bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity-dependent changes in synaptic protein complex composition are consistent in different detergents despite differential solubility
Authors: Lautz Jonathan D. , Gniffke Edward P. , Brown Emily A. , Immendorf Karen B. , Mendel Ryan D. , Smith Stephen E. P. 
Published: July 2019

AbstractAt the post-synaptic density (PSD), large protein complexes dynamically form and dissociate in response to synaptic activity, comprising the biophysical basis for learning and memory. The use of detergents to isolate the PSD and release its membrane-associated proteins complicates studies of these activity-dependent protein interaction networks, because detergents can simultaneously disrupt the very interactions under study. Despite widespread recognition that different detergents yield different experimental results, the effect of detergent on activity-dependent synaptic protein complexes has not been rigorously examined. Here, we characterize the effect of three detergents commonly used to study synaptic proteins on activity-dependent protein interactions. We first demonstrate that SynGAP-containing interactions are more abundant in 1% Deoxycholate (DOC), while Shank-, Homer- and mGluR5-containing interactions are more abundant in 1% NP-40 or Triton. All interactions were detected preferentially in high molecular weight complexes generated by size exclusion chromatography, although the detergent-specific abundance of proteins in high molecular weight fractions did not correlate with the abundance of detected interactions. Activity-dependent changes in protein complexes were consistent across detergent types, suggesting that detergents do not isolate distinct protein pools with unique behaviors. However, detection of activity-dependent changes is more or less feasible in different detergents due to baseline solubility. Collectively, our results demonstrate that detergents affect the solubility of individual proteins, but activity-dependent changes in protein interactions, when detectable, are consistent across detergent types.
Corridors best facilitate functional connectivity across a protected area network
Authors: Stewart Frances E. C. , Darlington Siobhan , Volpe John P. , McAdie Malcolm , Fisher Jason T. 
Published: July 2019

AbstractBiologging data allow animal ecologists to directly measure species’ fine-scale spatiotemporal responses to environments, such as movement – critical for our understanding of biodiversity declines in the Anthropocene. Animal movement between resource patches is a behavioral expression of multiple ecological processes that affect individual fitness. Protected area (PA) networks are a tool used to conserve biodiversity by sustaining habitat patches across vast heterogeneous landscapes. However, our ability to design PA networks that conserve biodiversity relies on our accurate understanding of animal movement and functional connectivity; this understanding is rarely tested in real-world situations due to the large geographic expanse of most PA networks. Using a tractable PA network mesocosm, we employ cutting-edge biologging technology to analyze animal movement decisions in response to a highly heterogeneous landscape. We analyze these data to test, in a novel way, three common hypotheses about functional connectivity – structural corridors, least cost paths, and stepping stones. Consistently, animals moved along structurally self-similar corridors. In reference to the Aichi 2020 Biodiversity Targets, relying on species to “stepping stone” across habitat remnants may not achieve protected area network conservation objectives.
Global view of the RAF-MEK-ERK module and its immediate downstream effectors
Authors: Santini Cristina C. , Longden James , Schoof Erwin M. , Simpson Craig D. , Jeschke Grace R. , Creixell Pau , Kim Jinho , Wu Xuewei , Turk Benjamin E. , Rosen Neal , Poulikakos Poulikos I. , Linding Rune 
Published: July 2019

AbstractSmall molecule inhibitors of BRAF and MEK have proven effective at inhibiting tumor growth in melanoma patients, however this efficacy is limited due to the almost universal development of drug resistance. To provide advanced insight into the signaling responses that occur following kinase inhibition we have performed quantitative (phospho)-proteomics of human melanoma cells treated with either dabrafenib, a BRAF inhibitor; trametinib, a MEK inhibitor or SCH772984, an ERK inhibitor. Over nine experiments we identified 7827 class I phosphorylation sites on 4960 proteins. This included 54 phosphorylation sites that were significantly down-modulated after exposure to all three inhibitors, 34 of which have not been previously reported. Functional analysis of these novel ERK targets identified roles for them in GTPase activity and regulation, apoptosis and cell-cell adhesion. Comparison of the results presented here with previously reported phosphorylation sites downstream of ERK showed a limited degree of overlap suggesting that ERK signaling responses may be highly cell line and cue specific. In addition we identified 26 phosphorylation sites that were only responsive to dabrafenib. We provide further orthogonal experimental evidence for 3 of these sites in human embryonic kidney cells over-expressing BRAF as well as further computational insights using KinomeXplorer. The validated phosphorylation sites were found to be involved in actin regulation, which has been proposed as a novel mechanism for inhibiting resistance development. These results would suggest that the linearity of the BRAF-MEK-ERK module is at least context dependent.
BAM8-22 and its receptor MRGPRX1 may attribute to cholestatic pruritus
Authors: Sanjel Babina , Maeng Han-Joo , Shim Won-Sik 
Published: July 2019

AbstractPruritus is an unexpected symptom observed in cholestasis and its mechanism is still unclear. Here, we show that bovine adrenal medulla (BAM) 8–22, an endogenous itch-inducing peptide, could be involved in cholestatic pruritus. It was found that bile duct ligation (BDL) mice, an obstructive cholestasis model, showed increased spontaneous scratching behaviour. Importantly, the mRNA level of proenkephalin, a precursor polypeptide of BAM8-22, was significantly increased in the skin of BDL mice. Furthermore, the mRNA level of Mrgprx1, which encodes a receptor for BAM8-22, was significantly increased in the dorsal root ganglia (DRG) of BDL mice. This was further confirmed by elevation of intracellular calcium levels upon BAM8-22 treatment in primarily-cultured DRG neurons. In addition, BDL mice showed augmented scratching behaviour by BAM8-22, indicating enhanced activity of MRGPRX1. Moreover, the skin homogenate of BDL mice induced elevation of intracellular calcium levels through MRGPRX1. Finally, among the various bile acids, chenodeoxycholic acid significantly increased proenkephalin transcription in a human keratinocyte cell line (HaCaT). In conclusion, cholestatic pruritus could be attributed in part to enhanced action of both BAM8-22 in the skin and its receptor MRGPRX1 in sensory neurons.
Heat capacities of thermally manipulated mechanical oscillator at strong coupling
Authors: Kolář Michal , Ryabov Artem , Filip Radim 
Published: July 2019

AbstractCoherent quantum oscillators are basic physical systems both in quantum statistical physics and quantum thermodynamics. Their realizations in lab often involve solid-state devices sensitive to changes in ambient temperature. We represent states of the solid-state optomechanical oscillator with temperature-dependent frequency by equivalent states of the mechanical oscillator with temperature-dependent energy levels. We interpret the temperature dependence as a consequence of strong coupling between the oscillator and the heat bath. We explore parameter regimes corresponding to anomalous behavior of mechanical and thermodynamic characteristics as a consequence of the strong coupling: (i) The localization and the purification induced by heating, and (ii) the negativity of two generalized heat capacities. The capacities can be used to witness non-linearity in the temperature dependency of the energy levels. Our phenomenological experimentally-oriented approach can stimulate development of new optomechanical and thermomechanical experiments exploring basic concepts of strong coupling thermodynamics.
MICA*049, not MICA*009, is associated with Behçet’s disease in a Chinese population
Authors: Zhu Weifeng , Deng Yan , Wang Jiucun , Guo Xinjian , Ding Weifeng , Chao Jiashuo , Lin Dan , Wang Yuqin , Zhou Xiaodong 
Published: July 2019

AbstractBehçet’s disease (BD) is a multi-systemic inflammatory disease. Previous reports indicated that MICA*009 confers susceptibility to BD. MICA*049 differs from MICA*009:01, a major MICA*009 subtype, only at codon 335 in exon 6. However, the potential association of MICA*049 with BD has not been addressed. In this study, we differentiated association among MICA*049, MICA*009 and HLA-B*51 with BD. A Han Chinese cohort consisting of 41 BD patients and 197 ethnically matched controls were examined with sequencing and T-ARMS-PCR for genotyping of MICA, and ARMS-PCR for HLA-B*51. The phenotype frequency of MICA*049 (41.5% versus 8.1%, OR = 8.01, P = 1.91 × 10−8) and HLA-B*51 (46.3% versus 15.7%, OR = 4.62, P = 1.21 × 10−5) were significantly higher in BD patients than those in controls, whereas MICA*009 showed no significant difference between the two groups (17.1% versus 13.2%, OR = 1.35, P = 0.51). After stratification for the effect of HLA-B*51, MICA*049 was still associated with BD in HLA-B*51 negative patients (OR = 40.61, P = 0.02). Our results indicate that MICA*049, not MICA*009, is a risk factor to BD, and that is independent from HLA-B*51 in the Han Chinese cohort.
Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis
Authors: Diani Marco , Casciano Fabio , Marongiu Laura , Longhi Matteo , Altomare Andrea , Pigatto Paolo D. , Secchiero Paola , Gambari Roberto , Banfi Giuseppe , Manfredi Angelo A. , Altomare Gianfranco , Granucci Francesca , Reali Eva 
Published: July 2019

AbstractThe aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8+ and CD4+ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8+ CCR6+ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8+ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3+ CD8+ T cells and CD69+ cells. CD4+ T cells in the two compartments shared many similarities with CD8+ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis.
Defective hierarchical porous copper-based metal-organic frameworks synthesised via facile acid etching strategy
Authors: Doan Huan V. , Sartbaeva Asel , Eloi Jean-Charles , A. Davis Sean , Ting Valeska P. 
Published: July 2019

AbstractIntroducing hierarchical pore structure to microporous materials such as metal-organic frameworks (MOFs) can be beneficial for reactions where the rate of reaction is limited by low rates of diffusion or high pressure drop. This advantageous pore structure can be obtained by defect formation, mostly via post-synthetic acid etching, which has been studied extensively on water-stable MOFs. Here we show that a water-unstable HKUST-1 MOF can also be modified in a corresponding manner by using phosphoric acid as a size-selective etching agent and a mixture of dimethyl sulfoxide and methanol as a dilute solvent. Interestingly, we demonstrate that the etching process which is time- and acidity- dependent, can result in formation of defective HKUST-1 with extra interconnected hexagonal macropores without compromising on the bulk crystallinity. These findings suggest an intelligent scalable synthetic method for formation of hierarchical porosity in MOFs that are prone to hydrolysis, for improved molecular accessibility and diffusion for catalysis.
Scalable Labeling for Cytoarchitectonic Characterization of Large Optically Cleared Human Neocortex Samples
Authors: Hildebrand Sven , Schueth Anna , Herrler Andreas , Galuske Ralf , Roebroeck Alard 
Published: July 2019

AbstractOptical clearing techniques and light sheet microscopy have transformed fluorescent imaging of rodent brains, and have provided a crucial alternative to traditional confocal or bright field techniques for thin sections. However, clearing and labeling human brain tissue through all cortical layers and significant portions of a cortical area, has so far remained extremely challenging, especially for formalin fixed adult cortical tissue. Here, we present MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling approach for optically cleared human cortex samples, which can be applied to large (up to 5 mm thick) formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dye protocols in combination with new refractive index matching solutions allows deep volume imaging. This greatly reduces time and cost of imaging cytoarchitecture in thick samples and enables classification of cytoarchitectonic layers over the full cortical depth. We demonstrate application of MASH to large archival samples of human visual areas, characterizing cortical architecture in 3D from the scale of cortical areas to that of single cells. In combination with scalable light sheet imaging and data analysis, MASH could open the door to investigation of large human cortical systems at cellular resolution and in the context of their complex 3-dimensional geometry.
Strong primary care and patients’ survival
Authors: Wensing Michel , Szecsenyi Joachim , Kaufmann-Kolle Petra , Laux Gunter 
Published: July 2019

AbstractPrimary healthcare is the cornerstone of any healthcare system. A major health system reform to strengthen primary care has been implemented in Germany since 2008. Key components include: voluntary participation, intensive management of patients with chronic diseases, coordination of access to medical specialists, continuous quality improvement, and capitation-based reimbursement. The objective of this study was to assess the effect of this reform on survival of enrolled patients. We conducted a comparative cohorts study with 5-year follow-up, starting in the year 2012 in Baden-Wuerttemberg, Germany. Participants were 1,003,336 enrolled patients and 725,310 control patients. A Cox proportional hazards regression model was applied to compare survival of enrolled patients with a composed control cohort of non-enrolled patients, adjusted for a range of patient and physician characteristics. Average age of enrolled patients was 57.3 years and 56.1% were women. Compared to control patients, they had lower mortality (Hazard Ratio: 0.978; 95% CI: 0.968; 0.989). Participation in chronic disease management programs had independent impact on survival rate (Hazard Ratio 0.744, 95% CI: 0.734; 0.753). We concluded that strong primary care is safe and potentially beneficial in terms of patients’ survival.
Antibody responses to flagellin C and Streptococcus gallolyticus pilus proteins in colorectal cancer
Authors: Butt Julia , Fernández de Larrea Nerea , Tjalsma Harold , Roelofs Rian , Kato Ikuko , Martín Vicente , Pérez-Gómez Beatriz , Moreno Victor , Dierssen-Sotos Trinidad , Castilla Jesús , Fernández-Tardón Guillermo , Amiano Pilar , Salas Dolores , Alguacil Juan , Jiménez-Moleón José Juan , Huerta José María , de Sanjosé Silvia , del Campo Rosa , Kogevinas Manolis , Pollán Marina , Pawlita Michael , Waterboer Tim , Boleij Annemarie , Aragonés Nuria 
Published: July 2019

AbstractAntibodies to Streptococcus gallolyticus subspecies gallolyticus (SGG) have been associated with colorectal cancer (CRC). Because SGG may correlate with impaired gut epithelia, we assessed the association of antibodies to bacterial flagellin C (FliC), a measure potentially related to this impairment, with CRC and the CRC-specific interaction with antibodies to SGG proteins. Antibodies to FliC and SGG pilus proteins Gallo2178 and Gallo2179 were measured in two independent studies, a combined study from Nijmegen and Detroit (93 CRC cases, 74 controls) and a replication data set including 576 cases and 576 controls from the Spanish multicenter multicase-control study (MCC-Spain). Logistic regression was applied to assess whether antibodies to FliC were associated with CRC and modified the association of antibodies to SGG proteins with CRC. Antibodies to FliC were associated with those to SGG Gallo2178 among CRC cases, resulting in an interaction in the association of antibodies to Gallo2178 with CRC (p = 0.007). This association was only present among individuals with high antibody responses to FliC (OR: 2.42, 95% CI: 1.45–4.06). In conclusion, our findings suggest that colorectal tumorigenesis could be accompanied by an impaired integrity of the epithelium that could result in associated increased antibody responses to bacterial proteins.
Plasma-based fast-gelling biohybrid gels for biomedical applications
Authors: Pal Amrita , Tripathi Kunal , Pathak Chandrashekhar , Vernon Brent L. 
Published: July 2019

AbstractBlood based biomaterials are widely researched and used in different biomedical applications including cell therapy, drug delivery, sealants etc. due to their biocompatibility and biodegradability. Blood derived gels are successfully used in clinical studies due to the presence of fibrinogen and several platelet growth factors. In spite of their wide applications, it is challenging to use blood-based biomaterials due to their low mechanical stability, poor adhesive property and contamination risk. In this study, we used porcine plasma to form gel in presence of biodegradable synthetic crosslinkers. Mechanical strength of this plasma gel could be tailored by altering the amount of crosslinkers for any desired biomedical applications. These plasma gels, formed by the synthetic crosslinkers, were utilized as a drug delivery platform for wound healing due to their low cytotoxicity. A model drug release study with these plasma gels indicated slow and sustained release of the drugs.
Optimal Semiconductors for 3H and 63Ni Betavoltaics
Authors: Maximenko Sergey I. , Moore Jim E. , Affouda Chaffra A. , Jenkins Phillip P. 
Published: July 2019

AbstractBetavoltaic power sources based on the conversion of radioisotope energy to electrical power are considered an appealing option for remote applications due to extended period of operation and high energy densities. However, to be competitive with other power sources, their efficiency must be increased. This can be done through optimization of the beta source and selection of the semiconductor absorber. This paper evaluates available on the market and developing wideband gap semiconductors as prospective absorbers with 3H and 63Ni sources. Simulation results indicate that among wide band gap materials 4H-SiC and diamond are two optimal semiconductors due to the combination of good coupling efficiencies with isotope sources and good electronic transport properties. Additionally, having good coupling efficiency, an ultra-wide bandgap, and the capability for both n- and p-type doping, c-BN is a promising material for betavoltaic applications.
Impact of local composition on the energetics of E-centres in Si1−xGex alloys
Authors: Christopoulos Stavros-Richard G. , Kuganathan Navaratnarajah , Chroneos Alexander 
Published: July 2019

AbstractThe energetics of the defect chemistry and processes in semiconducting alloys is both technologically and theoretically significant. This is because defects in semiconductors are critical to tune their electronic properties. These processes are less well understood in random semiconductor alloys such as silicon germanium as compared to elementary semiconductors (for example silicon). To model the random silicon germanium alloy we have employed density functional theory calculations in conjunction with the special quasirandom structures model for different compositions. Here we show that, the energetics of substitutional phosphorous-vacancy pairs (E-centres) in Si1−xGex alloys vary greatly with respect to the local Ge concentration and the composition of the alloy. The most energetically favourable E-centres have a Ge atom as a nearest neighbour, whereas the dependence of the binding energy of the E-centres with respect to alloy composition is non-linear.
MC4R and ENPP1 gene polymorphisms and their implication in maternal and neonatal risk for obesity
Authors: Mărginean Claudiu , Mărginean Cristina Oana , Iancu Mihaela , Meliț Lorena Elena , Tripon Florin , Bănescu Claudia 
Published: July 2019

AbstractThe aims of this study were to establish the role of MC4Rrs17782313 and ENPP1rs1044498 gene polymorphisms on pre-pregnancy BMI and the newborn’s status. We performed a cross-sectional study on 185 mothers and their offspring. The groups were divided into: control group- underweight or normal mothers with BMIinitial < 25 kg/m2 (n1 = 134) and study group-overweight/obese mothers with BMIinitial ≥ 25 kg/m2 (n2 = 51). All subjects underwent demographic, anthropometric, paraclinical, bioimpedance and genetic parameters. We found association between initial BMI and gestational weight gain (GWG), and a higher frequency of excessive GWG in overweight/obese women (p = 0.037). Higher values of anthropometric and bioimpedance parameters were observed in overweight/obese versus underweight/normal women. The MC4R rs17782313 and ENPP1 rs1044498 variant genotypes had an increased risk of pre-pregnancy overweight (OR = 1.41; 95% CI:[0.72; 2.78]; OR = 1.34; 95% CI:[0.65; 2.75]). The newborns from mothers with excessive GWG had a higher birth weight (BW) (p = 0.001). Higher MUAC values were noticed in newborns with MC4R rs17782313 wild-type genotype. Also, BW was correlated with GWG status smoking in pregnancy, gestational age and neonatal ENPP1rs1044498 variant genotype (p = 0.026). Our study pointed out the role of MC4R rs17782313 and ENPP1 rs1044498 genotypes in obesity determinisms in mothers and their newborns in correlation with BMI, MUAC, TST and bioimpedance parameters.