bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogen recognition of a novel C-type lectin from Marsupenaeus japonicus reveals the divergent sugar-binding specificity of QAP motif
Authors: Alenton Rod Russel R. , Koiwai Keiichiro , Miyaguchi Kohei , Kondo Hidehiro , Hirono Ikuo 
Published: April 2017

AbstractC-type lectins (CTLs) are calcium-dependent carbohydrate-binding proteins known to assist the innate immune system as pattern recognition receptors (PRRs). The binding specificity of CTLs lies in the motif of their carbohydrate recognition domain (CRD), the tripeptide motifs EPN and QPD bind to mannose and galactose, respectively. However, variants of these motifs were discovered including a QAP sequence reported in shrimp believed to have the same carbohydrate specificity as QPD. Here, we characterized a novel C-type lectin (MjGCTL) possessing a CRD with a QAP motif. The recombinant MjGCTL has a calcium-dependent agglutinating capability against both Gram-negative and Gram-positive bacteria, and its sugar specificity did not involve either mannose or galactose. In an encapsulation assay, agarose beads coated with rMjGCTL were immediately encapsulated from 0 h followed by melanization at 4 h post-incubation with hemocytes. These results confirm that MjGCTL functions as a classical CTL. The structure of QAP motif and carbohydrate-specificity of rMjGCTL was found to be different to both EPN and QPD, suggesting that QAP is a new motif. Furthermore, MjGCTL acts as a PRR binding to hemocytes to activate their adherent state and initiate encapsulation.
Glycation of paraoxonase 1 by high glucose instigates endoplasmic reticulum stress to induce endothelial dysfunction in vivo
Authors: Yu Wei , Liu Xiaoli , Feng Liru , Yang Hui , Yu Weiye , Feng Tiejian , Wang Shuangxi , Wang Jun , Liu Ning 
Published: April 2017

AbstractHigh-density lipoprotein (HDL) modulates low-density lipoprotein and cell membrane oxidation through the action of paraoxonase-1 (PON1). Endoplasmic reticulum (ER) stress has been linked to a wide range of human pathologies including diabetes, obesity, and atherosclerosis. Previous studies have reported that PON1 is glycated in diabetes. The aim of this study is to investigate whether and how PON1 glycation contributes to endothelial dysfunction in diabetes. ER stress markers were monitored by western blot. Endothelial function was determined by organ bath. Incubation of recombinant PON1 proteins with high glucose increased PON1 glycation and reduced PON1 activity. Exposure of HUVECs to glycated PON1 induced prolonged ER stress and reduced SERCA activity, which were abolished by tempol, apocynin, BAPTA, and p67 and p22 siRNAs. Chronic administration of amino guanidine or 4-PBA prevented endothelial dysfunction in STZ-injected rats. Importantly, injection of glycated PON1 but not native PON1 induced aberrant ER stress and endothelial dysfunction in rats, which were attenuated by tempol, BAPTA, and 4-PBA. In conclusion, glycation of PON1 by hyperglycemia induces endothelial dysfunction through ER stress. In perspectives, PON1 glycation is a novel risk factor of hyperglycemia-induced endothelial dysfunction. Therefore, inhibition of oxidative stress, chelating intracellular Ca2+, and ER chaperone would be considered to reduce vascular complications in diabetes.
Nucleotide Dependent Switching in Rho GTPase: Conformational Heterogeneity and Competing Molecular Interactions
Authors: Kumawat Amit , Chakrabarty Suman , Kulkarni Kiran 
Published: April 2017

AbstractRas superfamily of GTPases regulate myriad cellular processes through a conserved nucleotide (GTP/GDP) dependent switching mechanism. Unlike Ras family of GTPases, for the Rho GTPases, there is no clear evidence for the existence of “sub-states” such as state 1 & state 2 in the GTP bound form. To explore the nucleotide dependent conformational space of the Switch I loop and also to look for existence of state 1 like conformations in Rho GTPases, atomistic molecular dynamics and metadynamics simulations on RhoA were performed. These studies demonstrate that both the nucleotide-free state and the GDP bound “OFF” state have very similar conformations, whereas the GTP bound “ON” state has unique conformations with signatures of two intermediate states. The conformational free energy landscape for these systems suggests the presence of multiple intermediate states. Interestingly, the energetic penalty of exposing the non-polar residues in the GTP bound form is counter balanced by the favourable hydrogen bonded interactions between the γ-phosphate group of GTP with the highly conserved Tyr34 and Thr37 residues. These competing molecular interactions lead to a tuneable energy landscape of the Switch I conformation, which can undergo significant changes based on the local environment including changes upon binding to effectors.
Lack of spontaneous age-related brain pathology in Octodon degus: a reappraisal of the model
Authors: Bourdenx Mathieu , Dovero Sandra , Thiolat Marie-Laure , Bezard Erwan , Dehay Benjamin 
Published: April 2017

AbstractNeurodegenerative diseases are characterized by the degeneration of specific brain areas associated with accumulation of disease-related protein in extra- or intra-cellular deposits. Their preclinical investigations are mostly based on genetically-engineered animals. Despite their interest, these models are often based on high level of disease-related protein expression, thus questioning their relevance to human pathology and calling for the alternate use of ecological models. In the past few years, Octodon degus has emerged as a promising animal model displaying age-dependent Alzheimer’s disease-related pathology. As neurodegenerative-related proteins often co-deposit in the brain of patients, we assessed the occurrence of α-synuclein-related pathology in this model using state-of-the-art immunohistochemistry and biochemistry. Despite our efforts and in contrast with previously published results, our study argues against the use of Octodon degus as a suitable natural model of neurodegenerative disorder as we failed to identify either Parkinson’s disease- or Alzheimer’s disease-related brain pathologies.
Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress
Authors: Wang Lintao , Huang Zhouqing , Huang Weijian , Chen Xuemei , Shan Peiren , Zhong Peng , Khan Zia , Wang Jingying , Fang Qilu , Liang Guang , Wang Yi 
Published: April 2017

AbstractAtherosclerosis is a progressive disease leading to loss of vascular homeostasis and entails fibrosis, macrophage foam cell formation, and smooth muscle cell proliferation. Recent studies have reported that epidermal growth factor receptor (EGFR) is involved vascular pathophysiology and in the regulation of oxidative stress in macrophages. Although, oxidative stress and inflammation play a critical role in the development of atherosclerosis, the underlying mechanisms are complex and not completely understood. In the present study, we have elucidated the role of EGFR in high-fat diet-induced atherosclerosis in apolipoprotein E null mice. We show increased EGFR phosphorylation and activity in atherosclerotic lesion development. EGFR inhibition prevented oxidative stress, macrophage infiltration, induction of pro-inflammatory cytokines, and SMC proliferation within the lesions. We further show that EGFR is activated through toll-like receptor 4. Disruption of toll-like receptor 4 or the EGFR pathway led to reduced inflammatory activity and foam cell formation. These studies provide evidence that EGFR plays a key role on the pathogenesis of atherosclerosis, and suggests that EGFR may be a potential therapeutic target in the prevention of atherosclerosis development.
maLPA1-null mice as an endophenotype of anxious depression
Authors: Moreno-Fernández R D , Pérez-Martín M , Castilla-Ortega E , Rosell del Valle C , García-Fernández M I , Chun J , Estivill-Torrús G , Rodríguez de Fonseca F , Santín L J , Pedraza C 
Published: April 2017

AbstractAnxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1–6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression.
An interaction network of mental disorder proteins in neural stem cells
Authors: Moen M J , Adams H H H , Brandsma J H , Dekkers D H W , Akinci U , Karkampouna S , Quevedo M , Kockx C E M , Ozgür Z , van IJcken W F J , Demmers J , Poot R A 
Published: April 2017

AbstractMental disorders (MDs) such as intellectual disability (ID), autism spectrum disorders (ASD) and schizophrenia have a strong genetic component. Recently, many gene mutations associated with ID, ASD or schizophrenia have been identified by high-throughput sequencing. A substantial fraction of these mutations are in genes encoding transcriptional regulators. Transcriptional regulators associated with different MDs but acting in the same gene regulatory network provide information on the molecular relation between MDs. Physical interaction between transcriptional regulators is a strong predictor for their cooperation in gene regulation. Here, we biochemically purified transcriptional regulators from neural stem cells, identified their interaction partners by mass spectrometry and assembled a protein interaction network containing 206 proteins, including 68 proteins mutated in MD patients and 52 proteins significantly lacking coding variation in humans. Our network shows molecular connections between established MD proteins and provides a discovery tool for novel MD genes. Network proteins preferentially co-localize on the genome and cooperate in disease-relevant gene regulation. Our results suggest that the observed transcriptional regulators associated with ID, ASD or schizophrenia are part of a transcriptional network in neural stem cells. We find that more severe mutations in network proteins are associated with MDs that include lower intelligence quotient (IQ), suggesting that the level of disruption of a shared transcriptional network correlates with cognitive dysfunction.
Deficit of state-dependent risk attitude modulation in gambling disorder
Authors: Fujimoto A , Tsurumi K , Kawada R , Murao T , Takeuchi H , Murai T , Takahashi H 
Published: April 2017

AbstractGambling disorder (GD) is often considered as a problem of trait-like risk preference. However, the symptoms of GD cannot be fully understood by this trait view. In the present study, we hypothesized that GD patients also had problem with a flexible control of risk attitude (state-dependent strategy optimization), and aimed to investigate the mechanisms underlying abnormal risk-taking of GD. To address this issue, we tested GD patients without comorbidity (GD group: n=21) and age-matched healthy control participants (HC group: n=29) in a multi-step gambling task, in which participants needed to clear ‘block quota’ (required units to clear a block, 1000–7000 units) in 20 choices, and conducted a task-functional magnetic resonance imaging (fMRI) experiment. Behavioral analysis indeed revealed a less flexible risk-attitude change in the GD group; the GD group failed to avoid risky choice in a specific quota range (low-quota condition), in which risky strategy was not optimal to solve the quota. Accordingly, fMRI analysis highlighted diminished functioning of the dorsolateral prefrontal cortex (dlPFC), which has been heavily implicated in cognitive flexibility. To our knowledge, the present study provided the first empirical evidence of a deficit of state-dependent strategy optimization in GD. Focusing on flexible control of risk attitude under quota may contribute to a better understanding of the psychopathology of GDs.
Millimetre‐wave air‐filled substrate integrated waveguide slot array antenna
Authors: Parment F. , Ghiotto A. , Vuong T.‐P. , Duchamp J.‐M. , Wu K. 
Published: April 2017

An air‐filled substrate integrated waveguide (AFSIW) slot array antenna based on multilayer PCB process is proposed. For comparison and demonstration purposes, 1 × 4 slot array antennas based on both AFSIW and conventional dielectric‐filled SIW (DFSIW) operating at 30.5 GHz are designed, fabricated and measured. The exampled AFSIW 1 × 4 slot array antenna achieves 44 and 18% narrower measured H‐plane and E‐plane half‐power beamwidth, respectively, and simulated radiation efficiency improved by 1.6%, resulting in an overall measured gain improvement of 3.5 dB compared with its DFSIW counterpart. This antenna is of high interest for the design of efficient arrays based on high‐performance AFSIW feeding network.
Miniaturised bandstop frequency selective surface based on quasi‐lumped inductor and capacitor
Authors: Zhao Pengchao , Zong Zhiyuan , Li Bo , Wu Wen , Fang Dagang 
Published: April 2017

A novel frequency selective surface (FSS) based on quasi‐lumped inductor and capacitor is proposed to miniaturise FSS unit cell size. The quasi‐lumped inductor and capacitor, implemented by meander line and parallel‐plate capacitor, respectively, are connected in series to achieve a bandstop filtering response. This FSS provides the advantages of small unit cell size, independent control of the filtering response for different polarisations, and easy optimal design of desired resonant frequency and bandwidth. To validate the proposed design concept, a bandstop FSS operating at 2.42 GHz was designed, fabricated, and measured. Its unit cell size is only (λ0/28) × (λ0/28), where λ0 refers to the resonant wavelength in free space. Both the simulated and measured results exhibit stable filtering performance under different polarisations and incident angles (up to 60°).
Isolation, characterisation and enzymatic activity of Streptomyces sp. and its pH control during fermentation process
Authors: Baskaran Balraj , Muthukumarasamy Arulmozhi 
Published: April 2017

Streptomyces sp. with grey white mycelium was isolated from Kodiyakkarai marine segment of east coastal of India. The isolate produced spiny spores and did not produce any diffusible pigments. Various biochemical tests were carried out to confirm the isolate classification. The amylolytic enzyme activity was estimated using the isolated strain which was confirmed by golden yellowish zone formation after using the Gram's iodine stain. The amount of amylase produced by the isolate was 6.15 U/ml. Higher living cells always produce better enzymes, so that the process parameters especially pH was maintained in fermentation chamber for higher growth and also for large‐scale growth. For maintaining the pH a mathematical process model was developed using the data obtained during the process. The addition of Kalman's filter along with proportional–integral–derivative controller gave better stability in pH. By maintaining of pH 7, growth rate was significantly increased from 0.51to 0.59 gm/l on day 5 which are discussed in the results and discussions.
Variables Affecting Outcome of Early Intervention in Autism Spectrum Disorder
Authors: Ben-Itzchak Esther , Zachor Ditza 
Published: April 2017

AbstractHeterogeneity in autism spectrum disorder (ASD) is reflected in the child's characteristics, including clinical variability in the severity of autism symptoms, cognitive ability, and language skills. Also, substantial individual differences are apparent about treatment outcomes. The effects of early intervention in ASD constitute one of the important questions ASD researchers face today. To what extent do factors such as child and family characteristics, intervention approach, and specific treatment components, influence outcome? This review focused on which preintervention factors better predicted outcome in each of the different outcome measures used most frequently in ASD research, including autism severity, cognitive ability, and adaptive behavior skills. For outcome in autism severity, predictors included child's baseline age, cognitive ability, autism severity, and the type of treatment approach used. For cognitive gains, predictors included baseline autism severity, maternal and educational level, and the type and intensity of the treatment. For outcome in adaptive behavior skills, predictors included baseline cognitive ability, autism severity, maternal age, and the treatment approach and intensity. Future studies in this field should expand the scope of factors, look for more specific behaviors, and investigate the interplay between a child's characteristics, familial factors, and various treatment aspects that might affect the outcome of the intervention.
Infektassoziierte akute posteriore multifokale plakoide Pigmentepitheliopathie
Authors: Jordan F. , Voigt U. , Dawczynski J. , Augsten R. , Meller D. 
Published: April 2017

ZusammenfassungDie akute posteriore multifokale plakoide Pigmentepitheliopathie (APMPPE) ist eine seltene entzündliche Erkrankung in der tiefen sensorischen Netzhaut auf der Ebene des retinalen Pigmentepithels (RPE) und der Choriokapillaris. Es sind bevorzugt junge hellhäutige, oft myope Erwachsene zwischen 20 und 30 Jahren betroffen. Die Ätiologie ist bislang unbekannt. Aufgrund des gehäuften Auftretens im Anschluss an Infektionserkrankungen wird eine infektiöse Genese angenommen. Es handelt sich um eine meist bilaterale Erkrankung, die i. d. R. monophasisch und selbstlimitierend verläuft und durch eine plötzliche, jedoch in aller Regel nur vorübergehende Visusminderung charakterisiert ist. Rezidive sind sehr selten. Bei fovealer Beteiligung kann es zu einer dauerhaften Visusminderung kommen. Eine wirksame Therapie ist nicht bekannt. Aufgrund des prognostisch günstigen Spontanverlaufs steht oftmals ein abwartendes Verhalten mit engmaschigen Befundkontrollen im Vordergrund. Anhand von einem Fallbeispiel aus unserer Sprechstunde sollen das klinische Bild, Diagnostik und Therapiemöglichkeiten demonstriert werden.
Contrasting nitrogen and phosphorus budgets in urban watersheds and implications for managing urban water pollution
Authors: Hobbie Sarah E. , Finlay Jacques C. , Janke Benjamin D. , Nidzgorski Daniel A. , Millet Dylan B. , Baker Lawrence A. 
Published: April 2017

SignificanceUrban waters remain widely impaired by excess nutrients, despite substantial management efforts. We present a comparison of urban watershed nitrogen (N) and phosphorus (P) budgets. Household actions of lawn fertilization and pet ownership were responsible for the majority of watershed N and P inputs, respectively. N and P exhibited contrasting dynamics within watersheds. Watersheds exported most or all P inputs via stormwater runoff, likely contributing to surface water degradation. High apparent N retention likely resulted from unmeasured watershed N losses to the atmosphere and groundwater. These contrasting dynamics suggest that N management should emphasize reducing watershed inputs, whereas P management should focus on reducing watershed P inputs and transport from vegetated landscapes to streets and storm drains.
Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER–Golgi interface
Authors: Watanabe Satoshi , Harayama Manami , Kanemura Shingo , Sitia Roberto , Inaba Kenji 
Published: April 2017

Significance
The high-resolution structures presented herein explain how ERp44, a multifunctional chaperone cycling in the early secretory pathway, exploits the endoplasmic reticulum (ER)–Golgi pH gradient to bind clients in the acidic Golgi and release them into the neutral ER environment. Protonation of essential cysteine and histidine residues induces conformational changes that simultaneously expose Cys29 in the positively charged client-binding site and the C-terminal KDEL receptor-binding motif, making ERp44 a pH-sensitive molecular machine that controls fidelity of protein secretion.
Facilitated dissociation of transcription factors from single DNA binding sites
Authors: Kamar Ramsey I. , Banigan Edward J. , Erbas Aykut , Giuntoli Rebecca D. , Olvera de la Cruz Monica , Johnson Reid C. , Marko John F. 
Published: April 2017

Significance
Transcription factors (TFs) control biological processes by binding and unbinding to DNA. Therefore, it is crucial to understand the mechanisms that affect TF binding kinetics. Recent studies challenge the standard picture of TF binding kinetics by showing cases of proteins in solution accelerating TF dissociation rates through a facilitated dissociation (FD) process. Our study shows that FD can occur at the level of single binding sites without the action of large protein clusters or long DNA segments. Our results quantitatively support a model of FD in which competitor proteins invade partially dissociated states of DNA-bound TFs. FD is expected to be a general mechanism for modulating gene expression by altering the occupancy of TFs on the genome.
Selective Purcell enhancement of two closely linked zero-phonon transitions of a silicon carbide color center
Authors: Bracher David O. , Zhang Xingyu , Hu Evelyn L. 
Published: April 2017

Significance
Semiconductor point defects have shown great promise in their application to quantum information and sensing in the solid state. However, it is an ongoing challenge to efficiently access the light emitted by these spin-active defects and, furthermore, to enhance the emission at wavelengths that can be used to create indistinguishable photons. Such emission enhancement can be achieved by placing the defects within optical microcavities. Here, using 1D photonic crystal cavities, we report the significant enhancement of point-defect emission in silicon carbide, which hosts a suite of intriguing spin-active defects. In addition to measuring large enhancements, we also demonstrate how the cavity coupling can potentially allow access to a variety of information about the defects and their environment.