bluuebunny/crossref_metadata_2025 huggingface dataset:
HMGA2 promotes glioma invasion and poor prognosis via a long‐range chromatin interaction
Authors: Zhang Shanshan , Zhang Huibian , Yu Lin
Published: May 2018

To identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan‐Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP‐qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co‐immunoprecipitation were applied to identify HMGA2‐activated target sites, which were further verified by mRNA and protein expression detection. Transwell and orthotopic implantation were used to investigate the roles of HMGA2 in glioma cells. HMGA2 shRNA transfection inhibited glioblastoma invasion. Mechanistically, we first discovered that HMGA2, together with GCN5, facilitated the invasion of glioma cells via inducing chromatin conformational remodeling of the MMP2 gene promoter and epigenetically activating MMP2 gene transcription. Our results indicated that HMGA2, as a novel GCN5 recognition partner and histone acetylation modulator, may be novel prognostic indicator and promising glioma treatment target.
Synthesis of Lanostane‐Type Triterpenoid N‐Glycosides and Their Cytotoxicity against Human Cancer Cell Lines
Authors: Ukiya Motohiko , Hayakawa Teppei , Okazaki Kouta , Hikawa Maiko , Akazawa Hiroyuki , Li Wei , Koike Kazuo , Fukatsu Makoto
Published: May 2018

Seventeen lanostane‐type triterpenoid derivatives (2 – 18), including 11N‐glycosides (8 – 18), were synthesized from the natural triterpenoid, lanosterol (1), and were evaluated for their cytotoxicity against the human cancer cell lines, HL‐60, A549, and MKN45, as well as the normal human lung cells, WI‐38. Among them, N‐β‐d‐2‐acetamido‐2‐deoxyglucoside (10) showed cytotoxicity against HL‐60, A549, MKN45, and WI‐38 cells (IC50 0.0078 – 2.8 μm). However, N‐β‐d‐galactoside (12) showed cytotoxicity against HL‐60 and MKN45 cells (IC50 0.0021 – 4.0 μm), but not the normal WI‐38 cells. Furthermore, Western blot analysis suggested that 12 induces apoptosis by activation of caspases‐3, 8, and 9. These results will be useful for the synthesis of other tetracyclic triterpenoids or steroid N‐glycosides to increase their cytotoxicity and apoptosis‐inducing activities.
Generation of Polar Semi‐Saturated Bicyclic Pyrazoles for Fragment‐Based Drug‐Discovery Campaigns.
Authors: Luise Nicola , Wyatt Paul G.
Published: May 2018

Synthesising polar semi‐saturated bicyclic heterocycles can lead to better starting points for fragment‐based drug discovery (FBDD) programs. We report the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed.
Direct Enantioselective α‐Allylation of Unfunctionalized Cyclic Ketones with Alkynes through Pd‐Amine Cooperative Catalysis
Authors: Lee Jin Tu Danence , Zhao Yu
Published: May 2018

The first direct enantioselective α‐allylation of unfunctionalized cyclic ketones using alkynes as an economical choice of reagent is reported. This transformation uses a simple procedure with commercially available palladium, chiral bisphosphine ligand and chiral amine catalysts, and affords valuable ketones with a α‐tertiary stereocenter in good to high enantiopurity. In this transformation, a chiral palladium complex containing the (S)‐DIFLUORPHOS ligand catalyzes the isomerization of alkynes into an electrophilic allylpalladium species, which is attacked by the enamine generated in situ from the condensation of (R)‐prolinol with the ketone substrate.
Understanding health‐related quality of life in adult women with metastatic cancer who have dependent children
Authors: Park Eliza M. , Deal Allison M. , Yopp Justin M. , Edwards Teresa , Resnick Samuel J. , Song Mi‐Kyung , Nakamura Zev M. , Rosenstein Donald L.
Published: May 2018

BACKGROUND

Cancer is a leading cause of death among women of parenting age in the United States. Women living with advanced or incurable cancer who have dependent children experience high rates of depression and anxiety as well as unique parenting challenges. To the authors' knowledge, few studies to date have examined the parenting factors associated with health‐related quality of life (HRQOL) in women with advanced cancer.

METHODS

The authors conducted a cross‐sectional, Web‐based survey of the psychosocial concerns of 224 women with a tumor‐node‐metastasis staging system of the AJCC stage IV solid tumor malignancy who had at least 1 child aged <18 years. Participants completed validated measures of HRQOL (Functional Assessment of Cancer Therapy–General [FACT‐G]); depression and anxiety symptom severity; functional status; parenting concerns; and investigator‐designed questions to assess demographic, communication, and parenting characteristics. Multiple linear regression models were estimated to identify factors associated with FACT‐G total and subscale scores.

RESULTS

The mean FACT‐G score was 66 (standard deviation, 16). The mean Emotional Well‐Being subscale scores were particularly low (13; standard deviation, 5). In multivariable linear regression models, parenting variables explained nearly 40% of the HRQOL model variance. In the fully adjusted model, parenting concerns and the absence of parental prognostic communication with children both were found to be significantly associated with HRQOL scores. For each 1‐point increase in parenting concern severity, FACT‐G scores decreased by 4 points (P = .003).

CONCLUSIONS

Women with metastatic cancer who are parents of dependent children are at risk of high psychological distress and low HRQOL. Parenting factors may have a negative influence on HRQOL in this patient population. Cancer 2018;124:2629‐36. © 2018 American Cancer Society.
Numerical modelling of a peripheral arterial stenosis using dimensionally reduced models and kernel methods
Authors: Koeppl Tobias , Santin Gabriele , Haasdonk Bernard , Helmig Rainer
Published: May 2018

In this work, we consider 2 kinds of model reduction techniques to simulate blood flow through the largest systemic arteries, where a stenosis is located in a peripheral artery, i.e., in an artery that is located far away from the heart. For our simulations, we place the stenosis in one of the tibial arteries belonging to the right lower leg (right posterior tibial artery). The model reduction techniques that are used are on the one hand dimensionally reduced models (1‐D and 0‐D models, the so‐called mixed‐dimension model) and on the other hand surrogate models produced by kernel methods. Both methods are combined in such a way that the mixed‐dimension models yield training data for the surrogate model, where the surrogate model is parametrised by the degree of narrowing of the peripheral stenosis. By means of a well‐trained surrogate model, we show that simulation data can be reproduced with a satisfactory accuracy and that parameter optimisation or state estimation problems can be solved in a very efficient way. Furthermore, it is demonstrated that a surrogate model enables us to present after a very short simulation time the impact of a varying degree of stenosis on blood flow, obtaining a speedup of several orders over the full model.
Precisely Controlling Nanochannels of Graphene Oxide Membranes through Lignin‐Based Cation Decoration for Dehydration of Biofuels
Authors: Guan Kecheng , Liu Quan , Ji Yufan , Zhang Mengchen , Wu Yulin , Zhao Jing , Liu Gongping , Jin Wanqin
Published: May 2018

Lignin‐based cations introduced into graphene oxide (GO) have been found to bring about stabilization of the nanostructure and the active sites and to give rise to various interactions for subsequent modification with polyelectrolyte and nanospacers, with a view to precisely controlling the nanochannels of the GO‐based membranes. The resulting membranes exhibited excellent performance in biofuel dehydration with water flux of 4000–6000 g m−2 h−1, which exceeds that of the state‐of‐the‐art polymeric and GO‐based membranes.
Deactivation and Regeneration of Sulfonated Carbon Catalysts in Hydrothermal Reaction Environments
Authors: Scholz David , Kröcher Oliver , Vogel Frédéric
Published: May 2018

The deactivation pathways of sulfonated carbon catalysts prepared from different carbons were studied during the aqueous‐phase hydrolysis of cellobiose under continuous‐flow conditions. The sulfonation of carbon materials with a low degree of graphitization introduced sulfonic acid groups that are partially stable even during prolonged exposure to harsh hydrothermal treatment conditions (180 °C). The physicochemical characterization of hydrothermally treated materials coupled with the treatment of model compounds for sulfonic acids demonstrated that the stability is related to the presence of activating and deactivating substituents on the aromatic system. Besides sulfonic acid group leaching, a hitherto unknown mode of deactivation was identified that proceeds by the ion exchange of cations contained in the aqueous feed and protons of the sulfonic acid groups. Proton leaching is a fully reversible mode of deactivation by the treatment of the spent catalysts with strong Brønsted acids. Through a combined approach of physicochemical characterization, catalytic testing, and hydrothermal treatment, a methodology for the preparation of catalytically stable carbon materials that bear sulfonic acid groups was established.
Accurate near surface air temperature measurements are necessary to gauge large‐scale ecological responses to global climate change
Authors: Terando Adam , Youngsteadt Elsa , Meineke Emily , Prado Sara
Published: May 2018

Linked Article: https://doi.org/10.1002/ece3.3965
Development of a detection device for deteriorated ZnO surge arresters at AC traction substations
Authors: Akagi Masataka , Tanaka Hiroki , Imamura Hideki
Published: May 2018

This paper presents a novel detection device for deteriorated zinc‐oxide (ZnO) surge arresters. It is necessary to understand the state of ZnO surge arresters for AC traction substations under operation. The waveform distortion of leakage currents can be detected through an increase in multiple harmonic currents; therefore, this effect was employed to develop a device for diagnosing damage to the surge arrester. By adopting a Rogowski coil and band‐pass filters, we can obtain more output of the 5th–15th order harmonic currents in comparison with conventional devices. If the threshold value of harmonic elements is exceeded, the lights on the device may light up to indicate the deterioration. The validity of the device was verified by artificial deterioration tests using damaged ZnO elements and a capacitor. This developed device could indicate the soundness of the surge arresters that are in proper working order while being under the influence of feeding voltages, which include harmonic voltages.
Use of Response Surface Methodology (RSM) for the Identification of the Best Extraction Conditions for Headspace Solid‐Phase Micro Extraction (HS‐SPME) of the Volatile Profile of cv. Arbequina Extra‐Virgin Olive Oil
Authors: Borges Thays H. , Ramalhosa Elsa , Seiquer Isabel , Pereira José Alberto
Published: May 2018

The effect of the experimental conditions on assessing the global volatile profile of extra virgin olive oils (EVOO) by headspace solid‐phase microextraction/gas chromatography‐mass spectrometry (HS‐SPME/GC–MS) is studied to obtain maximization of the total peak areas of the compounds. Response Surface Methodology (RSM) is applied to Arbequina EVOO, and the influence of oil quantity, extraction time, and extraction temperature on the total area and extraction of the major desirable compounds is analyzed. The experimental data are adequately fitted into second‐order polynomial models with non‐significant lack of fit (p > 0.05) and coefficients of determination (R2 and R2‐adjusted) higher than 0.88 and 0.78, respectively. A strong similarity is found between the predicted and experimental values. Furthermore, the surface plots show that the extraction of the volatile compounds is favored with increasing extraction temperature, time, and oil quantity. The extraction conditions to obtain the maximum response of “green” volatile compounds from Arbequina olive oil by HS‐SPME placed in 50 mL vials are 4.6 g of oil, 43 min, and 59 °C.

Practical Applications: The findings of the present work show that specific conditions of HS‐SPME/GC–MS affect the extraction of volatile compounds from cv. Arbequina olive oil and establish the optimum extraction parameters to more efficiently determine the global profile of this fraction, taking into account the organoleptic characteristics of the cultivar. The results also contribute to the knowledge of the volatile profile of the monovarietal olive oil cv. Arbequina, which is one of most cultivated and consumed types of olive oil worldwide.

The effects of oil quantity, extraction time, and temperature on the extraction of volatile compounds from the olive oil of the widespread Arbequina variety are investigated. The main volatiles found are C6 compounds, including aldehydes, alcohols, and the corresponding esters. The volatile profile is more affected by temperature and time than the oil quantity. The application of long times and high temperatures increases the total area and the extraction of Z‐3‐hexen‐1‐ol acetate and E‐2‐hexenal to which are associated sensory traits of cut‐green, tomato, and medium bitter taste.
Green, Catalyst‐Free Reaction of Indoles with β‐Fluoro‐β‐nitrostyrenes in Water
Authors: Aldoshin Alexander S. , Tabolin Andrey A. , Ioffe Sema L. , Nenajdenko Valentine G.
Published: May 2018

The reaction of 2‐fluoro‐2‐nitrostyrenes with various indoles was investigated. We found that the reaction proceeds as a Michael addition in a highly regioselective manner to form 3‐(1‐aryl‐2‐fluoro‐2‐nitroethyl)‐1H‐indoles. Thus, a green and catalyst‐free synthesis of these compounds was developed using water as a reaction medium. The high effectiveness of this approach was demonstrated through the preparation of target products in up to 92 % isolated yield. Subsequent reduction of the nitro group was investigated. We found that due to the instability of the intermediate α‐fluoro amines, the reduction led to non‐fluorinated tryptamine derivatives.
Supporting Carers of Children and Adolescents with Eating Disorders in Austria (SUCCEAT): Study protocol for a randomised controlled trial
Authors: Franta Claudia , Philipp Julia , Waldherr Karin , Truttmann Stefanie , Merl Elisabeth , Schöfbeck Gabriele , Koubek Doris , Laczkovics Clarissa , Imgart Hartmut , Zanko Annika , Zeiler Michael , Treasure Janet , Karwautz Andreas , Wagner Gudrun
Published: May 2018

Supporting Carers of Children and Adolescents with Eating Disorders in Austria (SUCCEAT) is an intervention for carers of children and adolescents with anorexia nervosa and atypical anorexia nervosa. This paper describes the study protocol for a randomised controlled trial including the process and economic evaluation. Carers are randomly allocated to one of the 2 SUCCEAT intervention formats, either 8 weekly 2‐hr workshop sessions (n = 48) or web‐based modules (n = 48), and compared with a nonrandomised control group (n = 48). SUCCEAT includes the cognitive‐interpersonal model, cognitive behavioural elements, and motivational interviewing. The goal is to provide support for carers to improve their own well‐being and to support their children. Outcome measures include carers' distress, anxiety, depression, expressed emotions, needs, motivation to change, experiences of caregiving, and skills. Further outcome measures are the patients' eating disorder symptoms, emotional problems, behavioural problems, quality of life, motivation to change, and perceived expressed emotions. These are measured before and after the intervention, and 1‐year follow‐up.
Wildlife winners and losers in an oil sands landscape
Authors: Fisher Jason T , Burton A Cole
Published: May 2018

Energy development and consumption drive changes in global climate, landscapes, and biodiversity. The oil sands of western Canada are an epicenter of oil production, creating landscapes without current or historical analogs. Science and policy often focus on pipelines and species‐at‐risk declines, but we hypothesized that differential responses to anthropogenic disturbances shift the entire mammal community. Analysis of data collected from 3 years of camera trapping and species distribution models indicated that anthropogenic features best explained the distributions of the ten mammal species included in the study. Relative abundances of some mammals were positively correlated with anthropogenic feature density, and others were negatively correlated. Effect sizes were often larger than for natural features. Increasing anthropogenic spatial complexity, access to multiple habitats, and new forage sources favor generalist predators and browsers, to the detriment of specialists, likely altering ecological processes. This issue has far‐reaching implications: as the oil sands landscape changes so too does its mammal community, serving as a bellwether of future change for energy landscapes worldwide.
Networked and embedded scientific experiments will improve restoration outcomes
Authors: Gellie Nicholas JC , Breed Martin F , Mortimer Peter E , Harrison Rhett D , Xu Jianchu , Lowe Andrew J
Published: May 2018

Vast areas of degraded land have proliferated worldwide. In response to this transformation, ambitious targets have been set to restore degraded ecosystems, such as the the Bonn Challenge, which aims to restore 350 million ha of forestland by 2030. Achieving such goals will require a larger evidence base of restoration studies, which could be realized by systematically embedding scientific experiments within restoration programs. We examine the feasibility of this strategy with examples of successful transdisciplinary research involving embedded experiments in associated fields, and recommend that such field sites be linked to create a global network of embedded experiments. To unify a networked approach, we call on restoration stakeholders to develop acceptable industry standards of experimental design. Finally, we suggest how to use this strategy effectively to meet the biome‐scale challenges of the coming decades.
Early detection of invasive exotic insect infestations using eDNA from crop surfaces
Authors: Valentin Rafael E , Fonseca Dina M , Nielsen Anne L , Leskey Tracy C , Lockwood Julie L
Published: May 2018

The number of exotic species invasions has increased over recent decades, as have the ecological harm and economic burdens they impose. Rapid‐response eradication of nascent exotic populations is a viable approach to minimizing damage, but implementation is limited by the difficulty of detecting such species during the early stages of infestation due to their small numbers. The use of environmental DNA (eDNA) has helped address this issue in aquatic ecosystems, but to the best of our knowledge has not been trialed for surveillance of exotic species in terrestrial systems. Using a high‐resolution, real‐time (quantitative) polymerase chain reaction assay, we developed a highly efficient protocol to survey agricultural fields for the invasive non‐native brown marmorated stink bug (BMSB; Halyomorpha halys). We compared results using eDNA to those for conventional monitoring traps and documented substantially higher sensitivity and detection effectiveness. Our methodology is transferable to situations in which the DNA of terrestrial target species can be accumulated into a single substrate, suggesting that eDNA‐based approaches could transform our ability to detect exotic insects in non‐aquatic settings.
Diabetes, Plasma Glucose, and Incidence of Fatty Liver, Cirrhosis, and Liver Cancer: A Prospective Study of 0.5 Million People
Authors: Pang Yuanjie , Kartsonaki Christiana , Turnbull Iain , Guo Yu , Clarke Robert , Chen Yiping , Bragg Fiona , Yang Ling , Bian Zheng , Millwood Iona Y. , Hao Juanzhi , Han Xianyong , Zang Yajing , Chen Junshi , Li Liming , Holmes Michael V. , Chen Zhengming
Published: May 2018

The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We examined the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults and the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow‐up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalized nonalcoholic fatty liver disease (NAFLD), and 244 hospitalized alcoholic liver disease (ALD) cases were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen‐detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared to those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% confidence interval 1.30‐1.70) for liver cancer, 1.81 (1.57‐2.09) for cirrhosis, 1.76 (1.47‐2.16) for NAFLD, and 2.24 (1.42‐3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03‐1.06) for liver cancer, 1.07 (1.05‐1.09) for cirrhosis, 1.07 (1.05‐1.10) for NAFLD, and 1.10 (1.05‐1.15) for ALD. These associations did not differ by HBV infection. Conclusion: In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with higher risks of liver cancer and major chronic liver diseases.
Metal Organic Polyhedra: A Click‐and‐Clack Approach Toward Targeted Delivery
Authors: Samanta Soumen K. , Moncelet Damien , Vinciguerra Brittany , Briken Volker , Isaacs Lyle
Published: May 2018

Mixed self‐assembly of ligands 1 and 2, PXDA (3), and Pd(NO3)2 afforded metal organic polyhedra (MOP 1 – MOP 3) which bear 24 covalently attached CB[7] and cyclooctyne moieties. Post assembly modification (PAM) of MOP 3 by covalent strain promoted alkyne azide click reaction provided MOP 4R bearing covalently attached functionality (PEG, sulfonate, biotin, c‐RGD, fluorescein, and cyanine). Orthogonal CB[7]·guest mediated non‐covalent PAM of MOP 4R with Ad‐FITC afforded MOP 5RGD•Ad‐FITC and MOP 5biotin•Ad‐FITC. Flow cytometry analysis of the uptake of MOP 5RGD•Ad‐FITC toward U87 cells demonstrated improved uptake relative to control MOP lacking c‐RGD ligands. These results suggest a broad applicability of orthogonally functionalizable (covalent and non‐covalent) MOPs in targeted drug delivery and imaging applications.
Hydroclimatic significance of stable isotopes in precipitation from glaciers of Garhwal Himalaya, Upper Ganga Basin (UGB), India
Authors: Verma Akshaya , Kumar Amit , Gupta Anil K. , Tiwari Sameer K. , Bhambri Rakesh , Naithani Suneet
Published: May 2018

Stable isotopic composition of precipitation as preserved in continental proxy climate archives (e.g., ice cores, lacustrine sediments, tree rings, groundwater, and organic matter) can sensitively record fluctuations in local meteorological variables. These are important natural climatic tracers to understand the atmospheric circulation patterns and hydrological cycle and to reconstruct past climate from archives. Precipitation was collected at Dokriani Glacier to understand the response of glaciers to climate change in the Garhwal Central Himalaya, Upper Ganga Basin. The local meteoric water line deviates from the global meteoric water line and is useful for the identification of moisture source in the region. The data suggest different clusters of isotopic signals, that is, summer (June–September) and winter (November–April); the mean values of δ18O, δD, and d ‰ during summer are −13.03‰, −84.49‰, and 19.78 ‰, respectively, whereas during winter, the mean values of δ18O, δD, and d ‰ are −7.59‰, −36.28‰, and 24.46 ‰, respectively. Backward wind trajectory analysis ascertains that the major source of precipitation during summer is from the Indian Summer Monsoon and during winter from the westerlies. Regression analysis has been carried out in order to establish interrelationship between the precipitation isotopic signatures and meteorological variables such as air temperature, relative humidity, and precipitation. Temperature and precipitation have good correlation with the isotopic signatures of precipitation with R2 values >.5, suggesting that both temperature and amount effects prevail in the study region. Multiple regression analysis found strong relationships for both the seasons. The relationship of deuterium excess with δ18O, relative humidity, and precipitation are significant for the winter season. No significant relationships of deuterium excess were found with other meteorological variables such as temperature and radiation. The correlation and regression analysis performed are significant and valuable for interpretation of processes in the hydrological cycle as well as for interpretation of palaeoclimate records from the region.
High food availability linked to dominance of small zooplankton in a subtropical floodplain
Authors: Bomfim Francieli F. , Braghin Louizi S. M. , Bonecker Claudia C. , Lansac‐Tôha Fábio A.
Published: May 2018

Zooplankton body size is fundamentally affecting productivity, ecosystem respiration, nutrient cycling, and energy transfer and may be controlled by food availability but also water physical and chemical characteristics. However, the differences in control of water physical and chemical characteristics and food availability on zooplankton body size have rarely been investigated in subtropical systems. We tested the hypotheses that: (i) the type of environment, food availability, and water physical and chemical characteristics would influence body size distribution in the Upper Paraná River floodplain and nearby subsystems and (ii) in environments with higher food availability, small‐sized organisms would predominate showing higher abundance, whereas the opposite would occur in environments with lower food availability. To test these hypotheses, we performed partial redundancy and redundancy analyses (RDA). Our results showed that food availability, Secchi depth, and suspended inorganic matter influenced the body size structure of rotifers and cladocerans. Additionally, we observed that greater food availability was related to greater abundance of organisms, which were dominated by small‐sized zooplankton (size classes C2 and C1 in rotifers, and class C2′ in cladocerans). It was possible to associate different zooplankton body size spectra with phytoplankton biovolume and planktonic ciliate abundance. We suggest that large‐bodied cladocerans could have a competitive advantage over rotifers and small‐sized cladocerans when resources are scarce, because the large‐sized group could explore a wider range of resource types.
Regulation of microtubule stability by centrosomal proteins
Authors: Kumari Anuradha , Panda Dulal
Published: May 2018

The centrosome executes diverse functions including the nucleation and organization of microtubules. A subset of centrosomal proteins is found to be involved in regulating the nucleation, stability, and dynamics of microtubules. Literature is flooded with reports of centrosomal proteins regulating microtubule nucleation. However, the centrosomal proteins that regulate microtubule stability are underexplored. Here, we review the centrosomal proteins, which either enhance or reduce the stability of microtubules and thereby regulate microtubule dynamics. We also discuss unexplored aspects of the centrosomal proteins that influence microtubule stability. © 2018 IUBMB Life, 70(7):602–611, 2018
Polydimethylsiloxane/nano calcium phosphate composite tracheal stents: Mechanical and physiological properties
Authors: Bendo Demétrio Kétner , Giotti Cioato Marta Justina , Moreschi Alexandre , Oliveira Guilherme Augusto , Lorenzi William , Hehn de Oliveira Francine , Vieira de Macedo Neto Amarílio , Stefani Sanches Paulo Roberto , Xavier Rogerio Gastal , Loureiro dos Santos Luís Alberto
Published: May 2018

In this study, we report the production and characterization of tracheal stents composed of polydimethylsiloxane/nanostructured calcium phosphate composites obtained by reactive synthesis. Tracheal stents were produced by transfer molding, and in vivo tests were carried out. PDMS was combined with H3PO4 and Ca(OH)2 via an in situ reaction to obtain nanoparticles of calcium phosphate dispersed within the polymeric matrix. The incorporation of bioactive inorganic substances, such as calcium phosphates, improved biological properties, and the in situ reaction allowed tight coupling of particles to the matrix. Results showed the presence of the nanoparticles of DCPA and CDHA. The porosity generated during mixing decreased the tensile strength and tear properties. Composites presented higher values of cell viability compared with those for PDMS. In vivo tests indicated the presence of inflammatory tissue 30 days after implantation in both cases. Thus, the present biomaterial shows potential for application in tracheal disease, however further evaluation is needed. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 545–553, 2019.
In vitro cell response and in vivo primary osteointegration of highly porous Ta‐Nb alloys as implant materials
Authors: Liu Jue , Zhou Xiongwen , Wang Huifeng , Yang Hailin , Ruan Jianming
Published: May 2018

By combining the biocompatibility of Ta and excellent performance of Nb, the β‐type Ta‐xNb (x = 5, 10, and 15 wt %) alloys with three‐dimensional network structure was successfully fabricated. This work was designed to carry out the systematic study of in vitro/vivo biocompatibility of highly porous Ta‐Nb alloys. In the present study, the in vitro biological response was characterized by cell attachment, cytotoxicity test, and gene expression. Cells were well distributed on porous alloy surface and both bulk/porous Ta‐15Nb alloys showd a 0‐1 RGR level. Moreover, the upregulated gene expression may reveal an increase in bone regeneration. An assessment of primary osteogenic response in vivo was achieved by histological evaluation and pull‐out test. In vivo results demonstrated that the porous Ta‐15Nb alloy showed a higher pull‐out force than bulk Ta‐15Nb alloy and exhibited a more extensive contact between implants and bones after 12 weeks. Based on the present experiments, porous Ta‐Nb alloy scaffolds had a good biocompatibility and were promising for biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 573–581, 2019.
Incidental finding of a degrading zirconia dental implant 29 months after implantation: Histological and histomorphometrical analysis
Authors: Houshmand Alireza , Donkiewicz Phil , Smeets Ralf , Jung Ole , Barbeck Mike
Published: May 2018

With the emerging development and improvement of biomaterials, the application of ceramics in restorative medicine has experienced a renaissance. New production processes have reportedly helped to overcome unfavorable biomechanical characteristics of these materials, which lead to a wide application of zirconia as ground material for dental implants. Zirconia‐based implants are biocompatible, demonstrate ability to osseointegrate and have a teeth‐like color, rendering them to be an ideal replacement for titanium‐based implant systems, which represent the current gold standard in implantology. However, there is a lack of standardized guidelines on production of zirconia‐based implants and long‐term studies on the stability of this material in vivo are missing. In this study we demonstrate for the first time the accumulation of degradation products of a commercially available one‐piece zirconia‐based dental implant 29 months after implantation, which was recovered following a traumatic accident. Biopsy specimens from the implant and the surrounding tissue attached to it were processed for histological and histomorphometrical analysis. Although the implant was well integrated into the anchoring bone, degradation particles were observed in tissues adjacent to lower aspects of the implant. The observed implant degradation might seriously compromise implant stability several years after implantation. This incidental finding highlights the requirement of further research on zirconia‐based ceramics before they can be advertised as safe alternative to titanium‐based implant systems. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2919–2923, 2018.
Low Muscle Strength and Mass Is Associated With the Accelerated Decline of Bone Microarchitecture at the Distal Radius in Older Men: the Prospective STRAMBO Study
Authors: Wagner Philippe , Chapurlat Roland , Ecochard René , Szulc Pawel
Published: May 2018

Low muscle mass and strength are associated with poor bone microarchitecture. We studied the association of muscle mass and strength with changes in bone microarchitecture of distal radius in 821 older men during an 8-year prospective follow-up. Bone microarchitecture was assessed by high resolution peripheral quantitative computed tomography (XtremeCT-1, Scanco) at baseline, then after 4 and 8 years. Relative appendicular lean mass of the upper limbs (RALM-u.l.) was calculated as DXA-measured lean mass of upper limbs divided by (height)2. Relative grip strength was calculated as grip strength divided by height. Decrease in bone mineral content (BMC), total volumetric bone mineral density (Tt.vBMD), cortical thickness (Ct.Th), cortical area (Ct.Ar) and cortical vBMD (Ct.vBMD) accelerated with age. Trabecular area (Tb.Ar) expansion and trabecular bone deterioration accelerated with age. Men in the first RALM-u.l. quartile had more rapid loss of BMC, Tt.vBMD, Ct.Th, Ct.vBMD and Ct.Ar vs. the highest quartile. They had more rapid increase in Tb.Ar. Men in the lowest quartile of grip strength had greater decrease in BMC, Tt.vBMD, Ct.Th, Ct.vBMD, Ct.Ar, and greater increase in Tb.Ar vs. the highest quartile. In the models including ALM-u.l. and grip strength (not corrected for height), both muscle-related variables were associated with more rapid bone microarchitectural deterioration (slightly more so for grip strength). Trabecular vBMD (Tb.vBMD) and Central.Tb.vBMD increased in men having higher muscle mass and strength. Trends in trabecular number and thickness did not differ across the groups in all the analyses. Thus, in men, aging-related deterioration of bone microarchitecture was most rapid after the age of 80. Low grip strength (and slightly more weakly low RALM-u.l.) is associated with the more rapid decrease in Tt.vBMD and cortical variables, and with greater Tb.Ar expansion. In conclusion, dynapenia and sarcopenia contribute to the deterioration of bone microarchitecture in older men. © 2018 American Society for Bone and Mineral Research.
A Randomized, Single‐Center, Double‐Blind, Placebo‐Controlled Multiple‐Dose Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Imarikiren in Healthy Adult Nonelderly and Elderly Male Subjects
Authors: Matsuno Kumi , Tanaka Shingo , Hashimoto Takamasa , Nakamichi Hiroyuki , Kagawa Tomoya , Koumura Emiko
Published: May 2018

Imarikiren hydrochloride (TAK‐272/ SCO‐272) is a novel direct renin inhibitor. This randomized, double‐blind, phase I study evaluated the safety and pharmacokinetics/pharmacodynamics of multiple oral administrations of imarikiren in healthy nonelderly (aged 20‐45 years) and elderly (aged 65‐85 years) Japanese male subjects. Subjects were randomized within 1 of 3 cohorts to receive imarikiren or placebo: Cohort 1 (imarikiren 80 mg; nonelderly), Cohort 2 (imarikiren 160 mg; nonelderly), or Cohort 3 (imarikiren 80 mg; elderly). Imarikiren or placebo was administered orally, once daily, for 7 days. Accumulation of imarikiren did not occur during the 7‐day treatment period. Area under the plasma‐concentration time curve and maximum plasma concentration of imarikiren were higher in elderly than in nonelderly subjects (52% and 39% higher, respectively). Inhibition of plasma renin activity was observed for 7 days and was maintained for at least 71 hours after the last imarikiren administration at the 80‐mg (nonelderly and elderly) and 160‐mg (nonelderly) doses. Plasma active renin concentration increased in nonelderly and elderly subjects; peak concentrations were higher on day 7 than on day 1. Increase from baseline in plasma active renin concentration was smaller in elderly than in nonelderly subjects during the 7‐day treatment period and until 71 hours after last imarikiren administration. Treatment‐emergent adverse events were reported in 33.3% (elderly) and 22.2% (nonelderly) of imarikiren subjects. Multiple oral administrations of imarikiren for 7 days were safe and well tolerated with no drug accumulation and strong and sustained suppression of plasma renin activity.
Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting
Authors: Aung Ar Kar , Tang Mei Jie , Adler Nikki Rae , de Menezes Sara Lee , Goh Michelle Sue Yen , Tee Hui Wen , Trubiano Jason Anthony , Puy Robert , Zubrinich Celia Mary , Graudins Linda Velta
Published: May 2018

We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2‐year period (2015–2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1–10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4–5.5, and P = .04, OR 4.2, 95%CI 1.2–18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9–7.9, and P < .0001, OR 11.4, 95%CI 4.6–27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety.
Expanding the repertoire of aromatic chemicals by microbial production
Authors: Wu Fengli , Cao Peng , Song Guotian , Chen Wujiu , Wang Qinhong
Published: May 2018

Microbial production of aromatic chemicals would greatly contribute to solving the problems with fossil resource supply and environmentally sustainable development. Engineering and extending the shikimate/aromatic amino acid biosynthetic pathways are important routes for microbial production of various aromatic chemicals. With advances in metabolic engineering and synthetic biology, we can broaden the product spectrum and obtain several valuable and novel aromatic chemicals from renewable feedstocks. Here, in this review, the latest research progress on microbial production of various aromatic chemicals, and recent metabolic engineering and synthetic biology strategies targeting the central carbon metabolism, the shikimate and aromatic amino acid biosynthetic pathways are summarized and discussed. This work aims to provide some valuable tips for the construction of cost‐effective engineered strains for producing various aromatic chemicals. © 2018 Society of Chemical Industry
Beyond the breakpoint: reinstatement, renewal, and resurgence of ratio‐strained behavior
Authors: Kincaid Stephanie L. , Lattal Kennon A.
Published: May 2018

Three experiments were conducted using pigeons to assess the recurrence of responding eliminated by increasing the value of a progressive‐ratio schedule to the breakpoint of responding. The procedures used in these assessments were, in successive experiments, reinstatement, renewal and resurgence. Each was effective in returning temporarily the eliminated responding. Reinstatement occurred with both yoked‐time and fixed‐time food deliveries. Both renewal and resurgence resulted in immediate recurrence of the response, and, as in other experiments investigating resurgence, the key peck response resurged as the alternative response extinguished. The results of all three experiments suggest the generality of these recurrence procedures to responding under progressive‐ratio schedules, indicating that strained performance under these schedules is amenable to recovery under the investigated conditions.
Differential conduction and CGRP release in visceral versus cutaneous peripheral nerves in the mouse
Authors: De Col Roberto , Messlinger Karl , Hoffmann Tali
Published: May 2018

Cutaneous afferent nerves convey sensory information from the external, visceral nerves from the internal environment. The saphenous nerve arising from lumbar dorsal root ganglia and the vagus nerve originating in the nodosum ganglia are prototypic examples of such cutaneous and visceral nerves. Despite a common sensory role, these two nerves have distinct embryonic origin and vary in neuropeptide expression. Because of their distinct physiological roles, it is plausible that they differ also in conductive properties. We have tested calcitonin gene‐related peptide (CGRP) release in these nerves in response to electrical and chemical stimulation. Electrical stimulation at 3, 6, and 9 Hz increased the release in saphenous but not vagus nerves, with 6 Hz being the most potent stimulus. Similarly, both capsaicin and a depolarizing solution of 60 mM KCl evoked CGRP release in saphenous but not vagus nerves. Simultaneous recording of the superimposed (compound) action potentials of these nerves revealed that only saphenous nerves exhibit a progressive and marked activity‐dependent slowing of conduction velocity in response to electrical stimulation at 3, 6, and 9 Hz (30%, 44%, and 50%, respectively). Capsaicin caused an unexpected decrease in conduction latency (i.e., speeding) in contrast to the slowing seen in other nerves. Exposure of axons to 1 µM TTX rapidly blocked conduction in all nerves. Together our results demonstrate that vagus and saphenous primary afferents reveal different activation and conductive properties, presumably correlating their particular physiological roles in transmitting sensory signals. © 2018 Wiley Periodicals, Inc.
The competitive vs. complementary bacteria‐fungi interactions promote microbial release of Fe(III)‐fixed phosphorus: the roles of exogenous C application
Authors: Zhang Shirong , Ding Xiaodong
Published: May 2018

The phosphorus deficiency is very common in Fe(III)‐rich soil, and one of the key point is to clarify the condition in release or desorption of phosphorus from the Fe(III)‐rich minerals. The present study was to explore the effect of labile carbon on microbial reduction of Fe(III) and release of phosphorus in root‐free sub‐tropical soil. A two‐compartment microcosm was collected, in which the roots of Medicago sativa L. cultivar ‘Aohan' were confined within one compartment by a barrier of 30‐μm nylon mesh, while mycorrhizal hyphae could penetrate to the second compartment. Arbuscular mycorrhizal fungi (Funelliformis mosseae) were added to the root compartment and iron‐reducing bacteria (Klebsiella pneumoniae) were added to the hyphal compartment. Hyphal compartments were provided with two levels of additional carbon (0 and 23 mg C kg−1 soil as sodium acetate) and eight levels of inorganic phosphorus (0 to 35 mg P kg−1 soil as KH2PO4). At low phosphorus levels (< 5 mg P kg−1 soil), shoot biomass, and total biomass phosphorus were substantially less with added carbon in the presence of iron‐reducing bacteria. Carbon had little effect without iron‐reducing bacteria. At higher phosphorus levels (> 15 mg P kg−1 soil), the effect of added carbon was reversed; that is shoot biomass and total biomass phosphorus were greater with added carbon. Available soil phosphorus showed a similar response to added carbon—less at low levels of phosphorus and greater at higher levels of phosphorus. Microbial phosphorus in the presence of iron‐reducing bacteria was always higher with added carbon at all corresponding levels of soil phosphorus. Taken together, these results show that some phosphorus mobilized by iron‐reducing bacteria was converted into microbiological phosphorus, but there was an obligatory requirement for labile carbon for this to happen—reducing the amount of phosphorus that was absorbed by the mycorrhizal hyphae. Iron‐reducing bacteria and mycorrhizae showed a competitive interaction at lower levels of available soil phosphorus, and a complementary, or possibly a carbon‐dependent synergistic function at higher levels of available phosphorus. These results demonstrate that phosphorus released from ferralsols by iron‐reducing bacteria is positively mediated by both phosphorus and labile carbon and, hence, that phosphorus release and mobilization by iron‐reducing bacteria is likely to be enhanced by additions of exogenous carbon.