bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of periprocedural complications of carotid artery stenting - a multivariate analysis of a single-centre experience
Authors: Vatan Mehmet Bulent , Acar Bilgehan Atılgan , Aksoy Murat , Can Yusuf , Varım Ceyhun , Agac Mustafa Tarik , Kilic Harun , Tatli Ersan , Gunduz Huseyin , Akdemir Ramazan
Published: June 2016

Abstract. Background: Carotid artery stenting (CAS) is currently used as an alternative treatment to carotid endarterectomy (CEA). The objective of this study was to analyse our 5-year experience performing CAS. Secondarily, we sought to determine independent risk factors which predict periprocedural complications. Patients and Methods: A total of 146 patients who underwent 153 CAS procedures were analysed. The majority of patients (123, 84.2%) had symptomatic carotid stenosis. Demographic and interventional data, angiographic lesion characteristics, and periprocedural complications were recorded. Using univariate and multivariate logistic regression analyses, risk factors associated with adverse clinical outcomes were determined. Results: Periprocedural neurological complications, including four (2.7 %) major strokes, three (2 %) transient ischaemic attacks, one (0.7%) amaurosis fugax, and two (1.3 %) cases of hyperperfusion syndrome occurred in ten (6.8%) patients. The incidence of periprocedural complications significantly increased in female patients (r = 0.214, p = 0.009) and patients with longer lesions (r = 0.183, p = 0.027), contralateral stenosis ≥50 % (r = 0.222, p = 0.007), the presence of complicated plaques (r = 0.478, p < 0.001) and inadequate glycaemic control (r = 0.259, p = 0.002). Multivariate regression analysis also determined four variables to be potential independent risk factors for 30-day adverse events: higher age (Odds ratio [OR] = 1.283; 95 % CI, 1.051 to 1.566, p = 0.014); longer lesions (OR = 1.459, 95 % CI, 1.124 to 1.893, p = 0.004); higher tortuosity index (OR = 1.015, 95 % CI, 1.001 to 1.030, p = 0.034), and the presence of complicated plaque morphology (OR = 4.321, 95 % CI, 1.621 to 10.23, p = 0.001). Conclusions: Patient and lesion characteristics including age, lesion length, complicated plaque morphology and tortuosity index, may be associated with periprocedural complications.
Vascular puncture site complications - diagnosis, therapy, and prognosis
Authors: Mlekusch Wolfgang , Mlekusch Irene , Sabeti-Sandor Schila
Published: June 2016

Abstract. The numbers of endovascular procedures have been noted to substantially increase over the past two decades. Besides all the technical advances and the increasing skills of more and more trained interventionists, the vascular access site still offers the possibilities and carries the risk of access site complications, which have not been changed dramatically over the past years. Guidelines on the vascular puncture procedure itself are lacking. Complications at different vascular access sites presentclinically different, require different diagnostic work up and therapy. The aim of the following review is to systematically list the most likely vascular access site complications their diagnosis and if necessary the proper treatment.
The effect of ambient temperature on the onset of acute Stanford type B aortic dissection
Authors: Li Yeni , Ji Chao , Zhang Jian , Han Yanshuo
Published: June 2016

Abstract. Background: The aim of this work was to study the associations between weather conditions and the occurrence of type B acute aortic dissections (ABAD). Patients and methods: This study was a retrospective review of all ABAD cases between January 1st, 2006 and December 31st, 2015. Using a time-series design and distributed lag non-linear models (DLNM), we estimated the relative risk (RR) of ABAD presentation associated with mean daily temperatures, including cumulative RR for a 28-day period, and RR for individual daily lags through 28 days. Results: A total of 213 patients were admitted with ABAD. A significant association was found between the daily maximal temperature and the number of hospital admissions for ABAD. The lower the maximal temperature, the higher the incidence of ABAD (P = 0.044). Furthermore, the onset of ABAD was higher in winter than in summer and autumn (P = 0.009 and P = 0.001). Based on a time-series analysis, this study showed that the associations between mean daily temperature and ABAD presentation were not monotonic. Compared to the centered temperature at 8°C, the cumulative 28-day (lag 0 to lag 27) RR was significantly elevated at - 20 °C and - 19 °C for ABAD (RR = 1.39; 95%CI: 1.02, 1.98 and RR = 1.36; 95%CI: 1.02, 1.98). At the extreme low temperature (- 17.7 °C) in Shenyang, the cumulative 14-day (lag 0 to 13 day) and 21-day (lag 0 to 20 day) RR were remarkably increased for ABAD (RRlag14-day = 1.34; 95%CI: 1.08, 1.40 and RRlag21-day = 1.06; 95%CI: 1.06, 1.23). For the extreme high temperature, however, no particular finding was detected regarding acute and prolonged effects on ABAD. Conclusions: In general, low ambient temperature was significantly associated with ABAD presentations in comparison with high temperature. The effects of cold were delayed by two weeks and persisted for a few days.
Impact of sex and age on carotid plaque instability in asymptomatic patients-results from the Munich Vascular Biobank
Authors: Wendorff Carina , Wendorff Heiko , Kuehnl Andreas , Tsantilas Pavlos , Kallmayer Michael , Eckstein Hans-Henning , Pelisek Jaroslav
Published: June 2016

Abstract. Background: It is still a controversial issue whether carotid endarterectomy (CEA) for asymptomatic carotid stenosis is superior to best medical treatment. The aim of this study was therefore to analyze the impact of sex and age on carotid plaque instability in asymptomatic patients undergoing CEA. Patients and methods: Atherosclerotic plaques from 465 asymptomatic patients with high-grade carotid artery stenosis (2004 - 2013) at the Munich Vascular Biobank were analyzed. Ascertainment of lesion stability/instability was performed on formalin-fixed paraffin-embedded tissue samples using hematoxylin-eosin and elastic van Gieson staining. Unstable plaques were considered lesions with a fibrous cap < 200 µm overlaying lipid-rich atheroma. Results: The average age of the patients was 69.3 ± 8.2 years. Independent of age, asymptomatic men had in total more frequently unstable plaques in contrast to women (41 % versus 52%, p = 0.042). No differences were found in plaque instability between age-related quartiles (< 65, 65- 69, 70 - 74, > 74 years) for female sex (p = 0.422). In men, a continuous increase in plaque instability with age was observed, without achieving statistical significance (p = 0.125). The greatest differences between male and female sex were found in the last quartile (> 74 years), without achieving statistical significance (p = 0.053). The chance of unstable carotid plaques in men was significantly higher than in women (OR = 1.562, p = 0.040). The probability of age-associated quartiles related to the first quartile demonstrated significant increase in plaque instability in the group of 65- to 69-year-old patients (OR 1.867, p = 0.024) and for patients older than 74 years (OR 1.740, p = 0.040). Conclusions: Asymptomatic men had in total more frequently unstable plaques in contrast to women. Thus, male sex seems to be an additional risk factor for ischemic stroke.
Geoscientists React to Brexit Vote
Authors: Wendel JoAnna
Published: June 2016

What does Brexit mean for research?
Clinical and genetic findings in a Chinese family with VDR-associated hereditary vitamin D-resistant rickets
Authors: Pang Qianqian , Qi Xuan , Jiang Yan , Wang Ou , Li Mei , Xing Xiaoping , Dong Jin , Xia Weibo
Published: June 2016

Hereditary vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. This disorder is caused by homogeneous or heterogeneous mutations affecting the function of the vitamin D receptor (VDR), which lead to complete or partial target organ resistance to the action of 1,25-dihydroxy vitamin D. A non-consanguineous family of Chinese Han origin with one affected individual demonstrating HVDRR was recruited, with the proband evaluated clinically, biochemically and radiographically. To identify the presence of mutations in the VDR gene, all the exons and exon–intron junctions of the VDR gene from all family members were amplified using PCR and sequenced. The proband showed rickets, progressive alopecia, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. She also suffered from epilepsy, which is rarely seen in patients with HVDRR. Direct sequencing analysis revealed a homozygous missense mutation c.122G>A (p.C41Y) in the VDR gene of the proband, which is located in the first zinc finger of the DNA-binding domain. Both parents had a normal phenotype and were found to be heterozygous for this mutation. We report a Chinese Han family with one individual affected with HVDRR. A homozygous missense mutation c.122G>A (p.C41Y) in the VDR gene was found to be responsible for the patient’s syndrome. In contrast to the results of treatment of HVDRR in other patients, our patient responded well to a supplement of oral calcium and a low dose of calcitriol.
Enhancing digestibility and ethanol yield of Populus wood via expression of an engineered monolignol 4-O-methyltransferase
Authors: Cai Yuanheng , Zhang Kewei , Kim Hoon , Hou Guichuan , Zhang Xuebin , Yang Huijun , Feng Huan , Miller Lisa , Ralph John , Liu Chang-Jun
Published: June 2016

Producing cellulosic biofuels and bio-based chemicals from woody biomass is impeded by the presence of lignin polymer in the plant cell wall. Manipulating the monolignol biosynthetic pathway offers a promising approach to improved processability, but often impairs plant growth and development. Here, we show that expressing an engineered 4-O-methyltransferase that chemically modifies the phenolic moiety of lignin monomeric precursors, thus preventing their incorporation into the lignin polymer, substantially alters hybrid aspens’ lignin content and structure. Woody biomass derived from the transgenic aspens shows a 62% increase in the release of simple sugars and up to a 49% increase in the yield of ethanol when the woody biomass is subjected to enzymatic digestion and yeast-mediated fermentation. Moreover, the cell wall structural changes do not affect growth and biomass production of the trees. Our study provides a useful strategy for tailoring woody biomass for bio-based applications.
Alterations of the human gut microbiome in multiple sclerosis
Authors: Jangi Sushrut , Gandhi Roopali , Cox Laura M. , Li Ning , von Glehn Felipe , Yan Raymond , Patel Bonny , Mazzola Maria Antonietta , Liu Shirong , Glanz Bonnie L. , Cook Sandra , Tankou Stephanie , Stuart Fiona , Melo Kirsy , Nejad Parham , Smith Kathleen , Topçuolu Begüm D. , Holden James , Kivisäkk Pia , Chitnis Tanuja , De Jager Philip L. , Quintana Francisco J. , Gerber Georg K. , Bry Lynn , Weiner Howard L.
Published: June 2016

The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS,n=60) and healthy controls (n=43). Microbiome alterations in MS include increases inMethanobrevibacterandAkkermansiaand decreases inButyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances ofPrevotellaandSutterella, and decreasedSarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gutMethanobrevibacterin MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.
Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury
Authors: Peng Jiyun , Gu Nan , Zhou Lijun , B Eyo Ukpong , Murugan Madhuvika , Gan Wen-Biao , Wu Long-Jun
Published: June 2016

Microglia and peripheral monocytes contribute to hypersensitivity in rodent models of neuropathic pain. However, the precise respective function of microglia and peripheral monocytes has not been investigated in these models. To address this question, here we combined transgenic mice and pharmacological tools to specifically and temporally control the depletion of microglia and monocytes in a mouse model of spinal nerve transection (SNT). We found that although microglia and monocytes are required during the initiation of mechanical allodynia or thermal hyperalgesia, these cells may not be as important for the maintenance of hypersensitivity. Moreover, we demonstrated that either resident microglia or peripheral monocytes are sufficient in gating neuropathic pain after SNT. We propose that resident microglia and peripheral monocytes act synergistically to initiate hypersensitivity and promote the transition from acute to chronic pain after peripheral nerve injury.
Structural lubricity under ambient conditions
Authors: Cihan Ebru , İpek Semran , Durgun Engin , Baykara Mehmet Z.
Published: June 2016

Despite its fundamental importance, physical mechanisms that govern friction are poorly understood. While a state of ultra-low friction, termed structural lubricity, is expected for any clean, atomically flat interface consisting of two different materials with incommensurate structures, some associated predictions could only be quantitatively confirmed under ultra-high vacuum (UHV) conditions so far. Here, we report structurally lubric sliding under ambient conditions at mesoscopic (∼4,000–130,000 nm2) interfaces formed by gold islands on graphite. Ab initio calculations reveal that the gold–graphite interface is expected to remain largely free from contaminant molecules, leading to structurally lubric sliding. The experiments reported here demonstrate the potential for practical lubrication schemes for micro- and nano-electromechanical systems, which would mainly rely on an atomic-scale structural mismatch between the slider and substrate components, via the utilization of material systems featuring clean, atomically flat interfaces under ambient conditions.
Industrial-scale separation of high-purity single-chirality single-wall carbon nanotubes for biological imaging
Authors: Yomogida Yohei , Tanaka Takeshi , Zhang Minfang , Yudasaka Masako , Wei Xiaojun , Kataura Hiromichi
Published: June 2016

Single-chirality, single-wall carbon nanotubes are desired due to their inherent physical properties and performance characteristics. Here, we demonstrate a chromatographic separation method based on a newly discovered chirality-selective affinity between carbon nanotubes and a gel containing a mixture of the surfactants. In this system, two different selectivities are found: chiral-angle selectivity and diameter selectivity. Since the chirality of nanotubes is determined by the chiral angle and diameter, combining these independent selectivities leads to high-resolution single-chirality separation with milligram-scale throughput and high purity. Furthermore, we present efficient vascular imaging of mice using separated single-chirality (9,4) nanotubes. Due to efficient absorption and emission, blood vessels can be recognized even with the use of ∼100-fold lower injected dose than the reported value for pristine nanotubes. Thus, 1 day of separation provides material for up to 15,000 imaging experiments, which is acceptable for industrial use.
miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy
Authors: Badal Shawn S. , Wang Yin , Long Jianyin , Corcoran David L. , Chang Benny H. , Truong Luan D. , Kanwar Yashpal S. , Overbeek Paul A. , Danesh Farhad R.
Published: June 2016

How the kidney responds to the metabolic cues from the environment remains a central question in kidney research. This question is particularly relevant to the pathogenesis of diabetic nephropathy (DN) in which evidence suggests that metabolic events in podocytes regulate chromatin structure. Here, we show that miR-93 is a critical metabolic/epigenetic switch in the diabetic milieu linking the metabolic state to chromatin remodelling. Mice with inducible overexpression of a miR-93 transgene exclusively in podocytes exhibit significant improvements in key features of DN. We identify miR-93 as a regulator of nucleosomal dynamics in podocytes. miR-93 has a critical role in chromatin reorganization and progression of DN by modulating its target Msk2, a histone kinase, and its substrate H3S10. These findings implicate a central role for miR-93 in high glucose-induced chromatin remodelling in the kidney, and provide evidence for a previously unrecognized role for Msk2 as a target for DN therapy.
Social inheritance can explain the structure of animal social networks
Authors: Ilany Amiyaal , Akçay Erol
Published: June 2016

The social network structure of animal populations has major implications for survival, reproductive success, sexual selection and pathogen transmission of individuals. But as of yet, no general theory of social network structure exists that can explain the diversity of social networks observed in nature, and serve as a null model for detecting species and population-specific factors. Here we propose a simple and generally applicable model of social network structure. We consider the emergence of network structure as a result of social inheritance, in which newborns are likely to bond with maternal contacts, and via forming bonds randomly. We compare model output with data from several species, showing that it can generate networks with properties such as those observed in real social systems. Our model demonstrates that important observed properties of social networks, including heritability of network position or assortative associations, can be understood as consequences of social inheritance.
Mummified precocial bird wings in mid-Cretaceous Burmese amber
Authors: Xing Lida , McKellar Ryan C. , Wang Min , Bai Ming , O’Connor Jingmai K. , Benton Michael J. , Zhang Jianping , Wang Yan , Tseng Kuowei , Lockley Martin G. , Li Gang , Zhang Weiwei , Xu Xing
Published: June 2016

Our knowledge of Cretaceous plumage is limited by the fossil record itself: compression fossils surrounding skeletons lack the finest morphological details and seldom preserve visible traces of colour, while discoveries in amber have been disassociated from their source animals. Here we report the osteology, plumage and pterylosis of two exceptionally preserved theropod wings from Burmese amber, with vestiges of soft tissues. The extremely small size and osteological development of the wings, combined with their digit proportions, strongly suggests that the remains represent precocial hatchlings of enantiornithine birds. These specimens demonstrate that the plumage types associated with modern birds were present within single individuals of Enantiornithes by the Cenomanian (99 million years ago), providing insights into plumage arrangement and microstructure alongside immature skeletal remains. This finding brings new detail to our understanding of infrequently preserved juveniles, including the first concrete examples of follicles, feather tracts and apteria in Cretaceous avialans.
Comprehensive stabilization mechanism of electron-beam irradiated polyacrylonitrile fibers to shorten the conventional thermal treatment
Authors: Park Sejoon , Yoo Seung Hwa , Kang Ha Ri , Jo Seong Mu , Joh Han-Ik , Lee Sungho
Published: June 2016

An electron beam was irradiated on polyacrylonitrile (PAN) fibers prior to thermal stabilization. The electron-beam irradiation effectively shortened the thermal stabilization process by one fourth compared with the conventional thermal stabilization process. A comprehensive mechanistic study was conducted regarding this shortening of the thermal stabilization by electron-beam irradiation. Various species of chain radicals were produced in PAN fibers by electron-beam irradiation and existed for a relatively long duration, as observed by electron spin resonance spectroscopy. Subsequently, these radicals were gradually oxidized to peroxy radicals in the presence of oxygen under storage or heating. We found that these peroxy radicals (CO"Equation missing") enabled such an effective shortcut of thermal stabilization by acting as intermolecular cross-linking and partial aromatization points in the low temperature range (100–130 °C) and as earlier initiation seeds of successive cyclization reactions in the next temperature range (>130–140 °C) of thermal stabilization. Finally, even at a low irradiation dose (200 kGy), followed by a short heat treatment (230 °C for 30 min), the PAN fibers were sufficiently stabilized to produce carbon fibers with tensile strength and modulus of 2.3 and 216 GPa, respectively, after carbonization.
Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway
Authors: Basak Trayambak , Tanwar Vinay Singh , Bhardwaj Gourav , Bhardwaj Nitin , Ahmad Shadab , Garg Gaurav , V Sreenivas , Karthikeyan Ganesan , Seth Sandeep , Sengupta Shantanu
Published: June 2016

Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001) and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD.
BC1 RNA motifs required for dendritic transport in vivo
Authors: Robeck Thomas , Skryabin Boris V. , Rozhdestvensky Timofey S. , Skryabin Anastasiya B. , Brosius Jürgen
Published: June 2016

BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo.
Central tendency effects in time interval reproduction in autism
Authors: Karaminis Themelis , Cicchini Guido Marco , Neil Louise , Cappagli Giulia , Aagten-Murphy David , Burr David , Pellicano Elizabeth
Published: June 2016

Central tendency, the tendency of judgements of quantities (lengths, durations etc.) to gravitate towards their mean, is one of the most robust perceptual effects. A Bayesian account has recently suggested that central tendency reflects the integration of noisy sensory estimates with prior knowledge representations of a mean stimulus, serving to improve performance. The process is flexible, so prior knowledge is weighted more heavily when sensory estimates are imprecise, requiring more integration to reduce noise. In this study we measure central tendency in autism to evaluate a recent theoretical hypothesis suggesting that autistic perception relies less on prior knowledge representations than typical perception. If true, autistic children should show reduced central tendency than theoretically predicted from their temporal resolution. We tested autistic and age- and ability-matched typical children in two child-friendly tasks: (1) a time interval reproduction task, measuring central tendency in the temporal domain; and (2) a time discrimination task, assessing temporal resolution. Central tendency reduced with age in typical development, while temporal resolution improved. Autistic children performed far worse in temporal discrimination than the matched controls. Computational simulations suggested that central tendency was much less in autistic children than predicted by theoretical modelling, given their poor temporal resolution.
Characterization, correction and de novo assembly of an Oxford Nanopore genomic dataset from Agrobacterium tumefaciens
Authors: Deschamps Stéphane , Mudge Joann , Cameron Connor , Ramaraj Thiruvarangan , Anand Ajith , Fengler Kevin , Hayes Kevin , Llaca Victor , Jones Todd J. , May Gregory
Published: June 2016

The MinION is a portable single-molecule DNA sequencing instrument that was released by Oxford Nanopore Technologies in 2014, producing long sequencing reads by measuring changes in ionic flow when single-stranded DNA molecules translocate through the pores. While MinION long reads have an error rate substantially higher than the ones produced by short-read sequencing technologies, they can generate de novo assemblies of microbial genomes, after an initial correction step that includes alignment of Illumina sequencing data or detection of overlaps between Oxford Nanopore reads to improve accuracy. In this study, MinION reads were generated from the multi-chromosome genome of Agrobacterium tumefaciens strain LBA4404. Errors in the consensus two-directional (sense and antisense) “2D” sequences were first characterized by way of comparison with an internal reference assembly. Both Illumina-based correction and self-correction were performed and the resulting corrected reads assembled into high-quality hybrid and non-hybrid assemblies. Corrected read datasets and assemblies were subsequently compared. The results shown here indicate that both hybrid and non-hybrid methods can be used to assemble Oxford Nanopore reads into informative multi-chromosome assemblies, each with slightly different outcomes in terms of contiguity and accuracy.
Rotational symmetry breaking in the topological superconductor SrxBi2Se3 probed by upper-critical field experiments
Authors: Pan Y. , Nikitin A. M. , Araizi G. K. , Huang Y. K. , Matsushita Y. , Naka T. , de Visser A.
Published: June 2016

Recently it was demonstrated that Sr intercalation provides a new route to induce superconductivity in the topological insulator Bi2Se3. Topological superconductors are predicted to be unconventional with an odd-parity pairing symmetry. An adequate probe to test for unconventional superconductivity is the upper critical field,Bc2. For a standard BCS layered superconductorBc2shows an anisotropy when the magnetic field is applied parallel and perpendicular to the layers, but is isotropic when the field is rotated in the plane of the layers. Here we report measurements of the upper critical field of superconducting SrxBi2Se3crystals (Tc = 3.0 K). Surprisingly, field-angle dependent magnetotransport measurements reveal a large anisotropy ofBc2when the magnet field is rotated in the basal plane. The large two-fold anisotropy, while six-fold is anticipated, cannot be explained with the Ginzburg-Landau anisotropic effective mass model or flux flow induced by the Lorentz force. The rotational symmetry breaking ofBc2indicates unconventional superconductivity with odd-parity spin-triplet Cooper pairs (Δ4-pairing) recently proposed for rhombohedral topological superconductors, or might have a structural nature, such as self-organized stripe ordering of Sr atoms.
Electroacupuncture ameliorates memory impairments by enhancing oligodendrocyte regeneration in a mouse model of prolonged cerebral hypoperfusion
Authors: Ahn Sung Min , Kim Yu Ri , Kim Ha Neui , Shin Yong-Il , Shin Hwa Kyoung , Choi Byung Tae
Published: June 2016

We modeled prolonged cerebral hypoperfusion in mice using bilateral common carotid artery stenosis (BCAS) and electroacupuncture (EA) stimulation was applied at two acupoints, Baihui (GV20) and Dazhui (GV14). In behavioral tests of memory, BCAS produced impairments in spatial and short-term memory in mice that were attenuated by therapeutic EA stimulation. Therapeutic use of EA in BCAS also enhanced oligodendrocyte (OL) differentiation from oligodendrocyte precursor cells (OPCs), in association with white matter improvements in the corpus callosum (CC). In PCR analyses of growth factor gene expression, significant positive changes in 3 genes were observed following EA stimulation in BCAS, and here we highlight alterations in neurotrophin-4/5 (NT4/5). We confirmed EA-mediated positive changes in the expression of NT4/5 and its receptor, tyrosine receptor kinase B (TrkB). Treatment of naïve and BCAS + EA animals with a selective TrkB antagonist, ANA-12, produced losses of myelin and cognitive function that were ameliorated by EA therapy. Moreover, following BCAS we observed an EA-dependent increase in phospho-activated CREB (a downstream mediator of NT4/5-TrkB signaling) in OPCs and OLs of the CC. Our results suggest that EA stimulation promotes the recovery of memory function following white matter injury via a mechanism that promotes oligodendrocyte regeneration and involves NT4/5-TrkB signaling.
Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood
Authors: Almstrup Kristian , Lindhardt Johansen Marie , Busch Alexander S. , Hagen Casper P. , Nielsen John E. , Petersen Jørgen Holm , Juul Anders
Published: June 2016

Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.
New insights about pilus formation in gut-adapted Lactobacillus rhamnosus GG from the crystal structure of the SpaA backbone-pilin subunit
Authors: Chaurasia Priyanka , Pratap Shivendra , von Ossowski Ingemar , Palva Airi , Krishnan Vengadesan
Published: June 2016

Thus far, all solved structures of pilin-proteins comprising sortase-assembled pili are from pathogenic genera and species. Here, we present the first crystal structure of a pilin subunit (SpaA) from a non-pathogen host (Lactobacillus rhamnosus GG). SpaA consists of two tandem CnaB-type domains, each with an isopeptide bond and E-box motif. Intriguingly, while the isopeptide bond in the N-terminal domain forms between lysine and asparagine, the one in the C-terminal domain atypically involves aspartate. We also solved crystal structures of mutant proteins where residues implicated in forming isopeptide bonds were replaced. Expectedly, the E-box-substituted E139A mutant lacks an isopeptide bond in the N-terminal domain. However, the C-terminal E269A substitution gave two structures; one of both domains with their isopeptide bonds present and another of only the N-terminal domain, but with an unformed isopeptide bond and significant conformational changes. This latter crystal structure has never been observed for any other Gram-positive pilin. Notably, the C-terminal isopeptide bond still forms in D295N-substituted SpaA, irrespective of E269 being present or absent. Although E-box mutations affect SpaA proteolytic and thermal stability, a cumulative effect perturbing normal pilus polymerization was unobserved. A model showing the polymerized arrangement of SpaA within the SpaCBA pilus is proposed.
SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice
Authors: Shen Zu T. , Sigalov Alexander B.
Published: June 2016

During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.
Virus-derived small RNAs in the penaeid shrimp Fenneropenaeus chinensis during acute infection of the DNA virus WSSV
Authors: Liu Chengzhang , Li Fuhua , Sun Yumiao , Zhang Xiaojun , Yuan Jianbo , Yang Hui , Xiang Jianhai
Published: June 2016

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are two classes of small RNAs (sRNAs) that are critical for virus-host interplay via the RNA interference (RNAi) pathway. One virus-derived siRNA and numerous miRNAs has been reported for the double-stranded DNA virus white spot syndrome virus (WSSV), however, the expression profiles of these different types of sRNAs have not been assessed. Here, by sequencing the sRNAs and mRNAs of WSSV-infected Chinese shrimp (Fenneropenaeus chinensis), we found that the viral transcripts were universally targeted by WSSV-derived siRNAs, supporting a pivotal role for RNAi in the anti-viral immunity of shrimp. The genesis of WSSV-derived siRNAs was associated with long RNA structures. Moreover, by separating miRNAs from siRNAs, 12 WSSV miRNAs were identified. Investigation of conserved viral miRNA targets in different host species indicated the involvement of viral miRNAs in host immune responses. Collectively, our data provide new insights into the role of the RNAi pathway in the interplay between DNA viruses and crustaceans.
Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization
Authors: Wu Tse-Hsiang , Kuo Yuan-Yeh , Lee Hsiao-Hui , Kuo Jean-Cheng , Ou Meng-Hsin , Chang Zee-Fen
Published: June 2016

It is known that ribosomal RNA (rRNA) synthesis is regulated by cellular energy and proliferation status. In this study, we investigated rRNA gene transcription in response to cytoskeletal stress. Our data revealed that the cell shape constrained by isotropic but not elongated micropatterns in HeLa cells led to a significant reduction in rRNA transcription dependent on ROCK. Expression of a dominant-active form of ROCK also repressed rRNA transcription. Isotropic constraint and ROCK over-activation led to different types of aberrant F-actin organization, but their suppression effects on rRNA transcription were similarly reversed by inhibition of histone deacetylase (HDAC) or overexpression of a dominant negative form of Nesprin, which shields the signal transmitted from actin filament to the nuclear interior. We further showed that the binding of HDAC1 to the active fraction of rDNA genes is increased by ROCK over-activation, thus reducing H3K9/14 acetylation and suppressing transcription. Our results demonstrate an epigenetic control of active rDNA genes that represses rRNA transcription in response to the cytoskeletal stress.
Functional map of arrestin binding to phosphorylated opsin, with and without agonist
Authors: Peterhans Christian , Lally Ciara C. M. , Ostermaier Martin K. , Sommer Martha E. , Standfuss Jörg
Published: June 2016

Arrestins desensitize G protein-coupled receptors (GPCRs) and act as mediators of signalling. Here we investigated the interactions of arrestin-1 with two functionally distinct forms of the dim-light photoreceptor rhodopsin. Using unbiased scanning mutagenesis we probed the individual contribution of each arrestin residue to the interaction with the phosphorylated apo-receptor (Ops-P) and the agonist-bound form (Meta II-P). Disruption of the polar core or displacement of the C-tail strengthened binding to both receptor forms. In contrast, mutations of phosphate-binding residues (phosphosensors) suggest the phosphorylated receptor C-terminus binds arrestin differently for Meta II-P and Ops-P. Likewise, mutations within the inter-domain interface, variations in the receptor-binding loops and the C-edge of arrestin reveal different binding modes. In summary, our results indicate that arrestin-1 binding to Meta II-P and Ops-P is similarly dependent on arrestin activation, although the complexes formed with these two receptor forms are structurally distinct.
Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients
Authors: Menzel Mandy , Akbarshahi Hamid , Bjermer Leif , Uller Lena
Published: June 2016

Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD.
Changes in cerebral metabolites in obstructive sleep apnea: a systemic review and meta-analysis
Authors: Xia Yunyan , Fu Yiqun , Xu Huajun , Guan Jian , Yi Hongliang , Yin Shankai
Published: June 2016

Cognitive impairment is associated with changes in cerebral metabolites in patients with obstructive sleep apnea (OSA). Several studies have used magnetic resonance spectroscopy (MRS) to detect variations in cerebral metabolites; however, the results have been inconsistent. This meta-analysis summarizes the differences in cerebral metabolites between patients with OSA and controls. Two electronic databases, PubMed and Embase, were searched for articles (published before March 31, 2016) describing studies that used MRS to evaluate the cerebral metabolite changes. The overall effects were measured using the weighted mean difference with a 95% confidence interval. Subgroup analysis and sensitivity analysis were used to explore the sources of between-study heterogeneity and the stability of the results. Publication bias was also evaluated. Thirteen studies were ultimately included. In the hippocampus, the N-acetylaspartate (NAA)/creatine ratio was lower in patients with OSA. In the frontal lobe, only the NAA/choline ratio was lower in patients with OSA. Cerebral metabolites are significantly altered in the hippocampus in patients with OSA. Further clinical studies are needed to explore the underlying mechanisms between OSA and the changes in cerebral metabolites in the brain.
Adaptation to second order stimulus features by electrosensory neurons causes ambiguity
Authors: Zhang Zhubo D. , Chacron Maurice J.
Published: June 2016

Understanding the coding strategies used to process sensory input remains a central problem in neuroscience. Growing evidence suggests that sensory systems process natural stimuli efficiently by ensuring a close match between neural tuning and stimulus statistics through adaptation. However, adaptation causes ambiguity as the same response can be elicited by different stimuli. The mechanisms by which the brain resolves ambiguity remain poorly understood. Here we investigated adaptation in electrosensory pyramidal neurons within different parallel maps in the weakly electric fish Apteronotus leptorhynchus. In response to step increases in stimulus variance, we found that pyramidal neurons within the lateral segment (LS) displayed strong scale invariant adaptation whereas those within the centromedial segment (CMS) instead displayed weaker degrees of scale invariant adaptation. Signal detection analysis revealed that strong adaptation in LS neurons significantly reduced stimulus discriminability. In contrast, weaker adaptation displayed by CMS neurons led to significantly lesser impairment of discriminability. Thus, while LS neurons display adaptation that is matched to natural scene statistics, thereby optimizing information transmission, CMS neurons instead display weaker adaptation and would instead provide information about the context in which these statistics occur. We propose that such a scheme is necessary for decoding by higher brain structures.
A new strategy for exploring the hierarchical structure of cancers by adaptively partitioning functional modules from gene expression network
Authors: Xu Junmei , Jing Runyu , Liu Yuan , Dong Yongcheng , Wen Zhining , Li Menglong
Published: June 2016

The interactions among the genes within a disease are helpful for better understanding the hierarchical structure of the complex biological system of it. Most of the current methodologies need the information of known interactions between genes or proteins to create the network connections. However, these methods meet the limitations in clinical cancer researches because different cancers not only share the common interactions among the genes but also own their specific interactions distinguished from each other. Moreover, it is still difficult to decide the boundaries of the sub-networks. Therefore, we proposed a strategy to construct a gene network by using the sparse inverse covariance matrix of gene expression data and divide it into a series of functional modules by an adaptive partition algorithm. The strategy was validated by using the microarray data of three cancers and the RNA-sequencing data of glioblastoma. The different modules in the network exhibited specific functions in cancers progression. Moreover, based on the gene expression profiles in the modules, the risk of death was well predicted in the clustering analysis and the binary classification, indicating that our strategy can be benefit for investigating the cancer mechanisms and promoting the clinical applications of network-based methodologies in cancer researches.
Circularly polarized laser emission induced in isotropic and achiral dye systems
Authors: Cerdán Luis , García-Moreno Sara , Costela Angel , García-Moreno Inmaculada , de la Moya Santiago
Published: June 2016

The production of efficient, tunable, and switchable circularly polarized laser emission would have far reaching implications in optical communications or biophotonics. In this work, it is demonstrated the direct generation of circularly polarized (CP) laser emission in achiral and isotropic dye laser systems without the use of extracavity polarizing elements, and without resorting to chiral dyes, chiral liquid crystal matrices, or interferometric methods. The origin of this ellipticity arises from the dynamic birefringence induced by the strong and polarized laser pumping and the subsequent orientation anisotropy of the excited molecular dipoles. A complete polarimetric characterization of the polarization state of conventional dye laser oscillators as a function of different experimental parameters is performed and it is shown that the generated light always possesses a certain level of circularity that changes in a distinctive way with pump energy and polarization. These results demonstrate that it is possible to generate and modulate CP laser light from efficient and photostable conventional laser dyes.