bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
Authors: Shved Natallia , Warsow Gregor , Eichinger Felix , Hoogewijs David , Brandt Simone , Wild Peter , Kretzler Matthias , Cohen Clemens D. , Lindenmeyer Maja T.
Published: August 2017

Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. In our study, genome-wide expression profiles of more than 200 renal biopsies from patients with different CKD stages revealed significant correlation of HIF-target genes with eGFR in glomeruli and tubulointerstitium. These correlations were positive and negative and in part compartment-specific. Microarrays of proximal tubular cells and podocytes with stable HIF1α and/or HIF2α suppression displayed cell type-specific HIF1/HIF2-dependencies as well as dysregulation of several pathways. WGCNA analysis identified gene sets that were highly coregulated within modules. Characterization of the modules revealed common as well as cell group- and condition-specific pathways, GO-Terms and transcription factors. Gene expression analysis of the hypoxia-interconnected pathways in patients with different CKD stages revealed an increased dysregulation with loss of renal function. In conclusion, our data clearly point to a compartment- and cell type-specific dysregulation of hypoxia-associated gene transcripts and might help to improve the understanding of hypoxia, HIF dysregulation, and transcriptional program response in CKD.
Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia
Authors: Paerewijck Oonagh , Maertens Brecht , Dreesen Leentje , Van Meulder Frederik , Peelaers Iris , Ratman Dariusz , Li Robert W. , Lubberts Erik , De Bosscher Karolien , Geldhof Peter
Published: August 2017

The protozoan parasite Giardia is a highly prevalent intestinal pathogen with a wide host range. Data obtained in mice, cattle and humans revealed the importance of IL-17A in the development of a protective immune response against Giardia. The aim of this study was to further unravel the protective effector mechanisms triggered by IL-17A following G. muris infection in mice, by an RNA-sequencing approach. C57BL/6 WT and C57BL/6 IL-17RA KO mice were orally infected with G. muris cysts. Three weeks post infection, intestinal tissue samples were collected for RNA-sequencing, with samples from uninfected C57BL/6 WT and C57BL/6 IL-17RA KO animals serving as negative controls. Differential expression analysis showed that G. muris infection evoked the transcriptional upregulation of a wide array of genes, mainly in animals with competent IL-17RA signaling. IL-17RA signaling induced the production of various antimicrobial peptides, such as angiogenin 4 and α- and β-defensins and regulated complement activation through mannose-binding lectin 2. The expression of the receptor that regulates the secretion of IgA into the intestinal lumen, the polymeric immunoglobulin receptor, was also dependent on IL-17RA signaling. Interestingly, the transcriptome data showed for the first time the involvement of the circadian clock in the host response following Giardia infection.
Identification and Characterization of a Bacterial Homolog of Chloride Intracellular Channel (CLIC) Protein
Authors: Gururaja Rao Shubha , Ponnalagu Devasena , Sukur Sowmya , Singh Harkewal , Sanghvi Shridhar , Mei Yixiao , Jin Ding J. , Singh Harpreet
Published: August 2017

Chloride intracellular channels (CLIC) are non-classical ion channels lacking a signal sequence for membrane targeting. In eukaryotes, they are implicated in cell volume regulation, acidification, and cell cycle. CLICs resemble the omega class of Glutathione S-transferases (GST), yet differ from them in their ability to form ion channels. They are ubiquitously found in eukaryotes but no prokaryotic homolog has been characterized. We found that indanyloxyacetic acid-94 (IAA-94), a blocker of CLICs, delays the growth of Escherichia coli. In silico analysis showed that the E. coli stringent starvation protein A (SspA) shares sequence and structural homology with CLICs. Similar to CLICs, SspA lacks a signal sequence but contains an omega GST fold. Electrophysiological analysis revealed that SspA auto-inserts into lipid bilayers and forms IAA-94-sensitive ion channels. Substituting the ubiquitously conserved residue leucine 29 to alanine in the pore-forming region increased its single-channel conductance. SspA is essential for cell survival during acid-induced stress, and we found that acidic pH increases the open probability of SspA. Further, IAA-94 delayed the growth of wild-type but not sspA null mutant E. coli. Our results for the first time show that CLIC-like proteins exist in bacteria in the form of SspA, forming functional ion channels.
Soft electroporation for delivering molecules into tightly adherent mammalian cells through 3D hollow nanoelectrodes
Authors: Caprettini Valeria , Cerea Andrea , Melle Giovanni , Lovato Laura , Capozza Rosario , Huang Jian-An , Tantussi Francesco , Dipalo Michele , De Angelis Francesco
Published: August 2017

Electroporation of in-vitro cultured cells is widely used in biological and medical areas to deliver molecules of interest inside cells. Since very high electric fields are required to electroporate the plasma membrane, depending on the geometry of the electrodes the required voltages can be very high and often critical to cell viability. Furthermore, in traditional electroporation configuration based on planar electrodes there is no a priori certain feedback about which cell has been targeted and delivered and the addition of fluorophores may be needed to gain this information. In this study we present a nanofabricated platform able to perform intracellular delivery of membrane-impermeable molecules by opening transient nanopores into the lipid membrane of adherent cells with high spatial precision and with the application of low voltages (1.5–2 V). This result is obtained by exploiting the tight seal that the cells present with 3D fluidic hollow gold-coated nanostructures that act as nanochannels and nanoelectrodes at the same time. The final soft-electroporation platform provides an accessible approach for controlled and selective drug delivery on ordered arrangements of cells.
Decoding disease-causing mechanisms of missense mutations from supramolecular structures
Authors: Hijikata Atsushi , Tsuji Toshiyuki , Shionyu Masafumi , Shirai Tsuyoshi
Published: August 2017

The inheritance modes of pathogenic missense mutations are known to be highly associated with protein structures; recessive mutations are mainly observed in the buried region of protein structures, whereas dominant mutations are significantly enriched in the interfaces of molecular interactions. However, the differences in phenotypic impacts among various dominant mutations observed in individuals are not fully understood. In the present study, the functional effects of pathogenic missense mutations on three-dimensional macromolecular complex structures were explored in terms of dominant mutation types, namely, haploinsufficiency, dominant-negative, or toxic gain-of-function. The major types of dominant mutation were significantly associated with the different types of molecular interactions, such as protein-DNA, homo-oligomerization, or intramolecular domain-domain interactions, affected by mutations. The dominant-negative mutations were biased toward molecular interfaces for cognate protein or DNA. The haploinsufficiency mutations were enriched on the DNA interfaces. The gain-of-function mutations were localized to domain-domain interfaces. Our results demonstrate a novel use of macromolecular complex structures for predicting the disease-causing mechanisms through inheritance modes.
Neuronal Encoding of Self and Others’ Head Rotation in the Macaque Dorsal Prefrontal Cortex
Authors: Lanzilotto M. , Gerbella M. , Perciavalle V. , Lucchetti C.
Published: August 2017

Following gaze is a crucial skill, in primates, for understanding where and at what others are looking, and often requires head rotation. The neural basis underlying head rotation are deemed to overlap with the parieto-frontal attention/gaze-shift network. Here, we show that a set of neurons in monkey’s Brodmann area 9/46dr (BA 9/46dr), which is involved in orienting processes and joint attention, becomes active during self head rotation and that the activity of these neurons cannot be accounted for by saccade-related activity (head-rotation neurons). Another set of BA 9/46dr neurons encodes head rotation performed by an observed agent facing the monkey (visually triggered neurons). Among these latter neurons, almost half exhibit the intriguing property of encoding both execution and observation of head rotation (mirror-like neurons). Finally, by means of neuronal tracing techniques, we showed that BA 9/46dr takes part into two distinct networks: a dorso/mesial network, playing a role in spatial head/gaze orientation, and a ventrolateral network, likely involved in processing social stimuli and mirroring others’ head. The overall results of this study provide a new, comprehensive picture of the role of BA 9/46dr in encoding self and others’ head rotation, likely playing a role in head-following behaviors.
Mucus organisation is shaped by colonic content; a new view
Authors: Kamphuis J. B. J. , Mercier-Bonin M. , Eutamène H. , Theodorou V.
Published: August 2017

The colonic mucus barrier is commonly described as a continuous double layer covering the epithelium, separating the microbiota from the intestinal tissue. This model is currently considered valid throughout the colon. The colon is characterised by regional anatomo-functional specificities such as presence and consistency of contents and location. In this study, we characterised the organisation of the colonic mucus barrier in proximal and distal colon of rodents by histological and FISH staining, taking into account aforementioned specificities. By using longitudinal sections and imaging extensive areas of tissue with and without colonic contents, we have obtained a spatiotemporal overview of mucus organisation in the colon. We describe for the first time that the colonic mucus layer covers the faeces instead of the epithelium in the distal colon. This faecal mucus layer confines the microbiota to the faeces and prevents it from remaining in empty distal colon. In the proximal colon, the mucus did not form a separating layer between bacteria and epithelium. We conclude that the organisation of colonic mucus is reliant on the presence of the colonic content, and the location within the colon. Our findings reopen the discussion on the nature of the colonic mucus barrier.
Identification of Polo-like kinases as potential novel drug targets for influenza A virus
Authors: Pohl Marie O. , von Recum-Knepper Jessica , Rodriguez-Frandsen Ariel , Lanz Caroline , Yángüez Emilio , Soonthornvacharin Stephen , Wolff Thorsten , Chanda Sumit K. , Stertz Silke
Published: August 2017

In recent years genome-wide RNAi screens have revealed hundreds of cellular factors required for influenza virus infections in human cells. The long-term goal is to establish some of them as drug targets for the development of the next generation of antivirals against influenza. We found that several members of the polo-like kinases (PLK), a family of serine/threonine kinases with well-known roles in cell cycle regulation, were identified as hits in four different RNAi screens and we therefore studied their potential as drug target for influenza. We show that knockdown of PLK1, PLK3, and PLK4, as well as inhibition of PLK kinase activity by four different compounds, leads to reduced influenza virus replication, and we map the requirement of PLK activity to early stages of the viral replication cycle. We also tested the impact of the PLK inhibitor BI2536 on influenza virus replication in a human lung tissue culture model and observed strong inhibition of virus replication with no measurable toxicity. This study establishes the PLKs as potential drug targets for influenza and contributes to a more detailed understanding of the intricate interactions between influenza viruses and their host cells.
The mechanism for the different effects of texture on yield strength and hardness of Mg alloys
Authors: Guo Feilong , Yu Huihui , Wu Chenyu , Xin Yunchang , He Cong , Liu Qing
Published: August 2017

A study regarding the effect of texture on tensile yield strength and hardness of an extruded Mg-15Gd-0.5Zr rod was performed, with a great emphasis laid on the relevant mechanisms. A 7% pre-tension along the extrusion direction (ED) in the solid solution condition was used to transform the texture from a broad distribution of basal poles with a peak approximately 45° with respect to the ED into a texture with basal poles largely perpendicular to the ED. This texture variation enhances the yield strength of peak aged sample by approximately 103 MPa, while hardly increases the peak hardness. The analysis about the ratio of the critical resolved shear stress (CRSS) to Schmid factor shows that this texture variation results in a larger fraction of grains favoring prismatic slip with a higher activation stress under tension along the ED. In contrast, the complex stress state during hardness test initiates multiple deformation modes, which renders the value of hardness insensitive to the texture variation. This different dependence of deformation modes on texture mainly accounts for the different increments in hardness and tensile yield strength.
Visualization and Detection of Ciliary Beating Pattern and Frequency in the Upper Airway using Phase Resolved Doppler Optical Coherence Tomography
Authors: Jing Joseph C. , Chen Jason J. , Chou Lidek , Wong Brian J. F. , Chen Zhongping
Published: August 2017

Ciliary motion plays a critical role in the overall respiratory health of the upper airway. These cilia beat at a native frequency and in a synchronized pattern to continuously transport foreign particulate trapped in a layer of mucous out of the upper airway. Disruption of ciliary motion can lead to severe respiratory diseases and compromised respiratory function. Currently, the study of cilia requires expensive high speed cameras and high powered microscopes which is unsuitable for in vivo imaging and diagnosis. Doppler based optical coherence tomography has the potential to visualize the microscopic motion of cilia during their beating cycle. We demonstrate the development of a high-speed Doppler optical coherence tomography system that not only can rapidly determine the cilia beat frequency, but also simultaneously visualize the temporal cilia beating pattern which plays critical roles in cilia function.
Vitrification versus slow freezing for human ovarian tissue cryopreservation: a systematic review and meta-anlaysis
Authors: Shi Qingquan , Xie Yidong , Wang Yan , Li Shangwei
Published: August 2017

Vitrification is a well-accepted procedure for cryopreservation of gametes and embryos. Less is known, however, about its performance in preserving ovarian tissue, for which slow freezing is the current convention. Increasing interest is being focused on vitrification, but there are as yet no standard protocols for its use with ovarian tissue. In part, this is because of the variety of cell types and complex nature of ovarian tissue. We performed a meta-analysis of 14 studies that compared vitrification with slow freezing for cryopreservation of ovarian tissue. In the pooled analysis, there was no significant difference between the two methods in terms of the proportion of intact primordial follicles, but vitrification was associated with significantly less DNA damage. Secondary endpoints included the number of stromal cells, significantly higher with vitrification, and primordial follicle density, which did not differ between the two methods. The present meta-analysis suggests that vitrification may be more effective than slow freezing, with less primordial follicular DNA strand breaks and better preservation of stromal cells. These advantages should lead to improved ovarian function after transplantation.
Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts
Authors: Shi Jindong , Feng Jingjing , Xie Juan , Mei Zhoufang , Shi Tianyun , Wang Shengmei , Du Yong , Yang Gong , Wu Yougen , Cheng Xiaojiao , Li Shanqun , Zhu Liming , Yang Chung S. , Tu Shuiping , Jie Zhijun
Published: August 2017

To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) — lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor — SB431542 and/or JAK2/STAT3 inhibitor — JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days. In co-culture systems, MFs secreted high levels of IL-6, while cancer cells produced high levels of TGF-β. Recombinant IL-6 and MF-CM activated STAT3 and upregulated TGF-β in cancer cells. In contrast, cancer cell-CM or TGF-β stimulated MFs to produce IL-6. Blockade of JAK2/STAT3 and TGF-β signaling by specific inhibitors significantly inhibited cell proliferation in vitro and tumor growth in vivo of lung cancer cells. Our study demontrated that the TGF-β and IL-6/JAK2/STAT3 signaling pathways form a positive feedback signaling loop that mediated the interactions between MFs and lung cancer cells. Targeted inhibiton of this signaling loop could be a new approach for lung cancer prevention and therapy.
Vascular Hysteresis Loops and Vascular Architecture Mapping in Patients with Glioblastoma treated with Antiangiogenic Therapy
Authors: Stadlbauer Andreas , Zimmermann Max , Oberndorfer Stefan , Doerfler Arnd , Buchfelder Michael , Heinz Gertraud , Roessler Karl
Published: August 2017

In this study, we investigated the variability of vascular hysteresis loop (VHL) shapes and the spatial heterogeneity of neovascularization and microvascular alterations using vascular architecture mapping (VAM) in patients with recurrent glioblastoma during bevacizumab mono-therapy. VAM data were acquired in 13 patients suffering from recurrent glioblastoma prior to and 3 months after bevacizumab treatment onset using a dual contrast agent injections approach as part of routine MRI. Two patients were additionally examined after the first cycle of bevacizumab to check for early treatment response. VHLs were evaluated as biomarker maps of neovascularization activity: microvessel type indicator (MTI) and curvature (Curv) of the VHL-long-axis. Early response to bevacizumab was dominated by reduction of smaller microvasculature (around 10 µm). In the 3-month follow-up, responding tumors additionally showed a reduction in larger microvasculature (>20 µm). VAM biomarker images revealed spatially heterogeneous microvascular alterations during bevacizumab treatment. Responding, non-responding, progressive, and remote-progressive tumor areas were observed. MTI may be useful to predict responding and non-responding tumor regions, and Curv to assess severity of vasogenic edema. Analysis of VHLs in combination with VAM biomarkers may lead to a new perspective on investigating the spatial heterogeneity of neovascularization and microvascular alterations in glioblastoma during antiangiogenic therapy.
Inflammation and bone mineral density: A Mendelian randomization study
Authors: Huang Jian V. , Schooling C. Mary
Published: August 2017

Osteoporosis is a common age-related disorder leading to an increase in osteoporotic fractures and resulting in significant suffering and disability. Inflammation may contribute to osteoporosis, as it does to many other chronic diseases. We examined whether inflammation is etiologically relevant to osteoporosis, assessed from bone mineral density (BMD), as a new potential target of intervention, or whether it is a symptom/biomarker of osteoporosis. We obtained genetic predictors of inflammatory markers from genome-wide association studies and applied them to a large genome wide association study of BMD. Using two-sample Mendelian randomization, we obtained unconfounded estimates of the effect of high-sensitivity C-reactive protein (hsCRP) on BMD at the forearm, femoral neck,﻿ an﻿d lumbar spine. After removing potentially pleiotropic single nucleotide polymorphisms (SNPs) possibly acting via obesity-related traits, hsCRP, based on 16 SNPs from genes including CRP, was not associated with BMD. A causal relation of hsCRP with lower BMD was not evident in this study.
Microplastics in Spanish Table Salt
Authors: Iñiguez Maria E. , Conesa Juan A. , Fullana Andres
Published: August 2017

Marine debris is widely recognized as a global environmental problem. One of its main components, microplastics, has been found in several sea salt samples from different countries, indicating that sea products are irremediably contaminated by microplastics. Previous studies show very confusing results, reporting amounts of microparticles (MPs) in salt ranging from zero to 680 MPs/kg, with no mention of the possible causes of such differences. Several errors in the experimental procedures used were found and are reported in the present work. Likewise, 21 different samples of commercial table salt from Spain have been analyzed for MPs content and nature. The samples comprise sea salts and well salts, before and after packing. The microplastic content found was of 50–280 MPs/kg salt, being polyethylene-terephthalate (PET) the most frequently found polymer, followed by polypropylene (PP) and polyethylene (PE), with no significant differences among all the samples. The results indicate that even though the micro-particles might originate from multiple sources, there is a background presence of microplastics in the environment.
Identification of Endogenous Reference Genes for RT-qPCR Expression Analysis in Urochloa brizantha Under Abiotic Stresses
Authors: Takamori Luciana Midori , Pereira Alyne Valéria Carrion , Maia Souza Gustavo , Vieira Luiz Gonzaga Esteves , Ferreira Ribas Alessandra
Published: August 2017

Urochloa brizantha is one of the most important warm season forage grasses in tropical countries. Despite its importance, there are few studies on gene expression in this species under stressful conditions. Real-time (RT-qPCR) is an accurate technique for gene quantification analysis, but reference genes must be validated under the same conditions used to assess the expression of the target genes. Here, we evaluated the stability of nine reference genes: Actin 12, Eukaryotic initiation factor 4 A, Elongation factor-1 alpha, FTSH protease 4, U2 auxiliary fator, Succinol Co-enzyme A, Tubulin alfa-5, Tubulin beta-6, Ubiquitin conjugating enzyme. Total RNA was extract from leaf tissues of U. brizantha subjected to 6, 12 and 24 h of cold and heat stresses (10 and 45 °C, respectively), and drought, including moderate (−0.5 to −0.7 MPa), severe (−1.1 to −1.8 MPa) and recovery after re-watering. The RefFinder web-based tool was used to rank the most stable reference genes for each stress. Elongation factor-1 alpha, Elongation factor-1 alpha or Ubiquitin conjugating enzyme, and Eukaryotic initiation factor 4 A were the most stable genes for heat, cold and drought stress, respectively. The expression of Rubisco large subunit gene was normalized against the most stable gene selected by ReFfinder for each stress.
Characterization of polycrystalline lead oxide for application in direct conversion X-ray detectors
Authors: Semeniuk O. , Grynko O. , Decrescenzo G. , Juska G. , Wang K. , Reznik A.
Published: August 2017

While polycrystalline lead oxide (poly-PbO) is known to be one of the most promising photoconductors for utilization in X-ray detectors, its major performance parameters such as charge yield and mobility-lifetime product (μτ) are still not well established and require further investigation. Combining the conventional X-ray induced photocurrent and pulse height spectroscopy techniques we examine the X-ray photogeneration and recombination processes in poly-PbO. The measurements indicate that the amount of energy required to release a single electron hole pair W± (inverse of charge yield) strongly depends on applied electric field and at 10 V/μm reaches ~20 eV/ehp. Fitting the measured pulse height spectra with the Hecht formula provided μτ for holes and electrons to be 4.1 × 10−8 cm2/V and 10−9 cm2/V, respectively. Obtained μτ values combined with recently reported mobility values of charge carriers in PbO suggest a new direction towards improvement of PbO technology by incorporation of Frisch grid or X-ray transistor architectures.
Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems
Authors: Udhane Sameer S. , Legeza Balazs , Marti Nesa , Hertig Damian , Diserens Gaëlle , Nuoffer Jean-Marc , Vermathen Peter , Flück Christa E.
Published: August 2017

Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells. Microarray analysis revealed changes in 693 genes after metformin treatment. Using high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS-NMR), we determined 38 intracellular metabolites. With bioinformatic tools we created an integrated pathway analysis to understand different intracellular processes targeted by metformin. Combined metabolomics and transcriptomics data analysis showed that metformin affects a broad range of cellular processes centered on the mitochondrium. Data confirmed several known effects of metformin on glucose and androgen metabolism, which had been identified in clinical and basic studies previously. But more importantly, novel links between the energy metabolism, sex steroid biosynthesis, the cell cycle and the immune system were identified. These omics studies shed light on a complex interplay between metabolic pathways in steroidogenic systems.
Histone/protein deacetylase 11 targeting promotes Foxp3+ Treg function
Authors: Huang Jianbing , Wang Liqing , Dahiya Satinder , Beier Ulf H. , Han Rongxiang , Samanta Arabinda , Bergman Joel , Sotomayor Eduardo M. , Seto Edward , Kozikowski Alan P. , Hancock Wayne W.
Published: August 2017

Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models. Global HDAC11 deletion had no effect on health or development, and compared to WT controls, Foxp3+ Tregs lacking HDAC11 showed increased suppressive function, and increased expression of Foxp3 and TGF-β. Likewise, compared to WT recipients, conditional deletion of HDAC11 within Tregs led to long-term survival of fully MHC-mismatched cardiac allografts, and prevented development of transplant arteriosclerosis in an MHC class II-mismatched allograft model. The translational significance of HDAC11 targeting was shown by the ability of an HDAC11i to promote long-term allograft allografts in fully MHC-disparate strains. These data are powerful stimuli for the further development and testing of HDAC11-selective pharmacologic inhibitors, and may ultimately provide new therapies for transplantation and autoimmune diseases.
Genomic signatures of local adaptation reveal source-sink dynamics in a high gene flow fish species
Authors: Cure Katherine , Thomas Luke , Hobbs Jean-Paul A. , Fairclough David V. , Kennington W. Jason
Published: August 2017

Understanding source-sink dynamics is important for conservation management, particularly when climatic events alter species’ distributions. Following a 2011 ‘marine heatwave’ in Western Australia, we observed high recruitment of the endemic fisheries target speciesChoerodon rubescens, towards the cooler (southern) end of its distribution. Here, we use a genome wide set of 14 559 single-nucleotide polymorphisms (SNPs) to identify the likely source population for this recruitment event. Most loci (76%) showed low genetic divergence across the species’ range, indicating high levels of gene flow and confirming previous findings using neutral microsatellite markers. However, a small proportion of loci showed strong patterns of differentiation and exhibited patterns of population structure consistent with local adaptation. Clustering analyses based on these outlier loci indicated that recruits at the southern end ofC.rubescens’ range originated 400 km to the north, at the centre of the species’ range, where average temperatures are up to 3 °C warmer. Survival of these recruits may be low because they carry alleles adapted to an environment different to the one they now reside in, but their survival is key to establishing locally adapted populations at and beyond the range edge as water temperatures increase with climate change.
Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China
Authors: Huang Rui , Wang Guiyang , Tian Chen , Liu Yong , Jia Bei , Wang Jian , Yang Yue , Li Yang , Sun Zhenhua , Yan Xiaomin , Xia Juan , Xiong Yali , Song Peixin , Zhang Zhaoping , Ding Weimao , Wu Chao
Published: August 2017

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.
Constructing the novel ultrafine amorphous iron oxyhydroxide/g-C3N4 nanosheets heterojunctions for highly improved photocatalytic performance
Authors: Yang Hongcen , Zhang Shouwei , Cao Ruya , Deng Xiaolong , Li Zhipeng , Xu Xijin
Published: August 2017

Ultrafine particles, more heterojunction interfaces and amorphous materials can effectively enhance the photocatalytic activity of photocatalysts. In this work, a facile in-situ precipitation method was developed to prepare ultrafine amorphous iron oxyhydroxide/ultrathin g-C3N4 nanosheets heterojunction composites. The amorphous iron oxyhydroxide possessed an ultrafine particle size and a wide range of visible light absorption. In this process, the ultrafine particles not only shortened the diffusion distance of photogenerated carriers, but also facilitated the formation of more heterojunctions with ultrathin g-C3N4 nanosheets. The photocatalytic activities were evaluated using rhodamine B, methylene blue, and methyl orange as pollution models under visible light irradiation. Notably, the optimal photocatalytic activity of a-FeOOH/CNNS-800 composite is ~17.8 times higher than that of CNNS towards the degradation of rhodamine B under visible light. The outstanding photocatalytic activities were ascribed to the narrower band gap, the enhanced visible light absorbance, abundant heterojunction interfaces, and the effective separation of the photogenerated charges driven by the matched band edge in the heterostructures. We trusted that the facile and easy-to-extend synthesis method can be further expanded to synthesize other ultrafine semiconductors coupled with g-C3N4 for enhancing the photocatalytic activities.
Generation and intracellular trafficking of a polysialic acid-carrying fragment of the neural cell adhesion molecule NCAM to the cell nucleus
Authors: Westphal Nina , Loers Gabriele , Lutz David , Theis Thomas , Kleene Ralf , Schachner Melitta
Published: August 2017

Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane. These treatments lead to activation of the fibroblast growth factor (FGF) receptor, phospholipase C (PLC), protein kinase C (PKC) and phosphoinositide-3-kinase (PI3K), and subsequently to phosphorylation of MARCKS. Moreover, the NCAM antibody triggers calmodulin-dependent activation of nitric oxide synthase, nitric oxide (NO) production, NO-dependent S-nitrosylation of matrix metalloprotease 9 (MMP9) as well as activation of matrix metalloprotease 2 (MMP2) and MMP9, whereas the ED peptide activates phospholipase D (PLD) and MMP2, but not MMP9. These results indicate that the nuclear PSA-carrying NCAM fragment is generated by distinct and functionally defined signal transducing mechanisms.
Colloidal Cu/ZnO catalysts for the hydrogenation of carbon dioxide to methanol: investigating catalyst preparation and ligand effects
Authors: Pike Sebastian D. , García-Trenco Andrés , White Edward R. , Leung Alice H. M. , Weiner Jonathan , Shaffer Milo S. P. , Williams Charlotte K.
Published: August 2017

This paper reports on the influences of the catalyst preparation method and ligand effects for a series of highly active Cu/ZnO colloidal catalysts for the hydrogenation of CO2 to methanol.
Heteroaryldisilenes: heteroaryl groups serve as electron acceptors for SiSi double bonds in intramolecular charge transfer transitions
Authors: Kosai Tomoyuki , Ishida Shintaro , Iwamoto Takeaki
Published: August 2017

Heteroaryldisilenes and related disilenes were synthesized. In addition to anthracene and acridine units, thiophene and bithiophene units act as acceptors for the SiSi double bonds.
[Cd(H2O)6]@{Cd6Cl4(nico)12[Hg(Tab)2(μ-Cl)]2}: a heterometallic host–guest icosidodecahedron cage via hierarchical assembly
Authors: Tang Xiao-Yan , Yu Hong , Gao Bin-Bin , Lang Jian-Ping
Published: August 2017

A reaction of [Hg(Tab)2(nico)](PF6) (Tab = 4-(trimethylammonio)benzenethiolate, nico = nicotinate) with equimolar CdCl2·2.5H2O afforded a unique heterometallic cage complex [Cd(H2O)6]@{Cd6Cl4(nico)12[Hg(Tab)2(μ-Cl)]2}.
Emerging investigators series: advances and challenges of graphitic carbon nitride as a visible-light-responsive photocatalyst for sustainable water purification
Authors: Zheng Qinmin , Shen Hongchen , Shuai Danmeng
Published: August 2017

Graphitic carbon nitride (g-C3N4) is a promising visible-light-responsive photocatalyst for sustainable water purification.
Dietary fucoidan of Acaudina molpadioides alters gut microbiota and mitigates intestinal mucosal injury induced by cyclophosphamide
Authors: Shi Hongjie , Chang Yaoguang , Gao Yuan , Wang Xiong , Chen Xin , Wang Yuming , Xue Changhu , Tang Qingjuan
Published: August 2017

Cyclophosphamide (cy) is a widely used cancer drug.
A roll-to-roll process for multi-responsive soft-matter composite films containing CsxWO3 nanorods for energy-efficient smart window applications
Authors: Liang Xiao , Guo Chongshen , Chen Mei , Guo Shumeng , Zhang Lanying , Li Fasheng , Guo Shaojun , Yang Huai
Published: August 2017

This work provides a roll-to-roll processed flexible multi-responsive smart film containing tungsten bronze nanorods and a liquid crystal–polymer composite.
Total synthesis and mass spectrometric analysis of a Mycobacterium tuberculosis phosphatidylglycerol featuring a two-step synthesis of (R)-tuberculostearic acid
Authors: Burugupalli Satvika , Richardson Mark B. , Williams Spencer J.
Published: August 2017

A two-step synthesis of (R)-tuberculostearic acid enables the total synthesis of aMycobacterium tuberculosisphosphatidylglycerol. Mass spectrometric fragmentation of synthetic PG regioisomers of acylation patterns.
Palladium-catalyzed tandem cyclization/sulfonylation of homoallenyl amides with sodium sulfinates
Authors: Wan Yimei , Zhang Jian , Chen Yongtao , Kong Lichun , Luo Fang , Zhu Gangguo
Published: August 2017

A palladium-catalyzed cyclizative sulfonylation of homoallenyl amides has been developed using sodium sulfinates as the sulfonylation reagent and PhI(O2CCF3)2 as the oxidant, providing a facile access to 2-amino-5-sulfonylmethylfurans in good to excellent yields.
High photovoltaic performance of as-cast devices based on new quinoxaline-based donor–acceptor copolymers
Authors: Zhao Mingzhi , Qiao Zi , Chen Xiaofeng , Jiang Chenglin , Li Xiaoyu , Li Yongfang , Wang Haiqiao
Published: August 2017

Two new quinoxaline-based copolymers with different alkylthio side chains show high photovoltaic performance in as-cast devices.
A glutamic acid-modified cellulose fibrous composite used for the adsorption of heavy metal ions from single and binary solutions
Authors: Li Meng , Liu Zhijiang , Wang Lidong , James Tony D. , Xiao Hui-Ning , Zhu Wei-Hong
Published: August 2017

A new glutamic acid modified cellulose fibrous composite has been developed for Cu2+and Hg2+adsorption. The adsorption reaction follows a pseudo-second-order model, indicating the overall rates for the adsorption on GMC are controlled by chemical adsorption.
Paper-based patterned 3D neural cultures as a tool to study network activity on multielectrode arrays
Authors: Dermutz Harald , Thompson-Steckel Greta , Forró Csaba , de Lange Victoria , Dorwling-Carter Livie , Vörös János , Demkó László
Published: August 2017

High-throughput platform targeting activity patterns of 3D neural cultures with arbitrary topology, by combining network-wide intracellular and local extracellular signals.
Top-down synthesis of zinc oxide based inks for inkjet printing
Authors: Sharma Sonia , Pande Sumukh S. , Swaminathan P.
Published: August 2017

A top-down approach for synthesizing pure and doped inkjet printable metal oxide inks.
The effect of the LiCoO2/Li7La3Zr2O12 ratio on the structure and electrochemical properties of nanocomposite cathodes for all-solid-state lithium batteries
Authors: Wakayama Hiroaki , Kawai Yasuaki
Published: August 2017

A LiCoO2/Li7La3Zr2O12 nanocomposite synthesized using a self-assembled block copolymer template exhibited a high capacity per active material, 135 mA h g−1.
Facile preparation and the stepwise formation mechanistic investigation of gram-scale nitrogen-doped graphene quantum dots
Authors: Tian Renbing , Zhong Suting , Wu Juan , Geng Yongliang , Zhou Baojing , Wang Qinghua , Jiang Wei
Published: August 2017

Gram scale N-doped GQDs were prepared using a facile one-pot method by polymerization of nitrilotriacetic acid, showing a purity of over 99% without a dialysis process, a synthetic yield of 46% and a quantum yield of 45.8%.
(K,Na)NbO3ferroelectrics: a new class of solid-state photochromic materials with reversible luminescence switching behavior
Authors: Sun Haiqin , Liu Jian , Wang Xusheng , Zhang Qiwei , Hao Xihong , An Shengli
Published: August 2017

A kind of new photosensitive material, Sm doped K0.5Na0.5NbO3(KNN) ceramics, exhibits excellent photochromism and reversible luminescence switching properties.
Approach of implementing phase encoded quantum square root of NOT gate
Authors: Dey S. , Mukhopadhyay S.
Published: August 2017

Quantum logic gates are the building blocks of quantum computer. Here in this Letter the authors propose a new technique of implementing quantum square root of NOT gate by phase encoding mechanism.
Influence of hydrostatic pressure on creeping discharge characteristics over solid/liquid insulating interfaces under AC and DC voltages
Authors: Beroual Abderrahmane , Khaled Usama
Published: August 2017

This study deals with the influence of hydrostatic pressure on discharges propagating at solid/liquid insulating interface submitted to a divergent electric field under AC and DC voltages. The investigated insulator samples are of phenoplast resin (bakelite) and the considered liquid is mineral oil. The experimental results show that the hydrostatic pressure and the waveform, amplitude and polarity of voltage greatly influence the characteristic parameters of creepage discharges. The stopping (or final) length, Lf, which is the maximum extension of these discharges increases with voltage; it is reduced when applying a hydrostatic pressure. Lf increases quasi‐linearly with the voltage and decreases quasi‐linearly when the hydrostatic pressure is increased, whatever the voltage waveform. These results are of great interest especially for design and dimensioning of insulation systems in high voltage oil‐filled apparatus and especially non‐breathing components.
β-Lactam-Synthon-Interceded Metal/Acid-Free Diastereoselective Access to Highly Functionalized Oxazol-5-ones and Dihydroimidazoles
Authors: Kumar Vipan , Singh Amandeep , Kaur Harleen , Sharma Palak , Anand Amit ,   Shalini
Published: August 2017

Facile diastereoselective access to functionalized oxazol-5-ones and dihydroimidazoles was accomplished through base-promoted intramolecular amidolysis and methoxide-assisted tandem intramolecular amidolysis/ring opening/intramolecular cyclization, respectively, of C-3-functionalized azetidin-2-ones.
Trends in Perioperative Venous Thromboembolism Associated with Major Noncardiac Surgery
Authors: Smilowitz Nathaniel , Gupta Navdeep , Guo Yu , Maldonado Thomas , Eikelboom John , Goldhaber Samuel , Bangalore Sripal , Berger Jeffrey
Published: August 2017

Background Venous thromboembolism (VTE) is a common vascular complication of noncardiac surgery.

Methods We evaluated national trends in perioperative in-hospital VTE incidence, management, and outcomes using a large database of hospital admissions from the United States. Patients aged ≥ 45 years undergoing major noncardiac surgery from 2005 to 2013 were identified from the National Inpatient Sample. In-hospital perioperative VTE was defined as lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and the incidence was evaluated over time. Multivariable regression models with demographics and comorbidities as covariates were generated to estimate adjusted odds ratios (aOR).

Results Major noncardiac surgery was performed in 9,431,442 hospitalizations that met inclusion criteria, and perioperative VTE occurred in 99,776 patients (1,057 per 100,000), corresponding to an annual incidence of ≈53,000 after applying sample weights. Over time, perioperative VTE per 100,000 surgeries increased by 135 (95% confidence interval [CI]: 107–163), from 925 in 2005 to 1,060 in 2013 (p for trend <0.001; aOR [for 2013 vs. 2005]: 1.22, 95% CI: 1.19–1.26), due to increases in nonfatal VTE rates (from 840 [per 100,000 surgeries] in 2005 to 987 in 2013; p for trend <0.001). Perioperative VTE occurred most frequently in patients undergoing thoracic (2.0%) and vascular surgery (1.8%). Mortality was higher in patients with VTE than those without VTE (aOR: 3.12, 95% CI: 3.05–3.20).

Conclusion Perioperative VTE occurs in approximately 1% of patients ≥45 years undergoing major noncardiac surgery, with increasing incidence of nonfatal VTE over time.
Induction of Diabetes Abolishes the Antithrombotic Effect of Clopidogrel in Apolipoprotein E–Deficient Mice
Authors: Sugidachi A. , Ohno K. , Jakubowski J. , Ito Y. , Tomizawa A. , Mizuno M.
Published: August 2017

Patients with acute coronary syndrome with diabetes mellitus (DM) exhibit an impaired platelet inhibitory response to clopidogrel which is only partially understood. DM was induced by the administration of streptozotocin (STZ) to 9-week-old mice. The antithrombotic effects of clopidogrel (10 mg/kg/d, orally × 5 days) were determined using a FeCl3-induced thrombosis model employing wild-type (WT), apolipoprotein E (apoE)-deficient, and diabetic apoE-deficient mice at 21 weeks. Antiplatelet effects were determined using flow cytometry. The antithrombotic effects of clopidogrel were similar in WT and apoE-deficient mice but were attenuated in diabetic apoE-deficient mice with the percent inhibition of thrombus area (µm2) by clopidogrel being 85.5% (WT mice), 75.0% (apoE-deficient mice), and 1.9% (diabetic apoE-deficient mice). The time to first occlusion and lumen stenosis also reflected a significant loss of the antithrombotic effects of clopidogrel in diabetic apoE-deficient mice. Ex vivo platelet activation, which was assessed using ADP-induced expression of activated glycoprotein IIb/IIIa, was completely inhibited by clopidogrel in these three groups of mice. In contrast, the effect of clopidogrel on the ex vivo expression of platelet P-selectin induced by protease-activated receptor 4–activating peptide was diminished in diabetic apoE-deficient mice compared with that in WT and apoE-deficient mice. These data suggest that diabetic apoE-deficient mice may serve as a useful model to better understand the impaired responses to clopidogrel in patients with DM, which may partially reflect a reduction of the effect of clopidogrel on thrombin-induced platelet activation.