bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecotoxicity of halloysite nanotube–supported palladium nanoparticles in Raphanus sativus L
Authors: Bellani Lorenza , Giorgetti Lucia , Riela Serena , Lazzara Giuseppe , Scialabba Anna , Massaro Marina
Published: February 2016

Halloysite nanotubes (HNTs) are natural nanomaterials that are biocompatible and available in large amounts at low prices. They are emerging nanomaterials with appealing properties for applications like support for metal nanoparticles (NPs). The potential environmental impacts of NPs can be understood in terms of phytotoxicity. Current research has been focusing on HNT applications in cell or animal models, while their use in plants is limited so their ecotoxicological impact is poorly documented. To date there are no studies on the phytotoxic effects of functionalized halloysites (functionalized-HNTs). To develop a quantitative risk assessment model for predicting the potential impact of HNT–supported palladium nanoparticles (HNT-PdNPs) on plant life, an investigation was undertaken to explore their effects on seed germination, seedling development, and mitotic division in root tip cells of 2 lots of Raphanus sativus L. with different vigor. The results showed that exposure to 1500 mg/L of HNTs, functionalized-HNTs, and HNT-PdNPs had no significant influence on germination, seedling development, xylem differentiation, or mitotic index in both lots. Cytogenetic analyses revealed that treatments with functionalized-HNT significantly increased the number of aberrations in low-vigor seeds. These results suggest that low-vigor seeds represent a model for a stress test that would be useful to monitor the effects of NPs. Moreover the present study offers scientific evidence for the use of halloysite for environmental purposes, supporting the biological safety of HNT-PdNPs. Environ Toxicol Chem 2016;35:2503–2510. © 2016 SETAC
Genotyping of colorectal cancer for cancer precision medicine: Results from the IPH Center for Molecular Pathology
Authors: Jesinghaus Moritz , Pfarr Nicole , Endris Volker , Kloor Matthias , Volckmar Anna‐Lena , Brandt Regine , Herpel Esther , Muckenhuber Alexander , Lasitschka Felix , Schirmacher Peter , Penzel Roland , Weichert Wilko , Stenzinger Albrecht
Published: February 2016

Cancer precision medicine has opened up new avenues for the treatment of colorectal cancer (CRC). To fully realize its potential, high‐throughput sequencing platforms that allow genotyping beyond KRAS need to be implemented and require performance assessment. We comprehensively analyzed first‐year data of 202 consecutive formalin‐fixed paraffin embedded (FFPE) CRC samples for which prospective genotyping at our institution was requested. Deep targeted genotyping was done using a semiconductor‐based sequencing platform and a self‐designed panel of 30 CRC‐related genes. Additionally, microsatellite status (MS) was determined. Ninety‐seven percent of tumor samples were suitable for sequencing and in 88% MS could be assessed. The minimal drop‐out rates of 6 and 25 cases, respectively were due to too low amounts or heavy degradation of DNA. Of 557 nonsynonymous mutations, 90 (16%) have not been described in COSMIC at the time of data query. Forty‐three cases (22%) had double‐ or triple mutations affecting a single gene. Sixty‐four percent had genetic alterations influencing oncological therapy. Eight percent of patients (MSI phenotype: 6%; mutated POLE: 2%) were potentially eligible for treatment with immune checkpoint inhibitors. Of 56% of KRASwt CRC that potentially qualified for anti‐EGFR treatment, 30% presented with mutations in BRAF/NRAS. Mutated PIK3CA was detected in 21%. In conclusion, we here present real‐life routine diagnostics data that not only demonstrate the robustness and feasibility of deep targeted sequencing and MS‐analysis of FFPE CRC samples but also contribute to the understanding of CRC genetics. Most importantly, in more than half of the patients our approach enabled the selection of the best treatment currently available. © 2016 Wiley Periodicals, Inc.
The Ancient Rural Settlement Structure in the Hinterland of Pompeii Inferred from Spatial Analysis and Predictive Modeling of Villae Rusticae
Authors: Vogel Sebastian , Märker Michael , Esposito Domenico , Seiler Florian
Published: February 2016

Pompeii, buried by the explosive A.D. 79 eruption of Somma‐Vesuvius, is one of the most studied ancient cities in the Roman world. However, until very recently, the rural settlement in its hinterland had been largely ignored by systematic archaeological research. The ancient landscape around Pompeii consisted of a dense network of Roman farms (villae rusticae). They are believed to have played a vital role in ancient rural life and economy and thus represented the interactive rural–urban relationship in the Sarno River plain. The systematic investigation of published work combined with new fieldwork has yielded a data set of 140 villae rusticae in the Sarno River plain. Geographic information system based spatial statistics as well as predictive modeling were applied to gain a more detailed understanding of the ancient rural settlement structure in relation to the underlying paleoenvironmental and socioeconomic conditions. A high‐resolution pre‐A.D. 79 paleolandscape model of the Sarno River plain was utilized. The aim of this paper is to address theoretical considerations, the methodological implementation, and the archaeological discussion of the analysis of the ancient rural settlements and agriculture around Pompeii.
Principles of sodium homeostasis and sodium signalling in astroglia
Authors: Rose Christine R. , Verkhratsky Alexei
Published: February 2016

Sodium homeostasis is at the center stage of astrocyte (and brain) physiology because the large inwardly directed Na+ gradient provides the energy for transport of ions, neurotransmitters, amino acids and many other molecules across the plasmalemma and endomembranes. Cell imaging with commercially available chemical indicators allows analysis of dynamic changes in intracellular Na+ concentration (Na+]i), albeit further technological developments, such as genetically‐controlled or membrane targeted indicators or dyes usable for advanced microscopy (such as fluorescence‐lifetime imaging microscopy) are urgently needed. Thus, important questions related to the existence of Na+ gradients between different cellular compartments or occurrence of localised Na+ micro/nanodomains at the plasma membrane remain debatable. Extrusion of Na+ (and hence Na+ homeostasis) in astrocytes is mediated by the ubiquitously expressed Na+/K+‐ATPase (NKA), the major energy consumer of the brain. The activity of the NKA is counteracted by constant constitutive influx of Na+ through transporters such as the NKCC1 (Na+‐K+−2Cl‐‐co‐transport) or the NBC (Na+−2
‐co‐transport). In addition, Na+‐permeable ion channels at the plasma membrane as well as Na+‐dependent solute carrier transporters provide for Na+ influx into astrocytes. Activation of these pathways in response to neuronal activity results in an increase of [Na+]i in astrocytes and there is manifold evidence for diverse signalling functions of these [Na+]i transients. Thus, in addition to its established homeostatic functions, activity dependent fluctuations of astrocyte [Na+]i regulate signalling cascades by feeding back on Na+‐dependent transporters. The Na+ signalling system may be ideally placed for fast coordinating signalling between neuronal activity and glial “homeostatic” Na+‐dependent transporters. GLIA 2016;64:1611–1627
COMT Val158Met polymorphism influences the susceptibility to framing in decision‐making: OFC‐amygdala functional connectivity as a mediator
Authors: Gao Xiaoxue , Gong Pingyuan , Liu Jinting , Hu Jie , Li Yue , Yu Hongbo , Gong Xiaoliang , Xiang Yang , Jiang Changjun , Zhou Xiaolin
Published: February 2016

Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this “framing effect.” Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene–behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene–behavior association was mediated by resting‐state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision‐making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene–behavior association. Hum Brain Mapp 37:1880–1892, 2016. © 2016 Wiley Periodicals, Inc.
Functional integration of the posterior superior temporal sulcus correlates with facial expression recognition
Authors: Wang Xu , Song Yiying , Zhen Zonglei , Liu Jia
Published: February 2016

Face perception is essential for daily and social activities. Neuroimaging studies have revealed a distributed face network (FN) consisting of multiple regions that exhibit preferential responses to invariant or changeable facial information. However, our understanding about how these regions work collaboratively to facilitate facial information processing is limited. Here, we focused on changeable facial information processing, and investigated how the functional integration of the FN is related to the performance of facial expression recognition. To do so, we first defined the FN as voxels that responded more strongly to faces than objects, and then used a voxel‐based global brain connectivity method based on resting‐state fMRI to characterize the within‐network connectivity (WNC) of each voxel in the FN. By relating the WNC and performance in the “Reading the Mind in the Eyes” Test across participants, we found that individuals with stronger WNC in the right posterior superior temporal sulcus (rpSTS) were better at recognizing facial expressions. Further, the resting‐state functional connectivity (FC) between the rpSTS and right occipital face area (rOFA), early visual cortex (EVC), and bilateral STS were positively correlated with the ability of facial expression recognition, and the FCs of EVC‐pSTS and OFA‐pSTS contributed independently to facial expression recognition. In short, our study highlights the behavioral significance of intrinsic functional integration of the FN in facial expression processing, and provides evidence for the hub‐like role of the rpSTS for facial expression recognition. Hum Brain Mapp 37:1930–1940, 2016. © 2016 Wiley Periodicals, Inc.
Impacts of Synchronous Combustion of Small Amounts of Coal Particles with Natural Gas on Enhancing Radiative Characteristic and NOx Flame Pollutant Emission
Authors: Pourhoseini S.H. , Behzadan H. , Nikkar S. , Moghiman M.
Published: February 2016

Radiation is the most important regime of heat transfer of a flame which is directly affected by temperature and emissivity coefficient of the flame. Natural gas has a nonluminous flame, although, the flame temperature is high, but, the emissivity coefficient of the flame is small. In this paper the impacts of synchronous combustion of small amounts of anthracite coal particles with natural gas on the detailed emissivity coefficient of the flame, radiative species and pollutant emissions were investigated experimentally and numerically. A sprint CFD code was used in numerical solution and the pollutants were measured by a Testo 350XL gas analyzer. The results showed that a small amount of coal particles injected into the hot flame of natural gas increases the volume distribution and radiation view factor of high‐emissive intermediate solid soot particles in the flame which enhances the total flame emissivity coefficient. Also, coal particle injection leads to a decrease in the upstream flame temperature and an increase in the downstream region creating a more uniform temperature distribution and decreases the concentration of thermal NO pollutant of the natural gas flame. Furthermore, the role of solid soot particles on the total emissivity coefficient is remarkable, while an increase in CO2 and H2O concentrations has an insignificant effect on the flame emissivity coefficient.
Use of beta‐blockers, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta‐analysis
Authors: Raimondi Sara , Botteri Edoardo , Munzone Elisabetta , Cipolla Carlo , Rotmensz Nicole , DeCensi Andrea , Gandini Sara
Published: February 2016

Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta‐blocker (BB) drugs, angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta‐analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study‐specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between‐study heterogeneity by meta‐regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26–0.73 with I2 = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19–1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC‐specific survival. Clinical trials addressing this hypothesis are warranted.
In vitroosteogenic induction of human marrow‐derived mesenchymal stem cells by PCL fibrous scaffolds containing dexamethazone‐loaded chitosan microspheres
Authors: Omidvar Noushin , Ganji Fariba , Eslaminejad Mohamadreza Baghaban
Published: February 2016

This research reports the encapsulation of dexamethasone (Dex) within the chitosan microspheres (CSMs) embedded in a fibrous structure of poly(ɛ‐caprolactone) (PCL) to provide a platform for osteogenic differentiation of human mesenchymal stem cells (hMSCs). Dex loaded CSMs were prepared by spray drying a mixture of chitosan and Dex. Then, they were electrospun with PCL solution to create a bilayer fibrous scaffold (PCL/CSMs‐Dex). The CSMs act as good depots for sustained release of Dex over a period of 14 days, without noticeable burst release. This is mainly attributed to the core‐shell structure of the final PCL/CSMs‐Dex‐matrix, which could prolong the release and eliminate the initial burst. The water contact angle of PCL scaffolds decreased from 141.4 ± 3.8 to 118.4 ± 7.6 in the presence of CSMs. Improved proliferation of hMSCs cultured on PCL/CSMs‐Dex scaffolds was also evidenced. Furthermore, osteogenic assays showed an increase in alkaline phosphatase activity and mineral deposits. The expression of bone‐specific genes also confirmed the osteogenic differentiation of cells cultured on these Dex‐loaded core‐shell structures. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1657–1667, 2016.
Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L‐Carnitine
Authors: Blanca Antonio J. , Ruiz‐Armenta María V. , Zambrano Sonia , Salsoso Rocío , Miguel‐Carrasco José L. , Fortuño Ana , Revilla Elisa , Mate Alfonso , Vázquez Carmen M.
Published: February 2016

Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L‐carnitine (LC) in rat renal epithelial cells (NRK‐52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2•−) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2O2) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro‐inflammatory factors was also found in leptin‐treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK‐52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin‐induced renal damage. J. Cell. Biochem. 117: 2281–2288, 2016. © 2016 Wiley Periodicals, Inc.
Association between in‐hospital supportive visits by primary care physicians and patient outcomes: A population‐based cohort study
Authors: Brener Stacey S. , Bronksill Susan E. , Comrie Rebecca , Huang Anjie , Bell Chaim M.
Published: February 2016

BACKGROUND

One long‐standing method for continuity of care as patients transition between the hospital and community are supportive visits by primary care physicians during hospitalization.

METHODS

This retrospective cohort study used administrative data of adults hospitalized from 2008 to 2009 and primary care physicians who conduct supportive visits. Patients who received a visit from their primary care physician while hospitalized were compared to those who did not. Composite outcomes of death, emergency department visit, or emergent readmission within 30 and 90 days were assessed. Postdischarge home‐care utilization and primary care physician visits were also examined. Multivariate logistic regression models adjusted for age, sex, low income, rurality, and readmission risk.

RESULTS

Of the 164,059 patients linked to 3236 primary care physicians, 12.0% received visits while hospitalized. Visited patients had more readmissions, more deaths, and fewer emergency department visits than patients who did not. However, after adjusting, visited patients had a lower risk for the composite outcome at 30 days (adjusted OR [aOR]: 0.92; 95% confidence interval [CI]: 0.89‐0.96) and 90 days (aOR: 0.90; 95% CI: 0.87‐0.92). Visited patients were also more likely to access community primary care–provider visits and more home‐care services. The in‐hospital visit resulted in an increased likelihood of health services utilization at 30 days (aOR: 1.16; 95% CI: 1.11‐1.22) and 90 days (aOR: 1.20; 95% CI: 1.12‐1.27).

CONCLUSION

A hospital supportive‐care visit from a primary care physician resulted in lower risks of adverse patient outcomes and increased access to community health services. Journal of Hospital Medicine 2016;11:418–424. © 2016 Society of Hospital Medicine
Use of a prospective cohort study in the development of a bladder scanning protocol to assist in bladder filling consistency for prostate cancer patients receiving radiation therapy
Authors: Cramp Leah , Connors Vanessa , Wood Maree , Westhuyzen Justin , McKay Michael , Greenham Stuart
Published: February 2016

Introduction

Evidence of variations in bladder filling effecting prostate stability and therefore treatment and side‐effects is well established with intensity modulated radiation therapy (IMRT). This study aimed to increase bladder volume reproducibility for prostate radiation therapy by implementing a bladder scanning (BS) protocol that could assist patients' bladder filling at computed tomography (CT) simulation and treatment.

Methods

Based on a retrospective review of 524 prostate cancer patients, a bladder volume of 250–350 mL was adopted as ‘ideal’ for achieving planning dose constraints. A prospective cohort study was conducted to assess the clinical utility of measuring patients' bladder volumes at CT simulation using an ultrasound bladder scanner (Verathon 9400 BladderScan®). A revised bladder preparation protocol was utilised by a bladder scan group (BS) and a non‐BS group followed the standard departmental bladder preparation protocol. Time and volume data for the BS group (n = 17) were compared with the non‐BS group (n = 17).

Results

The BS cohort had a CT bladder volume range of 221–588 mL; mean 379 mL, SD 125 mL. The non‐BS group had a larger range: 184–757 mL; mean 373 mL, SD 160 mL (P = 0.9171). There was a positive correlation between CT volume and BS volume in the BS group (r = 0.797; P = 0.0002) although BS volumes were smaller: range 160–420 mL; mean 251 mL; SD 91 mL; P < 0.0001). The maximum bladder volume receiving 50 Gy (V50) from the BS group was 46.4%, mean 24.5%. The maximum bladder V50 from the non‐BS group was 50.9%, mean 27.3% (P = 0.5178). Treatment data from weekly cone beam CT scans were also compared over 6 weeks. They were assessed as being a pass if bladder and bowel requirements were acceptable. The BS group proceeded to treatment on the basis of a pass 92.7% of the time, whereas the pass rate for non‐BS group was 75%; difference 17.7% (P < 0.0001).

Conclusion

The BS is a useful tool for achieving consistent, appropriately sized bladder volumes in prostate cancer patients.
Which factors make the difference for explaining growth in newcomer organizational commitment? A latent growth modeling approach
Authors: Maia Leticia Gomes , Bastos Antônio Virgílio Bittencourt , Solinger Omar Nathanaël
Published: February 2016

Previous studies on newcomer socialization have evidenced quite consistently that newcomers' affective commitment tends to decline in the first years of employment. In this paper, we attempt to explain why a minority of Brazilian newcomers in a governmental organization (N = 194) display growth in commitment (33 per cent) in the first 3 years of employment, despite the fact that the odds are clearly in favor of decline (62 per cent). We reasoned that the minority displaying growing commitment may have had qualitatively different work experiences or would have different personal characteristics. We used latent growth modeling and post hoc tests to analyze the hypotheses. Concerning individual differences, newcomers with growing commitment were on average older but did not have higher work centrality. Concerning work experiences, newcomers whose training matched the job (high person–job fit) and whose tasks were challenging were more prevalent in the growing commitment group. The newcomers who showed declining commitment were more likely to feel overwhelmed by the amount of work in the new role (high role overload) and were typically not promoted to higher ranks. Change in commitment also predicted self‐reported performance (productivity and initiative) 3 years after organizational entry. Copyright © 2016 John Wiley & Sons, Ltd.
Exploring the possible effect of anthropogenic heat release due to global energy consumption upon global climate: a climate model study
Authors: Chen Bing , Dong Li , Liu X. , Shi G. Y. , Chen L. , Nakajima T. , Habib A.
Published: February 2016

The high‐resolution global distribution of anthropogenic heat release (AHR), which is generated by human energy consumption, is estimated by means of applying satellite remote sensing. Additionally, it was considered into a global climate model and the possible climatic effect of AHR is examined in this study. AHR is geographically concentrated and fundamentally correlates with economic activity in global scale. The current mean AHR flux on the global scale is approximately 0.03 W m−2; however, the flux reaches a level high enough to influence the regional climate in concentrated urban areas. Global climate model results indicate that AHR may disrupt the normal atmospheric circulation and could have an obvious effect on the surface temperature at middle and high latitudes in summer and winter over the Northern Hemisphere. The climatic effect of AHR differs in various seasons: the global mean surface temperature could increase by approximately 0.02 K in boreal summer and by 0.10 K in boreal winter. With the continued development of the global economy and urbanization, the climatic effect of AHR will become increasingly pronounced. The climatic effect of AHR should not be merely confined to the regional climate, AHR is a tiny but essential factor in global climate and long‐term climate change that should not be ignored.
Magnesium ring device to restore function of a transected anterior cruciate ligament in the goat stifle joint
Authors: Farraro Kathryn F. , Sasaki Norihiro , Woo Savio L‐Y. , Kim Kwang E. , Tei Matteo M. , Speziali Andrea , McMahon Patrick J.
Published: February 2016

A bioresorbable, mono‐crystalline magnesium (Mg) ring device and suture implantation technique were designed to connect the ends of a transected anterior cruciate ligament (ACL) to restabilize the knee and load the ACL to prevent disuse atrophy of its insertion sites and facilitate its healing. To test its application, cadaveric goat stifle joints were evaluated using a robotic/universal force‐moment sensor testing system in three states: Intact, ACL‐deficient, and after Mg ring repair, at 30°, 60°, and 90° of joint flexion. Under a 67‐N anterior tibial load simulating that used in clinical examinations, the corresponding anterior tibial translation (ATT) and in‐situ forces in the ACL and medial meniscus for 0 and 100 N of axial compression were obtained and compared with a control group treated with suture repair. In all cases, Mg ring repair reduced the ATT by over 50% compared to the ACL‐deficient joint, and in‐situ forces in the ACL and medial meniscus were restored to near normal levels, showing significant improvement over suture repair. These findings suggest that Mg ring repair could successfully stabilize the joint and load the ACL immediately after surgery, laying the framework for future in vivo studies to assess its utility for ACL healing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2001–2008, 2016.
First in vivo detection and characterization of hyaluronan‐coated extracellular vesicles in human synovial fluid
Authors: Mustonen Anne‐Mari , Nieminen Petteri , Joukainen Antti , Jaroma Antti , Kääriäinen Tommi , Kröger Heikki , Lázaro‐Ibáñez Elisa , Siljander Pia R‐M , Kärjä Vesa , Härkönen Kai , Koistinen Arto , Rilla Kirsi
Published: February 2016

Extracellular vesicles (EVs) function in intercellular signaling by transporting different membrane and cytosolic molecules, including hyaluronan (HA) and its synthesis machinery. As both EVs and HA are abundant in synovial fluid, we hypothesized that HA synthesized in synovial membrane would be carried on the surface of EVs. Synovial fluid (n = 15) and membrane samples (n = 5) were obtained from knee surgery patients. HA concentrations were analyzed in synovial fluid and HA and its synthesis machinery were examined with histochemical stainings in synovial membrane. To assess the size distribution of EVs in synovial fluid and to visualize HA on EVs, nanoparticle tracking analysis (NTA), confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM) were utilized. The average HA concentration in synovial fluid was 2.0 ± 0.21 mg/ml without significant differences between the patients with trauma/diagnostic arthroscopy and primary or post‐traumatic osteoarthritis. Positive stainings of HA synthases (HAS1–3), HA and its receptor CD44 in synovial cells indicated active HA secretion in synovial membrane. According to NTA, EVs were abundant in synovial fluid and their main populations were ≤300 nm in diameter after differential centrifugation. There were no significant differences in the EV counts between the patients with primary or post‐traumatic osteoarthritis. TEM verified that HA‐positive particles detected by CLSM were lipid membrane vesicles surrounded by a HA coat. Our results provide the first in vivo evidence that human synovial fluid contains HA‐positive EVs, one source of which presumably is the long HAS‐positive protrusions of synovial fibroblasts. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1960–1968, 2016.
Location‐dependent heterotopic ossification in the rat model: The role of activated matrix metalloproteinase 9
Authors: Davis Eleanor L. , Sonnet Corinne , Lazard ZaWaunyka W. , Henslee Gabrielle , Gugala Zbigniew , Salisbury Elizabeth A. , Strecker Edward V. , Davis Thomas A. , Forsberg Jonathan A. , Davis Alan R. , Olmsted‐Davis Elizabeth A.
Published: February 2016

Extremity amputation or traumatic injury can often lead to the formation of heterotopic ossification (HO). Studies to induce HO in rat muscle using cell‐based gene therapy show that this process appears to be location dependent. In the present study, HO was induced in mice and rats through injection of immunologically matched cells transduced with either a replication‐defective adenovirus possessing bone morphogenetic protein 2 (BMP2) or an empty adenovirus vector (control). Injection in rat near the skeletal bone resulted in HO, whereas cells injected into the same muscle group but distal from the bone did not result in bone formation. When cells were injected in the same limb at both locations at the same time, HO was formed at both sites. Characterization of the bone formation in rats versus mice demonstrated that different sources of osteogenic progenitors were involved, which may account for the location dependent bone formation observed in the rat. Further experimentation has shown that a potential reason for this difference may be the inability of rat to activate matrix metalloproteinase 9 (MMP9), an essential protease in mice necessary for recruitment of progenitors. Inhibition of active MMP9 in mice led to a significant decrease in HO. The studies reported here provide insight into the mechanisms and pathways leading to bone formation in different animals and species. It appears that not all animal models are appropriate for testing HO therapies, and our studies also challenge the conventional wisdom that larger animal models are better for testing treatments affecting bone. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 34:1894–1904, 2016.
Gelation properties of myofibrillar protein under malondialdehyde‐induced oxidative stress
Authors: Wang Lin , Zhang Min , Fang Zhongxiang , Bhandari Bhesh
Published: February 2016

BACKGROUND

The structure of myofibrillar protein (MP) can be readily altered by oxidation, leading to the unfolding of MP structure, which further promotes protein–protein interactions, and thus influences the MP gelling properties. The objective of the study was to investigate the effect of malondialdehyde‐induced oxidative stress on the gelation properties of myofibrillar protein (MP). Structural changes of the oxidised MPs were evaluated by the contents of carbonyl and total sulfhydryls, surface hydrophobicity, SDS‐PAGE and Fourier transform infrared spectroscopy. The oxidative stability of the MP gels as indicated by lipid hydroperoxide was also determined.

RESULTS

With the addition of an MDA concentration less than 10 mmol L−1, the MP gels showed an improved elasticity, gel strength, water holding capacity, and oxidative stability. Nevertheless, higher MDA concentration (25–50 mmol L−1) significantly reduced the gel quality, probably due to the formation of excessive covalent bonds in the system.

CONCLUSION

Results suggested that protein aggregation occurred in the oxidised system. Myosin was involved in gel formation through non‐disulfide covalent bond. © 2016 Society of Chemical Industry
Increasing anti‐Aβ‐induced neurotoxicity ability of Antrodia camphorata‐fermented product with deep ocean water supplementary
Authors: Shi Yeuching , Yang Shuyuan , Lee David Yuewei , Lee Chunlin
Published: February 2016

BACKGROUND

Antrodia camphorata is proven to probably inhibit the neurotoxicity of amyloid β‐peptide (Aβ), known as a risk factor toward the development of Alzheimer's disease. Deep ocean water (DOW), drawn from an ocean depth of more than 200 m, has proven to stimulate the growth and metabolite biosynthesis of fungi owing to its rich minerals and trace elements. Based on these advantages of DOW, this study used statistical response surface methodology (RSM) to investigate the effects of DOW on the growth and anti‐Aβ‐induced neurocytotoxicity ability of A. camphorata.

RESULTS

The results showed that DOW was useful for increasing the biomass of A. camphorata and enhancing its neuroprotective capability. The anti‐Aβ40‐induced neurocytotoxicity ability of filtrate was increased via raising the mycelium‐secreted components. Furthermore, the anti‐Aβ40‐induced neurocytotoxicity ability of mycelium was also increased by the DOW‐stimulated intracellular antioxidants. Using 80% DOW concentration, initial pH 3.3 and 20% inoculum size as the optimal culture conditions of A. camphorata significantly stimulated the biomass and mycelium‐mediated Aβ40‐induced cell viability from 302 ± 14 mg per 100 mL and 49.2 ± 2.2% to 452 ± 33 mg per 100 mL and 65.0 ± 7.4% respectively.

CONCLUSION

This study indicated that DOW could be used as a promising supplementary for the production of A. camphorata secondary metabolites with strong antioxidant activity to protect neuron cells from damage based on Aβ stimulation cytotoxicity. © 2016 Society of Chemical Industry
Fabrication and Characterization of Electrospun Dopants/PS Composite Fibers with Porous and Hollow‐Porous Structures
Authors: Tian Lidong , Gu Junwei , Lei Xingfeng , Lv Zhaoyuan , Qiao Mingtao , Yin Changjie , Zhang Qiuyu
Published: February 2016

Three different dopants are used to fabricate electrospun dopants/polystyrene (dopants/PS) composite fibers from PS solution and PS sol. The relative humidity and the influence of the dopants on the morphologies, diameter, porous structures, and dopant distribution of electrospun PS fibers are investigated. Compared to those obtained from PS solution, electrospun dopants/PS composite fibers from PS sol with hollow‐porous and multichannel hollow‐porous structures present significant advantages due to the multi‐stage degree of interfacial structure and diversity of the internal environment. In comparison to coaxial electrospun PS fibers, the electrospun dopants/PS composite fibers from PS sol obtained in one step have an improved yield and a simplified technological process simultaneously, leading to significant competitiveness in fields such as catalysis, fluidics gas storage, and sensing.

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The Caenorhabditis elegans p38 MAPK Gene plays a key role in protection from mycobacteria
Authors: Galbadage Thushara , Shepherd Tonya F. , Cirillo Suat L. G. , Gumienny Tina L. , Cirillo Jeffrey D.
Published: February 2016

Mitogen‐activated protein kinases (MAPK) are critical mediators of cellular responses to pathogens and are activated in response to infection, but investigation is difficult in multi‐cell hosts due to developmental lethality of mutations. Mycobacterium marinum (Mm) is an established model for tuberculosis, a disease afflicting nearly one‐third of the world's population. We found that Mm‐infected Caenorhabditis elegans display >80% mortality, but nonpathogenic M. smegmatis cause <15% mortality. C. elegans display pathological changes when infected with Mm, whereas Mm mutants produce lower mortality, suggesting that C. elegans is a promising virulence model for detailed genetic analysis. C. elegans MAPK mutants are hypersusceptible to mycobacterial infection; however, the C. elegans TOL‐like, TGF‐β and insulin‐like pathway genes do not play important roles in susceptibility. We show that pathogenic mycobacteria inhibit MAPK‐mediated protection through the MAPK phosphatase gene and demonstrate that C. elegans provide a genetically tractable pathogenicity model of both the host and pathogen.
Two parallel pathways for ferric and ferrous iron acquisition support growth and virulence of the intracellular pathogen Francisella tularensis Schu S4
Authors: Pérez Natalie , Johnson Richard , Sen Bhaswati , Ramakrishnan Girija
Published: February 2016

Iron acquisition mechanisms in Francisella tularensis, the causative agent of tularemia, include the Francisella siderophore locus (fsl) siderophore operon and a ferrous iron–transport system comprising outer‐membrane protein FupA and inner‐membrane transporter FeoB. To characterize these mechanisms and to identify any additional iron uptake systems in the virulent subspecies tularensis, single and double deletions were generated in the fsl and feo iron acquisition systems of the strain Schu S4. Deletion of the entire fsl operon caused loss of siderophore production that could be restored by complementation with the biosynthetic genes fslA and fslC and Major Facilitator Superfamily (MFS) transporter gene fslB. 55Fe‐transport assays demonstrated that siderophore‐iron uptake required the receptor FslE and MFS transporter FslD. A ΔfeoB′ mutation resulted in loss of ability to transport ferrous iron (55Fe2+). A ΔfeoB′ ΔfslA mutant that required added exogenous siderophore for growth in vitro was unable to grow within tissue culture cells and was avirulent in mice, indicating that no compensatory cryptic iron uptake systems were induced in vivo. These studies demonstrate that the fsl and feo pathways function independently and operate in parallel to effectively support virulence of F. tularensis.
Variable expressivity and co‐occurrence of LDLR and LDLRAP1 mutations in familial hypercholesterolemia: failure of the dominant and recessive dichotomy
Authors: Fahed Akl C. , Khalaf Ruby , Salloum Rony , Andary Rabih R. , Safa Raya , El‐Rassy Inaam , Moubarak Elie , Azar Sami T. , Bitar Fadi F. , Nemer Georges
Published: February 2016

Background

The familial inherited genetic disorder of lipoprotein metabolism affects more than 10 million individuals around the world. Lebanon is one of the several endemic areas for familial hypercholesterolemia (FH) with a founder mutation in the low‐density lipoprotein cholesterol receptor (LDLR) gene, responsible for most of the cases. We have previously shown that 16% of all familial cases with hypercholesterolemia do not show genotype segregation of LDLR with the underlying phenotype.

Methods

We used Sanger sequencing to genotype 25 Lebanese families with severe FH for the gene encoding the LDLR‐associated protein (LDLRAP1), responsible for the recessive form of the disease starting with the four families that did not show any genotype‐phenotype correlation in our previous screening.

Results

We showed that the previously reported p.Q136* variant is linked to the hypercholesterolemia phenotype in the four families. In addition, we showed a variable phenotype between families and between members of the same family. One family exhibits mutations in both LDLR and LDLRAP1 with family members showing differential phenotypes unexplained by the underlying genotypes of the two genes.

Conclusion

The p.Q136* variant in LDLRAP1 is yet another founder mutation in Lebanon and coupled with the LDLR p.C681* variant explains all the genetic causes of FH in Lebanon.
Rothmund–Thomson Syndrome: novel pathogenic mutations and frequencies of variants in the RECQL4 and USB1 (C16orf57) gene
Authors: Suter Aude‐Annick , Itin Peter , Heinimann Karl , Ahmed Munaza , Ashraf Tazeen , Fryssira Helen , Kini Usha , Lapunzina Pablo , Miny Peter , Sommerlund Mette , Suri Mohnish , Vaeth Signe , Vasudevan Pradeep , Gallati Sabina
Published: February 2016

Background

Poikiloderma is defined as a chronic skin condition presenting with a combination of punctate atrophy, areas of depigmentation, hyperpigmentation and telangiectasia. In a variety of hereditary syndromes such as Rothmund–Thomson syndrome (RTS), Clericuzio‐type poikiloderma with neutropenia (PN) and Dyskeratosis Congenita (DC), poikiloderma occurs as one of the main symptoms. Here, we report on genotype and phenotype data of a cohort of 44 index patients with RTS or related genodermatoses.

Methods

DNA samples from 43 patients were screened for variants in the 21 exons of the RECQL4 gene using PCR, SSCP‐PAGE analysis and/or Sanger sequencing. Patients with only one or no detectable mutation in the RECQL4 gene were additionally tested for variants in the 8 exons of the USB1 (C16orf57) gene by Sanger sequencing. The effect of novel variants was evaluated by phylogenic studies, single‐nucleotide polymorphism (SNP) databases and in silico analyses.

Results

We identified 23 different RECQL4 mutations including 10 novel and one homozygous novel USB1 (C16orf57) mutation in a patient with PN. Moreover, we describe 31 RECQL4 and 8 USB1 sequence variants, four of them being novel intronic RECQL4 sequence changes that may have some deleterious effects on splicing mechanisms and need further evaluation by transcript analyses.

Conclusion

The current study contributes to the improvement of genetic diagnostic strategies and interpretation in RTS and PN that is relevant in order to assess the patients' cancer risk, to avoid continuous and inconclusive clinical evaluations and to clarify the recurrence risk in the families. Additionally, it shows that the phenotype of more than 50% of the patients with suspected Rothmund–Thomson disease may be due to mutations in other genes raising the need for further extended genetic analyses.
Sulforaphene suppresses growth of colon cancer‐derived tumors via induction of glutathione depletion and microtubule depolymerization
Authors: Byun Sanguine , Shin Seung Ho , Park Jiman , Lim Semi , Lee Eunjung , Lee Chaeyoon , Sung Dongeun , Farrand Lee , Lee Seoung Rak , Kim Ki Hyun , Dong Zigang , Lee Sam W. , Lee Ki Won
Published: February 2016

Scope

Cruciferous vegetables harbor a number of isothiocyanates that have been recognized for their cancer‐related properties. Out of these, sulforaphene (a naturally occurring derivative of sulforaphane) has received little attention in studies of colon cancer and its mechanism of action remains to be elucidated.

Methods and results

We observed that sulforaphene inhibited growth of human colon cancer cell lines HCT116, HT‐29, KM12, SNU‐1040, and DLD‐1, while exhibiting negligible toxicity toward nonmalignant cells. Sulforaphene induced G2/M phase cell cycle arrest and apoptosis of colon cancer cells analyzed by flow cytometry, concomitant with phosphorylation of CDK1 and CDC25B at inhibitory sites, and upregulation of the p38 and JNK pathways. It was further determined that sulforaphene is a potent inhibitor of microtubule polymerization while generating reactive oxygen species via the depletion of glutathione. These observations further extended into inhibitory effects against colon tumor growth in a mouse xenograft model.

Conclusion

These findings demonstrate that sulforaphene may contribute to the anti‐tumor effects of cruciferous vegetables that contain sulforaphene and other isothiocyanates.
Blood oxygen‐level dependent functional assessment of cerebrovascular reactivity: Feasibility for intraoperative 3 Tesla MRI
Authors: Fierstra Jorn , Burkhardt Jan‐Karl , van Niftrik Christiaan Hendrik Bas , Piccirelli Marco , Pangalu Athina , Kocian Roman , Neidert Marian Christoph , Valavanis Antonios , Regli Luca , Bozinov Oliver
Published: February 2016

Purpose

To assess the feasibility of functional blood oxygen‐level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength.

Methods

Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel‐by‐voxel basis throughout the brain. The CVR range was then color‐coded and superimposed on an anatomical volume to create high spatial resolution CVR maps.

Results

Ten subjects (mean age 34.8 ± 13.4; 2 females) uneventfully underwent the intraoperative BOLD protocol, with no complications occurring. Whole‐brain CVR for all subjects was (mean ± SD) 0.69 ± 0.42, whereas CVR was markedly higher for tumor subjects as compared to vascular subjects, 0.81 ± 0.44 versus 0.33 ± 0.10, respectively. Furthermore, color‐coded functional maps could be robustly interpreted for a whole‐brain assessment of CVR.

Conclusion

We demonstrate that intraoperative BOLD MRI is feasible in creating functional maps to assess cerebrovascular reactivity throughout the brain in subjects undergoing a neurosurgical procedure. Magn Reson Med 77:806–813, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Vademecum‐based GFEM (V‐GFEM): optimal enrichment for transient problems
Authors: Canales Diego , Leygue Adrien , Chinesta Francisco , González David , Cueto Elías , Feulvarch Eric , Bergheau Jean‐Michel , Huerta Antonio
Published: February 2016

This paper proposes a generalized finite element method based on the use of parametric solutions as enrichment functions. These parametric solutions are precomputed off‐line and stored in memory in the form of a computational vademecum so that they can be used on‐line with negligible cost. This renders a more efficient computational method than traditional finite element methods at performing simulations of processes. One key issue of the proposed method is the efficient computation of the parametric enrichments. These are computed and efficiently stored in memory by employing proper generalized decompositions. Although the presented method can be broadly applied, it is particularly well suited in manufacturing processes involving localized physics that depend on many parameters, such as welding. After introducing the vademecum‐generalized finite element method formulation, we present some numerical examples related to the simulation of thermal models encountered in welding processes. Copyright © 2016 John Wiley & Sons, Ltd.
Using cognitive behaviour therapy to explore resilience in the life‐stories of 16 UK centenarians
Authors: Hutnik Nimmi , Smith Pam , Koch Tina
Published: February 2016

Aim

In 2010, we interviewed 16 UK centenarians about their lives and later published a paper on the socio‐emotional aspects of positive ageing. We were struck by their ability to ‘move on’ from difficult situations which we recognized conceptually as ‘resilience’. In the effort to understand aspects of resilience as portrayed in their stories, we re‐examined their data.

Methodology

In the original study, we used participatory action research (PAR) for its storytelling and group process components. Here, we re‐examine data from the centenarians’ life stories using a cognitive behavioural therapy (CBT) lens.

Design

We focused on the notion of resilience in the centenarians’ stories guided by CBT insights to analyse and develop psychosocial interpretations.

Results

Resilience comprised the ability to frame difficult life events in positive terms, accept what cannot be changed, manage worry and anxiety effectively, develop psychological flexibility in the face of change and continually seek opportunities for growth and development. We suggest that these resilient behaviours may have contributed to positive ageing.