Ιατρικά Άρθρα: 07/25/17

Τρίτη 25 Ιουλίου 2017

Effects of salinity on oil dispersant toxicity in the eastern mud snail, Ilyanassa obsoleta

Abstract

Chemical dispersants can be a beneficial method for breaking up oil slicks; however, their use in mitigation could pose potential toxic effects on the marine ecosystem. Dispersants may be transported to lower salinity habitats, where toxicity data for aquatic species have not been established. This study examined the effect of salinity on oil dispersant toxicity in the eastern mud snail, Ilyanassa obsoleta, using two dispersants authorized for oil spill response, Corexit® 9500A and Finasol® OSR 52. Median lethal toxicity values (LC50) and sublethal effects were examined at 10, 20, and 30 ppt salinity in adult and larval mud snails. Two biomarkers (lipid peroxidation and acetylcholinesterase) were used to measure sublethal effects. The 96-h static renewal LC50 values indicated significant differences in toxicity between dispersants and salinities. Larval snails were significantly more sensitive than adult snails to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Larval snails were more sensitive to dispersants at lower salinity, but adult snails were more sensitive at higher salinities. Dispersants increased lipid peroxidation and decreased acetylcholinesterase activity. These results demonstrate that dispersant toxicity varies among compounds and organism life stages, and that physicochemical properties of the environment, such as salinity, can affect the potential toxicity to estuarine species.

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The role of GLI2-ABCG2 signaling axis for 5Fu resistance in gastric cancer

Publication date: Available online 25 July 2017
Source:Journal of Genetics and Genomics
Author(s): Beiqin Yu, Dongsheng Gu, Xiaoli Zhang, Bingya Liu, Jingwu Xie
Gastric cancer is a leading cause of cancer-related mortality worldwide, and options to treat gastric cancer are limited. Fluorouracil (5Fu)-based chemotherapy is frequently used as a neoadjuvant or an adjuvant agent for gastric cancer therapy. Most patients with advanced gastric cancer eventually succumb to the disease despite the fact that some patients respond initially to chemotherapy. Thus, identifying molecular mechanisms responsible for chemotherapy resistance will help design novel strategies to treat gastric cancer. In this study, we discovered that residual cancer cells following 5Fu treatment have elevated expression of hedgehog target genes GLI1 and GLI2, suggestive of hedgehog (Hh) signaling activation. Hh signaling, a pathway essential for embryonic development, is an important regulator for putative cancer stem cells/residual cancer cells. We found that high GLI1/GLI2 expression is associated with some features of putative cancer stem cells, such as increased side population. We demonstrated that GLI2 knockdown sensitized gastric cancer cells to 5Fu treatment, decreased ABCG2 expression, and reduced side population. Elevated GLI2 expression is also associated with an increase in tumor sphere size, another marker for putative cancer stem cells. We believe that GLI2 regulates putative cancer stem cells through direct regulation of ABCG2. ABCG2 can rescue the Gli2 shRNA effects in 5Fu response, tumor sphere formation and side population changes, suggesting that ABCG2 is an important mediator for GLI2-associated 5Fu resistance. The relevance of our studies to gastric cancer patient care is reflected by our discovery that high GLI1/GLI2/ABCG2 expression is associated with a high incidence of cancer relapse in two cohorts of gastric cancer patients who underwent chemotherapy (containing 5Fu). Taken together, we have identified a molecular mechanism by which gastric cancer cells gain 5Fu resistance.

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Erratum to: Portuguese agriculture and the evolution of greenhouse gas emissions—can vegetables control livestock emissions?

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Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in a young female athlete at 36 weeks gestation: a case report

Publication date: Available online 25 July 2017
Source:Pathology - Research and Practice
Author(s): Hae Yoon Grace Choung, Monika Vyas, Daniel Jacoby, Brian West
A 26year old east African professional athlete presented to the obstetric clinic for a routine visit at 36 weeks gestation. She had a history of Right Ventricular Outflow Tract − Ventricular Tachycardia (RVOT-VT) with an episode of cardiac arrest in the past, and had been treated with ablation 4 years earlier. Her current visit was uneventful, her pregnancy progressing normally. Following the visit she went to a local restaurant where she suffered a cardiac arrest that was unresponsive to therapy. Chest compressions were continued from the time of her collapse until an emergency caesarian section was performed, delivering a healthy female infant. At autopsy a focal area of subtle pallor and myocardial thinning was present at the apex of the right ventricle. Histology showed myocyte degeneration and loss with focal full thickness replacement of myocardium by adipose tissue, consistent with the fatty form of arrhythmogenic right ventricular cardiomyopathy (ARVC). Molecular studies revealed a variant of unknown significance in the MYBPC3 gene, but no variant known to be associated with ARVC. In view of the subtlety of the lesion on gross examination this diagnosis could have been easily missed, emphasizing the importance of performing histologic examination of subtle gross cardiac lesions.

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Pancreatic Heterotropia in wall of Extra-hepatic Choledochal Cysts: A Retrospective Analysis of Thirteen of such cases from North India

Publication date: Available online 25 July 2017
Source:Pathology - Research and Practice
Author(s): Pragya Sharma, Tripti Nakra, Gaurav Khanna, Rajni Yadav, Rajesh Panwar, Madhusudhan KS, Khushbu khetan, Nihar R Dash, Sujoy Pal, Peush Sahni, Siddhartha Datta Gupta, Prasenjit Das
IntroductionHeterotopic pancreas (HP) has rarely been identified in the wall of choledochal cyst (CC).MethodsRetrospectively we screened 200 excised specimens of CC received at our Institute over a period of last eight years and looked for presence of HP rests in them. All the specimens were processed in their entirety.ResultHP was identified in the wall of 13 (6.5%) CCs, out of which 11 were Heinrich Type 2, and two were Heinrich Type 1. In half of the cases peribiliary mucous glands were observed intermingled with the HP rests. Features of chronic fibrosing pancreatitis were identified in these rests, with ulceration of overlying cyst lining.ConclusionsHP rests in the wall of CC though rare; their coexistence with peribiliary glands may possibly indicate their common embryonic origin. As a common site of inflammation, HP rest may be one of the common causes of CC.

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Effects of NOx on the molecular composition of secondary organic aerosol formed by the ozonolysis and photooxidation of α-pinene

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Jun-Hyun Park, Zaeem Bin Babar, Sun Jong Baek, Hyun Sik Kim, Ho-Jin Lim
The molecular composition of secondary organic aerosol (SOA), obtained from the ozonolysis and photooxidation of α-pinene, was investigated using ultrahigh-resolution Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) in negative ion mode electrospray ionization (ESI). SOA formation was performed in an indoor smog chamber. The molecular formulae of individual species were identified on the basis of the measured ionic mass using guidelines, such as number of atoms, elemental ratios, and the nitrogen rule. In each of the SOAs obtained, 815–3501 monomeric and oligomeric (mainly dimeric) species were identified below m/z 800. From ozonolysis, mainly 95% of the typical oxygenated species (CHO) were detected, whereas from photooxidation under high NOx conditions, 32% of nitrogen-containing species (CHON) were detected. Several common intense species (e.g., C9H14O6, C10H14O6, C10H16O5, C17H26O7, C19H28O9, C10H15NO8, and C10H15NO9) could be listed as candidate tracers for the conventional tracers for α-pinene SOA. The increased percentage of CHON as a primary effect of NOx on the SOA composition evidently affected other physicochemical parameters, such as elemental ratios (i.e., O/C, H/C, and N/C), the double-bond equivalent (DBE), the carbon oxidation state (OSC), and the organic-mass-to-carbon ratio (OM/OC). The O/C and OM/OC for CHON were greater than those observed for CHO, indicating that nitrogen preferentially exists in the oxidized form (e.g., -ONO2). The complexity of oligomerization was observed in DBE and OM/OC according to the number of carbon atoms.

Graphical abstract

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Differences between emissions measured in urban driving and certification testing of heavy-duty diesel engines

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Poornima Dixit, J. Wayne Miller, David R. Cocker, Adewale Oshinuga, Yu Jiang, Thomas D. Durbin, Kent C. Johnson
Emissions from eight heavy-duty diesel trucks (HDDTs) equipped with three different exhaust aftertreatment systems (ATS) for controlling nitrogen oxide (NOx) emissions were quantified on a chassis dynamometer using driving schedules representative of stop-and-go and free-flow driving in metropolitan areas. The three control technologies were: 1) cooled exhaust gas recirculation (CEGR) plus a diesel particulate filter (DPF); 2) CEGR and DPF plus advanced engine controls; and 3) CEGR and DPF plus selective catalytic reduction with ammonia (SCR). Results for all control technologies and driving conditions showed PM emission factors were less than the standard, while selected non-regulated emissions (ammonia, carbonyls, and C4–C12 hydrocarbons) and a greenhouse gas (nitrous oxide) were at measurement detection limits. However, NOx emission factors depended on the control technology, engine calibration, and driving mode. For example, emissions from engines with cooled-exhaust gas recirculation (CEGR) were 239% higher for stop-and-go driving as compared with free-flow. For CEGR plus selective catalytic reduction (SCR), the ratio was 450%. A deeper analysis was carried out with the assumption that emissions measured for a drive cycle on either the chassis or in-use driving would be similar. Applying the same NTE rules to the chassis data showed emissions during stop-and-go driving often exceeded the certification standard and >90% of the driving did not fall within the Not-To-Exceed (NTE) control area suggesting the NTE requirements do not provide sufficient emissions control under in-use conditions. On-road measurement of emissions using the same mobile lab while the vehicle followed a free-flow driving schedule verified the chassis results. These results have implications for scientists who build inventories using certification values instead of real world emission values and for metropolitan populations, who are exposed to elevated emissions. The differences in values between real world emissions and certification cycles should be narrowed. For example, one might use a different mix of cold and hot start testing to greater emphasize low temperature/load operation, a separate cycle to specifically characterize low-load operation, or broaden the in-use compliance testing requirements and associated conformity factors to incorporate a wider envelope of vehicle operation, especially at low load conditions. .

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New insights on humic-like substances associated with wintertime urban aerosols from central and southern Europe: Size-resolved chemical characterization and optical properties

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Aristeidis Voliotis, Roman Prokeš, Gerhard Lammel, Constantini Samara
Although Humic-LIke Substances (HULIS) are important contributors to the mass of organic aerosol in airborne particulate matter (PM), little is known about their chemical composition, while, their size-resolved optical properties have not been studied yet. Here, HULIS fractions were isolated from size-resolved aerosol samples (≤0.49, 0.49–0.95, 0.95–3 and 3–10 μm) collected in urban and suburban environments of four European cities during wintertime. The bulk (i.e., sum of all size fractions) concentration of HULIS ranged between 1.29 and 2.80 μg m⁻³ across sites with highest values in the ≤0.49 μm particle size fraction. The contribution of the carbon mass of HULIS (HULIS-C) to the water-soluble organic carbon content (WSOC) of PM was 32–43%, which is typical for urban sites affected by biomass burning. The Mass Absorption Efficiency (MAE), which characterizes the efficiency of absorbing solar energy per carbon mass of HULIS decreased with particle size, suggesting that the finest size fractions contain more light-absorbing chromophores, which could affect the light-absorbing ability of organic aerosols. The good correlation of HULIS with effective biomass tracers such as K⁺, as well as with secondary inorganic aerosol components, proposed that HULIS had both primary (i.e., biomass burning) and secondary sources. The Fourier Transfer Infrared coupled to Attenuation Total Reflectance (FTIR-ATR) spectra demonstrated prevalence of aromatic over carboxylic functional groups in most HULIS fractions, indicating contribution from coal combustion emissions in addition to fresh biomass burning aerosol. The new findings add to better understanding the sources and chemical structure of HULIS in urban and suburban environments.

Graphical abstract

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CFD modeling of particle dispersion and deposition coupled with particle dynamical models in a ventilated room

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Guangping Xu, Jiasong Wang
Two dynamical models, the traditional method of moments coupled model (MCM) and Taylor-series expansion method of moments coupled model (TECM) for particle dispersion distribution and gravitation deposition are developed in three-dimensional ventilated environments. The turbulent airflow field is modeled with the renormalization group (RNG) k–ε turbulence model. The particle number concentration distribution in a ventilated room is obtained by solving the population balance equation coupled with the airflow field. The coupled dynamical models are validated using experimental data. A good agreement between the numerical and experimental results can be achieved. Both models have a similar characteristic for the spatial distribution of particle concentration. Relative to the MCM model, the TECM model presents a more close result to the experimental data. The vortex structure existed in the air flow makes a relative large concentration difference at the center region and results in a spatial non-uniformity of concentration field. With larger inlet velocity, the mixing level of particles in the room is more uniform. In general, the new dynamical models coupled with computational fluid dynamics (CFD) in the current study provide a reasonable and accurate method for the temporal and spatial evolution of particles effected by the deposition and dispersion behaviors. In addition, two ventilation modes with different inlet velocities are proceeded to study the effect on the particle evolution. The results show that with the ceiling ventilation mode (CVM), the particles can be better mixed and the concentration level is also higher. On the contrast, with the side ceiling ventilation mode (SVM), the particle concentration has an obvious stratified distribution with a relative lower level and it makes a much better environment condition to the human exposure.

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Quo vadis: tracing the fate of neural crest cells

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Luis Zurkirchen, Lukas Sommer
The neural crest is a transient structure in vertebrate embryos that produces migratory cells with an astonishing developmental potential. While neural crest fate maps have originally been established through interspecies transplantation assays, dye labeling, and retroviral infection, more recent methods rely on approaches involving transgenesis and genome editing. These technologies allowed the identification of minor neural crest-derived cell populations in tissues of non-neural crest origin. Furthermore, in vivo multipotency at the single cell level and stage-dependent fate acquisitions were demonstrated using genetic technologies. Finally, recent reports indicate that neural crest-derived cells become activated in response to injury to secrete factors supporting tissue repair. Thus, neural crest-derived cells apparently contribute to tissue formation and regeneration by cell autonomous and non-autonomous mechanisms.

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Doxazosin nanoencapsulation improves its in vitro antiproliferative and anticlonogenic effects on breast cancer cells

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): J. Krai, A. Beckenkamp, M.M. Gaelzer, A.R. Pohlmann, S.S. Guterres, E.C. Filippi-Chiela, C. Salbego, A. Buffon, R.C.R. Beck
Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue^® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.

Graphical abstract

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Combined calcitriol and menadione reduces experimental murine triple negative breast tumor

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Luciana Bohl, Solange Guizzardi, Valeria Rodríguez, Lucila Hinrichsen, Viviana Rozados, David Cremonezzi, Nori Tolosa de Talamoni, Gabriela Picotto
BackgroundCalcitriol (D) or 1,25(OH)2D3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN+D resulted more effective than D or MEN alone.Objective: To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host.MethodsTumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN+D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination.ResultsNone of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN+D, P<0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth.ConclusionsAs previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects.

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Protective effects of wedelolactone on dextran sodium sulfate induced murine colitis partly through inhibiting the NLRP3 inflammasome activation via AMPK signaling

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Wencheng Wei, Meiling Ding, Kai Zhou, Haifeng Xie, Mian Zhang, Chaofeng Zhang
It has been reported that the ethanol extract of Wedelia chinensis attenuates murine colitis. Wedelolactone (WEL), a coumestane-type compound with many pharmacological activities, was isolated from W. chinensis. The present study aims to investigate the beneficial effects and underlying mechanisms of WEL on ulcerative colitis. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of WEL (50mg/kg) significantly attenuated pathological colonic damage and inhibited inflammatory infiltration, myeloperoxidase and alkaline phosphatase activities through MAPKs and NF-κB signaling pathways, while activating AMPK in colons treated with DSS. Further study revealed that WEL treatment dramatically inhibited NLRP3 inflammasome activation and caspase-1 phosphorylation to decrease IL-1β release in colons treated with DSS. In addition, WEL effectively regulates the disorder of skeleton proteins in colonic epithelial cells NCM460 exposed to TNF-α and protects the intestinal barrier function by activating AMPK in vivo. In summary, the AMPK-NLRP3-IL-1β signaling axis plays an important role in colitis following WEL treatments. These findings provide new insights into the pharmacological actions of WEL as a potential therapeutic agent for colitis.

Graphical abstract

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Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Josiane Weber Tessmann, Julieti Buss, Karine Rech Begnini, Lucas Moraes Berneira, Favero Reisdorfer Paula, Claudio Martin Pereira de Pereira, Tiago Collares, Fabiana Kömmling Seixas
Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a–2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer.

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MiR-136 controls neurocytes apoptosis by regulating Tissue Inhibitor of Metalloproteinases-3 in spinal cord ischemic injury

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Rilong Jin, Sanzhong Xu, Xiangjin Lin, Miaoda Shen
BackgroundSpinal cord ischemia is a serious injury that threatens human health and life. Furthermore, it was widely accepted that miR-136 was mediated in the spinal injury, while whether it regulated neurocytes apoptosis in I/R-induced spinal cord injury remains unclear.MethodsSpinal cord ischemia injury (SCII) rats were induced by clamping the nontraumatic vascular clip on the abdominal aorta. Real-time PCR was conducted to determine the mRNA expression, and western blot was carried out to measure protein expression. TUNEL assay was used to measure cell apoptosis.ResultsMiR-136 was up-regulated, while Tissue Inhibitor of Metalloproteinases-3 (TIMP3) was down-regulated in both SCII rats and hypoxic neurocytes. MiR-136 overexpression protected neurocytes against injury that induced by hypoxia. TIMP3 was the target gene of miR-136. Hypoxia supplementation decreased the expression of miR-136, promoted TIMP3 expression, and urged cell apoptosis, cells transfected with miR-136 mimic reversed the effect that induced by hypoxia, while cells co-transfected with pcDNA-TIMP3 abolished the results that induced by overexpressed miR-136.ConclusionMiR-136 regulated neurocytes apoptosis of SCII by mediating TIMP3.

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Long noncoding RNA PCAT1 regulates extrahepatic cholangiocarcinoma progression via the Wnt/β-catenin-signaling pathway

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Fumin Zhang, Ming Wan, Yi Xu, Zhenglong Li, Kaiming Leng, Pengcheng Kang, Yunfu Cui, Xingming Jiang
Extrahepatic cholangiocarcinoma (ECC) is a deadly disease that often responds poorly to conventional chemotherapy or radiotherapy. Long noncoding RNAs (lncRNAs) play important roles in human cancers, including ECC, and recent studies indicated that the lncRNA prostate cancer-associated transcript 1 (non-protein coding) (PCAT1) is involved in multiple cancers. However, the role of PCAT1 in ECC is unclear. Previously, we showed that PCAT1 is up-regulated in both ECC tissue samples and cell lines. Here, we showed that downregulation of PCAT1 following transfection with silencing RNA reduced ECC cell growth and increased cell apoptosis. Additionally, PCAT1 suppression inhibited ECC cell migration and invasion as determined by transwell assay. Furthermore, we determined that PCAT1 is a competing endogenous for microRNA (miR)-122, with bioinformatics analysis and luciferase-reporter assay results demonstrating that PCAT1 regulated WNT1 expression via miR-122. Moreover, PCAT1 downregulation increased levels of glycogen synthase kinase 3β and significantly decreased β-catenin levels in whole cell lysates and nuclear fractions, indicating that PCAT1 silencing inhibited the Wnt/β-catenin-signaling pathway. We also observed that exogenous expression of WNT1 reversed PCAT1-silencing-induced inhibition of ECC cell growth inhibition. These results indicated that PCAT1 silencing inhibited ECC progression by reducing Wnt/β-catenin signaling through miR-122 repression and WNT1 expression. Our findings revealed an important role of PCAT1 in ECC and suggested that PCAT1 might be a potential ECC-related therapeutic target.

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Diallyl trisulfide induces apoptosis and mitotic arrest in AGS human gastric carcinoma cells through reactive oxygen species-mediated activation of AMP-activated protein kinase

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Yung Hyun Choi
Diallyl trisulfide (DATS), one of the principal constituents of garlic oil, is a kind of organosulfur compound with high anti-cancer activity. Although inhibition of cancer cell proliferation by DATS is known to be associated with the induction of apoptosis and cell cycle arrest related to reactive oxygen species (ROS) production, it is still necessary to study the detailed mechanisms. In this study, we investigated the role of ROS on the activation of AMP-activated protein kinase (AMPK) in DATS-induced apoptosis and cell cycle arrest in AGS human gastric carcinoma cells. The results of the present study indicate that DATS inhibited proliferation of AGS cells by promoting apoptosis, and accumulating cellular portion of G2/M phase via the induction of cyclin B1 and cyclin-dependent kinase p21(WAF1/CIP1). The phosphorylation of histone H3 was also markedly increased following treatment with DATS, revealing that DATS stimulated a mitotic arrest, not the G2 phase. Furthermore, we found that DATS concurrently induced phosphorylation of AMPK; however, chemical inhibition of AMPK by compound C, an AMPK inhibitor, significantly blocked apoptosis induced by DATS, suggesting that DATS induces cytotoxicity of AGS cells through the AMPK-dependent pathway. Moreover, DATS provoked intracellular ROS generation and the loss of mitochondrial membrane potential, and in particular, when ROS production was blocked by antioxidant N-acety-l-cysteine, both AMPK activation and growth inhibition by DATS were completely abolished. Collectively, these findings suggest that DATS inhibited growth of AGS cells, which was mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis, and cell cycle arrest, through a ROS-dependent activation of AMPK pathway.

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Nanoscale deformation mechanisms and yield properties of hydrated bone extracellular matrix

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Jakob Schwiedrzik, Aidan Taylor, Daniele Casari, Uwe Wolfram, Philippe Zysset, Johann Michler
Bone features a hierarchical architecture combining antagonistic properties like toughness and strength. In order to better understand the mechanisms leading to this advantageous combination, its postyield and failure behavior was analyzed on the length scale of a single lamella. Micropillars were compressed to large strains under hydrated conditions to measure their anisotropic yield and post-yield behavior. An increase in strength compared to the macroscale by a factor of 1.55 and a strong influence of hydration with a decrease by 60% in yield stress compared to vacuum conditions were observed. Post-compression transmission electron microscopic analysis revealed anisotropic deformation mechanisms. In axial pillars, where fibrils were oriented along the loading axis, kink bands were observed and shear cracks emerged at the interface of ordered and disordered regions. Micromechanical analysis of fibril kinking allowed an estimate of the extrafibrillar matrix shear strength to be made: 120±40MPa . When two opposing shear planes met a wedge was formed, splitting the micropillar axially in a mode 1 crack. Making use of an analytical solution, the mode 1 fracture toughness of bone extracellular matrix for splitting along the fibril direction was estimated to be 0.07MPam. This is 1-2 orders of magnitude smaller than on the macroscale, which may be explained by the absence of extrinsic toughening mechanisms. In transverse pillars, where fibrils were oriented perpendicular to the loading axis, cracks formed in regions where adverse fibril orientation reduced the local fracture resistance. This study underlines the importance of bone's hierarchical microstructure for its macroscopic strength and fracture resistance and the need to study structure-property relationships as well as failure mechanisms under hydrated conditions on all length scales.Statement of SignificanceBone's hierarchical architecture combines toughness and strength. To understand the governing deformation mechanisms, its postyield behavior was analyzed at the microscale. Micropillars were compressed in physiological solution; an increased strength compared to macroscale and an influence of hydration was found. Transmission electron microscopy revealed cracks forming in regions with adverse fibril orientation in transverse pillars with fibrils oriented perpendicular to the loading axis. In axial pillars kink bands were observed and shear cracks emerged at the interface of ordered and disordered regions. It was estimated that bone's fracture toughness for splitting between fibrils is significantly smaller than on the macroscale. This study underlines the importance of bone's hierarchical microstructure and the need to study structure-property relationships on all length scales.

Graphical abstract

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Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with ultrahigh porosity and surface area imply potential drug delivery and cell engineering applications

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Ahmed El-Fiqi, Jennifer O. Buitrago, Sung Hee Yang, Hae-Won Kim
Here we communicate the generation of biomimetically grown apatite spheres from aggregated bioglass nanoparticles and the potential properties applicable for drug delivery and cell/tissue engineering. Ion releasing nanoparticulates of bioglass (85%SiO2-15%CaO) in a mineralizing medium show an intriguing dynamic phenomenon – aggregation, mineralization to apatite, integration and growth into micron-sized (1.5-3 μm) spheres. During the progressive ionic dissolution/precipitation reactions, nano-to-micro-morphology, glass-to-crystal composition, and the physico-chemical properties (porosity, surface area, and charge) change dynamically. With increasing reaction period, the apatite becomes more crystallized with increased crystallinity and crystal size, and gets a composition closer to the stoichiometry. The developed microspheres exhibit hierarchical surface nanostructure, negative charge (ς-potential of -20 mV), and ultrahigh mesoporosity (mesopore size of 6.1 nm, and the resultant surface area of 63.7 m²/g and pore volume of 0.153 cm³/g) at 14 days of mineralization, which are even higher than those of its precursor bioglass nanoparticles. Thanks to these properties, the biomimetic mineral microspheres take up biological molecules effectively, i.e., loading capacity of positive-charged protein is over 10%. Of note, the release is highly sustainable at a constant rate, i.e., profiling almost 'zero-order' kinetics for 4 weeks, suggesting the potential usefulness as protein delivery systems. The biomimetic mineral microspheres hold some remnant Si in the core region, and release calcium, phosphate, and silicate ions over the test period, implying the long-term ionic-related therapeutic functions. The mesenchymal stem cells favour the biomimetic spheres with an excellent viability. Due to the merit of sizes (a few micrometers), the spheres can be intercalated into cells, mediating cellular interactions in 3D cell-spheroid engineering, and also can stimulate osteogenic differentiation of cells when incorporated into cell-laden gels. The intriguing properties observed in this study, including biomimetic composition, high mesoporosity, release of therapeutic ions, effective loading and long-term release of proteins, and diverse yet favorable 3D cellular interactions, suggest great potential of the newly developed biomimetic microspheres in biomedical applications, such as drug delivery and cell/tissue engineering.Statement of SignificanceThis work reports the generation of apatite spheres with a few micrometers in size biomimetically grown from bioactive glass nanoparticles, through a series of intriguing yet unprecedented phenomenon involving aggregation of nanoparticles, mineralization and sphere growth. The mineral microspheres possess some unique physico-chemical properties including mesoporosity, ultrahigh surface area, and therapeutic ionic release. Furthermore, the spheres show excellent loading and delivery capacity of protein molecules, and mediate favorable cellular interactions in 2D and 3D culture conditions, demonstrating a future multifunctional microcarrier platform for the therapeutics delivery and cell/tissue engineering.

Graphical abstract

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Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Suzanne E. Thomson, Chloe Charalambous, Carol-Anne Smith, Penelope M Tsimbouri, Theophile Déjardin, Paul J. Kingham, Andrew M. Hart, Mathis O. Riehle
Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model. Linear topographical cues enhanced neurite outgrowth and our results demonstrated that the mTOR pathway is important in regulating these responses.mTOR gene expression peaked between 48-72 hours, coincident with the onset of rapid neurite outgrowth and glial migration, and correlated with neurite length at 48 hours. mTOR protein was located to glia and in a punctate distribution along neurites. mTOR levels peaked at 72 hours and were significantly increased by patterned topography (p < 0.05). Furthermore, the topographical cues could override pharmacological inhibition. Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin highlighted mTORC2 as an important mediator, and more specific therapeutic target. Quantitative immunohistochemistry confirmed the presence of the mTORC2 component rictor at the regenerating front where it co-localised with F-actin and vinculin. Collectively, these results provide a deeper understanding of the mechanism of action of topography on neural regeneration, and support the incorporation of topographical patterning in combination with pharmacological mTORC2 potentiation within biomaterial constructs used to repair peripheral nerves.Statement of SignificancePeripheral nerve injury is common and functionally devastating. Despite microsurgical repair, healing is slow and incomplete, with lasting functional deficit. There is a clear need to translate bioengineering approaches and increase our knowledge of the molecular processes controlling nerve regeneration to improve the rate and success of healing. Topographical cues are powerful determinants of neurite outgrowth and represent a highly translatable engineering strategy. Here we demonstrate, for the first time, that microtopography potentiates neurite outgrowth via the mTOR pathway, with the mTORC2 subtype being of particular importance. These results give further evidence for the incorporation of microtopographical cues into peripheral nerve regeneration conduits and indicate that mTORC2 may be a suitable therapeutic target to potentiate nerve regeneration.

Graphical abstract

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Stretching Single Fibrin Fibers Hampers Their Lysis

Publication date: Available online 25 July 2017
Source:Acta Biomaterialia
Author(s): Wei Li, Tomas Lucioni, Rongzhong Li, Keith Bonin, Samuel S. Cho, Martin Guthold
Blood clots, whose main structural component is a mesh of microscopic fibrin fibers, experience mechanical strain from blood flow, clot retraction and interactions with platelets and other cells. We developed a transparent, striated and highly stretchable substrate made from fugitive glue (a styrenic block copolymer) to investigate how mechanical strain affects lysis of single, suspended fibrin fibers. In this suspended fiber assay, lysis manifested itself by fiber elongation, thickening (disassembly), fraying and collapse. Stretching single fibrin fibers significantly hampered their lysis. This effect was seen in uncrosslinked and crosslinked fibers. Crosslinking (without stretching) also hampered single fiber lysis.Our data suggest that strain is a novel mechanosensitive factor that regulates blood clot dissolution (fibrinolysis) at the single fiber level. At the molecular level of single fibrin molecules, strain may distort, or hinder access to, plasmin cleavage sites and thereby hamper lysis.Statement of SignificanceFibrin fibers are the major structural component of a blood clot. We developed a highly stretchable substrate made from fugitive glue and a suspended fibrin fiber lysis assay to investigate the effect of stretching on single fibrin fibers lysis. The key findings from our experiments are: 1) Fibers thicken and elongate upon lysis; 2) stretching strongly reduces lysis; 3) this effect is more pronounced for uncrosslinked fibers; and 4) stretching fibers has similar effect on reducing lysis as crosslinking fibers. On the molecular level, strain may distort plasmin cleavage sites, or restrict access to those sites. Our results suggest that strain may be a novel mechanobiological factor that regulates fibrinolysis.

Graphical abstract

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Big GABA: Edited MR spectroscopy at 24 research sites

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Mark Mikkelsen, Peter B. Barker, Pallab K. Bhattacharyya, Maiken K. Brix, Pieter F. Buur, Kim M. Cecil, Kimberly L. Chan, David Y.-T. Chen, Alexander R. Craven, Koen Cuypers, Michael Dacko, Niall W. Duncan, Ulrike Dydak, David A. Edmondson, Gabriele Ende, Lars Ersland, Fei Gao, Ian Greenhouse, Ashley D. Harris, Naying He, Stefanie Heba, Nigel Hoggard, Tun-Wei Hsu, Jacobus F.A. Jansen, Alayar Kangarlu, Thomas Lange, R. Marc Lebel, Yan Li, Chien-Yuan E. Lin, Jy-Kang Liou, Jiing-Feng Lirng, Feng Liu, Ruoyun Ma, Celine Maes, Marta Moreno-Ortega, Scott O. Murray, Sean Noah, Ralph Noeske, Michael D. Noseworthy, Georg Oeltzschner, James J. Prisciandaro, Nicolaas A.J. Puts, Timothy P.L. Roberts, Markus Sack, Napapon Sailasuta, Muhammad G. Saleh, Michael-Paul Schallmo, Nicholas Simard, Stephan P. Swinnen, Martin Tegenthoff, Peter Truong, Guangbin Wang, Iain D. Wilkinson, Hans-Jörg Wittsack, Hongmin Xu, Fuhua Yan, Chencheng Zhang, Vadim Zipunnikov, Helge J. Zöllner, Richard A.E. Edden
Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.

http://ift.tt/2vZ36Zn

3D-MB-MUSE: A robust 3D multi-slab, multi-band and multi-shot reconstruction approach for ultrahigh resolution diffusion MRI

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Iain P. Bruce, Hing-Chiu Chang, Christopher Petty, Nan-Kuei Chen, Allen W. Song
Recent advances in achieving ultrahigh spatial resolution (e.g. sub-millimeter) diffusion MRI (dMRI) data have proven highly beneficial in characterizing tissue microstructures in organs such as the brain. However, the routine acquisition of in-vivo dMRI data at such high spatial resolutions has been largely prohibited by factors that include prolonged acquisition times, motion induced artifacts, and low SNR. To overcome these limitations, we present here a framework for acquiring and reconstructing 3D multi-slab, multi-band and interleaved multi-shot EPI data, termed 3D-MB-MUSE. Through multi-band excitations, the simultaneous acquisition of multiple 3D slabs enables whole brain dMRI volumes to be acquired in-vivo on a 3 T clinical MRI scanner at high spatial resolution within a reasonably short amount of time. Representing a true 3D model, 3D-MB-MUSE reconstructs an entire 3D multi-band, multi-shot dMRI slab at once while simultaneously accounting for coil sensitivity variations across the slab as well as motion induced artifacts commonly associated with both 3D and multi-shot diffusion imaging. Such a reconstruction fully preserves the SNR advantages of both 3D and multi-shot acquisitions in high resolution dMRI images by removing both motion and aliasing artifacts across multiple dimensions. By enabling ultrahigh resolution dMRI for routine use, the 3D-MB-MUSE framework presented here may prove highly valuable in both clinical and research applications.

http://ift.tt/2v6y1qg

Investigations into within- and between-subject resting-state amplitude variations

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Janine Bijsterbosch, Samuel Harrison, Eugene Duff, Fidel Alfaro-Almagro, Mark Woolrich, Stephen Smith
The amplitudes of spontaneous fluctuations in brain activity may be a significant source of within-subject and between-subject variability, and this variability is likely to be carried through into functional connectivity (FC) estimates (whether directly or indirectly). Therefore, improving our understanding of amplitude fluctuations over the course of a resting state scan and variation in amplitude across individuals is of great relevance to the interpretation of FC findings. We investigate resting state amplitudes in two large-scale studies (HCP and UK Biobank), with the aim of determining between-subject and within-subject variability. Between-subject clustering distinguished between two groups of brain networks whose amplitude variation across subjects were highly correlated with each other, revealing a clear distinction between primary sensory and motor regions ('primary sensory/motor cluster') and cognitive networks. Within subjects, all networks in the primary sensory/motor cluster showed a consistent increase in amplitudes from the start to the end of the scan. In addition to the strong increases in primary sensory/motor amplitude, a large number of changes in FC were found when comparing the two scans acquired on the same day (HCP data). Additive signal change analysis confirmed that all of the observed FC changes could be fully explained by changes in amplitude. Between-subject correlations in UK Biobank data showed a negative correlation between primary sensory/motor amplitude and average sleep duration, suggesting a role of arousal. Our findings additionally reveal complex relationships between amplitude and head motion. These results suggest that network amplitude is a source of significant variability both across subjects, and within subjects on a within-session timescale. Future rfMRI studies may benefit from obtaining arousal-related (self report) measures, and may wish to consider the influence of amplitude changes on measures of (dynamic) functional connectivity.

http://ift.tt/2vYYdjl

Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Candace R. Lewis, Katrin H. Preller, Rainer Kraehenmann, Lars Michels, Philipp Staempfli, Franz X. Vollenweider
Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations.

http://ift.tt/2v6xcxF

Accelerating permutation testing in voxel-wise analysis through subspace tracking: A new plugin for SnPM

Publication date: 1 October 2017
Source:NeuroImage, Volume 159
Author(s): Felipe Gutierrez-Barragan, Vamsi K. Ithapu, Chris Hinrichs, Camille Maumet, Sterling C. Johnson, Thomas E. Nichols, Vikas Singh
Permutation testing is a non-parametric method for obtaining the max null distribution used to compute corrected p-values that provide strong control of false positives. In neuroimaging, however, the computational burden of running such an algorithm can be significant. We find that by viewing the permutation testing procedure as the construction of a very large permutation testing matrix, T, one can exploit structural properties derived from the data and the test statistics to reduce the runtime under certain conditions. In particular, we see that T is low-rank plus a low-variance residual. This makes T a good candidate for low-rank matrix completion, where only a very small number of entries of T (∼0.35% of all entries in our experiments) have to be computed to obtain a good estimate. Based on this observation, we present RapidPT, an algorithm that efficiently recovers the max null distribution commonly obtained through regular permutation testing in voxel-wise analysis. We present an extensive validation on a synthetic dataset and four varying sized datasets against two baselines: Statistical NonParametric Mapping (SnPM13) and a standard permutation testing implementation (referred as NaivePT). We find that RapidPT achieves its best runtime performance on medium sized datasets (50≤n≤200), with speedups of 1.5× - 38× (vs. SnPM13) and 20x-1000× (vs. NaivePT). For larger datasets (n≥200) RapidPT outperforms NaivePT (6× - 200×) on all datasets, and provides large speedups over SnPM13 when more than 10000 permutations (2× - 15×) are needed. The implementation is a standalone toolbox and also integrated within SnPM13, able to leverage multi-core architectures when available.

http://ift.tt/2vZgL2P

Editorial Board

Publication date: October 2017
Source:Microbiological Research, Volume 203

http://ift.tt/2vHK62k

Ethanol production from chitosan by the nematophagous fungus Pochonia chlamydosporia and the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

Publication date: Available online 25 July 2017
Source:Microbiological Research
Author(s): Almudena Aranda-Martinez, Miguel Ángel Naranjo Ortiz, Isabel Sofía Abihssira García, Ernesto A. Zavala-Gonzalez, Luis Vicente Lopez-Llorca
Ethanol production is mainly obtained from plant biomass. Chitin is the second most abundant biopolymer after cellulose and virtually unexplored as raw material for bioethanol production. In this paper, we investigate chitosan, the deacetylated form of chitin which is the main component of shellfish waste, as substrate for bioethanol production by fungi. Fungal parasites of invertebrates such as the nematophagous Pochonia chlamydosporia (Pc) or the entomopathogens Beauveria bassiana (Bb) and Metarhizium anisopliae (Ma) are biocontrol agents of plant parasitic nematodes (eg. Meloidogyne spp.) or insect pests such as the red palm weevil (Rhynchophorus ferrugineus). These fungi degrade chitin-rich barriers for host penetration. We have therefore tested the chitin/chitosanolytic capabilities of Pc, Bb and Ma for generating reducing sugars using chitosan as only nutrient. Among the microorganisms used in this study, Pc is the best chitosan degrader, even under anaerobic conditions. These fungi have alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) encoding genes in their genomes. We have therefore analyzed their ethanol production under anaerobic conditions using chitosan as raw material. P. chlamydosporia is the largest ethanol producer from chitosan. Our studies are a starting point to develop chitin-chitosan based biofuels.

http://ift.tt/2uvzaWR

Idiopathic Intracranial Hypertension Progressing to Venous Sinus Thrombosis, Subarachnoid Hemorrhage, and Stroke.

Idiopathic intracranial hypertension (IIH) is a syndrome characterized by increased intracranial pressure (ICP), the absence of structural lesions on neuroimaging, and normal cerebrospinal fluid composition. Cerebral venous sinus thrombosis (CVST) is a common cause of increased ICP and can be differentiated from IIH with magnetic resonance venography. We describe a young woman with typical IIH who underwent lumbar puncture and was treated with a short course of high-dose corticosteroids followed by acetazolamide. She subsequently developed CVST, subarachnoid hemorrhage, and stroke. Risk factors that may have resulted in CVST are discussed. (C) 2017 by North American Neuro-Ophthalmology Society

http://ift.tt/2uV2pmY

Role of Nocturnal Arterial Hypotension in Nonarteritic Anterior Ischemic Optic Neuropathy.

No abstract available

http://ift.tt/2uzkepo

Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy?: Response.

No abstract available

http://ift.tt/2uVlZjk

Extraocular Muscle Findings in Myasthenia Gravis Associated Treatment-Resistant Ophthalmoplegia: A Case Report.

We report the histopathological and ultrastructural tissue analysis of extraocular muscle (EOM) obtained from a patient with seronegative myasthenia gravis (MG) with treatment-resistant ophthalmoplegia for 3.5 years. The EOM demonstrated predominantly myopathic features and ultrastructural evidence of mitochondrial dysfunction, but the most striking features were increased endomysial collagen and adipocyte replacement of muscle fibers. By contrast, control EOM from a patient undergoing strabismus surgery for a sensory exotropia in a nonseeing eye and a similar duration of deviation, showed normal muscle histology. Although the histopathological and ultrastructural findings largely resemble those of limb muscle in MG, the abundant endomysial collagen may be nonspecific and secondary to poor force generation as a result of chronic ophthalmoplegia. (C) 2017 by North American Neuro-Ophthalmology Society

http://ift.tt/2uzik83

Information/Education Pages (I/EPs)

Publication date: August 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 8

http://ift.tt/2tAUpUF

Editorial Board

Publication date: August 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 8

http://ift.tt/2uXFaby

Publication date: August 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 8

http://ift.tt/2tAUo33

Editors' Selections From This Issue: Volume 98 / Number 8 / August 2017

Publication date: August 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 8

http://ift.tt/2uXCP0C

Masthead

Publication date: August 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 8

http://ift.tt/2tBkRx7

Correction

Publication date: August 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 8

http://ift.tt/2uXGBa7

Is the neglect of exercise in anorexia nervosa research a case of “running out” of ideas or do we need to take a “LEAP” of faith into the future?

http://ift.tt/2vZ3J5e

The prone bridge test: Performance, validity, and reliability among older and younger adults

Publication date: Available online 25 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Richard W. Bohannon, Michal Steffl, Susan S. Glenney, Michelle Green, Leah Cashwell, Kveta Prajerova, Jennifer Bunn
IntroductionThe prone bridge maneuver, or plank, has been viewed as a potential alternative to curl-ups for assessing trunk muscle performance. The purpose of this study was to assess prone bridge test performance, validity, and reliability among younger and older adults.MethodSixty younger (20-35 years old) and 60 older (60-79 years old) participants completed this study. Groups were evenly divided by sex. Participants completed surveys regarding physical activity and abdominal exercise participation. Height, weight, body mass index (BMI), and waist circumference were measured. On two occasions, 5–9 days apart, participants held a prone bridge until volitional exhaustion or until repeated technique failure. Validity was examined using data from the first session: convergent validity by calculating correlations between survey responses, anthropometrics, and prone bridge time, known groups validity by using an ANOVA comparing bridge times of younger and older adults and of men and women. Test-retest reliability was examined by using a paired t-test to compare prone bridge times for Session1 and Session 2. Furthermore, an intraclass correlation coefficient (ICC) was used to characterize relative reliability and minimal detectable change (MDC95%) was used to describe absolute reliability.ResultsThe mean prone bridge time was 145.3 ± 71.5 s, and was positively correlated with physical activity participation (p ≤ 0.001) and negatively correlated with BMI and waist circumference (p ≤ 0.003). Younger participants had significantly longer plank times than older participants (p = 0.003). The ICC between testing sessions was 0.915.ConclusionThe prone bridge test is a valid and reliable measure for evaluating abdominal performance in both younger and older adults.

http://ift.tt/2uXCIlx

Timed Up and Go evaluation with wearable devices: Validation in Parkinson's disease

Publication date: Available online 25 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Ana Kleiner, Ilaria Pacifici, Alessandro Vagnini, Filippo Camerota, Claudia Celletti, Maria Francesca De Pandis, Manuella Galli
The Timed Up and Go test (TUG) is used to assess individual mobility. It evaluates static and dynamic balance by means of the total time required to complete the test, usually measured by a stopwatch. In recent years tools based on portable inertial measurement units (IMU) for clinical application are increasingly available on the market. More specifically, a tool (hardware and dedicated software) to quantify the TUG test based on IMU is now available. However, it has not yet been validated in subjects with Parkinson's disease (PD). Thus, the aim of this study is to compare measurements from instrumented TUG tests (or iTUG) acquired by an IMU with those obtained using an optoelectronic system (the gold standard) and by a stopwatch, to gain an in-depth understanding of IMU behavior in computing iTUG in subjects with PD. To do this, three TUG test trials were carried out on 30 subjects with PD and measured with all three systems simultaneously. System agreements were evaluated using Intraclass Correlation Coefficient and Bland-Altman plots. The device tested showed excellent reliability, accuracy and precision in quantifying total TUG test duration. Since TUG is a widely used test in rehabilitation settings, its automatic quantification through IMUs could potentially improve the quality of assessments in the quantification of PD gait ability.

http://ift.tt/2tBhkPk

Effects of movement impairment based treatment in the management of mechanical neck pain

Publication date: Available online 24 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): T.M. Ashwini, H. Karvannan, V. Prem
BackgroundNeck pain is a common musculoskeletal complaint in computer users due to prolonged static or awkward work postures. It has been shown that pathogenesis of neck pain is associated with scapular movement impairment syndromes. However, there is a dearth of literature in treatment based on these syndromes.AimTo identify the effects of movement impairment based treatment in the management of mechanical neck pain in computer users.MethodsIn the present study, twenty-seven subjects were recruited. Based on the scapular impairment syndrome identified, they were trained with scapular movement impairment based exercises for four weeks. Pain, disability and cervical range of motion were measured with numeric pain rating scale, neck disability index and inclinometer respectively at baseline and at four weeks.ResultsTwenty-one subjects completed the study. After four weeks, a significant difference of 4.81 points for numeric pain rating scale and 24.47% for neck disability index at 95% CI were found. The cervical range of motion showed a significant change (p < 0.05) of 10.09° for flexion, 24.47° for extension, 7.42° for right lateral flexion, 6.23° for left lateral flexion, 15.52° for right rotation and 14.95° for left rotation at 95% CI.ConclusionsExercises based on scapular impairment syndromes were given for four weeks. It was found to be effective in relieving pain and reducing dysfunction in computer users with mechanical neck pain.

http://ift.tt/2uXCw5W

A fundamental critique of the fascial distortion model and its application in clinical practice

Publication date: Available online 25 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Mag. Christoph Thalhamer
IntroductionThe therapeutic techniques used in the fascial distortion model (FDM) have become increasingly popular among manual therapists and physical therapists. The reasons for this trend remain to be empirically explored. Therefore this paper pursues two goals: first, to investigate the historical and theoretical background of FDM, and second, to discuss seven problems associated with the theory and practice of FDM.Materials and methodsThe objectives of this paper are based on a review of the literature. The research mainly focuses on clinical proofs of concept for FDM treatment techniques in musculoskeletal medicine.ResultsFDM as a treatment method was founded and developed in the early 1990s by Stephen Typaldos. It is based on the concept that all musculoskeletal complaints can be traced back to three-dimensional deformations or distortions of the fasciae. The concept is that these distortions can be undone through direct application of certain manual techniques. A literature review found no clinical trials or basic research studies to support the empirical foundations of the FDM contentions.DiscussionBased on the absence of proof of concept for FDM treatment techniques along with certain theoretical considerations, seven problems emerge, the most striking of which include (1) diagnostic criteria for FDM, (2) the biological implausibility of the model, (3) the reduction of all such disorders to a single common denominator: the fasciae, (4) the role of FDM research, and (5) potentially harmful consequences related to FDM treatment.ConclusionThe above problems can only be invalidated through high-quality clinical trials. Allegations that clinical experience is sufficient to validate therapeutic results have been abundantly refuted in the literature.

http://ift.tt/2tBwt3c

Editorial Board

Publication date: July 2017
Source:Journal of Bodywork and Movement Therapies, Volume 21, Issue 3

http://ift.tt/2uXBvdX

Inside Front Cover - Editorial Board Page/Cover image legend if applicable

Publication date: August 2017
Source:Acta Oecologica, Volume 83

http://ift.tt/2uXuEkT

Characterization of two peptides isolated from the venom of social wasp Chartergellus communis (Hymenoptera: Vespidae): Influence of multiple alanine residues and C-terminal amidation on biological effects

Publication date: Available online 25 July 2017
Source:Peptides
Author(s): Kamila Soares Lopes, Gabriel Avohay Alves Campos, Luana Cristina Camargo, Adolfo Carlos Barros de Souza, Beatriz Vasconcelos Ibituruna, Ana Carolina Martins Magalhães, Lucas Ferreira da Rocha, Alessa Bembom Garcia, Mosar Correa Rodrigues, Dagon Manuel Ribeiro, Michelle Cruz Costa, Manuel Humberto Mera López, Luciana Marangni Nolli, Fernando Zamudio-Zuniga, Lourival Domingos Possani, Elisabeth Ferroni Schwartz, Márcia Renata Mortari
Chatergellus communis is a wasp species endemic to the neotropical region and its venom constituents have never been described. In this study, two peptides from C. communis venom, denominated Communis and Communis-AAAA, were chemically and biologically characterized. In respect to the chemical characterization, the following amino acid sequences and molecular masses were identified:Communis: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da)Communis-AAAA: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH2 (1836.3Da).Furthermore, their biological effects were compared, accounting for the differences in structural characteristics between the two peptides. To this end, three biological assays were performed in order to evaluate the hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis-AAAA, unlike Communis, showed a potent hemolytic activity with EC50=142.6μM. Moreover, the highest dose of Communis-AAAA (2nmol/animal) induced hyperalgesia in mice. On the other hand, Communis (10nmol/animal) was able to induce edema but did not present hemolytic or hyperalgesic activity. Although both peptides have similarities in linear structures, we demonstrated the distinct biological effects of Communis and Communis-AAAA. This is the first study with Chartegellus communis venom, and both Communis and Communis-AAAA are unpublished peptides.

http://ift.tt/2v6J2YJ

Inhibitory action of tongue sole LPXRFa, the piscine ortholog of gonadotropin-inhibitory hormone, on the signaling pathway induced by tongue sole kisspeptin in COS-7 cells transfected with their cognate receptors

Publication date: Available online 25 July 2017
Source:Peptides
Author(s): Bin Wang, Guokun Yang, Quan Liu, Jingkai Qin, Yongjiang Xu, Wensheng Li, Xuezhou Liu, Bao Shi
Kisspeptin (Kiss) acts as a positive regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the intricate web of intracellular signal transduction pathways in response to Kiss is still far from being fully understood in teleosts. Accordingly, we investigated the molecular mechanism of Kiss action and its possible interaction with LPXRFa signaling in this study. In vitro functional analysis revealed that synthetic tongue sole Kiss2 decapeptide increased the cAMP responsive element-dependent luciferase (CRE-luc) activity in COS-7 cells transfected with its cognate receptor, while this stimulatory effect was markedly reduced by two inhibitors of the adenylate cyclase (AC)/protein kinase A (PKA) pathway. Similarly, Kiss2 also significantly stimulated serum responsive element-dependent luciferase (SRE-luc) activity, whereas this stimulatory effect was evidently attenuated by two inhibitors of the phospholipase C (PLC)/protein kinase C (PKC) pathway. In addition, LPXRFa-2 suppressed Kiss2-elicited CRE-luc activity in a dose-dependent manner. Taken together, Kiss2 utilizes both AC/PKA and PLC/PKC pathways to exert its functions via its cognate receptor and LPXRFa may antagonize the action of Kiss2 by inhibiting kisspeptin signaling. As far as we know, this study is the first to characterize the half-smooth tongue sole kisspeptin and LPXRFa signaling pathway in COS-7 cells transfected with their cognate receptors and provides novel information on the interaction between LPXRFa system and kisspeptin system in teleosts.

http://ift.tt/2vZ26EP

Vermeidung unbeabsichtigter perioperativer Hypothermie: ein Leitfaden

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 554-562
DOI: 10.1055/s-0041-103653

Die unbeabsichtigte perioperative Hypothermie (Körperkerntemperatur < 36 °C) ist ein potenziell komplikationsträchtiges, schwerwiegendes Ereignis: Sie führt zu einer erhöhten Inzidenz an Wundinfektionen und vermehrten Blutverlusten/Transfusionsbedarf. Dieser Beitrag thematisiert die praktische Umsetzung der AWMF-S3-Leitlinie „Vermeidung von perioperativer Hypothermie" von 2014 1. Er soll als Leitfaden für die tägliche klinische Arbeit dienen.
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