bluuebunny/crossref_metadata_2025_split huggingface dataset:
'Exacerbation-free time' to assess the impact of exacerbations in patients with chronic obstructive pulmonary disease (COPD): a prospective observational study
Authors: Boer L. M. , Bischoff E. W. , Borgijink X. , Vercoulen J. H. , Akkermans R. P. , Kerstjens H. A. M. , Assendelft W. J. , Schermer T. R. 
Published: April 2018

AbstractCOPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman’s rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was −0.71 (p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = −0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers (β = −5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does.
The oscillation of intracellular Ca2+ influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium
Authors: Ihara Tatsuya , Mitsui Takahiko , Nakamura Yuki , Kanda Mie , Tsuchiya Sachiko , Kira Satoru , Nakagomi Hiroshi , Sawada Norifumi , Kamiyama Manabu , Hirayama Yuri , Shigetomi Eiji , Shinozaki Youichi , Yoshiyama Mitsuharu , Nakao Atsuhito , Takeda Masayuki , Koizumi Schuichi 
Published: April 2018

AbstractWe previously showed that bladder functions are controlled by clock genes with circadian rhythm. The sensation of bladder fullness (SBF) is sensed by mechano-sensor such as Piezo1 and TRPV4 in the mouse bladder urothelium. However, functional circadian rhythms of such mechano-sensors remain unknown. To investigate functional circadian changes of these mechano-sensors, we measured circadian changes in stretch-evoked intracellular Ca2+ influx ([Ca2+]
i
) using mouse primary cultured urothelial cells (MPCUCs). Using Ca2+ imaging, stretch-evoked [Ca2+]
i
was quantified every 4 h in MPCUCs derived from wild-type (WT) and Clock
Δ19/Δ19
mice, which showed a nocturia phenotype. Furthermore, a Piezo1 inhibitor GsMTx4 and a TRPV4 inhibitor Ruthenium Red were applied and stretch-evoked [Ca2+]
i
in MPCUCs was measured to investigate their contribution to SBF. Stretch-evoked [Ca2+]
i
showed a circadian rhythm in the WT mice. In contrast, Clock
Δ19/Δ19
mice showed disrupted circadian rhythm. The administration of both GsMTx4 and Ruthenium Red eliminated the circadian rhythm of stretch-evoked [Ca2+]
i
in WT mice. We conclude that SBF may have a circadian rhythm, which is created by functional circadian changes of Piezo1 and TRPV4 being controlled by clock genes to be active during wakefulness and inactive during sleep. Abnormalities of clock genes disrupt SBF, and induce nocturia.
A Multi-scale Biophysical Approach to Develop Structure-Property Relationships in Oral Biofilms
Authors: Pattem J. , Davrandi M. , Aguayo S. , Allan E. , Spratt D. , Bozec L. 
Published: April 2018

AbstractOver the last 5–10 years, optical coherence tomography (OCT) and atomic force microscopy (AFM) have been individually applied to monitor the morphological and mechanical properties of various single-species biofilms respectively. This investigation looked to combine OCT and AFM as a multi-scale approach to understand the role sucrose concentration and age play in the morphological and mechanical properties of oral, microcosm biofilms, in-vitro. Biofilms with low (0.1% w/v) and high (5% w/v) sucrose concentrations were grown on hydroxyapatite (HAP) discs from pooled human saliva and incubated for 3 and 5 days. Distinct mesoscale features of biofilms such as regions of low and high extracellular polymeric substances (EPS) were identified through observations made by OCT. Mechanical analysis revealed increasing sucrose concentration decreased Young’s modulus and increased cantilever adhesion (p < 0.0001), relative to the biofilm. Increasing age was found to decrease adhesion only (p < 0.0001). This was due to mechanical interactions between the indenter and the biofilm increasing as a function of increased EPS content, due to increasing sucrose. An expected decrease in EPS cantilever contact decreased adhesion due to bacteria proliferation with biofilm age. The application OCT and AFM revealed new structure-property relationships in oral biofilms, unattainable if the techniques were used independently.
Coarse particulate matter (PM2.5–10) in Los Angeles Basin air induces expression of inflammation and cancer biomarkers in rat brains
Authors: Ljubimova Julia Y. , Braubach Oliver , Patil Rameshwar , Chiechi Antonella , Tang Jie , Galstyan Anna , Shatalova Ekaterina S. , Kleinman Michael T. , Black Keith L. , Holler Eggehard 
Published: April 2018

AbstractAir pollution is linked to brain inflammation, which accelerates tumorigenesis and neurodegeneration. The molecular mechanisms that connect air pollution with brain pathology are largely unknown but seem to depend on the chemical composition of airborne particulate matter (PM). We sourced ambient PM from Riverside, California, and selectively exposed rats to coarse (PM2.5–10: 2.5–10 µm), fine (PM<2.5: <2.5 µm), or ultrafine particles (UFPM: <0.15 µm). We characterized each PM type via atomic emission spectroscopy and detected nickel, cobalt and zinc within them. We then exposed rats separately to each PM type for short (2 weeks), intermediate (1–3 months) and long durations (1 year). All three metals accumulated in rat brains during intermediate-length PM exposures. Via RNAseq analysis we then determined that intermediate-length PM2.5–10 exposures triggered the expression of the early growth response gene 2 (EGR2), genes encoding inflammatory cytokine pathways (IL13-Rα1 and IL-16) and the oncogene RAC1. Gene upregulation occurred only in brains of rats exposed to PM2.5–10 and correlated with cerebral nickel accumulation. We hypothesize that the expression of inflammation and oncogenesis-related genes is triggered by the combinatorial exposure to certain metals and toxins in Los Angeles Basin PM2.5–10.
Formation of trihalomethanes as disinfection byproducts in herbal spa pools
Authors: Fakour Hoda , Lo Shang-Lien 
Published: April 2018

AbstractHerbal spa treatments are favorite recreational activities throughout the world. The water in spas is often disinfected to control pathogenic microorganisms and guarantee hygiene. However, chlorinated water may cause the formation of disinfection byproducts (DBPs). Although there have been many studies on DBP formation in swimming pools, the role of organic matter derived from herbal medicines applied in herbal spa water has been largely neglected. Accordingly, the present study investigated the effect of herbal medicines on the formation of trihalomethanes (THMs) in simulated herbal spa water. Water samples were collected from a spa pool, and then, disinfection and herbal addition experiments were performed in a laboratory. The results showed that the organic molecules introduced by the herbal medicines are significant precursors to the formation of THMs in spa pool water. Since at least 50% of THMs were produced within the first six hours of the reaction time, the presence of herbal medicines in spa water could present a parallel route for THM exposure. Therefore, despite the undeniable benefits of herbal spas, the effect of applied herbs on DBP formation in chlorinated water should be considered to improve the water quality and health benefits of spa facilities.
Proteomic approach to understand the molecular physiology of symbiotic interaction between Piriformospora indica and Brassica napus
Authors: Shrivastava Neeraj , Jiang Li , Li Pan , Sharma Archana Kumari , Luo Xingyuan , Wu Sanling , Pandey Rashmi , Gao Qikang , Lou Binggan 
Published: April 2018

AbstractMany studies have been now focused on the promising approach of fungal endophytes to protect the plant from nutrient deficiency and environmental stresses along with better development and productivity. Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we used integrated in-depth proteome analyses to characterize the relationship between endophyte Piriformospora indica and Brassica napus plant highlighting its potential involvement in symbiosis and overall growth and development of the plant. An LC-MS/MS based label-free quantitative technique was used to evaluate the differential proteomics under P. indica treatment vs. control plants. In this study, 8,123 proteins were assessed, of which 46 showed significant abundance (34 downregulated and 12 upregulated) under high confidence conditions (p-value ≤ 0.05, fold change ≥2, confidence level 95%). Mapping of identified differentially expressed proteins with bioinformatics tools such as GO and KEGG pathway analysis showed significant enrichment of gene sets involves in metabolic processes, symbiotic signaling, stress/defense responses, energy production, nutrient acquisition, biosynthesis of essential metabolites. These proteins are responsible for root’s architectural modification, cell remodeling, and cellular homeostasis during the symbiotic growth phase of plant’s life. We tried to enhance our knowledge that how the biological pathways modulate during symbiosis?
Visualizing the bidirectional optical transfer function for near-field enhancement in waveguide coupled plasmonic transducers
Authors: Otto Lauren M. , Ogletree D. Frank , Aloni Shaul , Staffaroni Matteo , Stipe Barry C. , Hammack Aeron T. 
Published: April 2018

AbstractWe report visualizations of the bidirectional near-field optical transfer function for a waveguide-coupled plasmonic transducer as a metrology technique essential for successful development for mass-fabricated near-field devices. Plasmonic devices have revolutionized the observation of nanoscale phenomena, enabling optical excitation and readout from nanoscale regions of fabricated devices instead of as limited by optical diffraction. Visualizations of the plasmonic transducer modes were acquired both by local near-field excitation of the antenna on the front facet of a waveguide using the focused electron beam of a scanning electron microscope as a probe of the near-field cathodoluminescence during far-field collection from the back facet of the waveguide, and by local mapping of the optical near-field for the same antenna design using scattering scanning near-field optical microscopy as a probe of the near-field optical mode density for far-field light focused into the back facet of the waveguide. Strong agreement between both measurement types and numerical modeling was observed, indicating that the method enables crucial metrological comparisons of as fabricated device performance to as-modeled device expectations for heat-assisted magnetic recording heads, which can be extended to successful development of future near-field-on-chip devices such as optical processor interconnects.
Unravelling the inhibitory activity of Chlamydomonas reinhardtii sulfated polysaccharides against α-Synuclein fibrillation
Authors: Choudhary Sinjan , Save Shreyada N. , Vavilala Sirisha L. 
Published: April 2018

Abstractα-Synuclein (α-Syn) is an intrinsically disordered presynaptic protein, whose aggregation is critically involved in Parkinson’s disease (PD). Many of the currently available drugs for the treatment of PD are not sufficiently effective in preventing progress of the disease and have multiple side-effects. With this background, efficient drug candidates, sulfated polysaccharides from Chlamydomonas reinhardtii (Cr-SPs) were isolated and investigated for their effect on inhibition of α-Syn fibrillation and dissolution of preformed α-Syn fibrillar structures through a combination of spectroscopic and microscopic techniques. The kinetics of α-Syn fibrillation demonstrates that Cr-SPs are very effective in inhibiting α-Syn fibrillation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis gel-image shows presence of soluble protein in the presence of Cr-SPs after completion of the fibrillation process. The morphological changes associated with fibrillation monitored by transmission electron microscopy showed that Cr-SPs efficiently bind with α-Syn and delay the conversion of α-helical intermediate into β-sheet rich structures. Cr-SPs are also effective even if onset of α-Syn fibrillation has already started and they also have the ability to dissolve pre-formed fibrils. Thus, the current work has substantial therapeutic implications towards unlocking the immense potential of algal products to function as alternative therapeutic agents against PD and other protein aggregation related disorders.
Surface display of PbrR on Escherichia coli and evaluation of the bioavailability of lead associated with engineered cells in mice
Authors: Hui Changye , Guo Yan , Zhang Wen , Gao Chaoxian , Yang Xueqin , Chen Yuting , Li Limei , Huang Xianqing 
Published: April 2018

AbstractHuman exposure to lead mainly occurs by ingestion of contaminated food, water and soil. Blocking lead uptake in the gastrointestinal tract is a novel prevention strategy. Whole-cell biosorbent for lead was constructed with PbrR genetically engineered on the cell surface of Escherichia coli (E. coli), a predominant strain among intestinal microflora, using lipoprotein (Lpp)-OmpA as the anchoring protein. In vitro, the PbrR displayed cells had an enhanced ability for immobilizing toxic lead(II) ions from the external media at both acidic and neutral pH, and exhibited a higher specific adsorption for lead compared to other physiological two valence metal ions. In vivo, the persistence of recombinant E. coli in the murine intestinal tract and the integrity of surface displayed PbrR were confirmed. In addition, oral administration of surface-engineered E. coli was safe in mice, in which the concentrations of physiological metal ions in blood were not affected. More importantly, lead associated with PbrR-displayed E. coli was demonstrated to be less bioavailable in the experimental mouse model with exposure to oral lead. This is reflected by significantly lower blood and femur lead concentrations in PbrR-displayed E. coli groups compared to the control. These results open up the possibility for the removal of toxic metal ions in vivo using engineered microorganisms as adsorbents.
Ocular Blood Flow in Rabbits under Deep Anesthesia: A Real-Time Measurement Technique and Its Application in Characterizing Retinal Ischemia
Authors: Bhatti Mehwish Saba , Tang Tong Boon , Chen Hui Cheng 
Published: April 2018

AbstractIn this study, we reported a new technique based on laser speckle flowgraphy to record the ocular blood flow in rabbits under deep anesthesia, and proposed parameters to characterize retinal ischemia. We applied the proposed technique to study the correlation of blood flow between the eyes of normal non-anesthetized animals, and to characterize the occlusion of the internal carotid artery (ICA) and external carotid artery (ECA). We established a correlation in blood flow between the eyes of non-anesthetized animals, and derived two new parameters, namely, the laterality index and vascular perfusion estimate (VPE). Our experimental results from 16 eyes (of 13 New Zealand white rabbits) showed a reduction in ocular blood flow with a significant decrease in the VPE after the occlusion of the ECA (p < 0.001). A low/minimal effect on blood flow was observed with the occlusion of the ICA. In conclusion, we demonstrated a means for the real-time measurement of the ocular blood flow in rabbits under deep anesthesia by using laser speckle flowgraphy and the VPE as an indicator of successful occlusion. The proposed technique might be applicable in quantifying the efficacy of new drugs and interventions for the treatment of retinal ischemia.
Loss of MeCP2 in adult 5-HT neurons induces 5-HT1A autoreceptors, with opposite sex-dependent anxiety and depression phenotypes
Authors: Philippe Tristan J. , Vahid-Ansari Faranak , Donaldson Zoe R. , Le François Brice , Zahrai Amin , Turcotte-Cardin Valérie , Daigle Mireille , James Jonathan , Hen René , Merali Zul , Albert Paul R. 
Published: April 2018

AbstractThe 5-HT1A autoreceptor mediates feedback inhibition of serotonin (5-HT) neurons, and is implicated in major depression. The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription. Since chronic stress alters HTR1A methylation and expression, we addressed whether recruitment of methyl-binding protein MeCP2 may alter Deaf1 regulation at the HTR1A locus. We show that MeCP2 enhances Deaf1 binding to its HTR1A site and co-immunoprecipitates with Deaf1 in cells and brain tissue. Chromatin immunoprecipitation assays showed Deaf1-dependent recruitment of MeCP2 to the mouse HTR1A promoter, and MeCP2 modulated human and mouse HTR1A gene transcription in a Deaf1-dependent fashion, enhancing Deaf1-induced repression at the Deaf1 site. To address the role of MeCP2 in HTR1A regulation in vivo, mice with conditional knockout of MeCP2 in adult 5-HT neurons (MeCP2 cKO) were generated. These mice exhibited increased 5-HT1A autoreceptor levels and function, consistent with MeCP2 enhancement of Deaf1 repression in 5-HT neurons. Interestingly, female MeCP2-cKO mice displayed reduced anxiety, while males showed increased anxiety and reduced depression-like behaviors. These data uncover a novel role for MeCP2 in 5-HT neurons to repress HTR1A expression and drive adult anxiety- and depression-like behaviors in a sex-specific manner.
Prediction of spacer-α6 complex: a novel insight into binding of ADAMTS13 with A2 domain of von Willebrand factor under forces
Authors: Fang Xiang , Lin Jiangguo , Fang Ying , Wu Jianhua 
Published: April 2018

AbstractForce-regulated cleavage of A2 domain of von Willebrand factor (vWF) by ADAMTS13 is a key event in preventing thrombotic thrombocytopenic purpura (TTP). Recognition and cleavage depend on cooperative and modular contacts between several ADAMTS13 subdomains and discrete segments of vWF A2 domain. Spacer domain of ADAMTS13 contains an important exosite interacting with α6 helix of unfold A2 domain, but it remains unclear whether stretching of α6 regulates binding to spacer. To understand the molecular mechanism underlying the interactions between spacer and α6 under stretching, we successfully predicted spacer-α6 complex by a novel computer strategy combined the steered molecular dynamics (SMD) and flexible docking techniques. This strategy included three steps: (1) constant-velocity SMD simulation of α6; (2) zero-velocity SMD simulations of α6, and (3) flexible dockings of α6 to spacer. In our spacer-α6 complex model, 13 key residues, six in α6 and seven in spacer, were identified. Our data demonstrated a biphasic extension-regulated binding of α6 to spacer. The binding strength of the complex increased with α6 extension until it reaches its optimum of 0.25 nm, and then decreased as α6 extension further increased, meaning that spacer is in favor to binding with a partially extended α6, which may contribute to the optimal contact and proteolysis. Changes of interface area and intermolecular salt bridge may serve as the molecular basis for this characteristic. These findings provide a novel insight into mechano-chemical regulation on interaction between ADAMTS13 and vWF A2 domain under forces.
3D artificial round section micro-vessels to investigate endothelial cells under physiological flow conditions
Authors: Sfriso Riccardo , Zhang Shengye , Bichsel Colette Andrea , Steck Oliver , Despont Alain , Guenat Olivier Thierry , Rieben Robert 
Published: April 2018

AbstractIn the context of xenotransplantation, in ischemia/reperfusion injury as well as in cardiovascular research, the study of the fascinating interplay between endothelial cells (EC) and the plasma cascade systems often requires in vitro models. Blood vessels are hardly reproducible with standard flat-bed culture systems and flow-plate assays are limited in their low surface-to-volume ratio which impedes the study of the anticoagulant properties of the endothelial cells. According to the 3R regulations (reduce, replace and refine animal experimentation) we developed a closed circuit microfluidic in vitro system in which endothelial cells are cultured in 3D round section microchannels and subjected to physiological, pulsatile flow. In this study, a 3D monolayer of porcine aortic EC was perfused with human serum to mimic a xenotransplantation setting. Complement as well as EC activation was assessed in the presence or absence of complement inhibitors showing the versatility of the model for drug testing. Complement activation products as well as E-selectin expression were detected and visualized in situ by high resolution confocal microscopy. Furthermore, porcine pro-inflammatory cytokines as well as soluble complement components in the recirculating fluid phase were detected after human serum perfusion providing a better overview of the artificial vascular environment.
Genetic diversity and phylogenetic characteristics of Chinese Tibetan and Yi minority ethnic groups revealed by non-CODIS STR markers
Authors: He Guanglin , Wang Zheng , Zou Xing , Chen Xu , Liu Jing , Wang Mengge , Hou Yiping 
Published: April 2018

AbstractNon-CODIS STRs, with high polymorphism and allele frequency difference among ethnically and geographically different populations, play a crucial role in population genetics, molecular anthropology, and human forensics. In this work, 332 unrelated individuals from Sichuan Province (237 Tibetan individuals and 95 Yi individuals) are firstly genotyped with 21 non-CODIS autosomal STRs, and phylogenetic relationships with 26 previously investigated populations (9,444 individuals) are subsequently explored. In the Sichuan Tibetan and Yi, the combined power of discrimination (CPD) values are 0.9999999999999999999 and 0.9999999999999999993, and the combined power of exclusion (CPE) values are 0. 999997 and 0.999999, respectively. Analysis of molecular variance (AMOVA), principal component analysis (PCA), multidimensional scaling plots (MDS) and phylogenetic analysis demonstrated that Sichuan Tibetan has a close genetic relationship with Tibet Tibetan, and Sichuan Yi has a genetic affinity with Yunnan Bai group. Furthermore, significant genetic differences have widely existed between Chinese minorities (most prominently for Tibetan and Kazakh) and Han groups, but no population stratifications rather a homogenous group among Han populations distributed in Northern and Southern China are observed. Aforementioned results suggested that these 21 STRs are highly polymorphic and informative in the Sichuan Tibetan and Yi, which are suitable for population genetics and forensic applications.