bluuebunny/crossref_metadata_2025_split huggingface dataset:
Handheld Photoacoustic Microscopy Probe
Authors: Park Kyungjin , Kim Jin Young , Lee Changho , Jeon Seungwan , Lim Geunbae , Kim Chulhong 
Published: October 2017

AbstractOptical resolution photoacoustic microscopy (OR-PAM) is a non-invasive, label-free method of in vivo imaging with microscopic resolution and high optical contrast. Based on intrinsic contrasts, OR-PAM has expanded to include in vivo vessel imaging, flow cytometry, physiological parameter analysis, and single-cell characterization. However, since conventional OR-PAM systems have a fixed tabletop configuration, a large system size, and slow imaging speed, their use in preclinical and clinical studies remains limited. In this study, using microelectromechanical systems (MEMS) technology, we developed a handheld PAM probe with a high signal-to-noise ratio and image rate. To enable broader application of the OR-PAM system, we reduced its size and combined its fast scanning capabilities into a small handheld probe that uses a 2-axis waterproof MEMS scanner (2A-WP-MEMS scanner). All acoustical, optical, and mechanical components are integrated into a single probe with a diameter of 17 mm and a weight of 162 g. This study shows phantom and in vivo images of various samples acquired with the probe, including carbon fibers, electrospun microfibers, and the ear, iris, and brain of a living mouse. In particular, this study investigated the possibility of clinical applications for melanoma diagnosis by imaging the boundaries and morphology of a human mole.
β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development
Authors: Ling Yue-Ming , Chen Jin-Yu , Guo Libin , Wang Chen-Yi , Tan Wen-Ting , Wen Qing , Zhang Shu-Dong , Deng Guo-Hong , Lin Yao , Kwok Hang Fai 
Published: October 2017

Abstractβ-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest β-defensin 1 plays an important role in protecting HCV progression and liver cancer development.
Host heterozygosity and genotype rarity affect viral dynamics in an avian subspecies complex
Authors: Eastwood Justin R. , Ribot Raoul F. H. , Rollins Lee Ann , Buchanan Katherine L. , Walder Ken , Bennett Andrew T. D. , Berg Mathew L. 
Published: October 2017

AbstractGenetic diversity at community, population and individual levels is thought to influence the spread of infectious disease. At the individual level, inbreeding and heterozygosity are associated with increased risk of infection and disease severity. Host genotype rarity may also reduce infection risk if pathogens are co-adapted to common or local hosts, but to date, no studies have investigated the relative importance of genotype rarity and heterozygosity for infection in a wild, sexually reproducing vertebrate. With beak and feather disease virus (BFDV) infection in a wild parrot (Platycercus elegans), we show that both heterozygosity and genotype rarity of individual hosts predicted infection, but in contrasting ways. Heterozygosity was negatively associated with probability of infection, but not with infection load. In contrast, increased host genotype rarity was associated with lower viral load in infected individuals, but did not predict infection probability. These effects were largely consistent across subspecies, but were not evident at the population level. Subspecies and age were also strongly associated with infection. Our study provides novel insights into infection dynamics by quantifying rarity and diversity simultaneously. We elucidate roles that host genetic diversity can play in infection dynamics, with implications for understanding population divergence, intraspecific diversity and conservation.
Size Variation under Domestication: Conservatism in the inner ear shape of wolves, dogs and dingoes
Authors: Schweizer Anita V. , Lebrun Renaud , Wilson Laura A. B. , Costeur Loïc , Schmelzle Thomas , Sánchez-Villagra Marcelo R. 
Published: October 2017

AbstractA broad sample of wolves, dingoes, and domesticated dogs of different kinds and time periods was used to identify changes in size and shape of the organs of balance and hearing related to domestication and to evaluate the potential utility of uncovered patterns as markers of domestication. Using geometric morphometrics coupled with non-invasive imaging and three-dimensional reconstructions, we exposed and compared complex structures that remain largely conserved. There is no statistically significant difference in the levels of shape variation between prehistoric and modern dogs. Shape variance is slightly higher for the different components of the inner ear in modern dogs than in wolves, but these differences are not significant. Wolves express a significantly greater level of variance in the angle between the lateral and the posterior canal than domestic dog breeds. Wolves have smaller levels of size variation than dogs. In terms of the shape of the semicircular canals, dingoes reflect the mean shape in the context of variation in the sample. This mirrors the condition of feral forms in other organs, in which there is an incomplete return to the characteristics of the ancestor. In general, morphological diversity or disparity in the inner ear is generated by scaling.
Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors
Authors: Bogusz Jozefina , Zrubek Karol , Rembacz Krzysztof P. , Grudnik Przemyslaw , Golik Przemyslaw , Romanowska Malgorzata , Wladyka Benedykt , Dubin Grzegorz 
Published: October 2017

AbstractPIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Two of the reported structures (CX-4945 and Ro-3306) explain the off-target effect on PIM1 of respectively casein kinase 2 and cyclin-dependent kinase 1 dedicated inhibitors. In turn, the structure with CX-6258 demonstrates a binding mode of a potent, selective inhibitor of PIM1, PIM2, PIM3 and Flt-3 kinases. The consequences of our findings for future inhibitor development are discussed.
Efficient induction of comprehensive immune responses to control pathogenic E. coli by clay nano-adjuvant with the moderate size and surface charge
Authors: Chen Weiyu , Zuo Huali , Mahony Timothy J. , Zhang Bing , Rolfe Barbara , Xu Zhi Ping 
Published: October 2017

AbstractIn recent decades, diseases caused by pathogenic Escherichia coli (E. coli), enterohaemorrhagic E. coli (EHEC) O26 have been increasingly reported worldwide, which are as severe as those caused by EHEC strain O157:H7 and require effective intervention strategies. Herein, we report the application of clay nanoparticles, i.e. hectorites as effective nano-adjuvants for vaccination against EHEC O26 colonization. We show that medium size HEC (hectorite, around 73~77 nm diameter) is able to induce efficient humoral and cellular immune responses against EHEC antigen - intimin β (IB), which are significantly higher than those triggered by commercially used adjuvants - QuilA and Alum. We also demonstrate that mice immunized with IB adjuvanted with HEC nanoparticles elicit sufficient secretion of mucosal IgA, capable of providing effective protection against EHEC O26 binding to ruminant and human cells. In addition, we demonstrate for the first time that hectorites are able to initiate maturation of RAW 264.7 macrophages, inducing expression of co-stimulatory cytokines at a low nanoparticle concentration (10 μg/mL). Together these data strongly suggest that hectorite with optimized size is a highly efficient vaccine nano-adjuvant.
A Microscopic Shell Structure with Schwarz’s D-Surface
Authors: Han Seung Chul , Choi Jeong Myung , Liu Gang , Kang Kiju 
Published: October 2017

AbstractRecently, materials with micro-architecture of hollow trusses and ultralow density (less than 10–2 Mg/m3) have gained attention. The materials have been fabricated by forming templates based on 3D lithographical techniques, followed by hard coating on the surface, and finally etching out the template. Here, we describe a novel fabrication method for another micro architecture composed of a single continuous smooth-curved shell with D-surface, named Shellular; its template is prepared based on weaving flexible polymer wires. Compression test results reveal that these D-surfaced Shellulars have strength and Young’s modulus comparable to those of their hollow truss-based competitors. The best virtue of this weaving-based technology is its mass-productivity and large-size potential. Also, this technology can be applied to fabricate not only D-surfaced but also P- or G-surfaced Shellular. The unique geometry of Shellular, composed of a single continuous, smooth, and interfacial shell or membrane separating two equivalent sub-volumes intertwined with each other, appears to possess huge application potential such as non-clogging tissue engineering scaffolds and compact light-weight fuel cells with high energy density.
Bone Microarchitecture and Biomechanics of the Necrotic Femoral Head
Authors: Ma Jian-xiong , He Wei-wei , Zhao Jie , Kuang Ming-jie , Bai Hao-hao , Sun Lei , Lu Bin , Tian Ai-xian , Wang Ying , Dong Ben-chao , Wang Yan , Ma Xin-long 
Published: October 2017

AbstractThe mechanism behind osteonecrosis of the femoral head (ONFH) remains unclear. The aim of this study was to explore the pathogenesis of ONFH from a biomechanical standpoint to provide a theoretical basis for improved treatments. We compared the bone structure of fractured femoral heads with that of necrotic femoral heads by Micro-CT scanning and histological evaluation. In addition, we compared the biomechanical properties of each zone in fractured femoral heads with those in necrotic femoral heads by using biomechanical tests. Compared with fractured femoral heads, bone microarchitecture and bone morphometry in necrotic zone and sclerotic zone of necrotic femoral heads have altered markedly. In addition, the biomechanical properties of the necrotic zone in femoral heads weaken markedly, while those of the sclerotic zone strengthen. We hypothesize that discordance between bone structure and function of the femoral head may be involved in the pathogenesis of ONFH and that more attention should be paid to the prevention and treatment of such discordance.
GLRB variants regulate nearby gene expression in human brain tissues
Authors: Wu Qing-jian , Yang Ming-feng , Hao Pi-da , Yan Cheng-jun , Du Chun-jing , Li Han-xia , Hou Ya-jun , Sun Bao-liang , Sun Shu-yin 
Published: October 2017

AbstractA recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis. Here, we investigated the effect of these four genetic variants and the expression of three nearby genes including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6) and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that both rs17035816 and rs7688285 variants could significantly regulate PDGFC and GLRB gene expression. In Braineac dataset, the results showed that rs17035816 variant could significantly regulate GLRB and GRIA2 gene expression. We believe that these findings further provide important supplementary information about the regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.
Developmental stage-dependent regulation of spine formation by calcium-calmodulin-dependent protein kinase IIα and Rap1
Authors: Cornelia Koeberle Solveigh , Tanaka Shinji , Kuriu Toshihiko , Iwasaki Hirohide , Koeberle Andreas , Schulz Alexander , Helbing Dario-Lucas , Yamagata Yoko , Morrison Helen , Okabe Shigeo 
Published: October 2017

AbstractThe roles of calcium-calmodulin-dependent protein kinase II-alpha (CaMKIIα) in the expression of long-term synaptic plasticity in the adult brain have been extensively studied. However, how increased CaMKIIα activity controls the maturation of neuronal circuits remains incompletely understood. Herein, we show that pyramidal neurons without CaMKIIα activity upregulate the rate of spine addition, resulting in elevated spine density. Genetic elimination of CaMKIIα activity specifically eliminated the observed maturation-dependent suppression of spine formation. Enhanced spine formation was associated with the stabilization of actin in the spine and could be reversed by increasing the activity of the small GTPase Rap1. CaMKIIα activity was critical in the phosphorylation of synaptic Ras GTPase-activating protein (synGAP), the dispersion of synGAP from postsynaptic sites, and the activation of postsynaptic Rap1. CaMKIIα is already known to be essential in learning and memory, but our findings suggest that CaMKIIα plays an important activity-dependent role in restricting spine density during postnatal development.
Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide
Authors: Dodacki Agnès , Wortman Matthew , Saubaméa Bruno , Chasseigneaux Stéphanie , Nicolic Sophie , Prince Nathalie , Lochus Murielle , Raveu Anne-Laure , Declèves Xavier , Scherrmann Jean-Michel , Patel Shailendra B. , Bourasset Fanchon 
Published: October 2017

AbstractABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-β peptide (Aβ). ABCG4 is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary endothelial cells. Modelling studies of the Abcg4 dimer suggested that desmosterol showed thermodynamically favorable binding at the putative sterol-binding site, and this was greater than for cholesterol. Additionally, unbiased docking also showed Aβ binding at this site. Using a novel Abcg4-deficient mouse model, we show that Abcg4 was able to export Aβ and desmosterol at the BBB level and these processes could be inhibited by probucol and L-thyroxine. Our assay also showed that desmosterol antagonized the export of Aβ, presumably as both bind at the sterol-binding site on Abcg4. We show for the first time that Abcg4 may function in vivo to export Aβ at the BBB, in a process that can be antagonized by its putative natural ligand, desmosterol (and possibly cholesterol).
Composition-dependent nanoelectronics of amido-phenazines: non-volatile RRAM and WORM memory devices
Authors: Maiti Dilip K. , Debnath Sudipto , Nawaz Sk. Masum , Dey Bapi , Dinda Enakhi , Roy Dipanwita , Ray Sudipta , Mallik Abhijit , Hussain Syed A. 
Published: October 2017

AbstractA metal-free three component cyclization reaction with amidation is devised for direct synthesis of DFT-designed amido-phenazine derivative bearing noncovalent gluing interactions to fabricate organic nanomaterials. Composition-dependent organic nanoelectronics for nonvolatile memory devices are discovered using mixed phenazine-stearic acid (SA) nanomaterials. We discovered simultaneous two different types of nonmagnetic and non-moisture sensitive switching resistance properties of fabricated devices utilizing mixed organic nanomaterials: (a) sample-1(8:SA = 1:3) is initially off, turning on at a threshold, but it does not turn off again with the application of any voltage, and (b) sample-2 (8:SA = 3:1) is initially off, turning on at a sharp threshold and off again by reversing the polarity. No negative differential resistance is observed in either type. These samples have different device implementations: sample-1 is attractive for write-once-read-many-times memory devices, such as novel non-editable database, archival memory, electronic voting, radio frequency identification, sample-2 is useful for resistive-switching random access memory application.
Simultaneous hydrolysis of carbaryl and chlorpyrifos by Stenotrophomonas sp. strain YC-1 with surface-displayed carbaryl hydrolase
Authors: Yang Chao , Xu Xiaoqing , Liu Yanping , Jiang Hong , Wu Yunbo , Xu Ping , Liu Ruihua 
Published: October 2017

AbstractMany sites are often co-contaminated with multiple pesticides. To date, there are no reports on simultaneous degradation of different classes of pesticides by a natural microorganism. In this work, we aim at constructing a live biocatalyst able to simultaneously hydrolyze carbaryl and chlorpyrifos. For this purpose, carbaryl hydrolase (CH) was displayed on the cell surface of a chlorpyrifos-degrading bacterium Stenotrophomonas sp. strain YC-1 using N- and C-terminal domain of ice nucleation protein (INPNC) from Pseudomonas syringae INA5 as an anchoring motif. The localization of INPNC-CH fusion protein in the outer membrane fraction was demonstrated by cell fractionation followed by Western blot analysis. Surface display of INPNC-CH was further confirmed by proteinase accessibility experiment and immunofluorescence microscope. CH was present in an active form on cell surface without causing any growth inhibition, suggesting that the INP-based display system is a useful tool for surface expression of macromolecular heterologous proteins on the bacterial cell surface. Because surface-displayed CH has free access to pesticides, this bacterium can be used as a whole-cell biocatalyst for efficient hydrolysis of pesticides.
Proteomic analysis of human lacrimal and tear fluid in dry eye disease
Authors: Jung Jae Hun , Ji Yong Woo , Hwang Ho Sik , Oh Jae Won , Kim Hyun Chang , Lee Hyung Keun , Kim Kwang Pyo 
Published: October 2017

AbstractTo understand the pathophysiology of dry eye disease (DED), it is necessary to characterize proteins in the ocular surface fluids, including tear fluid (TF) and lacrimal fluid (LF). There have been several reports of TF proteomes, but few proteomic studies have examined LF secreted from the lacrimal gland (LG). Therefore, we characterized the proteins constituting TF and LF by liquid chromatography mass spectrometry. TF and LF were collected from patients with non-Sjögren syndrome DED and from healthy subjects. Through protein profiling and label-free quantification, 1165 proteins from TF and 1448 from LF were identified. In total, 849 proteins were present in both TF and LF. Next, candidate biomarkers were verified using the multiple reaction monitoring assay in both TF and LF of 17 DED patients and 17 healthy controls. As a result, 16 marker proteins were identified (fold-change > 1.5, p-value < 0.05), of which 3 were upregulated in TF and 8 up- and 5 down-regulated in LF. In conclusion, this study revealed novel DED markers originating from the LG and tears by in-depth proteomic analysis and comparison of TF and LF proteins.
TIPE2 negatively regulates mycoplasma pneumonia-triggered immune response via MAPK signaling pathway
Authors: Zhang Yuanyuan , Mei Shufen , Zhou Yunlian , Yang Dehua , Pan Ting , Chen Zhimin , Wang Qingqing 
Published: October 2017

AbstractExcessive immune responses played an important role in pathophysiology ofmycoplasma pneumonia(MP) infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immune response. This study investigated the expression change of TIPE2 and its role in immune defense against MP infection, as well as the underlying mechanisms. Expressions of TIPE2 both in patients and in macrophagesin vitroafter MP infection were measured. We further studied cytokine production and mitogen-activated protein kinase (MAPK) signaling function in macrophages with interfered expression of TIPE2 upon MP infection. A significant decrease of TIPE2 mRNA expression was observed in peripheral blood mononuclear cells (PBMCs) from MP patients, which was correlated with the severity of infection. Accordingly we found down-regulation of TIPE2 expression in macrophages after MP infection.In vitrostudy further suggested that TIPE2 jeopardized inflammatory cytokine production trigged by MP infection via inhibiting MAPK signaling pathway. These findings provided evidences of the novel function of TIPE2 in anti-MP immunity and its possible clinical utility related clinical significance.
3D- Printed Poly(ε-caprolactone) Scaffold Integrated with Cell-laden Chitosan Hydrogels for Bone Tissue Engineering
Authors: Dong Liang , Wang Shao-Jie , Zhao Xin-Rong , Zhu Yu-Fang , Yu Jia-Kuo 
Published: October 2017

AbstractSynthetic polymeric scaffolds are commonly used in bone tissue engineering (BTE) due to their biocompatibility and adequate mechanical properties. However, their hydrophobicity and the lack of specific cell recognition sites confined their practical application. In this study, to improve the cell seeding efficiency and osteoinductivity, an injectable thermo-sensitive chitosan hydrogel (CSG) was incorporated into a 3D-printed poly(ε-caprolactone) (PCL) scaffold to form a hybrid scaffold. To demonstrate the feasibility of this hybrid system for BTE application, rabbit bone marrow mesenchymal stem cells (BMMSCs) and bone morphogenetic protein-2 (BMP-2) were encapsulated in CSG. Pure PCL scaffolds were used as controls. Cell proliferation and viability were investigated. Osteogenic gene expressions of BMMSCs in various scaffolds were determined with reverse transcription polymerase chain reaction (RT-PCR). Growth factor releasing profile and mechanical tests were performed. CCK-8 assay confirmed greater cell retention and proliferation in chitosan and hybrid groups. Confocal microscopy showed even distribution of cells in the hybrid system. After 2-week osteogenic culture in vitro, BMMSCs in hybrid and chitosan scaffolds showed stronger osteogenesis and bone-matrix formation. To conclude, chitosan/PCL hybrid scaffolds are a favorable platform for BTE due to its capacity to carry cells and drugs, and excellent mechanical strength.