bluuebunny/crossref_metadata_2025 huggingface dataset:
Principal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb
Authors: Breton-Provencher Vincent , Bakhshetyan Karen , Hardy Delphine , Bammann Rodrigo Roberto , Cavarretta Francesco , Snapyan Marina , Côté Daniel , Migliore Michele , Saghatelyan Armen
Published: August 2016

Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing.
Observation of an anisotropic Dirac cone reshaping and ferrimagnetic spin polarization in an organic conductor
Authors: Hirata Michihiro , Ishikawa Kyohei , Miyagawa Kazuya , Tamura Masafumi , Berthier Claude , Basko Denis , Kobayashi Akito , Matsuno Genki , Kanoda Kazushi
Published: August 2016

The Coulomb interaction among massless Dirac fermions in graphene is unscreened around the isotropic Dirac points, causing a logarithmic velocity renormalization and a cone reshaping. In less symmetric Dirac materials possessing anisotropic cones with tilted axes, the Coulomb interaction can provide still more exotic phenomena, which have not been experimentally unveiled yet. Here, using site-selective nuclear magnetic resonance, we find a non-uniform cone reshaping accompanied by a bandwidth reduction and an emergent ferrimagnetism in tilted Dirac cones that appear on the verge of charge ordering in an organic compound. Our theoretical analyses based on the renormalization-group approach and the Hubbard model show that these observations are the direct consequences of the long-range and short-range parts of the Coulomb interaction, respectively. The cone reshaping and the bandwidth renormalization, as well as the magnetic behaviour revealed here, can be ubiquitous and vital for many Dirac materials.
Magnetic measurements with atomic-plane resolution
Authors: Rusz Ján , Muto Shunsuke , Spiegelberg Jakob , Adam Roman , Tatsumi Kazuyoshi , Bürgler Daniel E. , Oppeneer Peter M. , Schneider Claus M.
Published: August 2016

Rapid development of magnetic nanotechnologies calls for experimental techniques capable of providing magnetic information with subnanometre spatial resolution. Available probes of magnetism either detect only surface properties, such as spin-polarized scanning tunnelling microscopy, magnetic force microscopy or spin-polarized low-energy electron microscopy, or they are bulk probes with limited spatial resolution or quantitativeness, such as X-ray magnetic circular dichroism or classical electron magnetic circular dichroism (EMCD). Atomic resolution EMCD methods have been proposed, although not yet experimentally realized. Here, we demonstrate an EMCD technique with an atomic size electron probe utilizing a probe-corrected scanning transmission electron microscope in its standard operation mode. The crucial element of the method is a ramp in the phase of the electron beam wavefunction, introduced by a controlled beam displacement. We detect EMCD signals with atomic-plane resolution, thereby bringing near-atomic resolution magnetic circular dichroism spectroscopy to hundreds of laboratories worldwide.
Dimensional crossover in semiconductor nanostructures
Authors: McDonald Matthew P. , Chatterjee Rusha , Si Jixin , Jankó Boldizsár , Kuno Masaru
Published: August 2016

Recent advances in semiconductor nanostructure syntheses provide unprecedented control over electronic quantum confinement and have led to extensive investigations of their size- and shape-dependent optical/electrical properties. Notably, spectroscopic measurements show that optical bandgaps of one-dimensional CdSe nanowires are substantially (approximately 100 meV) lower than their zero-dimensional counterparts for equivalent diameters spanning 5–10 nm. But what, exactly, dictates the dimensional crossover of a semiconductor’s electronic structure? Here we probe the one-dimensional to zero-dimensional transition of CdSe using single nanowire/nanorod absorption spectroscopy. We find that carrier electrostatic interactions play a fundamental role in establishing dimensional crossover. Moreover, the critical length at which this transition occurs is governed by the aspect ratio-dependent interplay between carrier confinement and dielectric contrast/confinement energies.
Impact of Preemptive Analgesia on inflammatory responses and Rehabilitation after Primary Total Knee Arthroplasty: A Controlled Clinical Study
Authors: Jianda Xu , Yuxing Qu , Yi Gao , Hong Zhao , Libo Peng , Jianning Zhao
Published: August 2016

The aim of this study was to investigate the effects of preemptive analgesia on the inflammatory response and rehabilitation in TKA. 75 patients with unilateral primary knee osteoarthritis were conducted in this prospective study. All patients were randomly divided into two groups (MMA with/without preemptive analgesia group). The following parameters were used to evaluate analgesic efficacy: knee flexion, pain at rest and walking, functional walking capacity (2 MWT and 6 MWT), WOMAC score and hs-CRP level. Patients in MMA with preemptive analgesia group had lower hs-CRP level and less pain at rest and walking during the first week postoperatively (P < 0.05). The 2 MWT was significantly better in MMA with preemptive analgesia group (17.13 ± 3.82 VS 14.19 ± 3.56, P = 0.001). The 6 MWT scores and WOMAC scores increased significantly within Groups (P = 0.020, 0.000), but no difference between groups postoperatively (P > 0.05). Less cumulative consumption of morphine was found in MMA with preemptive analgesia group at 48 h (P = 0.017, 0.023), but no difference at total requirement (P = 0.113). Preemptive analgesia added to a multimodal analgesic regime improved analgesia, reduced inflammatory reaction and accelerated functional recovery at the first week postoperatively, but not improved long-term function.
Combined neonicotinoid pesticide and parasite stress alter honeybee queens’ physiology and survival
Authors: Dussaubat Claudia , Maisonnasse Alban , Crauser Didier , Tchamitchian Sylvie , Bonnet Marc , Cousin Marianne , Kretzschmar André , Brunet Jean-Luc , Le Conte Yves
Published: August 2016

Honeybee colony survival strongly relies on the queen to overcome worker losses exposed to combined stressors like pesticides and parasites. Queen’s capacity to withstand these stressors is however very little known. The effects of the common neonicotinoid pesticide imidacloprid in a chronic and sublethal exposure together with the wide distributed parasite Nosema ceranae have therefore been investigated on queen’s physiology and survivorship in laboratory and field conditions. Early physiological changes were observed on queens, particularly the increase of enzyme activities (catalase [CAT] and glutathione-S-transferase [GST] in the heads) related to protective responses to xenobiotics and oxidative stress against pesticide and parasite alone or combined. Stressors also alter the activity of two other enzymes (carboxylesterase alpha [CaE α] and carboxylesterase para [CaE p] in the midguts) involved in metabolic and detoxification functions. Furthermore, single and combined effects of pesticide and parasite decrease survivorship of queens introduced into mating hives for three months. Because colony demographic regulation relies on queen’s fertility, the compromise of its physiology and life can seriously menace colony survival under pressure of combined stressors.
Empathy promotes altruistic behavior in economic interactions
Authors: Klimecki Olga M. , Mayer Sarah V. , Jusyte Aiste , Scheeff Jonathan , Schönenberg Michael
Published: August 2016

What are the determinants of altruism? While economists assume that altruism is mainly driven by fairness norms, social psychologists consider empathy to be a key motivator for altruistic behavior. To unite these two theories, we conducted an experiment in which we compared behavior in a standard economic game that assesses altruism (the so-called Dictator Game) with a Dictator Game in which participants’ behavioral choices were preceded either by an empathy induction or by a control condition without empathy induction. The results of this within-subject manipulation show that the empathy induction substantially increased altruistic behavior. Moreover, the increase in experienced empathy predicted over 40% of the increase in sharing behavior. These data extend standard economic theories that altruism is based on fairness considerations, by showing that empathic feelings can be a key motivator for altruistic behavior in economic interactions.
Fermi level pinning characterisation on ammonium fluoride-treated surfaces of silicon by energy-filtered doping contrast in the scanning electron microscope
Authors: Chee Augustus K. W.
Published: August 2016

Two-dimensional dopant profiling using the secondary electron (SE) signal in the scanning electron microscope (SEM) is a technique gaining impulse for its ability to enable rapid and contactless low-cost diagnostics for integrated device manufacturing. The basis is doping contrast from electricalp-njunctions, which can be influenced by wet-chemical processing methods typically adopted in ULSI technology. This paper describes the results of doping contrast studies by energy-filtering in the SEM from siliconp-njunction specimens that were etched in ammonium fluoride solution. Experimental SE micro-spectroscopy and numerical simulations indicate that Fermi level pinning occurred on the surface of the treated-specimen and that the doping contrast can be explained in terms of the ionisation energy integral for SEs, which is a function of the dopant concentration and surface band-bending effects that prevail in the mechanism for doping contrast as patch fields from the specimen are suppressed.
Minimum Copies of Schrödinger’s Cat State in the Multi-Photon System
Authors: Lu Yiping , Zhao Qing
Published: August 2016

Multi-photon entanglement has been successfully studied by many theoretical and experimental groups. However, as the number of entangled photons increases, some problems are encountered, such as the exponential increase of time necessary to prepare the same number of copies of entangled states in experiment. In this paper, a new scheme is proposed based on the Lagrange multiplier and Feedback, which cuts down the required number of copies of Schrödinger’s Cat state in multi-photon experiment, which is realized with some noise in actual measurements, and still keeps the standard deviation in the error of fidelity unchanged. It reduces about five percent of the measuring time of eight-photon Schrödinger’s Cat state compared with the scheme used in the usual planning of actual measurements, and moreover it guarantees the same low error in fidelity. In addition, we also applied the same approach to the simulation of ten-photon entanglement, and we found that it reduces in priciple about twenty two percent of the required copies of Schrödinger’s Cat state compared with the conventionally used scheme of the uniform distribution; yet the distribution of optimized copies of the ten-photon Schrödinger’s Cat state gives better fidelity estimation than the uniform distribution for the same number of copies of the ten-photon Schrödinger’s Cat state.
Doxorubicin Conjugated to Immunomodulatory Anticancer Lactoferrin Displays Improved Cytotoxicity Overcoming Prostate Cancer Chemo resistance and Inhibits Tumour Development in TRAMP Mice
Authors: Shankaranarayanan Jayanth Suryanarayanan , Kanwar Jagat R. , AL-Juhaishi Afrah Jalil Abd , Kanwar Rupinder K.
Published: August 2016

Advanced, metastatic, castration resistant and chemo-resistant prostate cancer has triggered change in the drug development landscape against prostate cancer. Bovine lactoferrin (bLf) is currently attracting attention in clinics for its anti-cancer properties and proven safety profile. bLf internalises into cancer cells via receptor mediated endocytosis, boosts immunity and complements chemotherapy. We employed bLf as an excellent functional carrier protein for delivering doxorubicin (Dox) into DU145 cells, CD44+/EpCAM+ double positive enriched DU145 3D prostaspheres and drug resistant ADR1000-DU145 cells, thus circumventing Dox efflux, to overcome chemo-resistance. Successful bLf-Dox conjugation with iron free or iron saturated bLf forms did not affect the integrity and functionality of bLf and Dox. bLf-Dox internalised into DU145 cells within 6 h, enhanced nuclear Dox retention up to 24 h and proved significantly effective (p < 0.001) in reducing LC50 value of Dox from 5.3 μM to 1.3 μM (4 fold). Orally fed iron saturated bLf-Dox inhibited tumour development, prolonged survival, reduced Dox induced general toxicity, cardiotoxicity, neurotoxicity in TRAMP mice and upregulated serum levels of anti-cancer molecules TNF-α, IFN-γ, CCL4 and CCL17. The study identifies promising potential of a novel and safer bLf-Dox conjugate containing a conventional cytotoxic drug along with bLf protein to target drug resistance.
The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering
Authors: Moreno-Jiménez Inés , Hulsart-Billstrom Gry , Lanham Stuart A. , Janeczek Agnieszka A. , Kontouli Nasia , Kanczler Janos M. , Evans Nicholas D. , Oreffo Richard OC
Published: August 2016

Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.
Biosimilar structural comparability assessment by NMR: from small proteins to monoclonal antibodies
Authors: Japelj Boštjan , Ilc Gregor , Marušič Jaka , Senčar Jure , Kuzman Drago , Plavec Janez
Published: August 2016

Biosimilar drug products must have a demonstrated similarity with respect to the reference product’s molecules in order to ensure both the effectiveness of the drug and the patients’ safety. In this paper the fusion framework of a highly sensitive NMR fingerprinting approach for conformational changes and mathematically-based biosimilarity metrics is introduced. The final goal is to translate the complex spectral information into biosimilarity scores, which are then used to estimate the degree of similarity between the biosimilar and the reference product. The proposed method was successfully applied to a small protein, i.e., filgrastim (neutropenia treatment), which is the first biosimilar approved in the United States, and a relatively large protein, i.e., monoclonal antibody rituximab (lymphoma treatment). This innovative approach introduces a new level of sensitivity to structural changes that are induced by, e.g., a small pH shift or other changes in the protein formulation.
TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis
Authors: Liu Jing , Dong Zheng , Zhu Qi , He Dongyi , Ma Yanyun , Du Aiping , He Fan , Zhao Dongbao , Xu Xia , Zhang Hui , jin Li , Wang Jiucun
Published: August 2016

While previous studies have researched in association analyses between TNFα promoter polymorphisms and responses to TNF blockers in spondyloarthritis patients, their results were conflicting. Therefore, we aimed to determine whether TNFα promoter polymorphisms could predict response to TNF blockers and find the source of heterogeneity. Data were extracted and analyzed from published articles and combined with our unpublished data. We found that the greatest potential sources of heterogeneity in the results were gender ratio, disease type, continents and TNF blockers. Then Stratification analysis showed that the TNFα −308 G allele and the −238 G allele predicted a good response to TNF blockers (OR = 2.64 [1.48–4.73]; 2.52 [1.46–4.37]). However, G alleles of TNFα −308 and −238 could predict the response to etanercept (OR = 4.02 [2.24–7.23]; 5.17 [2.29–11.67]) much more powerfully than the response to infiliximab/adalimumab (OR = 1.68 [1.02–2.78]; 1.28 [0.57–2.86]). TNFα −857 could not predict the response in either subgroup. Cumulative meta-analysis performed in ankylosing spondylitis patients presented the odds ratio decreased with stricter response criteria. In conclusion, TNFα −308 A/G and −238 A/G are more powerful to predict the response to Etanercept and it is dependent on the criteria of response.
Fully integrated reflection-mode photoacoustic, two-photon and second harmonic generation microscopy in vivo
Authors: Song Wei , Xu Qiang , Zhang Yang , Zhan Yang , Zheng Wei , Song Liang
Published: August 2016

The ability to obtain comprehensive structural and functional information from intact biological tissue in vivo is highly desirable for many important biomedical applications, including cancer and brain studies. Here, we developed a fully integrated multimodal microscopy that can provide photoacoustic (optical absorption), two-photon (fluorescence) and second harmonic generation (SHG) information from tissue in vivo, with intrinsically co-registered images. Moreover, using a delicately designed optical-acoustic coupling configuration, a high-frequency miniature ultrasonic transducer was integrated into a water-immersion optical objective, thus allowing all three imaging modalities to provide a high lateral resolution of ~290 nm with reflection-mode imaging capability, which is essential for studying intricate anatomy, such as that of the brain. Taking advantage of the complementary and comprehensive contrasts of the system, we demonstrated high-resolution imaging of various tissues in living mice, including microvasculature (by photoacoustics), epidermis cells, cortical neurons (by two-photon fluorescence) and extracellular collagen fibers (by SHG). The intrinsic image co-registration of the three modalities conveniently provided improved visualization and understanding of the tissue microarchitecture. The reported results suggest that, by revealing complementary tissue microstructures in vivo, this multimodal microscopy can potentially facilitate a broad range of biomedical studies, such as imaging of the tumor microenvironment and neurovascular coupling.
Drosophila Dullard functions as a Mad phosphatase to terminate BMP signaling
Authors: Urrutia Hugo , Aleman Abigail , Eivers Edward
Published: August 2016

Bone morphogenetic proteins (BMPs) are growth factors that provide essential signals for normal embryonic development and adult tissue homeostasis. A key step in initiating BMP signaling is ligand induced phosphorylation of receptor Smads (R-Smads) by type I receptor kinases, while linker phosphorylation of R-Smads has been shown to cause BMP signal termination. Here we present data demonstrating that the phosphatase Dullard is involved in dephosphorylating the Drosophila R-Smad, Mad and is integral in controlling BMP signal duration. We show that a hypomorphic Dullard allele or Dullard knockdown leads to increased Mad phosphorylation levels, while Dullard overexpression resulted in reduced Mad phosphorylations. Co-immunoprecipitation binding assays demonstrate phosphorylated Mad and Dullard physically interact, while mutation of Dullard’s phosphatase domain still allowed Mad-Dullard interactions but abolished its ability to regulate Mad phosphorylations. Finally, we demonstrate that linker and C-terminally phosphorylated Mad can be regulated by one of two terminating mechanisms, degradation by proteasomes or dephosphorylation by the phosphatase Dullard.
Tensile deformation mechanisms of an in-situ Ti-based metallic glass matrix composite at cryogenic temperature
Authors: Bai J. , Li J. S. , Qiao J. W. , Wang J. , Feng R. , Kou H. C. , Liaw P. K.
Published: August 2016

Remarkable tensile ductility was first obtained in an in-situ Ti-based bulk metallic glass (BMG) composite at cryogenic temperature (77 K). The novel cryogenic tensile plasticity is related to the effective accommodation of ductile body-centered cubic dendrites at 77 K, characteristic of the prevailing slip bands and dislocations, as well as lattice disorder, which can effectively hinder the propagation of critical shear bands. The greatly increased yield strength of dendrites contributes to the high yield strength of composite at 77 K. A trend of stronger softening is observed at low temperature and a criterion is proposed to understand the softening behavior. The current research could also provide a guidance to the promising cryogenic application of these new advanced BMG composites.
CRISPR/Cas9-mediated efficient targeted mutagenesis in Chardonnay (Vitis vinifera L.)
Authors: Ren Chong , Liu Xianju , Zhang Zhan , Wang Yi , Duan Wei , Li Shaohua , Liang Zhenchang
Published: August 2016

The type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system (CRISPR/Cas9) has been successfully applied to edit target genes in multiple plant species. However, it remains unknown whether this system can be used for genome editing in grape. In this study, we described genome editing and targeted gene mutation in ‘Chardonnay’ suspension cells and plants via the CRISPR/Cas9 system. Two single guide RNAs (sgRNAs) were designed to target distinct sites of the L-idonate dehydrogenase gene (IdnDH). CEL I endonuclease assay and sequencing results revealed the expected indel mutations at the target site, and a mutation frequency of 100% was observed in the transgenic cell mass (CM) as well as corresponding regenerated plants with expression of sgRNA1/Cas9. The majority of the detected mutations in transgenic CM were 1-bp insertions, followed by 1- to 3-nucleotide deletions. Off-target activities were also evaluated by sequencing the potential off-target sites, and no obvious off-target events were detected. Our results demonstrated that the CRISPR/Cas9 system is an efficient and specific tool for precise genome editing in grape.
Achieving ultranarrow graphene perfect absorbers by exciting guided-mode resonance of one-dimensional photonic crystals
Authors: Long Yongbing , Shen Liang , Xu Haitao , Deng Haidong , Li Yuanxing
Published: August 2016

Graphene perfect absorbers with ultranarrow bandwidth are numerically proposed by employing a subwavelength dielectric grating to excite the guided-mode resonance of one-dimensional photonic crystals (1DPCs). Critical coupling of the guided-mode resonance of 1DPCs to graphene can produce perfect absorption with a ultranarrow bandwidth of 0.03 nm. The quality factor of the absorption peak reaches a ultrahigh value of 20000. It is also found that the resonant absorption peaks can be tuned by controlling the dispersion line of the guided mode and the period of the grating. When the parameters of the grating and the 1DPCs are suitably set, the perfect absorption peaks can be tuned to any randomly chosen wavelength in the visible wavelength range.
Characterization and genome functional analysis of a novel metamitron-degrading strain Rhodococcus sp. MET via both triazinone and phenyl rings cleavage
Authors: Fang Hua , Xu Tianheng , Cao Duantao , Cheng Longyin , Yu Yunlong
Published: August 2016

A novel bacterium capable of utilizing metamitron as the sole source of carbon and energy was isolated from contaminated soil and identified as Rhodococcus sp. MET based on its morphological characteristics, BIOLOG GP2 microplate profile and 16S rDNA phylogeny. Genome sequencing and functional annotation of the isolate MET showed a 6,340,880 bp genome with a 62.47% GC content and 5,987 protein-coding genes. In total, 5,907 genes were annotated with the COG, GO, KEGG, Pfam, Swiss-Prot, TrEMBL and nr databases. The degradation rate of metamitron by the isolate MET obviously increased with increasing substrate concentrations from 1 to 10 mg/l and subsequently decreased at 100 mg/l. The optimal pH and temperature for metamitron biodegradation were 7.0 and 20–30 °C, respectively. Based on genome annotation of the metamitron degradation genes and the metabolites detected by HPLC-MS/MS, the following metamitron biodegradation pathways were proposed: 1) Metamitron was transformed into 2-(3-hydrazinyl-2-ethyl)-hydrazono-2-phenylacetic acid by triazinone ring cleavage and further mineralization; 2) Metamitron was converted into 3-methyl-4-amino-6(2-hydroxy-muconic acid)-1,2,4-triazine-5(4H)-one by phenyl ring cleavage and further mineralization. The coexistence of diverse mineralization pathways indicates that our isolate may effectively bioremediate triazinone herbicide-contaminated soils.
Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis
Authors: Solé Cristina , Solà Elsa , Morales-Ruiz Manuel , Fernàndez Guerau , Huelin Patricia , Graupera Isabel , Moreira Rebeca , de Prada Gloria , Ariza Xavier , Pose Elisa , Fabrellas Núria , Kalko Susana G. , Jiménez Wladimiro , Ginès Pere
Published: August 2016

ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1 and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1 and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis.
Patient characteristics and risk factors of early and late death in incident peritoneal dialysis patients
Authors: Liu Xinhui , Huang Rong , Wu Haishan , Wu Juan , Wang Juan , Yu Xueqing , Yang Xiao
Published: August 2016

This study was conducted to identify key patient characteristics and risk factors for peritoneal dialysis (PD) mortality in terms of different time-point of death occurrence. The incident PD patients from January 1, 2006 to December 31, 2013 in our PD center were recruited and followed up until December 31, 2015. Patients who died in the early period (the first 3 months) were older, had higher neutrophil to lymphocyte ratio (N/L), serum phosphorus and uric acid level and had lower diastolic pressure, hemoglobin, serum albumin and calcium levels. After adjustment of gender, age and PD inception, higher N/L level [hazard ratio (HR) 1.115, P = 0.006], higher phosphorus lever (HR 1.391, P < 0.001), lower hemoglobin level (HR 0.596, P < 0.001) and lower serum albumin level (HR 0.382, P = 0.017) were risk factors for early mortality. While, presence of diabetes (HR 1.627, P = 0.001), presence of cardiovascular disease (HR 1.847, P < 0.001) and lower serum albumin level (HR 0.720, P = 0.023) were risk factors for late mortality (over 24 months). In conclusion, patient characteristics and risk factors associated with early and late mortality in incident PD patients were different, which indicated specific management according to patient characteristics at the initiation of PD should be established to improve PD patient survival.
Time series analysis of temporal trends in the pertussis incidence in Mainland China from 2005 to 2016
Authors: Zeng Qianglin , Li Dandan , Huang Gui , Xia Jin , Wang Xiaoming , Zhang Yamei , Tang Wanping , Zhou Hui
Published: August 2016

Short-term forecast of pertussis incidence is helpful for advanced warning and planning resource needs for future epidemics. By utilizing the Auto-Regressive Integrated Moving Average (ARIMA) model and Exponential Smoothing (ETS) model as alterative models with R software, this paper analyzed data from Chinese Center for Disease Control and Prevention (China CDC) between January 2005 and June 2016. The ARIMA (0,1,0)(1,1,1)12 model (AICc = 1342.2 BIC = 1350.3) was selected as the best performing ARIMA model and the ETS (M,N,M) model (AICc = 1678.6, BIC = 1715.4) was selected as the best performing ETS model and the ETS (M,N,M) model with the minimum RMSE was finally selected for in-sample-simulation and out-of-sample forecasting. Descriptive statistics showed that the reported number of pertussis cases by China CDC increased by 66.20% from 2005 (4058 cases) to 2015 (6744 cases). According to Hodrick-Prescott filter, there was an apparent cyclicity and seasonality in the pertussis reports. In out of sample forecasting, the model forecasted a relatively high incidence cases in 2016, which predicates an increasing risk of ongoing pertussis resurgence in the near future. In this regard, the ETS model would be a useful tool in simulating and forecasting the incidence of pertussis and helping decision makers to take efficient decisions based on the advanced warning of disease incidence.
MicroRNA-3713 regulates bladder cell invasion via MMP9
Authors: Wu Wen-Bo , Wang Wei , Du Yi-Heng , Li Hao , Xia Shu-Jie , Liu Hai-Tao
Published: August 2016

Transitional cell carcinoma (TCC) is the most common type of bladder cancer but its carcinogenesis remains not completely elucidated. Dysregulation of microRNAs (miRNAs) is well known to be involved in the development of various cancers, including TCC, whereas a role of miR-3713 in the pathogenesis of TCC has not been appreciated. Here, we reported that significantly higher levels of matrix metallopeptidase 9 (MMP9) and significantly lower levels of miR-3713 were detected in TCC tissue, compared to the adjacent non-tumor tissue and were inversely correlated. Moreover, the low miR-3713 levels in TCC specimens were associated with poor survival of the patients. In vitro, overexpression of miR-3713 significantly decreased cell invasion and depletion of miR-3713 increased cell invasion in TCC cells. The effects of miR-3713 on TCC cell growth appeared to result from its modification of MMP9 levels, in which miR-3713 was found to bind to the 3′-UTR of MMP9 mRNA to inhibit its protein translation in TCC cells. This study highlights miR-3713 as a previously unrecognized factor that controls TCC invasiveness, which may be important for developing innovative therapeutic targets for TCC treatment.
Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems
Authors: Lomnitz Jason G. , Savageau Michael A.
Published: August 2016

An overarching goal in molecular biology is to gain an understanding of the mechanistic basis underlying biochemical systems. Success is critical if we are to predict effectively the outcome of drug treatments and the development of abnormal phenotypes. However, data from most experimental studies is typically noisy and sparse. This allows multiple potential mechanisms to account for experimental observations, and often devising experiments to test each is not feasible. Here, we introduce a novel strategy that discriminates among putative models based on their repertoire of qualitatively distinct phenotypes, without relying on knowledge of specific values for rate constants and binding constants. As an illustration, we apply this strategy to two synthetic gene circuits exhibiting anomalous behaviors. Our results show that the conventional models, based on their well-characterized components, cannot account for the experimental observations. We examine a total of 40 alternative hypotheses and show that only 5 have the potential to reproduce the experimental data, and one can do so with biologically relevant parameter values.
Oxygen Displacement in Cuprates under Ionic Liquid Field-Effect Gating
Authors: Dubuis Guy , Yacoby Yizhak , Zhou Hua , He Xi , Bollinger Anthony T. , Pavuna Davor , Pindak Ron , Božović Ivan
Published: August 2016

We studied structural changes in a 5 unit cell thick La1.96Sr0.04CuO4 film, epitaxially grown on a LaSrAlO4 substrate with a single unit cell buffer layer, when ultra-high electric fields were induced in the film by applying a gate voltage between the film (ground) and an ionic liquid in contact with it. Measuring the diffraction intensity along the substrate-defined Bragg rods and analyzing the results using a phase retrieval method we obtained the three-dimensional electron density in the film, buffer layer and topmost atomic layers of the substrate under different applied gate voltages. The main structural observations were: (i) there were no structural changes when the voltage was negative, holes were injected into the film making it more metallic and screening the electric field; (ii) when the voltage was positive, the film was depleted of holes becoming more insulating, the electric field extended throughout the film, the partial surface monolayer became disordered and equatorial oxygen atoms were displaced towards the surface; (iii) the changes in surface disorder and the oxygen displacements were both reversed when a negative voltage was applied; and (iv) the c-axis lattice constant of the film did not change in spite of the displacement of equatorial oxygen atoms.
Pathogenic marine microbes influence the effects of climate change on a commercially important tropical bivalve
Authors: Turner Lucy M. , Alsterberg Christian , Turner Andrew D. , Girisha S. K. , Rai Ashwin , Havenhand Jonathan N. , Venugopal M. N. , Karunasagar Indrani , Godhe Anna
Published: August 2016

There is growing evidence that climate change will increase the prevalence of toxic algae and harmful bacteria, which can accumulate in marine bivalves. However, we know little about any possible interactions between exposure to these microorganisms and the effects of climate change on bivalve health, or about how this may affect the bivalve toxin-pathogen load. In mesocosm experiments, mussels, Perna viridis, were subjected to simulated climate change (warming and/or hyposalinity) and exposed to harmful bacteria and/or toxin-producing dinoflagellates. We found significant interactions between climate change and these microbes on metabolic and/or immunobiological function and toxin-pathogen load in mussels. Surprisingly, however, these effects were virtually eliminated when mussels were exposed to both harmful microorganisms simultaneously. This study is the first to examine the effects of climate change on determining mussel toxin-pathogen load in an ecologically relevant, multi-trophic context. The results may have considerable implications for seafood safety.
The oncometabolite R-2-hydroxyglutarate activates NF-κB-dependent tumor-promoting stromal niche for acute myeloid leukemia cells
Authors: Chen Jing-Yi , Lai You-Syuan , Tsai Hui-Jen , Kuo Cheng-Chin , Yen B. Linju , Yeh Su-Peng , Sun H. Sunny , Hung Wen-Chun
Published: August 2016

Mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 in acute myeloid leukemia (AML) cells produce the oncometabolite R-2-hydroxyglutarate (R-2HG) to induce epigenetic alteration and block hematopoietic differentiation. However, the effect of R-2HG released by IDH-mutated AML cells on the bone marrow microenvironment is unclear. Here, we report that R-2HG induces IκB kinase-independent activation of NF-κB in bone marrow stromal cells. R-2HG acts via a reactive oxygen species/extracellular signal-regulated kinase (ERK)-dependent pathway to phosphorylate NF-κB on the Thr254 residue. This phosphorylation enhances the interaction of NF-κB and the peptidyl-prolyl cis-trans isomerase PIN1 and increases the protein stability and transcriptional activity of NF-κB. As a consequence, R-2HG enhances NF-κB-dependent expression of cytokines including IL-6, IL-8 and complement 5a to stimulate proliferation of AML cells. In addition, R-2HG also upregulates vascular endothelial adhesion molecule 1 and CXCR4 in stromal cells to enhance the contact between AML and stromal cells and attenuates chemotherapy-induced apoptosis. More importantly, we validated the R-2HG-activated gene signature in the primary bone marrow stromal cells isolated from IDH-mutated AML patients. Collectively, our results suggest that AML cell-derived R-2HG may be helpful for the establishment of a supportive bone marrow stromal niche to promote AML progression via paracrine stimulation.
Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams
Authors: Raschke S. , Spickermann S. , Toncian T. , Swantusch M. , Boeker J. , Giesen U. , Iliakis G. , Willi O. , Boege F.
Published: August 2016

Ultra-short proton pulses originating from laser-plasma accelerators can provide instantaneous dose rates at least 107-fold in excess of conventional, continuous proton beams. The impact of such extremely high proton dose rates on A549 human lung cancer cells was compared with conventionally accelerated protons and 90 keV X-rays. Between 0.2 and 2 Gy, the yield of DNA double strand breaks (foci of phosphorylated histone H2AX) was not significantly different between the two proton sources or proton irradiation and X-rays. Protein nitroxidation after 1 h judged by 3-nitrotyrosine generation was 2.5 and 5-fold higher in response to conventionally accelerated protons compared to laser-driven protons and X-rays, respectively. This difference was significant (p < 0.01) between 0.25 and 1 Gy. In conclusion, ultra-short proton pulses originating from laser-plasma accelerators have a similar DNA damaging potential as conventional proton beams, while inducing less immediate nitroxidative stress, which probably entails a distinct therapeutic potential.
A New Strategy for Analyzing Time-Series Data Using Dynamic Networks: Identifying Prospective Biomarkers of Hepatocellular Carcinoma
Authors: Huang Xin , Zeng Jun , Zhou Lina , Hu Chunxiu , Yin Peiyuan , Lin Xiaohui
Published: August 2016

Time-series metabolomics studies can provide insight into the dynamics of disease development and facilitate the discovery of prospective biomarkers. To improve the performance of early risk identification, a new strategy for analyzing time-series data based on dynamic networks (ATSD-DN) in a systematic time dimension is proposed. In ATSD-DN, the non-overlapping ratio was applied to measure the changes in feature ratios during the process of disease development and to construct dynamic networks. Dynamic concentration analysis and network topological structure analysis were performed to extract early warning information. This strategy was applied to the study of time-series lipidomics data from a stepwise hepatocarcinogenesis rat model. A ratio of lyso-phosphatidylcholine (LPC) 18:1/free fatty acid (FFA) 20:5 was identified as the potential biomarker for hepatocellular carcinoma (HCC). It can be used to classify HCC and non-HCC rats, and the area under the curve values in the discovery and external validation sets were 0.980 and 0.972, respectively. This strategy was also compared with a weighted relative difference accumulation algorithm (wRDA), multivariate empirical Bayes statistics (MEBA) and support vector machine-recursive feature elimination (SVM-RFE). The better performance of ATSD-DN suggests its potential for a more complete presentation of time-series changes and effective extraction of early warning information.
High fat diet drives obesity regardless the composition of gut microbiota in mice
Authors: Rabot Sylvie , Membrez Mathieu , Blancher Florence , Berger Bernard , Moine Déborah , Krause Lutz , Bibiloni Rodrigo , Bruneau Aurélia , Gérard Philippe , Siddharth Jay , Lauber Christian L. , Chou Chieh Jason
Published: August 2016

The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1st week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.
Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats
Authors: Liu Zhi-Hua , Ding Jin-Jun , Yang Qian-Qian , Song Hua-Zeng , Chen Xiang-Tao , Xu Yi , Xiao Gui-Ran , Wang Hui-Li
Published: August 2016

Bisphenol-A (BPA, 4, 4′-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.
Metagenomic approach reveals microbial diversity and predictive microbial metabolic pathways in Yucha, a traditional Li fermented food
Authors: Zhang Jiachao , Wang Xiaoru , Huo Dongxue , Li Wu , Hu Qisong , Xu Chuanbiao , Liu Sixin , Li Congfa
Published: August 2016

Yucha is a typical traditional fermented food of the Li population in the Hainan province of China, and it is made up of cooked rice and fresh fish. In the present study, metagenomic approach and culture-dependent technology were applied to describe the diversity of microbiota and identify beneficial microbes in the Yucha. At the genus level, Lactobacillus was the most abundant genus (43.82% of the total reads), followed by Lactococcus, Enterococcus, Vibrio, Weissella, Pediococcus, Enterobacter, Salinivibrio, Acinetobacter, Macrococcus, Kluyvera and Clostridium; this result was confirmed by q-PCR. PCoA based on Weighted UniFrac distances showed an apparent clustering pattern for Yucha samples from different locations, and Lactobacillus sakei, Lactobacillus saniviri and Staphylococcus sciuri represented OTUs according to the major identified markers. At the microbial functional level, it was observed that there was an enrichment of metabolic functional features, including amino acid and carbohydrate metabolism, which implied that the microbial metabolism in the Yucha samples tended to be vigorous. Accordingly, we further investigated the correlation between the predominant microbes and metabolic functional features. Thirteen species of Lactobacillus (147 strains) were isolated, and Lactobacillus plantarum (60 isolates) and Lactobacillus pentosus (34 isolates) were isolated from every sample.
Influence of HLA on human partnership and sexual satisfaction
Authors: Kromer J. , Hummel T. , Pietrowski D. , Giani A. S. , Sauter J. , Ehninger G. , Schmidt A. H. , Croy I.
Published: August 2016

The major histocompatibility complex (MHC, called HLA in humans) is an important genetic component of the immune system. Fish, birds and mammals prefer mates with different genetic MHC code compared to their own, which they determine using olfactory cues. This preference increases the chances of high MHC variety in the offspring, leading to enhanced resilience against a variety of pathogens. Humans are also able to discriminate HLA related olfactory stimuli, however, it is debated whether this mechanism is of behavioural relevance. We show on a large sample (N = 508), with high-resolution typing of HLA class I/II, that HLA dissimilarity correlates with partnership, sexuality and enhances the desire to procreate. We conclude that HLA mediates mate behaviour in humans.