bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple roles of afadin in the ultrastructural morphogenesis of mouse hippocampal mossy fiber synapses
Authors: Sai Kousyoku , Wang Shujie , Kaito Aika , Fujiwara Takeshi , Maruo Tomohiko , Itoh Yu , Miyata Muneaki , Sakakibara Shotaro , Miyazaki Naoyuki , Murata Kazuyoshi , Yamaguchi Yuuki , Haruta Tomohiro , Nishioka Hideo , Motojima Yuki , Komura Miyuki , Kimura Kazushi , Mandai Kenji , Takai Yoshimi , Mizoguchi Akira
Published: May 2017

A hippocampal mossy fiber synapse, which is implicated in learning and memory, has a complex structure in which mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions (PAJs) and wrap around a multiply‐branched spine, forming synaptic junctions. Here, we electron microscopically analyzed the ultrastructure of this synapse in afadin‐deficient mice. Transmission electron microscopy analysis revealed that typical PAJs with prominent symmetrical plasma membrane darkening undercoated with the thick filamentous cytoskeleton were observed in the control synapse, whereas in the afadin‐deficient synapse, atypical PAJs with the symmetrical plasma membrane darkening, which was much less in thickness and darkness than those of the control typical PAJs, were observed. Immunoelectron microscopy analysis revealed that nectin‐1, nectin‐3, and N‐cadherin were localized at the control typical PAJs, whereas nectin‐1 and nectin‐3 were localized at the afadin‐deficient atypical PAJs to extents lower than those in the control synapse and N‐cadherin was localized at their nonjunctional flanking regions. These results indicate that the atypical PAJs are formed by nectin‐1 and nectin‐3 independently of afadin and N‐cadherin and that the typical PAJs are formed by afadin and N‐cadherin cooperatively with nectin‐1 and nectin‐3. Serial block face‐scanning electron microscopy analysis revealed that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities, and the density of synaptic vesicles docked to active zones were decreased in the afadin‐deficient synapse. These results indicate that afadin plays multiple roles in the complex ultrastructural morphogenesis of hippocampal mossy fiber synapses.
Size, Shape, and Lateral Correlation of Highly Uniform, Mesoscopic, Self‐Assembled Domains of Fluorocarbon–Hydrocarbon Diblocks at the Air/Water Interface: A GISAXS Study
Authors: Veschgini Mariam , Abuillan Wasim , Inoue Shigeto , Yamamoto Akihisa , Mielke Salomé , Liu Xianhe , Konovalov Oleg , Krafft Marie Pierre , Tanaka Motomu
Published: May 2017

The shape and size of self‐assembled mesoscopic surface domains of fluorocarbon–hydrocarbon (FnHm) diblocks and the lateral correlation between these domains were quantitatively determined from grazing incidence small‐angle X‐ray scattering (GISAXS). The full calculation of structure and form factors unravels the influence of fluorocarbon and hydrocarbon block lengths on the diameter and height of the domains, and provides the inter‐domain correlation length. The diameter of the domains, as determined from the form factor analysis, exhibits a monotonic increase in response to the systematic lengthening of each block, which can be attributed to the increase in van der Waals attraction between molecules. The pair correlation function in real space calculated from the structure factor implies that the inter‐domain correlation can reach a distance that is over 25 times larger than the domain's size. The full calculation of the GISAXS signals introduced here opens a potential towards the hierarchical design of mesoscale domains of self‐assembled small organic molecules, covering several orders of magnitude in space.
Photo‐Chromium: Sensitizer for Visible‐Light‐Induced Oxidative C−H Bond Functionalization—Electron or Energy Transfer?
Authors: Otto Sven , Nauth Alexander M. , Ermilov Eugenyi , Scholz Norman , Friedrich Aleksej , Resch‐Genger Ute , Lochbrunner Stefan , Opatz Till , Heinze Katja
Published: May 2017

The chromium(III) sensitizer [Cr(ddpd)2]3+ (ddpd=N,N′‐dimethyl‐N,N′‐dipyridine‐2‐ylpyridine‐2,6‐diamine), based on an earth‐abundant metal centre, possesses a unique excited‐state potential‐energy landscape. The very large energy gap between the redox‐active and substitutionally labile 4T2 state and the long‐lived low‐energy 2E spin‐flip state enables a selective, efficient sensitization of triplet dioxygen to give singlet dioxygen. Ultrafast intersystem crossing after the Franck Condon point from the 4T2 to the 2E excited state within 3.5 ps precludes intermolecular electron‐transfer pathways from the ultrashort‐lived excited 4T2 state. This specific excited‐state reactivity enables a selective visible‐light‐induced C−H bond activation of tertiary amines with 1O2 and subsequent trapping with cyanide to yield α‐aminonitriles in good to excellent yields.
White broadband power line communication: Exploiting the TVWS for indoor multimedia smart grid applications
Authors: Heggo Mohammad , Zhu Xu , Sumei Sun , Huang Yi
Published: May 2017

Balancing the energy production and consumption in smart grids influences the integration of new high‐speed communication technologies, to support monitoring services. Sharing the television white space (TVWS) spectrum between licensed and unlicensed users has been recommended by the federal communications commission in 2004. Federal communications commission allows the unlicensed users to access both the very high frequency (VHF) and the ultra‐high frequency channels in TVWS. On the other hand, broadband power line communication (BPLC) has drawn the researchers' attention over the last decade as a high‐speed indoor communication technology. One application for BPLC is the multimedia service in smart grid applications. In this article, we present an overview of the standards, regulations, and channel models of the TVWS and BPLC as 2 separate technologies. We then propose the deployment of the BPLC technology in the TVWS VHF band to build up the white BPLC (WBPLC) communication systems. The WBPLC incorporates the TVWS and the BPLC technologies into multiple‐input multiple‐output communication systems in the VHF band. The simulation results show significant throughput enhancement in the WBPLC over both the TVWS and BPLC communication systems, indicating that WBPLC can be a promising technology to serve the growing needs for the multimedia services in future smart grids.
Short‐term Memory in Childhood Dyslexia: Deficient Serial Order in Multiple Modalities
Authors: Cowan Nelson , Hogan Tiffany P. , Alt Mary , Green Samuel , Cabbage Kathryn L. , Brinkley Shara , Gray Shelley
Published: May 2017

In children with dyslexia, deficits in working memory have not been well‐specified. We assessed second‐grade children with dyslexia, with and without concomitant specific language impairment, and children with typical development. Immediate serial recall of lists of phonological (non‐word), lexical (digit), spatial (location) and visual (shape) items were included. For the latter three modalities, we used not only standard span but also running span tasks, in which the list length was unpredictable to limit mnemonic strategies. Non‐word repetition tests indicated a phonological memory deficit in children with dyslexia alone compared with those with typical development, but this difference vanished when these groups were matched for non‐verbal intelligence and language. Theoretically important deficits in serial order memory in dyslexic children, however, persisted relative to matched typically developing children. The deficits were in recall of (1) spoken digits in both standard and running span tasks and (2) spatial locations, in running span only. Children with dyslexia with versus without language impairment, when matched on non‐verbal intelligence, had comparable serial order memory, but differed in phonology. Because serial orderings of verbal and spatial elements occur in reading, the careful examination of order memory may allow a deeper understanding of dyslexia and its relation to language impairment. Copyright © 2017 John Wiley & Sons, Ltd.
Implantation of a left ventricular assist device to provide long‐term support for end‐stage Duchenne muscular dystrophy‐associated cardiomyopathy
Authors: Stoller Douglas , Araj Faris , Amin Alpesh , Fitzsimmons Catherine , Morlend Robert , Thibodeau Jennifer T. , Ramaciotti Claudio , Drazner Mark H. , Meyer Dan M. , Mammen Pradeep P.A.
Published: May 2017

A young man with Duchenne muscular dystrophy presented to the UT Southwestern Neuromuscular Cardiomyopathy Clinic with advanced heart failure. Despite maximal medical therapy, his cardiac function continued to decline requiring initiation of inotrope therapy. Given the patient's clinical deterioration, a left ventricular assist device (LVAD) was implanted as destination therapy after undergoing a multidisciplinary assessment. The patient tolerated the surgical implantation of the LVAD without any significant complications, and he has had a relatively unremarkable course 38 months post‐LVAD implantation. A critical factor contributing to the long‐term success of this patient was the decision to select an LVAD that would not disrupt the diaphragm and thus preserve the respiratory muscle strength. This case demonstrates that permanent mechanical LVADs should be considered for appropriately selected Duchenne muscular dystrophy patients with medically refractory end‐stage cardiomyopathy.
The Thermodynamic Effects of Ligand Structure on the Molecular Recognition of Mononuclear Ruthenium Polypyridyl Complexes with B‐DNA
Authors: Mikek Clinton G. , DuPont Jesse I. , Machha Venkata R. , White Jake C. , Martin Logan R. , Alatrash Nagham , MacDonnell Frederick M. , Lewis Edwin A.
Published: May 2017

The ruthenium(II) polypyridyl complexes (RPCs), [(phen)2Ru(tatpp)]Cl2 (3Cl2) and [(phen)2Ru (tatpp)Ru(phen)2]Cl4 (4Cl4), containing the large planar and redox‐active tetraazatetrapyrido‐pentacene (tatpp) ligand, cleave DNA in the presence of reducing agents in cell‐free assays and show significant tumor regression in mouse tumor models with human non‐small cell lung carcinoma xenografts. ITC, CD, and ESI‐MS techniques were used to study the thermodynamics of RPC·DNA complex formation and the complex structure for binding three different RPCs to duplex DNA. The specific RPCs were [Ru(phen)3]2+ (12+), [Ru(phen)2(dppz)]2+ (22+), and [Ru(phen)2(tatpp)]2+ (32+). We examined the enatiomerically pure Δ‐RPC and Λ‐RPC isomers as well as the racemic mixture in terms of their binding to B‐DNA. B‐DNA binding of the three RPCs is characterized by a combination of groove binding (including electrostatic effects) and intercalation, with the thermodynamics being very similar for binding both the enantiomerically pure compounds and the racemic mixture. 12+ is the weakest DNA binder, exhibiting a Ka = 1.3 × 104 m–1 while 22+ binds with significantly higher affinity, Ka,1 = 1.4 × 106 m–1, and 32+ exhibits the tightest binding, Ka = 4.7 × 106 m–1. The trend is to increase the affinity as longer bridging ligands engage in additional π‐bonding with the DNA base pairs via an intercalative binding mode. A second binding mode, two orders of magnitude weaker was also seen for 22+. The ITC values for binding the racemic mixtures exhibit ΔGs ranging from –5.6 to –9.1 kcal mol–1 (12+·DNA and 32+·DNA respectively), while the ITC values for ΔH range from +4.9 to –5.0 kcal mol–1 (32+·DNA and mode 2 binding for 22+·DNA respectively). All of the primary complexes exhibit very negative values for –TΔS ranging from –7.3 to –14.0 kcal mol–1 (mode 1 binding for 22+·DNA and 32+·DNA respectively). To further understand the intercalation vs. groove binding contributions to the overall binding energy we compared the thermodynamics for formation of the 12+·DNA, 22+·DNA, and 32+·DNA complexes to the thermodynamics for formation of the 44+·DNA complex. The RPC binding affinities to duplex DNA follow the trend: 12+ < 44+ < 22+ < 32+. Differences in the affinity for binding 12+ vs. 22+ or 32+ are almost entirely due to the size of the intercalating moiety, e.g. phen which can only be partially intercalated in comparison to dppz and tatpp which can be completely intercalated. The lower affinity for the dinuclear ruthenium 44+ is due to the solvation penalty for the second Ru core complex that extends out from the major groove. Comparing these results, we have begun to develop the structure function relationships for the interaction of RPCs with B‐DNA.
Determination of strobilurin fungicide residues in fruits and vegetables by nonaqueous micellar electrokinetic capillary chromatography with indirect laser‐induced fluorescence
Authors: Guo Xin , Wang Kun , Chen Guan‐Hua , Shi Jie , Wu Xian , Di Lu‐Lu , Wang Yi
Published: May 2017

A nonaqueous micellar electrokinetic capillary chromatography method with indirect LIF was developed for the determination of strobilurin fungicide residues in fruits and vegetables. Hydrophobic CdTe quantum dots (QDs) synthesized in aqueous phase were used as background fluorescent substance. The BGE solution, QD concentration, and separation voltage were optimized to obtain the best separation efficiency and the highest signal intensity. The optimal BGE solution consists of 40 mM phosphate, 120 mM sodium dodecyl sulfate, 15% v/v water and 15% v/v hydrophobic CdTe QDs in formamide, of which apparent pH is 9.5. The optimized separation voltage is controlled as 25 kV. The resultant detection limits of azoxystrobin, kresoxim‐methyl, and pyraclostrobin are all 0.001 mg/kg, their linear dynamic ranges are 0.005–2.5 mg/kg, and the recoveries of the spiked samples are 81.7–96.1%, 86.5–95.7%, and 87.3–97.4%, respectively. This method has been proved to be sensitive enough to detect the aforementioned fungicides in fruits and vegetables at the maximum residue limits.
Effects of chemical management for invasive plants on the performance of Lithobates pipiens tadpoles
Authors: Curtis Amanda N. , Bidart M. Gabriela
Published: May 2017

Invasive plants impact amphibians by altering habitat, altering species interactions, and releasing potentially toxic secondary chemicals. Despite being costly and having the potential to affect nontarget wildlife, chemical management is commonly used to control invasive plants. Prior research has indicated that individual effects of invasive plants or herbicides can be harmful to aquatic organisms; however, information is lacking on the combined effect of these factors on amphibians. A laboratory experiment was performed to assess the impact of leachates of the invasive plants Eurasian watermilfoil (Myriophyllum spicatum) and European buckthorn (Rhamnus cathartica), the herbicide Renovate® 3 (triclopyr [3, 5, 6-trichloro-2-pyridinyloxyacetic acid]), and the combined effects of each plant leachate and the herbicide on the growth, morphology, and survival of northern leopard frog (Lithobates pipiens) tadpoles. No effects of treatment on survival were observed. Tadpole exposure to M. spicatum reduced body mass by 17%, exposure to R. cathartica increased body mass by 36%, and exposure to R. cathartica + low herbicide increased body mass by 38% (although only early in the experiment). Exposure to Renovate 3 induced a 16% and 29% decrease in tadpole size in lower (0.22 mg triclopyr active ingredient [a.i.]/L) and higher (0.92 mg triclopyr a.i./L) concentration treatments, respectively. Results from the present study highlight the importance of considering both individual and combined effects of invasive plants and herbicides because they may have different outcomes for tadpole growth and development. Environ Toxicol Chem 2017;36:2958–2964. © 2017 SETAC
Application of the Fog computing paradigm to Smart Factories and cyber‐physical systems
Authors: de Brito M.S. , Hoque S. , Steinke R. , Willner A. , Magedanz T.
Published: May 2017

Since the invention of the steam engine in the 18th century, innovation drove the development of industrial processes. The next industrial revolution will form an ecosystem of over 20 billion connected devices with unforeseeable influence to the gross domestic product by 2020, and connected assets will generate about 44ZB of data, which pose interesting challenges related to privacy, connectivity, scalability, and others. A current line of action that leads to this direction is the development of cyber‐physical systems; considered as the coupling of physical processes and the digital world, its influence in the next industrial revolution is essential. In this work, we discuss its implementation, taking the Fog computing paradigm into consideration. As a starting point, we are extending a standard‐compliant machine‐to‐machine communication architecture to support container‐based orchestration mechanisms to enable cyber‐physical systems to be programmable, autonomous, and to communicate peer‐to‐peer. As the primary field of application, we are considering Industrial Internet domains in general and Smart Factory environments in particular. In this paper, we present an architecture for Fog Nodes, as well a more in‐depth discussion on the orchestration system and programmable characteristics of the Fog Node. On the basis of a simulation model, we show the advantages of having a programmable Fog Node supported by an orchestration system. Finally, we open a discussion about our solution and its application in the field of Smart Factories.
FASPM: Fuzzy logic‐based adaptive security protocol for multihop data dissemination in intelligent transport systems
Authors: Javed Muhammad Awais , Zeadally Sherali , Usman Muhammad , Sidhu Guftaar Ahmad Sardar
Published: May 2017

Intelligent transport systems (ITSs) utilize secure wireless communications to enable vehicle‐to‐vehicle or vehicle‐to‐infrastructure connectivity on the road. Single‐hop and multihop communications are used to ensure that the vehicles and the infrastructure road side units are notified of current traffic conditions in a timely manner. While security improves network defense against malicious users, it also adds significant computational delay to network transmissions. In particular, for multihop communications, this can result in increased network delays and increased number of retransmissions that cause further network congestions for single‐hop safety messages. We present an approach called the fuzzy logic‐based adaptive security protocol for multihop (FASPM) traffic to improve the quality of service of ITS applications. FASPM prioritizes the signature verification of ITS messages according to their delay requirements. Moreover, FASPM uses fuzzy adaptation of multihop security levels to reduce network congestion. Simulation results demonstrate that FASPM achieves significant quality‐of‐service improvements for road safety applications.
Combining distributed queuing with energy harvesting to enable perpetual distributed data collection applications
Authors: Vazquez‐Gallego Francisco , Tuset‐Peiró Pere , Alonso Luis , Alonso‐Zarate Jesus
Published: May 2017

This paper presents, models, and evaluates energy harvesting–aware distributed queuing (EH‐DQ), a novel medium access control protocol that combines distributed queuing with energy harvesting (EH) to address data collection applications in industrial scenarios using long‐range and low‐power wireless communication technologies. We model the medium access control protocol operation using a Markov chain and evaluate its ability to successfully transmit data without depleting the energy stored at the end devices. In particular, we compare the performance and energy consumption of EH‐DQ with that of time‐division multiple access (TDMA), which provides an upper limit in data delivery, and EH‐aware reservation dynamic frame slotted ALOHA, which is an improved variation of frame slotted ALOHA. To evaluate the performance of these protocols, we use 2 performance metrics: delivery ratio and time efficiency. Delivery ratio measures the ability to successfully transmit data without depleting the energy reserves, whereas time efficiency measures the amount of data that can be transmitted in a certain amount of time. Results show that EH‐DQ and TDMA perform close to the optimum in data delivery and outperform EH‐aware reservation dynamic frame slotted ALOHA in data delivery and time efficiency. Compared to TDMA, the time efficiency of EH‐DQ is insensitive to the amount of harvested energy, making it more suitable for energy‐constrained applications. Moreover, compared to TDMA, EH‐DQ does not require updated network information to maintain a collision‐free schedule, making it suitable for very dynamic networks.
Bounding the causal effect of unemployment on mental health: Nonparametric evidence from four countries
Authors: Cygan‐Rehm Kamila , Kuehnle Daniel , Oberfichtner Michael
Published: May 2017

An important, yet unsettled, question in public health policy is the extent to which unemployment causally impacts mental health. The recent literature yields varying findings, which are likely due to differences in data, methods, samples, and institutional settings. Taking a more general approach, we provide comparable evidence for four countries with different institutional settings—Australia, Germany, the UK, and the United States—using a nonparametric bounds analysis. Relying on fairly weak and partially testable assumptions, our paper shows that unemployment has a significant negative effect on mental health in all countries. Our results rule out effects larger than a quarter of a standard deviation for Germany and half a standard deviation for the Anglo‐Saxon countries. The effect is significant for both men and women and materialises already for short periods of unemployment. Public policy should hence focus on early prevention of mental health problems among the unemployed.
Differential resistance to platinum‐based drugs and 5‐fluorouracil in p22phox‐overexpressing oral squamous cell carcinoma: Implications of alternative treatment strategies
Authors: Hung Chih‐Chang , Chien Chen‐Yu , Chu Pei‐Yu , Wu Yu‐Jen , Lin Chang‐Shen , Huang Chih‐Jen , Chan Leong‐Perng , Wang Yen‐Yun , Yuan Shyng‐Shiou F. , Hour Tzyh‐Chyuan , Chen Jeff Yi‐Fu
Published: May 2017

Background

We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown.

Methods

The p22phox expression in tissues and apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo chemoresistance of p22phox‐overexpressing tumors was confirmed by the xenograft mouse model.

Results

The p22phox was upregulated in tumors of patients with OSCC refractory to cisplatin treatment. The p22phox overexpression markedly increased the resistance to cisplatin and carboplatin, but not oxaliplatin and 5‐fluorouracil (5‐FU), in OSCC cells by differentially inhibiting the drug‐induced apoptosis. Furthermore, p22phox‐dependent resistance to cisplatin, but not 5‐FU, was demonstrated in mouse xenograft tumors.

Conclusion

The p22phox expression may not only be a prognostic biomarker for prediction of chemotherapy outcomes, but the indication for alternative treatment strategies in oral cancer.
Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice
Authors: Slijepcevic Davor , Roscam Abbing Reinout L.P. , Katafuchi Takeshi , Blank Antje , Donkers Joanne M. , van Hoppe Stéphanie , de Waart Dirk. R. , Tolenaars Dagmar , van der Meer Jonathan H.M. , Wildenberg Manon , Beuers Ulrich , Oude Elferink Ronald P.J. , Schinkel Alfred H. , van de Graaf Stan F.J.
Published: May 2017

The Na+‐taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild‐type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1‐transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno‐associated virus–mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α‐hydroxylase Cyp7a1 expression was strongly down‐regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B–treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte‐models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. Conclusion: NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631–1643).
Broad Th2 neutralization and anti‐inflammatory action of pentosan polysulfate sodium in experimental allergic rhinitis
Authors: Sanden Caroline , Mori Michiko , Jogdand Prajakta , Jönsson Jimmie , Krishnan Ravi , Wang Xiangdong , Erjefält Jonas S.
Published: May 2017

Background

Th2 cytokines like interleukin‐4, ‐5, and ‐13 are regarded as important drivers of the immunopathology underlying allergic rhinitis (AR) and asthma. The present study explores the capacity of pentosan polysulfate sodium (PPS), a semi‐synthetic heparin‐like macromolecular carbohydrate, to bind Th2 cytokines and exert biological neutralization in vitro, as well as anti‐inflammatory actions in vivo.

Methodology

The capacity of PPS to bind recombinant Th2 cytokines was tested with surface plasmon resonance (SPR) technology and biological Th2 neutralization was assessed by Th2‐dependent proliferation assays. The in vivo anti‐inflammatory action of PPS was studied using a validated Guinea‐pig model of AR.

Results

Binding studies revealed a strong and specific binding of PPS to IL‐4, IL‐5, and IL‐13 with IC values suggesting as stronger cytokine binding than for heparin. Cytokine binding translated to a biological neutralization as PPS dose dependently inhibited Th2‐dependent cell proliferation. Topical administration of PPS 30 min prior to nasal allergen challenge of sensitized animals significantly reduced late phase plasma extravasation, luminal influx of eosinophils, neutrophils, and total lavage leukocytes. Similar, albeit not statistically secured, effects were found for tissue leukocytes and mucus hyper‐secretion. The anti‐inflammatory effects of PPS compared favorably with established topical nasal steroid treatment.

Conclusion

This study points out PPS as a potent Th2 cytokine‐binding molecule with biological neutralization capacity and broad anti‐inflammatory effects in vivo. As such PPS fulfills the role as a potential candidate molecule for the treatment of AR and further studies of clinical efficacy seems highly warranted.
Taxonomy of Student Veterans: A Suggested Protocol for Institutional Research Professionals
Authors: Daly Dion D. , Fox Garrity Bonnie K.
Published: May 2017

This chapter provides a taxonomy of student veterans in the form of a codebook to assist in institutional data collection and analysis.
For‐Profit Institutions and Student Veteran Data
Authors: Jones Kevin C. , Fox Garrity Bonnie K.
Published: May 2017

This chapter explores the lack of data about student veterans and reasons this lack of data raises particular concerns about for‐profit institutions, which enroll a large percentage of student veterans.
Macromolecular structures: Quality assessment and biological interpretation
Authors: Salunke Dinakar M. , Nair Deepak T.
Published: May 2017

Structure determination using X‐ray crystallography involves collection of diffraction data, determination of initial phases followed by iterative rounds of model building and crystallographic refinement to improve the phases and minimize the differences between calculated and observed structure factors. At each of these stages, a variety of statistical filters exist to ensure appropriate validation. Biologically important observations often come from interpretations of signals that need to be carefully deciphered from noise, and therefore human intervention is as important as the automated methods and filters. Currently, all structural data are deposited in the Protein Data Bank (PDB), and this repository is continuously evolving to incorporate new developments in macromolecular crystallography. The journals that publish data arising from structural studies modulate their policies to take cognizance of new improved methodologies. Together, the PDB and journals have evolved an accepted protocol to ensure the integrity of crystallographic results. As a result, the quality of available data and associated interpretations have improved over the years. Typically, if there are differences regarding the mechanism of action of a protein revealed by crystallography then new experiments are carried out to provide further evidence for or against a particular hypothesis. Hence, the scientific systems in structural biology are robust and to a large extent capable of correcting any errors in interpretation of structural results. However, this process is hindered by spurious challenges to published research, based on misuse of validation mechanisms. Such activities are counterproductive and will cause damage to the field of structural biology. © 2017 IUBMB Life, 69(8):563–571, 2017
Synergistic effects of fibronectin and bone morphogenetic protein on the bioactivity of titanium metal
Authors: Biao M. N. , Chen Y. M. , Xiong S. B. , Wu B. Y. , Yang B. C.
Published: May 2017

To improve the biological properties of bioactive titanium metal, recombinant human bone morphogenetic protein 2(rhBMP‐2) and fibronectin (Fn) were adsorbed on its surface solely or contiguously to modify the anodic oxidized titanium (AO‐Ti), acid–alkali‐treated titanium (AA‐Ti), and polished titanium (P‐Ti). It is found that the different bioactive titanium surface structures had great influence on protein adsorption. The adsorption amounts of BMP adsorbed solely and Fn/BMP adsorbed contiguously were AA‐Ti > P‐Ti > AO‐Ti, and that for Fn adsorbed solely was AA‐Ti ≈ P‐Ti > AO‐Ti. The conformation of proteins was changed remarkably after the adsorption. For BMP, the α‐helix decreased on AA‐Ti and stabilized on P‐Ti and AO‐Ti. For Fn, the β‐sheet on PT‐Ti and AA‐Ti increased significantly. For Fn/BMP, the percentage of β‐sheet on AA‐Ti increased, and that of α‐helix on all samples was stable. MSCs showed greater adhesion and spreading on Fn/BMP groups. MTT and Elisa tests showed that the synergistic effects of proteins made the cells proliferate and differentiate faster. It indicated both the surface structure and the synergistic effects of proteins could influence the biological properties of titanium metals. It provides research foundation for improving the biological properties of bioactive titanium metals by simultaneous application of several proteins. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2485–2498, 2017.
Licochalcone A Suppresses Specificity Protein 1 as a Novel Target in Human Breast Cancer Cells
Authors: Kang Tae‐Ho , Seo Ji‐Hye , Oh Hana , Yoon Goo , Chae Jung‐Il , Shim Jung‐Hyun
Published: May 2017

Licochalcone A (LCA), isolated from the root of Glycyrrhiza inflata, are known to have medicinal effect such as anti‐oxidant, anti‐bacterial, anti‐viral, and anti‐cancer. Though, as a pharmacological mechanism regulator, anti‐cancer studies on LCA were not investigated in human breast cancer. We investigated the anti‐proliferative and apoptotic effect of LCA in human breast cancer cells MCF‐7 and MDA‐MB‐231 through MTS assay, PI staining, Annexin‐V/7‐AAD assay, mitochondrial membrane potential assay, multi‐caspase assay, RT‐PCR, Western blot analysis, and anchorage‐independent cell transformation assay. Our results showed the little difference between two cells, as MCF‐7 cell is both estrogen/progesterone receptor positive, there were only effect on Sp1 protein level, but not in mRNA level. Adversely, estrogen/progesterone/human epidermal growth factor receptor 2 triple negative, MDA‐MB‐231 showed decreased Sp1 mRNA, and protein levels. To confirm the participation of Sp1 in breast cancer cell viability, siRNA techniques were introduced. Both cells showed dysfunction of mitochondrial membrane potential and mitochondrial ROS production, which reflects it passed intracellular mitochondrial apoptosis pathway. Additionally, LCA showed the anti‐proliferative and apoptotic effect in breast cancer cells through regulating Sp1 and apoptosis‐related proteins in a dose‐ and a time‐dependent manner. Consequently, LCA might be a potential anti‐breast cancer drug substitute. J. Cell. Biochem. 118: 4652–4663, 2017. © 2017 Wiley Periodicals, Inc.
SNX10 Plays a Critical Role in MMP9 Secretion via JNK‐p38‐ERK Signaling Pathway
Authors: Zhou Chun , Wang Ying , Peng Jin , Li Cuixian , Liu Peiqing , Shen Xiaoyan
Published: May 2017

Matrix metalloproteinases (MMPs) plays a critical role in the degradation of extracellular matrix (ECM). Sorting nexin (SNX) 10 is a member of the SNX family, which functions in regulation of endosomal sorting and osteoclast activation, has been implicated to play an important role in the bone erosion of rheumatoid arthritis. In this study, we aimed to investigate the possible role of SNX10 on MMP9 secretion and the potential mechanism. By immunostaining and co‐immunoprecipitation, we found that SNX10 was extensively co‐localized with MMP9, indicating that SNX10 might participate in MMP9 trafficking. After knocking down SNX10 via siRNA, the secretion and activity of MMP9 was significantly reduced, but the amount of protein was increased. By contraries, over‐expression of SNX10 could increase the secretion and activity levels. Deficiency of SNX10 impaired the differentiation and bone resorption function of osteoclast, with a low activity of MMP9 compared to WT one. In SNX10 knockout osteoclast, the phosphorylation levels of JNK, p38, and ERK were obviously down‐regulated. Our results first identified the role of SNX10 in MMP9 trafficking and secretion, and provided an evidence for SNX10 as a possible therapeutic target for bone destructing disease. J. Cell. Biochem. 118: 4664–4671, 2017. © 2017 Wiley Periodicals, Inc.
A Mercaptoacetamide‐Based Class II Histone Deacetylase Inhibitor Suppresses Cell Migration and Invasion in Monomorphic Malignant Human Glioma Cells by Inhibiting FAK/STAT3 Signaling
Authors: Nam Jin Han , Cho Hyun‐Ji , Kang Hyejin , Lee Ju‐Young , Jung Mira , Chang Young‐Chae , Kim Keetae , Hoe Hyang‐Sook
Published: May 2017

Histone deacetylase inhibitors (HDACIs) have emerged as potential anticancer agents for the treatment of solid and hematopoietic cancers. Several HDACIs delay cell growth, induce differentiation, or activate apoptosis in multiple types of tumors, including glioblastomas. In the present study, we showed that the mercaptoacetamide‐based HDACI W2 inhibits cell migration and invasion in monomorphic malignant human glioma cells. W2 treatment significantly decreased the activity and expression levels of matrix metalloprotease‐2 in malignant A172 cells but not in U373MG cells. Key signaling pathways involved in cell migration and invasion, including PI3K‐AKT, ERK‐JNK‐P38, and FAK/STAT3, were examined to identify the mechanism of action of W2. W2 increased the phosphorylation of AKT and altered cell migration and invasion in an AKT‐independent manner. W2 inhibited the phosphorylation of FAK/STAT3, and treatment with a FAK/STAT3 inhibitor significantly suppressed cancer cell migration and MMP‐2 activity in the presence of W2. In addition, W2 significantly inhibited the nuclear translocation of phospho‐STAT3. Taken together, our results suggest that W2 suppresses cancer cell migration and invasion by inhibiting FAK/STAT3 signaling and STAT3 translocation to the nucleus in monomorphic malignant human glioma cells. J. Cell. Biochem. 118: 4672–4685, 2017. © 2017 Wiley Periodicals, Inc.
Synthesis and Pharmacological Evaluation of Novel GABAA Subtype Receptor Ligands with Potential Anxiolytic‐like and Anti‐hyperalgesic Effect
Authors: Guerrini Gabriella , Ciciani Giovanna , Crocetti Letizia , Daniele Simona , Ghelardini Carla , Giovannoni Maria Paola , Di Cesare Mannelli Lorenzo , Martini Claudia , Vergelli Claudia
Published: May 2017

The identification of selective benzodiazepine site ligands, endowed with anxiolytic and anti‐hyperalgesic action, is a relevant opportunity for the treatment of pain syndromes. Previously, we selected a compound with a promising anti‐hyperalgesic profile, the 3‐iodo‐8‐benzylaminopyrazolo [5,1‐c][1,2,4]benzotriazine 5‐oxide. Aimed to verify the structure–activity relationship, the corresponding 7‐arylakylamino derivatives were synthesized. Compounds were tested for their affinity at GABAA‐receptor subtype; the compound 12 was further investigated in animal models of anxiety and persistent pain.
Investigation of aerosol effects on the Arctic surface temperature during the diurnal cycle: part 2 – Separating aerosol effects
Authors: Stofferahn Eric , Boybeyi Zafer
Published: May 2017

Temperature changes in the Arctic due to anthropogenic climate change are larger in magnitude than those at lower latitudes, with sea ice extent and thickness diminishing since the dawn of the satellite era. Aerosols play a role in determining the changes to the Arctic surface temperature. While Part 1 of this two‐part study investigated the changes in Arctic surface temperature due to the total aerosol effect, in Part 2, the total aerosol effect is separated into the changes caused by the aerosol direct effect, the aerosol semi‐direct effect, and the aerosol indirect effects through the use of additional Weather Research and Forecasting Chemistry (WRF‐Chem) runs. While Part 1 of the study showed that aerosols may have both a cooling and warming effect, largely depending upon the time of day and aerosol concentration, Part 2 of this study shows that the indirect effects are the dominant component of the total aerosol effect on the cooling and warming of the Arctic surface temperature throughout the diurnal cycle. It is also shown that the size distribution of aerosols is important, as smaller aerosols dominate the aerosol indirect effects. The aerosol direct effect contributes to cooling in the region, while the semi‐direct effect is negligible.
Geographic distribution of global climate zones under future scenarios
Authors: Zhang Xianliang , Yan Xiaodong , Chen Zhenju
Published: May 2017

Possible future climate change can be projected by general circulation models (GCMs), and the future geographic distribution of global climate zones can be projected based on these GCM simulations. In this study, the performance of 33 GCMs in simulating the distribution of global climate zones was evaluated using Kappa values. The results show that certain models are more skillful than other models in simulating the present distribution of global climate zones. The ensemble mean of all the GCMs showed worse performance than some individual models in simulating the present distribution of climate zones. The ensemble mean based on the three GCMs that showed superior performance achieved the optimum results in simulating the future distribution of climate zones. Based on the simulations of the ensemble mean of these three GCMs, the distributions of global climate zones in the future were projected for three scenarios (Representative Concentration Pathways, RCP) (RCP2.6, RCP4.5, and RCP8.5). The climate types in the temperate zone were susceptible to climate changes under the three scenarios. The shift in the distribution of climate zones was mainly caused by the joint variations of temperature and precipitation among different climate zones.
Trauma‐Related Pain, Reexperiencing Symptoms, and Treatment of Posttraumatic Stress Disorder: A Longitudinal Study of Veterans
Authors: Bartoszek Gregory , Hannan Susan M. , Kamm Janina , Pamp Barbara , Maieritsch Kelly P.
Published: May 2017

Research has demonstrated a strong positive association between posttraumatic stress disorder (PTSD) symptoms and physical pain. However, few studies have explored the impact of pain problems on the symptoms and treatment of PTSD, and results remain inconsistent. This longitudinal study examined whether trauma‐related and trauma‐unrelated pain differentially and uniquely predicted reexperiencing symptoms. We also examined whether levels of reexperiencing symptoms mediated the relationship between pain intensity and posttreatment symptoms of avoidance, numbing, and hyperarousal (ANH). Analyses were conducted using archival data from 99 treatment‐seeking veterans who reported the etiology and intensity of their pain and severity of PTSD symptoms pre‐ and posttreatment. Among veterans with trauma‐related pain, pain intensity (a) uniquely corresponded to greater posttreatment reexperiencing symptoms (b = 1.09), and (b) was indirectly predictive of ANH symptoms via the reexperiencing symptoms (b = 1.93). However, veterans with trauma‐unrelated pain evidenced no associations between pain intensity and reexperiencing (b = 0.04) or ANH symptoms (b = 0.06). We thus found that trauma‐related pain was indirectly related to poor PTSD treatment outcomes via reexperiencing symptoms. These findings offer additional insight into factors that may influence PTSD treatment outcomes for pain‐suffering trauma survivors.
Robotic microlaryngeal phonosurgery: Testing of a “steady‐hand” microsurgery platform
Authors: Akst Lee M. , Olds Kevin C. , Balicki Marcin , Chalasani Preetham , Taylor Russell H.
Published: May 2017

Objectives/Hypothesis

To evaluate gains in microlaryngeal precision achieved by using a novel robotic “steady hand” microsurgery platform in performing simulated phonosurgical tasks.

Study Design

Crossover comparative study of surgical performance and descriptive analysis of surgeon feedback.

Methods

A novel robotic ear, nose, and throat microsurgery system (REMS) was tested in simulated phonosurgery. Participants navigated a 0.4‐mm‐wide microlaryngeal needle through spirals of varying widths, both with and without robotic assistance. Fail time (time the needle contacted spiral edges) was measured, and statistical comparison was performed. Participants were surveyed to provide subjective feedback on the REMS.

Results

Nine participants performed the task at three spiral widths, yielding 27 paired testing conditions. In 24 of 27 conditions, robot‐assisted performance was better than unassisted; five trials were errorless, all achieved with the robot. Paired analysis of all conditions revealed fail time of 0.769 ± 0.568 seconds manually, improving to 0.284 ± 0.584 seconds with the robot (P = .003). Analysis of individual spiral sizes showed statistically better performance with the REMS at spiral widths of 2 mm (0.156 ± 0.226 seconds vs. 0.549 ± 0.545 seconds, P = .019) and 1.5 mm (0.075 ± 0.099 seconds vs. 0.890 ± 0.518 seconds, P = .002). At 1.2 mm, all nine participants together showed similar performance with and without robotic assistance (0.621 ± 0.923 seconds vs. 0.868 ± 0.634 seconds, P = .52), though subgroup analysis of five surgeons most familiar with microlaryngoscopy showed statistically better performance with the robot (0.204 ± 0.164 seconds vs. 0.664 ± 0.354 seconds, P = .036).

Conclusions

The REMS is a novel platform with potential applications in microlaryngeal phonosurgery. Further feasibility studies and preclinical testing should be pursued as a bridge to eventual clinical use.

Level of Evidence

NA. Laryngoscope, 128:126–132, 2018
The malleus to oval window revision stapedotomy: Efficacy and longitudinal study outcome
Authors: Benedict Peter A. , Zhou Ling , Peng Robert , Kohan Darius
Published: May 2017

Objective

To determine the longitudinal effectiveness of the malleus to oval window stapedotomy technique among patients undergoing revision surgery when the incus is unavailable.

Study Design

Retrospective, case series.

Methods

Charts of 15 patients who underwent 17 malleus attachment stapedotomies performed by a single surgeon from 2000 to 2015 were reviewed. Surgery was ambulatory, transcanal, with laser technique, and under local anesthesia.

Results

Of 17 stapedotomies performed, there were nine first revisions, six second revisions, one third revision, and one fourth revision. There were no surgical complications. Mean preoperative air‐bone gap (ABG) was 32.3 dB. Mean postoperative ABG at 6 months was 10.7 dB, and at last follow‐up was 16.3 dB. Average length of follow‐up was 36.5 months. At last follow‐up, 100% of first revisions achieved ABG ≤ 20 dB (77.8% ≤ 10 dB), compared to 50% of second revisions with ABG ≤ 20 dB (none ≤ 10 dB), and 0% of third or fourth revisions with ABG ≤ 20 dB. Trend lines for second and third/fourth revisions showed a deterioration (widening) in postoperative ABG by 0.18 and 0.72 dB per month, respectively. The first‐revision trend line, conversely, showed negligible change with time, demonstrating the superior durability of first revisions compared to subsequent surgeries.

Conclusion

The malleus to oval window stapedotomy technique is more effective and longer lasting in first‐revision surgery compared to subsequent procedures. Standard or implantable amplification devices may be preferable for patients with multiple prior procedures.

Level of Evidence

4. Laryngoscope, 128:461–467, 2018
Socioeconomic disparities and comorbidities, not race, affect salivary gland malignancy survival outcomes
Authors: Iwata Ayaka J. , Williams Amy M. , Taylor Andrew R. , Chang Steven S.
Published: May 2017

Objectives/Hypothesis

This study sought to determine whether comorbidities, race, and socioeconomic factors affect 5‐ and 10‐year survival outcomes for patients with salivary gland malignancies treated at a single large academic institution with a large African American population.

Study Design

A retrospective cohort study was performed of all patients with salivary gland malignancies, from 1990 to 2015, at a large academic medical center.

Methods

Standard statistical analysis was performed using Kaplan‐Meier survival curve analysis and Cox proportional hazard models.

Results

The overall 5‐ and 10‐year survival rates decreased with age ≥ 60 years (P < .001), stage 3 or 4 (P < .001), clinical T stage 3 or 4 (P < .001), and clinical N stage 1, 2, or 3 (P < .001). Living in a ZIP code with an increasing proportion of residents with a high school degree or less (P < .05), being male (P < .05), increasing age at the time of diagnosis (P < .001), and increasing Charlson comorbidity index (P < .05) detrimentally impacted survival at 5 and 10 years. Race was associated with socioeconomic variables, but race was not a prognostic indicator of survival.

Conclusions

Socioeconomic factors and comorbidities, not race, were negative prognostic indicators of survival of patients with salivary gland malignancies. Using race as a marker for socioeconomic status should be used with caution.

Level of Evidence

4. Laryngoscope, 127:2545–2550, 2017