bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term stability and infectivity of herpesviruses in water
Authors: Dayaram Anisha , Franz Mathias , Schattschneider Alexander , Damiani Armando M. , Bischofberger Sebastian , Osterrieder Nikolaus , Greenwood Alex D. 
Published: April 2017

AbstractFor viruses to utilize environmental vectors (hard surfaces, soil, water) for transmission, physical and chemical stability is a prerequisite. There are many factors including pH, salinity, temperature, and turbidity that are known to contribute to the ability of viruses to persist in water. Equine herpesvirus type-1 (EHV-1) is a pathogenic alphaherpesvirus associated with domestic horses and wild equids. EHV-1 and recombinants of EHV-1 and EHV-9 are able to cause infections in non-equid animal species, particularly in captive settings. Many of the captive non-equid mammals are not naturally sympatric with equids and do not share enclosures, however, in many cases water sources may overlap. Similarly, in the wild, equids encounter many species at waterholes in times of seasonal drought. Therefore, we hypothesized that EHV-1 is stable in water and that water may act as a vector for EHV-1. In order to establish the conditions promoting or hindering EHV-1 longevity, infectivity and genomic stability in water; we exposed EHV-1 to varied water environments (pH, salinity, temperature, and turbidity) in controlled experiments over 21 days. The presence and infectivity of the virus was confirmed by both qPCR and cell culture experiments. Our results show that EHV-1 remains stable and infectious under many conditions in water for up to three weeks.
Sirtuins in the phylum Basidiomycota: A role in virulence in Cryptococcus neoformans
Authors: Arras Samantha D. M. , Chitty Jessica L. , Wizrah Maha S. I. , Erpf Paige E. , Schulz Benjamin L. , Tanurdzic Milos , Fraser James A. 
Published: April 2017

AbstractVirulence of Cryptococcus neoformans is regulated by a range of transcription factors, and is also influenced by the acquisition of adaptive mutations during infection. Beyond the temporal regulation of virulence factor production by transcription factors and these permanent microevolutionary changes, heritable epigenetic modifications such as histone deacetylation may also play a role during infection. Here we describe the first comprehensive analysis of the sirtuin class of NAD+ dependent histone deacetylases in the phylum Basidiomycota, identifying five sirtuins encoded in the C. neoformans genome. Each sirtuin gene was deleted and a wide range of phenotypic tests performed to gain insight into the potential roles they play. Given the pleiotropic nature of sirtuins in other species, it was surprising that only two of the five deletion strains revealed mutant phenotypes in vitro. However, cryptic consequences of the loss of each sirtuin were identified through whole cell proteomics, and mouse infections revealed a role in virulence for SIR2, HST3 and HST4. The most intriguing phenotype was the repeated inability to complement mutant phenotypes through the reintroduction of the wild-type gene. These data support the model that regulation of sirtuin activity may be employed to enable a drastic alteration of the epigenetic landscape and virulence of C. neoformans.
RETRACTED ARTICLE: Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity
Authors: Konstantinou Eleni K. , Notomi Shoji , Kosmidou Cassandra , Brodowska Katarzyna , Al-Moujahed Ahmad , Nicolaou Fotini , Tsoka Pavlina , Gragoudas Evangelos , Miller Joan W. , Young Lucy H. , Vavvas Demetrios G. 
Published: April 2017

AbstractVerteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth. Here, in a series of experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced HMWC require the presence of light. Furthermore, we showed that the mechanism of this cross-linking, which involves both singlet oxygen and radical generation, can occur very efficiently even after lysis of the cells, if the lysate is not protected from ambient light. This work offers a better understanding regarding VP’s mechanisms of action and suggests caution when one studies the non-light mediated actions of this drug.
A large-scale benchmark of gene prioritization methods
Authors: Guala Dimitri , Sonnhammer Erik L. L. 
Published: April 2017

AbstractIn order to maximize the use of results from high-throughput experimental studies, e.g. GWAS, for identification and diagnostics of new disease-associated genes, it is important to have properly analyzed and benchmarked gene prioritization tools. While prospective benchmarks are underpowered to provide statistically significant results in their attempt to differentiate the performance of gene prioritization tools, a strategy for retrospective benchmarking has been missing, and new tools usually only provide internal validations. The Gene Ontology(GO) contains genes clustered around annotation terms. This intrinsic property of GO can be utilized in construction of robust benchmarks, objective to the problem domain. We demonstrate how this can be achieved for network-based gene prioritization tools, utilizing the FunCoup network. We use cross-validation and a set of appropriate performance measures to compare state-of-the-art gene prioritization algorithms: three based on network diffusion, NetRank and two implementations of Random Walk with Restart, and MaxLink that utilizes network neighborhood. Our benchmark suite provides a systematic and objective way to compare the multitude of available and future gene prioritization tools, enabling researchers to select the best gene prioritization tool for the task at hand, and helping to guide the development of more accurate methods.
Micelle-template synthesis of hollow silica spheres for improving water vapor permeability of waterborne polyurethane membrane
Authors: Bao Yan , Wang Tong , Kang Qiaoling , Shi Chunhua , Ma Jianzhong 
Published: April 2017

AbstractHollow silica spheres (HSS) with special interior spaces, high specific surface area and excellent adsorption and permeability performance were synthesized via micelle-template method using cetyl trimethyl ammonium bromide (CTAB) micelles as soft template and tetraethoxysilane (TEOS) as silica precursor. SEM, TEM, FT-IR, XRD, DLS and BET-BJH were carried out to characterize the morphology and structure of as-obtained samples. The results demonstrated that the samples were amorphous with a hollow structure and huge specific surface area. The growth of HSS was an inward-growth mechanism along template. Notably, we have provided a new and interesting fundamental principle for HSS materials by precisely controlling the ethanol-to-water volume ratio. In addition, the as-obtained HSS were mixed with waterborne polyurethane (WPU) to prepare WPU/HSS composite membrane. Various characterizations (SEM, TEM, FT-IR and TGA) revealed the morphology, polydispersity and adherence between HSS and WPU. Performance tests showed that the introduction of HSS can improve the water vapor permeability of composite membrane, promoting its water resistance and mechanical performance at the same time.
The small G protein Arf6 expressed in keratinocytes by HGF stimulation is a regulator for skin wound healing
Authors: Miura Yuki , Ngo Thai Bich Van , Furuya Momoko , Hasegawa Hiroshi , Takahashi Satoru , Katagiri Naohiro , Hongu Tsunaki , Funakoshi Yuji , Ohbayashi Norihiko , Kanaho Yasunori 
Published: April 2017

AbstractThe earlier step of cutaneous wound healing process, re-epithelialization of the wounded skin, is triggered by a variety of growth factors. However, molecular mechanisms through which growth factors trigger skin wound healing are less understood. Here, we demonstrate that hepatocyte growth factor (HGF)/c-Met signaling-induced expression of the small G protein Arf6 mRNA in keratinocytes is essential for the skin wound healing. Arf6 mRNA expression was dramatically induced in keratinocytes at the wounded skin, which was specifically suppressed by the c-Met inhibitor. Wound healing of the skin was significantly delayed in keratinocyte-specific Arf6 conditional knockout mice. Furthermore, Arf6 deletion from keratinocytes remarkably suppressed HGF-stimulated cell migration and peripheral membrane ruffle formation, but did not affect skin morphology and proliferation/differentiation of keratinocytes. These results are consistent with the notion that Arf6 expressed in skin keratinocytes through the HGF/c-Met signaling pathway in response to skin wounding plays an important role in skin wound healing by regulating membrane dynamics-based motogenic cellular function of keratinocytes.
Attogram mass sensing based on silicon microbeam resonators
Authors: Baek In-Bok , Byun Sangwon , Lee Bong Kuk , Ryu Jin-Hwa , Kim Yarkyeon , Yoon Yong Sun , Jang Won Ik , Lee Seongjae , Yu Han Young 
Published: April 2017

AbstractUsing doubly-clamped silicon (Si) microbeam resonators, we demonstrate sub-attogram per Hertz (ag/Hz) mass sensitivity, which is extremely high sensitivity achieved by micro-scale MEMS mass sensors. We also characterize unusual buckling phenomena of the resonators. The thin-film based resonator is composed of a Si microbeam surrounded by silicon nitride (SiN) anchors, which significantly improve performance by providing fixation on the microbeam and stabilizing oscillating motion. Here, we introduce two fabrication techniques to further improve the mass sensitivity. First, we minimize surface stress by depositing a sacrificial SiN layer, which prevents damage on the Si microbeam. Second, we modify anchor structure to find optimal design that allows the microbeam to oscillate in quasi-one dimensional mode while achieving high quality factor. Mass loading is conducted by depositing Au/Ti thin films on the local area of the microbeam surface. Using sequential mass loading, we test effects of changing beam dimensions, position of mass loading, and distribution of a metal film on the mass sensitivity. In addition, we demonstrate that microbeams suffer local micro-buckling and global buckling by excessive mass loading, which are induced by two different mechanisms. We also find that the critical buckling length is increased by additional support from the anchors.
CD200-positive cancer associated fibroblasts augment the sensitivity of Epidermal Growth Factor Receptor mutation-positive lung adenocarcinomas to EGFR Tyrosine kinase inhibitors
Authors: Ishibashi Masayuki , Neri Shinya , Hashimoto Hiroko , Miyashita Tomoyuki , Yoshida Tatsuya , Nakamura Yuka , Udagawa Hibiki , Kirita Keisuke , Matsumoto Shingo , Umemura Shigeki , Yoh Kiyotaka , Niho Seiji , Tsuboi Masahiro , Masutomi Kenkichi , Goto Koichi , Ochiai Atsushi , Ishii Genichiro 
Published: April 2017

AbstractCancer associated fibroblasts (CAFs) play important roles in the chemotherapeutic process, especially through influencing the resistance of tumor cells to molecular targeted therapy. Here we report the existence of a special subpopulation of patient-specific-CAFs that augment the sensitivity of EGFR gene mutation-positive lung cancer to the EGFR-tyrosine kinase inhibitor (EGFR-TKI), gefitinib. When cocultured with EGFR mutation positive lung cancer cells, these CAFs increased the apoptic effect of gefitinib on cancer cells, whereas, in the absence of gefitinib, they did not affect cancer cell viability. The assay using different single cell-derived clones demonstrated that the aforementioned sensitizing ability is clone-specific. Microarray analysis revealed that CD200 was expressed at much higher levels in this CAFs. Knocking down of CD200 expression deprived CAFs of their sensitizing potential, suggesting that CD200 is the functional molecule responsible for the effect. Immunohistochemical analysis of samples from patients receiving postoperative gefitinib treatment revealed that the individuals whose resected lung adenocarcinomas contained CD200-positive CAFs tended to have longer progression free survival of gefitinib when they recurred after surgery. These results suggest that CD200-positive CAFs can augment the sensitivity to EGFR-TKIs and may possess far reaching applications in the therapeutic use of EGFR-TKIs.
Soft Electronics Enabled Ergonomic Human-Computer Interaction for Swallowing Training
Authors: Lee Yongkuk , Nicholls Benjamin , Sup Lee Dong , Chen Yanfei , Chun Youngjae , Siang Ang Chee , Yeo Woon-Hong 
Published: April 2017

AbstractWe introduce a skin-friendly electronic system that enables human-computer interaction (HCI) for swallowing training in dysphagia rehabilitation. For an ergonomic HCI, we utilize a soft, highly compliant (“skin-like”) electrode, which addresses critical issues of an existing rigid and planar electrode combined with a problematic conductive electrolyte and adhesive pad. The skin-like electrode offers a highly conformal, user-comfortable interaction with the skin for long-term wearable, high-fidelity recording of swallowing electromyograms on the chin. Mechanics modeling and experimental quantification captures the ultra-elastic mechanical characteristics of an open mesh microstructured sensor, conjugated with an elastomeric membrane. Systematic in vivo studies investigate the functionality of the soft electronics for HCI-enabled swallowing training, which includes the application of a biofeedback system to detect swallowing behavior. The collection of results demonstrates clinical feasibility of the ergonomic electronics in HCI-driven rehabilitation for patients with swallowing disorders.
A non-canonical binding interface in the crystal structure of HIV-1 gp120 core in complex with CD4
Authors: Duan Liang-Wei , Zhang Hui , Zhao Meng-Ting , Sun Ji-Xue , Chen Wen-Li , Lin Jian-Ping , Liu Xin-Qi 
Published: April 2017

AbstractNumerous crystal structures of HIV gp120 have been reported, alone or with receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without stabilization by an antibody is available. Here, we report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. Interestingly, in addition to the canonical binding surface, a second interacting interface was identified. A mutagenesis study on critical residues revealed that the stability of this interface is important for the efficiency of Env-mediated membrane fusion. Furthermore, we found that a broad neutralizing antibody, ibalizumab, which targets CD4 in the absence of gp120, occupies the same binding surface as the second interface identified here on gp120. Therefore, we identified the possibility of the involvement of a second gp120-CD4 interaction interface during viral entry, and also provided a reasonable explanation for the broad activity of neutralizing antibody ibalizumab.
Interleukin-6 increases the expression and activity of insulin-degrading enzyme
Authors: Kurauti Mirian A. , Costa-Júnior José M. , Ferreira Sandra M. , Santos Gustavo J. , Sponton Carlos H. G. , Carneiro Everardo M. , Telles Guilherme D. , Chacon-Mikahil Mara P. T. , Cavaglieri Cláudia R. , Rezende Luiz F. , Boschero Antonio C. 
Published: April 2017

AbstractImpairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml−1, increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.
Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways
Authors: Zhang Li , Wang Handong , Fan Youwu , Gao Yongyue , Li Xiang , Hu Zhigang , Ding Ke , Wang Yujie , Wang Xiaoliang 
Published: April 2017

AbstractFucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes effects. However, its roles in brain injury models have not been fully understood. The objective of this study was to investigate the neuroprotection of fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and Nrf2-autophagy pathways in the putative neuroprotection. We found that fucoxanthin alleviated TBI-induced secondary brain injury, including neurological deficits, cerebral edema, brain lesion and neuronal apoptosis. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fucoxanthin treatment. Furthermore, our in vitro studies demonstrated that fucoxanthin increased the neuron survival and reduced the reactive oxygen species (ROS) level. In addition, fucoxanthin activated the Nrf2-ARE pathway and autophagy both in vivo and in vitro, which was proven by the results of immunohistochemistry, western blot and electrophoretic mobility shift assay (EMSA). However, fucoxanthin failed to provide neuroprotection and activated autophagy following TBI in Nrf2−/− mice. In conclusion, our studies indicated that fucoxanthin provided neuroprotective effects in models of TBI, potentially via regulation of the Nrf2-ARE and Nrf2-autophagy pathways.
Compact InP spot‐size converter with vertically tapered core layer formed by micro‐loading effect
Authors: Ueda Y. , Ogiso Y. , Kashio N. , Hashizume Y. , Kikuchi N. , Ishikawa M. , Kohtoku M. 
Published: April 2017

A compact (200 μm) spot‐size converter (SSC) with a vertically tapered core layer is developed, which is fabricated with a simple wafer process using the micro‐loading effect. It is confirmed that the vertical spot size of the SSC exceeded 2 μm, which was double that of the original waveguide. As a result, an InP waveguide integrated with the SSCs exhibited a coupling loss of <1 dB per facet for a lensed fibre with a 2.5 μm mode‐field diameter. The fluctuation in the total of coupling and excess losses of the SSC was <0.5 dB.
Role of the LF-SINE–Derived Distal ISL1 Enhancer in Patients with Classic Bladder Exstrophy
Authors: Zhang Rong , Knapp Michael , Kause Franziska , Reutter Heiko , Ludwig Michael 
Published: April 2017

AbstractA genome-wide association study and meta-analysis identified ISL1 as the first genome-wide significant susceptibility gene for classic bladder exstrophy (CBE). A short interspersed repetitive element (SINE), first detected in lobe-finned fishes (LF-SINE), was shown to drive Isl1 expression in embryonic mouse genital eminence. Hence, we assumed this enhancer a conclusive target for mutations associated with CBE formation and analyzed a cohort of 200 CBE patients. Although we identified two enhancer variants in five CBE patients, their clinical significance seems unlikely, implying that sequence variants in the ISL1 LF-SINE enhancer are not frequently associated with CBE.
Comparison of Intact Parathyroid Hormone, Alkaline Phosphatase, Phosphate Levels for Diagnosing Severe Metabolic Bone Disease in Infants with Severe Bronchopulmonary Dysplasia
Authors: Tkach Erin , White Ammie , Dysart Kevin , Waber Brenda , Nawab Ursula , Zhang Huayan , Jensen Erik 
Published: April 2017

Objective We compared the accuracy of serum intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and phosphate (phos) levels for diagnosing severe metabolic bone disease (MBD) in very low-birth-weight (VLBW) infants with severe bronchopulmonary dysplasia (BPD).
Study Design Retrospective analysis of VLBW infants with severe BPD admitted between 2010 and 2012 and with ≥ 1 iPTH, ALP, and phos level collected within a similar 72-hour period. MBD severity was classified by serial radiography.
Results Laboratory values were available for 65 infants, of whom 24 (36.9%) developed severe MBD. A maximum ALP > 660 IU/L was the most accurate for diagnosing severe MBD (area under the curve: 88.4%; 95% confidence interval [CI]: 77.2–94.5%). Maximum iPTH was the least accurate (optimal cut point > 130 pg/mL; area under the curve: 70.5%; 95% CI: 58.2–81.4).
Conclusion Maximum ALP was more accurate than iPTH or phos for diagnosing severe MBD among preterm infants with severe BPD.
Unique molecular profile of exosomes derived from primary human proximal tubular epithelial cells under diseased conditions
Authors: Wang Xiangju , Wilkinson Ray , Kildey Katrina , Potriquet Jeremy , Mulvenna Jason , Lobb Richard J. , Möller Andreas , Cloonan Nicole , Mukhopadhyay Pamela , Kassianos Andrew J. , Healy Helen 
Published: April 2017

ABSTRACTHuman proximal tubular epithelial cells (PTEC) of the kidney are known to respond to and mediate the disease process in a wide range of kidney diseases, yet their exosomal production and exosome molecular cargo remain a mystery. Here we investigate, for the first time, the production and molecular content of exosomes derived from primary human PTEC cultured under normal and diseased conditions representing a spectrum of in vivo disease severity from early inflammation, experienced in multiple initial kidney disease states, through to hypoxia, frequently seen in late stage chronic kidney disease (CKD) due to fibrosis and vascular compromise. We demonstrate a rapid reproducible methodology for the purification of PTEC‐derived exosomes, identify increased numbers of exosomes from disease‐state cultures and identify differential expression levels of both known and unique miRNA and protein species from exosomes derived from different disease‐culture conditions. The validity of our approach is supported by the identification of miRNA, proteins and pathways with known CKD associations, providing a rationale to further evaluate these novel and known pathways as targets for therapeutic intervention.