibody-drug conjugates for treatment of B-cell non-Hodgkin's lymphomas

Publication date: 30 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 103
Author(s): Libin Zhang, Yixin Fang, Jindřich Kopeček, Jiyuan Yang
The aim of this study was to develop a new class of antibody-drug conjugates (ADCs) with the potential to not only enhance treatment efficacy but also improve tolerability for patients with B-cell lymphomas. Classic ADCs consist of monoclonal antibodies (mAbs) linked to drugs or toxins. They selectively deliver toxic moieties to tumor cells. As such, they greatly improve the therapeutic index compared to traditional chemotherapeutic agents. However, the therapeutic efficacy and safety of ADCs are dependent on linker stability and payload toxicity. Limited payload number on a single antibody (drug-to-antibody ratio, or DAR) has been driving investigators to use extremely toxic agents; however, even very low off-target binding of these ADCs may kill patients. Herein we report a new design of ADCs that consists of rituximab (RTX) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer–epirubicin conjugates. The latter was selectively attached to RTX via reduced disulfide bonds. Such design allows the introduction of a large payload of drug on the antibody without adding attachment sites and without compromising the antigen-targeting ability. The binding of the new conjugate, namely RTX-P-EPI, to Ramos cells (with high CD20 expression) was confirmed. The cytotoxicity of RTX-P-EPI against Raji and Ramos cells was also determined. Interestingly, two-fold inhibition of cell proliferation was observed when using RTX-P-EPI compared with their equivalent physical mixture of RTX and P-EPI. Treatment of male SCID mice bearing subcutaneous Ramos B-cell lymphoma tumors demonstrated that RTX-P-EPI possessed superior efficacy when compared to combination of RTX with chemotherapy EPI (RTX+EPI) and P-EPI (RTX+P-EPI), whereas single RTX and a non-specific conjugate IgG-P-EPI only showed marginal effect. The conjugate RTX-EPI in which EPI was directly attached to RTX demonstrated much less antitumor activity compared with RTX-P-EPI. The results suggest that this new design possesses synergistic potential of immunotherapy combined with established macromolecular therapy; moreover, a conventional chemo-agent could be utilized to generate highly effective ADCs and to achieve lower risk of off-target toxicity.

Graphical abstract

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Professor Arto Urtti —A northern light from the land of the midnight sun

Publication date: 30 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 103





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Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits

Publication date: 30 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 103
Author(s): Cristina García-Caballero, Esther Prieto-Calvo, Patricia Checa-Casalengua, Elena García-Martín, Vicente Polo-Llorens, Julián García-Feijoo, Irene Teresa Molina-Martínez, Irene Bravo-Osuna, Rocío Herrero-Vanrell
Local long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs is not known. We evaluated the GDNF levels after a single intravitreal injection of GDNF/VitE MSs. Biodegradable MSs were prepared by the solid-oil-in-water emulsion-solvent evaporation technique and characterized. Rabbits received a single intravitreal injection (50μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24h, 1, 4, 6, 8, 12, 18, and 24weeks after injection, the eyes were enucleated, and the intravitreal GDNF levels were quantified. Pharmacokinetic data were analysed according to non-compartmental model. Intraocular GDNF levels of 717.1±145.1pg/mL were observed at 24h for GDNF-loaded MSs, followed by a plateau (745.3±25.5pg/mL) until day 28. After that, a second plateau (17.4±3.7pg/mL) occurred from 8 to 24weeks post-injection, significantly higher than the basal levels. Eyes injected with GDNF/vitE and Blank-MSs did not show any abnormalities during the six-months follow up after administration. The single injection of GDNF/VitE MSs provided a sustained controlled release of the neurotrophic factor in a controlled fashion for up to six months.

Graphical abstract

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