bluuebunny/crossref_metadata_2025 huggingface dataset:
PP2A-B′ holoenzyme substrate recognition, regulation and role in cytokinesis
Authors: Wu Cheng-Guo , Chen Hui , Guo Feng , Yadav Vikash K , Mcilwain Sean J , Rowse Michael , Choudhary Alka , Lin Ziqing , Li Yitong , Gu Tingjia , Zheng Aiping , Xu Qingge , Lee Woojong , Resch Eduard , Johnson Benjamin , Day Jenny , Ge Ying , Ong Irene M , Burkard Mark E , Ivarsson Ylva , Xing Yongna
Published: August 2017

Protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase; it forms diverse heterotrimeric holoenzymes that counteract kinase actions. Using a peptidome that tiles the disordered regions of the human proteome, we identified proteins containing [LMFI]xx[ILV]xEx motifs that serve as interaction sites for B′-family PP2A regulatory subunits and holoenzymes. The B′-binding motifs have important roles in substrate recognition and in competitive inhibition of substrate binding. With more than 100 novel ligands identified, we confirmed that the recently identified LxxIxEx B′α-binding motifs serve as common binding sites for B′ subunits with minor variations, and that S/T phosphorylation or D/E residues at positions 2, 7, 8 and 9 of the motifs reinforce interactions. Hundreds of proteins in the human proteome harbor intrinsic or phosphorylation-responsive B′-interaction motifs, and localize at distinct cellular organelles, such as midbody, predicting kinase-facilitated recruitment of PP2A-B′ holoenzymes for tight spatiotemporal control of phosphorylation at mitosis and cytokinesis. Moroever, Polo-like kinase 1-mediated phosphorylation of Cyk4/RACGAP1, a centralspindlin component at the midbody, facilitates binding of both RhoA guanine nucleotide exchange factor (epithelial cell transforming sequence 2 (Ect2)) and PP2A-B′ that in turn dephosphorylates Cyk4 and disrupts Ect2 binding. This feedback signaling loop precisely controls RhoA activation and specifies a restricted region for cleavage furrow ingression. Our results provide a framework for further investigation of diverse signaling circuits formed by PP2A-B′ holoenzymes in various cellular processes.
Erratum: Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen
Authors: Qian Linping , Wang Zhen , Beletskiy Evgeny V. , Liu Jingyue , dos Santos Haroldo J. , Li Tiehu , Rangel Maria do C. , Kung Mayfair C. , Kung Harold H.
Published: August 2017

Nature Communications 8 Article number: 14881 (2017); Published: 28 March 2017; Updated: 11 August 2017 The original version of this Article contained an error in which the second affiliation ‘Chemical and Biological Engineering Department, Northwestern University, Evanston, Illinois 60208, USA’; was inadvertently switched with the third affiliation ‘School of Materials Science and Engineering, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, China’.
Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B
Authors: Wroblewski M. , Bauer R. , Cubas Córdova M. , Udonta F. , Ben-Batalla I. , Legler K. , Hauser C. , Egberts J. , Janning M. , Velthaus J. , Schulze C. , Pantel K. , Bokemeyer C. , Loges S.
Published: August 2017

Resistance towards VEGF-centered anti-angiogenic therapy still represents a substantial clinical challenge. We report here that mast cells alter the proliferative and organizational state of endothelial cells which reduces the efficacy of anti-angiogenic therapy. Consequently, absence of mast cells sensitizes tumor vessels for anti-angiogenic therapy in different tumor models. Mechanistically, anti-angiogenic therapy only initially reduces tumor vessel proliferation, however, this treatment effect was abrogated over time as a result of mast cell-mediated restimulation of angiogenesis. We show that mast cells secrete increased amounts of granzyme b upon therapy, which mobilizes pro-angiogenic laminin- and vitronectin-bound FGF-1 and GM-CSF from the tumor matrix. In addition, mast cells also diminish efficacy of anti-angiogenic therapy by secretion of FGF-2. These pro-angiogenic factors act beside the targeted VEGFA–VEGFR2-axis and reinduce endothelial cell proliferation and angiogenesis despite the presence of anti-angiogenic therapy. Importantly, inhibition of mast cell degranulation with cromolyn is able to improve efficacy of anti-angiogenic therapy. Thus, concomitant mast cell-targeting might lead to improved efficacy of anti-angiogenic therapy.
Pathogenic bacteria enhance dispersal through alteration of Drosophila social communication
Authors: Keesey Ian W. , Koerte Sarah , Khallaf Mohammed A. , Retzke Tom , Guillou Aurélien , Grosse-Wilde Ewald , Buchon Nicolas , Knaden Markus , Hansson Bill S.
Published: August 2017

Pathogens and parasites can manipulate their hosts to optimize their own fitness. For instance, bacterial pathogens have been shown to affect their host plants’ volatile and non-volatile metabolites, which results in increased attraction of insect vectors to the plant, and, hence, to increased pathogen dispersal. Behavioral manipulation by parasites has also been shown for mice, snails and zebrafish as well as for insects. Here we show that infection by pathogenic bacteria alters the social communication system of Drosophila melanogaster. More specifically, infected flies and their frass emit dramatically increased amounts of fly odors, including the aggregation pheromones methyl laurate, methyl myristate, and methyl palmitate, attracting healthy flies, which in turn become infected and further enhance pathogen dispersal. Thus, olfactory cues for attraction and aggregation are vulnerable to pathogenic manipulation, and we show that the alteration of social pheromones can be beneficial to the microbe while detrimental to the insect host.
Diagnosing peri-implant disease using the tongue as a 24/7 detector
Authors: Ritzer J. , Lühmann T. , Rode C. , Pein-Hackelbusch M. , Immohr I. , Schedler U. , Thiele T. , Stübinger S. , Rechenberg B. v. , Waser-Althaus J. , Schlottig F. , Merli M. , Dawe H. , Karpíšek M. , Wyrwa R. , Schnabelrauch M. , Meinel L.
Published: August 2017

Our ability of screening broad communities for clinically asymptomatic diseases critically drives population health. Sensory chewing gums are presented targeting the tongue as 24/7 detector allowing diagnosis by “anyone, anywhere, anytime”. The chewing gum contains peptide sensors consisting of a protease cleavable linker in between a bitter substance and a microparticle. Matrix metalloproteinases in the oral cavity, as upregulated in peri-implant disease, specifically target the protease cleavable linker while chewing the gum, thereby generating bitterness for detection by the tongue. The peptide sensors prove significant success in discriminating saliva collected from patients with peri-implant disease versus clinically asymptomatic volunteers. Superior outcome is demonstrated over commercially available protease-based tests in saliva. “Anyone, anywhere, anytime” diagnostics are within reach for oral inflammation. Expanding this platform technology to other diseases in the future features this diagnostic as a massive screening tool potentially maximizing impact on population health.
Decreased high density lipoprotein cholesterol is an independent predictor for persistent organ failure, pancreatic necrosis and mortality in acute pancreatitis
Authors: Zhang Yushun , Guo Feng , Li Shoukang , Wang Feiyang , Meng Zibo , Zhao Jingyuan , Liu Zhiqiang , Wang Bo , Fan Ping , Wang Chunyou , Wu Heshui
Published: August 2017

High density lipoprotein cholesterol (HDL-C) has been reported as a significant indicator of systemic inflammation. The association underlying HDL-C and persistent organ failure (POF), pancreatic necrosis (PNec) and mortality in acute pancreatitis (AP) has not been evaluated. From 2007 to 2016, consecutive AP patients with admission lipid profiles assessment were included in this study. The association of HDL-C value and other lipids with outcomes was explored with Cox proportional regression models, which were adjusted for confounding factors. 1131 consecutive AP patients were clinically eligible. Overall, 17.9% of the patients developed with POF, 27.1% experienced PNec, and 6.7% died during hospitalization. Lower HDL-C median (<1.06 mmol/L) was identified as an independent prognostic factor of the outcomes. Moreover, there was a positive trend for the association across increasing HDL-C quartiles and POF, PNec and mortality after multivariable analysis (p values were <0.001, <0.001 and 0.043, respectively). The AUC of HDL-C for the outcomes were comparable to that of Ranson score for diagnosing POF (0.778 vs. 0.678; P < 0.001), PNec (0.734 vs. 0.701; P = 0.143) and mortality (0.768 vs. 0.745; P = 0.516). Decreased HDL-C value is an independent risk factor for the incidence of POF, PNec and in-hospital mortality in AP.
Ikk2 regulates cytokinesis during vertebrate development
Authors: Shen Hongyuan , Shin Eun Myoung , Lee Serene , Mathavan Sinnakaruppan , Koh Hiromi , Osato Motomi , Choi Hyungwon , Tergaonkar Vinay , Korzh Vladimir
Published: August 2017

NFκB signaling has a pivotal role in regulation of development, innate immunity, and inflammation. Ikk2 is one of the two critical kinases that regulate the NFκB signaling pathway. While the role of Ikk2 in immunity, inflammation and oncogenesis has received attention, an understanding of the role of Ikk2 in vertebrate development has been compounded by the embryonic lethality seen in mice lacking Ikk2. We find that despite abnormal angiogenesis in IKK2 zygotic mutants of zebrafish, the maternal activity of Ikk2 supports embryogenesis and maturation of fertile animals and allows to study the role of IKK2 in development. Maternal-zygotic ikk2 mutants represent the first vertebrates globally devoid of maternal and zygotic Ikk2 activity. They are defective in cell proliferation as evidenced by abnormal cytokinesis, nuclear enlargement and syncytialisation of a significant portion of blastoderm. We further document that reduced phosphorylation of Aurora A by Ikk2 could underlie the basis of these defects in cell division.
Cascaded counter-propagating nonlinear interactions in highly-efficient sub-µm periodically poled crystals
Authors: Zukauskas Andrius , Viotti Anne-Lise , Liljestrand Charlotte , Pasiskevicius Valdas , Canalias Carlota
Published: August 2017

Mirrorless optical parametric oscillators (MOPOs) are very attractive parametric devices that rely on the nonlinear interaction of counter-propagating photons to inherently establish distributed feedback, without the use of external mirrors or surface coatings. These devices offer unique spectral and coherence properties that will benefit a large variety of applications ranging from spectroscopy to quantum communications. The major obstacle in exploiting their full potential is ascribed to the difficulty in engineering a nonlinear material in which the generation of counter-propagating waves can be phase matched. Here we present a reliable and consistent technique for fabrication of highly-efficient sub-micrometer periodically poled Rb-doped KTiOPO4. We experimentally demonstrate the first cascaded counter-propagating interactions in which the generated forward signal serves as a pump for a secondary MOPO process, reaching pump depletion larger than 60%. The cascaded process exemplifies the high efficiency of our nonlinear photonic structures. Our domain-engineering technique paves the way to realize counter-propagating schemes and devices that have been deemed unfeasible until now.
The influence of affective state on exogenous attention to emotional distractors: behavioral and electrophysiological correlates
Authors: Carboni Alejandra , Kessel Dominique , Capilla Almudena , Carretié Luis
Published: August 2017

The interplay between exogenous attention to emotional distractors and the baseline affective state has not been well established yet. The present study aimed to explore this issue through behavioral measures and event-related potentials (ERPs). Participants (N = 30) completed a digit categorization task depicted over negative, positive or neutral distractor background pictures, while they experienced negative, positive and neutral affective states elicited by movie scenes. Behavioral results showed higher error rates and longer reaction times for negative distractors than for neutral and positive ones, irrespective of the current emotional state. Neural indices showed that the participants’ affective state modulated N1 amplitudes, irrespective of distractor type, while the emotional charge of distractors modulated N2, irrespective of the emotional state. Importantly, an interaction of state and distractor type was observed in LPP. These results demonstrate that exogenous attention to emotional distractors is independent from modulating effects of the emotional baseline state at early, automatic stages of processing. However, attention to emotional distractors and affective state interact at later latencies.
Elevated Long Term Resting Heart Rate Variation is Associated with Increased Risk of All-cause Mortality in Northern China
Authors: Wang Binhao , Li Huihua , Han Xu , Yang Yiheng , Chen Yue , Li Wenyu , Yang Xiaolei , Xing Aijun , Wang Yanxiu , Hidru Tesfaldet Habtemariam , Wu Shouling , Xia Yunlong
Published: August 2017

Elevated resting heart rate (RHR) predicts all-cause death. However, the relationship between RHR variation over years and mortality are still unknown. We aimed to analyze the association between RHR variation and all-cause mortality in the general population without cardiovascular diseases. A total of 46,873 subjects were included from the Kailuan Study (2006–2011). RHR readings were taken during three separate examinations and the RHR variation was defined using the standard deviation (RHR-SD) and the coefficient of variation. Participants were divided into four groups according to the quartiles of RHR-SD. All subjects were followed for a median of 49.4 months from the date of the 3rd examination to December 31, 2014. Up until the follow-up examinations, 973 (2.08%) participants had died. In a multivariate analysis, adjusting for variables potentially associated with death, the highest quartile of RHR-SD remained an independent predictor of all-cause mortality (Hazards ratio = 1.43, 95% confidence interval 1.18–1.74, P < 0.001). These findings suggest that an elevated long-term RHR variation is an independent risk marker for all-cause mortality in the general population without known cardiovascular diseases.
Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates
Authors: Kalashnikov Maxim , Mueller Marc , McBeth Christine , Lee Jean C. , Campbell Jennifer , Sharon Andre , Sauer-Budge Alexis F.
Published: August 2017

Bacteremia is a life-threatening condition for which antibiotics must be prescribed within hours of clinical diagnosis. Since the current gold standard for bacteremia diagnosis is based on conventional methods developed in the mid-1800s—growth on agar or in broth—identification and susceptibility profiling for both Gram-positive and Gram-negative bacterial species requires at least 48–72 h. Recent advancements in accelerated phenotypic antibiotic susceptibility testing have centered on the microscopic growth analysis of small bacterial populations. These approaches are still inherently limited by the bacterial growth rate. Our approach is fundamentally different. By applying environmental stress to bacteria in a microfluidic platform, we can correctly assign antibiotic susceptibility profiles of clinically relevant Gram-negative bacteria within two hours of antibiotic introduction rather than 8–24 h. The substantial expansion to include a number of clinical isolates of important Gram-negative species—Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa—reported here underscores the broad utility of our approach, complementing the method’s proven utility for Gram-positive bacteria. We also demonstrate that the platform is compatible with antibiotics that have varying mechanisms of action—meropenem, gentamicin, and ceftazidime—highlighting the versatility of this platform.
Financial fluctuations anchored to economic fundamentals: A mesoscopic network approach
Authors: Sharma Kiran , Gopalakrishnan Balagopal , Chakrabarti Anindya S. , Chakraborti Anirban
Published: August 2017

We demonstrate the existence of an empirical linkage between nominal financial networks and the underlying economic fundamentals, across countries. We construct the nominal return correlation networks from daily data to encapsulate sector-level dynamics and infer the relative importance of the sectors in the nominal network through measures of centrality and clustering algorithms. Eigenvector centrality robustly identifies the backbone of the minimum spanning tree defined on the return networks as well as the primary cluster in the multidimensional scaling map. We show that the sectors that are relatively large in size, defined with three metrics, viz., market capitalization, revenue and number of employees, constitute the core of the return networks, whereas the periphery is mostly populated by relatively smaller sectors. Therefore, sector-level nominal return dynamics are anchored to the real size effect, which ultimately shapes the optimal portfolios for risk management. Our results are reasonably robust across 27 countries of varying degrees of prosperity and across periods of market turbulence (2008–09) as well as periods of relative calmness (2012–13 and 2015–16).
The fabrication of an ICA-SF/PLCL nanofibrous membrane by coaxial electrospinning and its effect on bone regeneration in vitro and in vivo
Authors: Yin Lihua , Wang Kaijuan , Lv Xiaoqin , Sun Rui , Yang Shaohua , Yang Yujie , Liu Yanyun , Liu Jiatao , Zhou Jing , Yu Zhanhai
Published: August 2017

GBR is currently accepted as one of the most effective approaches for bone defect regeneration relating to dental implant. Icariin is the main active ingredient in the extraction of total flavonoids from the Chinese traditional herb Epimediumbrevicornum Maxim. In this study, ICA was successfully incorporated into the nanofibers barrier membrane (ICA-SF/PLCL) as osteoinduction factor by coaxial electrospinning and was released in a sustained and controlled manner. The entire release period included two stages: an initial burst stage (47.54 ± 0.06% on 5 d) and a decreasing and constant stage (82.09 ± 1.86% on 30 d). The membrane has good biocompatibility with BMMSCs anchored and significantly promoted its osteogenic activity. Moreover, in vivo experiment, bone defect covered by ICA-SF/PLCL membrane in rat cranium were statistically repaired compare to other groups. 12 weeks after implantation, in the test group, the new bone formation spread to cover most of the defect region with volume and density of approximately 15.95 ± 3.58 mm3 and 14.02 ± 0.93%. These results demonstrated that ICA-SF/PLCL nanofibrous membrane could be a promising barrier applicated for GBR.
Health care claims for primary open-angle glaucoma and retinal vein occlusion from an 11-year nationwide dataset
Authors: Park Hae-Young Lopilly , Jung Younhea , Han Kyungdo , Lee Mee Yon , Park Chan Kee
Published: August 2017

To evaluate the risk of retinal vein occlusion (RVO) development after primary open-angle glaucoma (POAG) and the risk of POAG development after RVO, we conducted a nationwide, population-based 11-year longitudinal study. National registry data were collected from the Korean National Health Insurance Research Database, comparing 1 025 340 (~2.2%) subjects who were selected from 46 605 433 Korean residents in 2002. Each sampled patients was tracked until 2013. POAG developed in 0.92% of the RVO group (n = 6 826) and in 0.22% of the comparison group. RVO developed in 0.99% of the POAG group (n = 4 138) and in 0.37% of the comparison group. RVO was associated with an increased risk of POAG development (hazard ratio [HR], 3.25; 95% confidence interval [CI], 2.39–4.42) and POAG was associated with an increased risk of RVO development (HR, 5.05; 95% CI, 3.94–6.47). Comorbidity of systemic hypertension and diabetes mellitus further increased the risk of POAG development in the RVO group (HR, 3.58 and HR, 5.98, respectively). Patients with RVO exhibit a significantly higher risk of POAG development and patients with POAG exhibit a significantly higher risk of RVO development, based on an 11-year follow-up period.
Specific calpain inhibition protects kidney against inflammaging
Authors: Hanouna Guillaume , Mesnard Laurent , Vandermeersch Sophie , Perez Joëlle , Placier Sandrine , Haymann Jean-Philippe , Campagne Fabien , Moroch Julien , Bataille Aurélien , Baud Laurent , Letavernier Emmanuel
Published: August 2017

Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice. In addition, we analysed inflammatory response in the kidney of aged CalpTG and wild-type mice, and in both in vivo (monosodium urate peritonitis) and in vitro models of inflammation. At two years, CalpTG mice had preserved kidney tissue, less vascular remodelling and less markers of senescence than wild-type mice. Nevertheless, CalpTG mice lifespan was not extended, due to the development of lethal spleen tumors. Inflammatory pathways were less expressed in aged CalpTG mice, especially cytokines related to NF-κB and NLRP3 inflammasome activation. CalpTG mice had reduced macrophage infiltration with aging and CalpTG mice produced less IL-1α and IL-1β in vivo in response to inflammasome activators. In vitro, macrophages from CalpTG mice produced less IL-1α in response to particulate activators of inflammasome. Calpains inhibition protects against inflammaging, limiting kidney and vascular lesions related to aging.
Multipolar second harmonic generation in a symmetric nonlinear metamaterial
Authors: Wolf Omri , Campione Salvatore , Yang Yuanmu , Brener Igal
Published: August 2017

Optical nonlinearities are intimately related to the spatial symmetry of the nonlinear media. For example, the second order susceptibility vanishes for centrosymmetric materials under the dipole approximation. The latter concept has been naturally extended to the metamaterials’ realm, sometimes leading to the (erroneous) hypothesis that second harmonic (SH) generation is negligible in highly symmetric meta-atoms. In this work we aim to show that such symmetric meta-atoms can radiate SH light efficiently. In particular, we investigate in-plane centrosymmetric meta-atom designs where the approximation for meta-atoms breaks down. In a periodic array this building block allows us to control the directionality of the SH radiation. We conclude by showing that the use of symmetry considerations alone allows for the manipulation of the nonlinear multipolar response of a meta-atom, resulting in e.g. dipolar, quadrupolar, or multipolar emission on demand. This is because the size of the meta-atom is comparable with the free-space wavelength, thus invalidating the dipolar approximation for meta-atoms.
The N-P-K soil nutrient balance of Portuguese cropland in the 1950s: The transition from organic to chemical fertilization
Authors: Carmo Miguel , García-Ruiz Roberto , Ferreira Maria Isabel , Domingos Tiago
Published: August 2017

Agricultural nutrient balances have been receiving increasing attention in both historical and nutrient management research. The main objectives of this study were to further develop balance methodologies and to carry out a comprehensive assessment of the functioning and nutrient cycling of 1950s agroecosystems in Portugal. Additionally, the main implications for the history of agriculture in Portugal were discussed from the standpoint of soil fertility. We used a mass balance approach that comprises virtually all nitrogen (N), phosphorus (P) and potassium (K) inputs and outputs from cropland topsoil for average conditions in the period 1951–56. We found a consistent deficit in N, both for nationwide (−2.1 kg.ha−1.yr−1) and arable crops (−1.6 kg.ha−1.yr−1) estimates, that was rectified in the turn to the 1960 decade. P and K were, in contrast, accumulating in the soil (4.2–4.6 kg.ha−1.yr−1and 1.0–3.0 kg.ha−1.yr−1, respectively). We observed that the 1950s is the very moment of inflection from an agriculture fertilized predominantly through reused N in biomass (livestock excretions plus marine, plant and human waste sources) to one where chemical fertilizers prevailed. It is suggested that N deficiency played an important role in this transition.
Knockdown of lncRNA MIR31HG inhibits adipocyte differentiation of human adipose-derived stem cells via histone modification of FABP4
Authors: Huang Yiping , Jin Chanyuan , Zheng Yunfei , Li Xiaobei , Zhang Shan , Zhang Yixin , Jia Lingfei , Li Weiran
Published: August 2017

Adipogenesis plays an important role in the regulation of whole-body energy homeostasis and is inextricably related to obesity. Several studies have highlighted the relevance of microRNAs in adipocyte differentiation, but the contributions of long non-coding RNAs (lncRNAs) are still largely uncharacterized. Here, we determined that lncRNA MIR31HG is related to adipocyte lineage commitment. We demonstrated that knockdown of MIR31HG inhibited adipocyte differentiation, whereas overexpression of MIR31HG promoted adipogenesis in vitro and in vivo. Furthermore, inhibition of MIR31HG reduced the enrichment of active histone markers, histone H3 lysine 4 trimethylation (H3K4me3) and acetylation (AcH3), in the promoter of the adipogenic-related gene, fatty acid binding protein 4 (FABP4), leading to suppression of its expression and adipogenesis. These results provide new insights into the molecular mechanisms of MIR31HG in terms of adipogenesis and may have implications for obesity and associated disorders.
Carotid Body-Mediated Chemoreflex Drive in The Setting of low and High Output Heart Failure
Authors: Del Rio Rodrigo , Andrade David C. , Toledo Camilo , Diaz Hugo S. , Lucero Claudia , Arce-Alvarez Alexis , Marcus Noah J. , Schultz Harold D.
Published: August 2017

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in MI-CHF rats compared to Sham and AV-CHF rats. MI-CHF rats exhibited a significantly enhanced hypoxic ventilatory response compared to AV-CHF rats. However, apnea/hypopnea incidence was similarly increased in both MI-CHF and AV-CHF rats compared to control. Kruppel-like factor 2 expression, a flow sensitive transcription factor, was reduced in the CBs of MI-CHF rats but not in AV-CHF rats. Our results indicate that in the setting of HF, potentiation of the CB chemoreflex is strongly associated with a reduction in cardiac output and may not be related to other pathophysiological consequences of HF.
Tuning the Fermi velocity in Dirac materials with an electric field
Authors: Díaz-Fernández A. , Chico Leonor , González J. W. , Domínguez-Adame F.
Published: August 2017

Dirac materials are characterized by energy-momentum relations that resemble those of relativistic massless particles. Commonly denominated Dirac cones, these dispersion relations are considered to be their essential feature. These materials comprise quite diverse examples, such as graphene and topological insulators. Band-engineering techniques should aim to a full control of the parameter that characterizes the Dirac cones: the Fermi velocity. We propose a general mechanism that enables the fine-tuning of the Fermi velocity in Dirac materials in a readily accessible way for experiments. By embedding the sample in a uniform electric field, the Fermi velocity is substantially modified. We first prove this result analytically, for the surface states of a topological insulator/semiconductor interface, and postulate its universality in other Dirac materials. Then we check its correctness in carbon-based Dirac materials, namely graphene nanoribbons and nanotubes, thus showing the validity of our hypothesis in different Dirac systems by means of continuum, tight-binding and ab-initio calculations.
IP-10 Levels as an Accurate Screening Tool to Detect Acute HIV Infection in Resource-Limited Settings
Authors: Pastor Lucía , Casellas Aina , Carrillo Jorge , Alonso Sergi , Parker Erica , Fuente-Soro Laura , Jairoce Chenjerai , Mandomando Inacio , Blanco Julià , Naniche Denise
Published: August 2017

Acute HIV infection (AHI) is the period prior to seroconversion characterized by high viral replication, hyper-transmission potential and commonly, non-specific febrile illness. AHI detection requires HIV-RNA viral load (VL) determination, which has very limited access in low-income countries due to restrictive costs and implementation constraints. We sought to identify a biomarker that could enable AHI diagnosis in scarce-resource settings, and to evaluate the feasibility of its implementation. HIV-seronegative adults presenting at the Manhiça District Hospital, Mozambique, with reported-fever were tested for VL. Plasma levels of 49 inflammatory biomarkers from AHI (n = 61) and non-HIV infected outpatients (n = 65) were determined by Luminex and ELISA. IP-10 demonstrated the best predictive power for AHI detection (AUC = 0.88 [95%CI 0.80–0.96]). A cut-off value of IP-10 ≥ 161.6 pg/mL provided a sensitivity of 95.5% (95%CI 85.5–99.5) and a specificity of 76.5% (95%CI 62.5–87.2). The implementation of an IP-10 screening test could avert from 21 to 84 new infections and save from US$176,609 to US$533,467 to the health system per 1,000 tested patients. We conclude that IP-10 is an accurate biomarker to screen febrile HIV-seronegative individuals for subsequent AHI diagnosis with VL. Such an algorithm is a cost-effective strategy to prevent disease progression and a substantial number of further HIV infections.
Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells
Authors: Ito Naoki , Kii Isao , Shimizu Noriaki , Tanaka Hirotoshi , Takeda Shin’ichi
Published: August 2017

Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells. These reprogrammed cells formed Dystrophin-positive mature muscle fibers when transplanted into a mouse model of Duchenne muscular dystrophy. These results highlight the new marker for heterogenous population of cultured satellite cells, potential therapeutic approaches and cell sources for degenerative muscle diseases.
Prognostic value of routine laboratory variables in prediction of breast cancer recurrence
Authors: Zhu Zhu , Li Ling , Ye Zhong , Fu Tong , Du Ye , Shi Aiping , Wu Di , Li Ke , Zhu Yifan , Wang Chun , Fan Zhimin
Published: August 2017

The prognostic value of routine laboratory variables in breast cancer has been largely overlooked. Based on laboratory tests commonly performed in clinical practice, we aimed to develop a new model to predict disease free survival (DFS) after surgical removal of primary breast cancer. In a cohort of 1,596 breast cancer patients, we analyzed the associations of 33 laboratory variables with patient DFS. Based on 3 significant laboratory variables (hemoglobin, alkaline phosphatase, and international normalized ratio), together with important demographic and clinical variables, we developed a prognostic model, achieving the area under the curve of 0.79. We categorized patients into 3 risk groups according to the prognostic index developed from the final model. Compared with the patients in the low-risk group, those in the medium- and high-risk group had a significantly increased risk of recurrence with a hazard ratio (HR) of 1.75 (95% confidence interval [CI] 1.30–2.38) and 4.66 (95% CI 3.54–6.14), respectively. The results from the training set were validated in the testing set. Overall, our prognostic model incorporating readily available routine laboratory tests is powerful in identifying breast cancer patients who are at high risk of recurrence. Further study is warranted to validate its clinical application.
Octahedron Iron Oxide Nanocrystals Prohibited Clostridium difficile Spore Germination and Attenuated Local and Systemic Inflammation
Authors: Lee Wei-Ting , Wu Ya-Na , Chen Yi-Hsuan , Wu Shang-Rung , Shih Tsai-Miao , Li Tsung-Ju , Yang Li-Xing , Yeh Chen-Sheng , Tsai Pei-Jane , Shieh Dar-Bin
Published: August 2017

Clinical management of Clostridium difficile infection is still far from satisfactory as bacterial spores are resistant to many chemical agents and physical treatments. Certain types of nanoparticles have been demonstrated to exhibit anti-microbial efficacy even in multi-drug resistance bacteria. However, most of these studies failed to show biocompatibility to the mammalian host cells and no study has revealed in vivo efficacy in C. difficile infection animal models. The spores treated with 500 µg/mL Fe3-δO4 nanoparticles for 20 minutes, 64% of the spores were inhibited from transforming into vegetative cells, which was close to the results of the sodium hypochlorite-treated positive control. By cryo-electron micro-tomography, we demonstrated that Fe3-δO4 nanoparticles bind on spore surfaces and reduce the dipicolinic acid (DPA) released by the spores. In a C. difficile infection animal model, the inflammatory level triple decreased in mice with colonic C. difficile spores treated with Fe3-δO4 nanoparticles. Histopathological analysis showed a decreased intense neutrophil accumulation in the colon tissue of the Fe3-δO4 nanoparticle-treated mice. Fe3-δO4 nanoparticles, which had no influence on gut microbiota and apparent side effects in vivo, were efficacious inhibitors of C. difficile spore germination by attacking its surface and might become clinically feasible for prophylaxis and therapy.
A combinatorial approach for the discovery of cytochrome P450 2D6 inhibitors from nature
Authors: Hochleitner Johannes , Akram Muhammad , Ueberall Martina , Davis Rohan A. , Waltenberger Birgit , Stuppner Hermann , Sturm Sonja , Ueberall Florian , Gostner Johanna M. , Schuster Daniela
Published: August 2017

The human cytochrome P450 2D6 (CYP2D6) enzyme is part of phase-I metabolism and metabolizes at least 20% of all clinically relevant drugs. Therefore, it is an important target for drug-drug interaction (DDI) studies. High-throughput screening (HTS) assays are commonly used tools to examine DDI, but show certain drawbacks with regard to their applicability to natural products. We propose an in silico – in vitro workflow for the reliable identification of natural products with CYP2D6 inhibitory potential. In order to identify candidates from natural product-based databases that share similar structural features with established inhibitors, a pharmacophore model was applied. The virtual hits were tested for the inhibition of recombinant human CYP2D6 in a bioluminescence-based assay. By controlling for unspecific interferences of the test compounds with the detection reaction, the number of false positives were reduced. The success rate of the reported workflow was 76%, as most of the candidates identified in the in silico approach were able to inhibit CYP2D6 activity. In summary, the workflow presented here is a suitable and cost-efficient strategy for the discovery of new CYP2D6 inhibitors with natural product libraries.
Generation of broadband ultraviolet frequency-entangled photons using cavity quantum plasmonics
Authors: Oka Hisaki
Published: August 2017

Application of quantum entangled photons is now extending to various fields in physics, chemistry and biology. In particular, in terms of application to molecular science, broadband ultraviolet frequency-entangled photons are desired because molecules inducing photochemical reactions of interest often have electronic transition energies in the ultraviolet region. Recent standard method for generating such entangled photons is a chirped quasi-phase-matching method, however this method is not suitable for the generation of ultraviolet frequency-entangled photons because it requires down-conversion of a photon with a wavelength shorter than ultraviolet into an entangled photon pair. Here we propose a simple method for generating broadband ultraviolet frequency-entangled photons using cavity quantum plasmonics, in which conventional cavity quantum electrodynamics theory is applied to quantum plasmonics. We introduce a cavity-plasmon system in which localised surface plasmon (LSP) is coupled to the cavity fields of a state-of-the-art microcavity. Using this system, we theoretically show that broadband ultraviolet frequency-entangled photons can be generated simply by utilising the absorption saturation effect of LSP.
Outbreak and genotyping of canine distemper virus in captive Siberian tigers and red pandas
Authors: Zhang He , Shan Fen , Zhou Xia , Li Bing , Zhai Jun-Qiong , Zou Shu-Zhan , Wu Meng-Fan , Chen Wu , Zhai Shao-Lun , Luo Man-Lin
Published: August 2017

In this study, four canine distemper virus (CDV) strains were isolated from captive Siberian tigers (Panthera tigris altaica) and red pandas (Ailurus fulgens) during two separate CDV outbreaks in a zoo in Guangdong province, China. Sequence alignment and phylogenetic analyses based on the full-length hemagglutinin (H) and fusion (F) genes showed that they were closely identical to genotype Asia-1. Prior to confirmation of CDV in Siberian tigers, to control spread of the disease, a live attenuated combination CDV vaccine was used among almost all carnivore animals except for red pandas in which another recombinant combination CDV vaccine was used. However, about two months later, CDV re-emerged and caused the death among red pandas. Based on the vaccination records, the live combination vaccine could be considered an ideal weapon against CDV in zoo carnivore animals. Although the recombinant combination CDV vaccine was safe for red pandas, its protection effectiveness remains to be further investigated. Moreover, according to the outbreak interval time and sequence characterization, we suspected that stray cats circulating in the zoo were the intermediate host, which contributed to CDV spread from stray dogs to zoo animals. This study revealed the importance of vaccination and biosecurity for zoo animals.
Altered awareness of action in Parkinson’s disease: evaluations by explicit and implicit measures
Authors: Saito Naho , Takahata Keisuke , Yamakado Hodaka , Sawamoto Nobukatsu , Saito Satoshi , Takahashi Ryosuke , Murai Toshiya , Takahashi Hidehiko
Published: August 2017

Deficits in the integration of motor prediction and its feedback have been reported in Parkinson’s disease. Conscious awareness of action is proposed to emerge under the integration of motor prediction and its feedback. Thus, it may lead to changes in the awareness of the authorship of action (in other words, the sense of agency) in Parkinson’s disease. We have employed both explicit and implicit measures to assess the awareness of action in Parkinson’s disease and matched controls. As an explicit measure, an action recognition task requiring explicit judgments was used. Patients showed less attribution of their movements to non-biased and angular-biased visual feedbacks. As an implicit measure, the temporal attraction between the perceived time of actions and their effects, which is known as intentional binding task, was used. While action-effect association was observed in the control group, actions were not experienced as having shifted towards their subsequent effects in the patient group. These tendencies were consistent regardless of the side of the asymmetrical motor symptoms. These results may reflect an underlying abnormality in the awareness of voluntary action in Parkinson’s disease.
Study of dynamical heterogeneities in colloidal nanoclay suspensions approaching dynamical arrest
Authors: Gadige Paramesh , Saha Debasish , Behera Sanjay Kumar , Bandyopadhyay Ranjini
Published: August 2017

The dynamics of aqueous Laponite clay suspensions slow down with increasing sample waiting time (t
w
). This behavior, and the material fragility that results, closely resemble the dynamical slowdown in fragile supercooled liquids with decreasing temperature, and are typically ascribed to the increasing sizes of distinct dynamical heterogeneities in the sample. In this article, we characterize the dynamical heterogeneities in Laponite suspensions by invoking the three-point dynamic susceptibility formalism. The average time-dependent two-point intensity autocorrelation and its sensitivity to t
w
are probed in dynamic light scattering experiments. Distributions of relaxation time scales, deduced from the Kohlrausch-Williams-Watts equation, are seen to widen with increasing t
w
. The calculated three-point dynamic susceptibility of Laponite suspensions exhibits a peak, with the peak height increasing with evolving t
w
at fixed volume fraction or with increasing volume fraction at fixed t
w
, thereby signifying the slowdown of the sample dynamics. The number of dynamically correlated particles, calculated from the peak-height, is seen to initially increase rapidly with increasing t
w
, before eventually slowing down close to the non-ergodic transition point. This observation is in agreement with published reports on supercooled liquids and hard sphere colloidal suspensions and offers a unique insight into the colloidal glass transition of Laponite suspensions.
On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
Authors: Ciupka Daniel , Gohlke Holger
Published: August 2017

The pyruvate phosphate dikinase (PPDK) reaction mechanism is characterized by a distinct spatial separation of reaction centers and large conformational changes involving an opening-closing motion of the nucleotide-binding domain (NBD) and a swiveling motion of the central domain (CD). However, why PPDK is active only in a dimeric form and to what extent an alternate binding change mechanism could underlie this fact has remained elusive. We performed unbiased molecular dynamics simulations, configurational free energy computations, and rigidity analysis to address this question. Our results support the hypothesis that PPDK dimerization influences the opening-closing motion of the NBDs, and that this influence is mediated via the CDs of both chains. Such an influence would be a prerequisite for an alternate binding change mechanism to occur. To the best of our knowledge, this is the first time that a possible explanation has been suggested as to why only dimeric PPDK is active.
Effects of One-Week Empirical Antibiotic Therapy on the Early Development of Gut Microbiota and Metabolites in Preterm Infants
Authors: Zhu Danping , Xiao Sa , Yu Jialin , Ai Qing , He Yu , Cheng Chen , Zhang Yunhui , Pan Yun
Published: August 2017

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.
Spontaneous detachment of Streptococcus mutans biofilm by synergistic effect between zwitterion and sugar alcohol
Authors: Lim Jong Hyun , Song Sang-Hun , Park Hyun-Sub , Lee Jeong Rae , Lee Sang-Min
Published: August 2017

A biofilm, a community of microorganisms, is highly resistant to antibiotics, resulting in massive losses in various areas. We herein present a strategy to remove Streptococcus mutans biofilms through a spontaneous exfoliation by the synergistic effect between zwitterion and sugar alcohols. It is assumed that the anionic site of zwitterion can be coupled with sugar alcohols and the cationic site remains in the state of lacking electrons. The cationic site allows the complexes to be delivered to negatively charged exopolysaccharides of biofilms. This strategy facilitates a significant increase in the ability of sugar alcohols to disperse aggregated exopolysaccharides. In this work, it was demonstrated that the mixture of betaine and erythritol existed as a complex in water and that the complex induced a spontaneous detachment of biofilms from the surface to which the biofilms had been adhered. This detachment resulted from a reduction in adhesive forces of the biofilms due to an increase in solubility of bacterial exopolysaccharides. The effects triggered by the formation of complex between zwitterion and sugar alcohol provide a simple and safe way to remove biofilms without antibiotics and physical forces.