bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease
Authors: van Kessel Sebastiaan P. , Frye Alexandra K. , El-Gendy Ahmed O. , Castejon Maria , Keshavarzian Ali , van Dijk Gertjan , El Aidy Sahar 
Published: January 2019

AbstractHuman gut microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we characterize gut-associated bacteria in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases. Bacterial tyrosine decarboxylases efficiently convert levodopa to dopamine, even in the presence of tyrosine, a competitive substrate, or inhibitors of human decarboxylase. In situ levels of levodopa are compromised by high abundance of gut bacterial tyrosine decarboxylase in patients with Parkinson’s disease. Finally, the higher relative abundance of bacterial tyrosine decarboxylases at the site of levodopa absorption, proximal small intestine, had a significant impact on levels of levodopa in the plasma of rats. Our results highlight the role of microbial metabolism in drug availability, and specifically, that abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen of levodopa treatment in Parkinson’s disease patients.
Disulfiram and BKM120 in Combination with Chemotherapy Impede Tumor Progression and Delay Tumor Recurrence in Tumor Initiating Cell-Rich TNBC
Authors: Wu Ling , Meng Fanyan , Dong Lun , Block C. James , Mitchell Allison V. , Wu Jason , Jang Hyejeong , Chen Wei , Polin Lisa , Yang Qifeng , Dou Q. Ping , Wu Guojun 
Published: January 2019

AbstractTumor initiating cells (TIC) have been suggested as a mechanism for driving chemoresistance and tumor recurrence in human cancers including triple negative breast cancer (TNBC). Significant progress has been made in targeting TICs. However, methods for simultaneously targeting heterogeneous TIC populations are lacking. In this study, we found that treating TNBC cells with chemotherapeutic agents led to a significant accumulation of the ALDH+ TIC population. Treating TNBC cells with a disulfiram and copper mixture (DSF/Cu) specifically decreased the ALDH+ TIC population and treatment with BKM120, a pan-PI3K inhibitor, significantly decreased the CD44+/CD24− TIC population. Furthermore, treatment with DSF/Cu or BKM120 induced higher levels of apoptosis in ALDH+ or CD44+/CD24− populations, respectively, than in bulk tumor cells. Combining DSF/Cu and BKM120 treatment simultaneously decreased the ALDH+ and CD44+/CD24− TICs. Using a TNBC tumor xenograft mouse model, we found that DSF/BKM in combination with Taxol significantly reduced the tumor burden and delayed tumor recurrence compared to Taxol treatment alone. Our study is the first of its kind to use two different drugs to abolish two major TIC subtypes simultaneously and inhibit tumor recurrence. These results lay a foundation for developing a novel therapy that can improve chemotherapeutic efficacy.
Proteo-Transcriptomic Dynamics of Cellular Response to HIV-1 Infection
Authors: Golumbeanu Monica , Desfarges Sébastien , Hernandez Céline , Quadroni Manfredo , Rato Sylvie , Mohammadi Pejman , Telenti Amalio , Beerenwinkel Niko , Ciuffi Angela 
Published: January 2019

AbstractThroughout the HIV-1 replication cycle, complex host-pathogen interactions take place in the infected cell, leading to the production of new virions. The virus modulates the host cellular machinery in order to support its life cycle, while counteracting intracellular defense mechanisms. We investigated the dynamic host response to HIV-1 infection by systematically measuring transcriptomic, proteomic, and phosphoproteomic expression changes in infected and uninfected SupT1 CD4+ T cells at five time points of the viral replication process. By means of a Gaussian mixed-effects model implemented in the new R/Bioconductor package TMixClust, we clustered host genes based on their temporal expression patterns. We identified a proteo-transcriptomic gene expression signature of 388 host genes specific for HIV-1 replication. Comprehensive functional analyses of these genes confirmed the previously described roles of some of the genes and revealed novel key virus-host interactions affecting multiple molecular processes within the host cell, including signal transduction, metabolism, cell cycle, and immune system. The results of our analysis are accessible through a freely available, dedicated and user-friendly R/Shiny application, called PEACHi2.0. This resource constitutes a catalogue of dynamic host responses to HIV-1 infection that provides a basis for a more comprehensive understanding of virus-host interactions.
Gene activated adipose tissue fragments as advanced autologous biomaterials for bone regeneration: osteogenic differentiation within the tissue and implications for clinical translation
Authors: Ren Bin , Betz Volker M. , Thirion Christian , Salomon Michael , Klar Roland M. , Jansson Volkmar , Müller Peter E. , Betz Oliver B. 
Published: January 2019

AbstractCost-effective, expedited approaches for bone regeneration are urgently needed in an ageing population. Bone Morphogenetic Proteins (BMPs) stimulate osteogenesis but their efficacy is impeded by their short half-life. Delivery by genetically modified cells can overcome this problem. However, cell isolation and propagation represent significant obstacles for the translation into the clinic. Instead, complete gene activated fragments of adipose tissue hold great potential for bone repair. Here, using an in-vitro culture system, we investigated whether adenoviral transduction with human BMP-2 can promote osteogenic differentiation within adipose tissue fragments. Osteoinduction in adipose tissue fragments was evaluated by quantitative reverse transcriptase polymerase chain reaction, immunohistology and histomorphometry. BMP-2 transduced adipose tissue synthesized BMP-2 protein over 30 days peaking by day six, which significantly promoted osteogenic differentiation as indicated by increased calcium depositions, up-regulation of bone marker genes, and bone-related protein expression. Our results demonstrate that cells within adipose tissue fragments can differentiate osteogenically after BMP-2 transduction of cells on the surface of the adipose tissue. BMP-2 gene activated adipose tissue represents an advanced osteo-regenerative biomaterial that can actively contribute to osteogenesis and potentially enable the development of a novel, cost-effective, one-step surgical approach to bone repair without the need for cell isolation.
Proper direction of male genitalia is prerequisite for copulation in Drosophila, implying cooperative evolution between genitalia rotation and mating behavior
Authors: Inatomi Momoko , Shin Dongsun , Lai Yi-Ting , Matsuno Kenji 
Published: January 2019

AbstractAnimal morphology and behavior often appear to evolve cooperatively. However, it is difficult to assess how strictly these two traits depend on each other. The genitalia morphologies and courtship behaviors in insects, which vary widely, may be a good model for addressing this issue. In Diptera, phylogenetic analyses of mating positions suggested that the male-above position evolved from an end-to-end one. However, with this change in mating position, the dorsoventral direction of the male genitalia became upside down with respect to that of the female genitalia. It was proposed that to compensate for this incompatibility, the male genitalia rotated an additional 180° during evolution, implying evolutionary cooperativity between the mating position and genitalia direction. According to this scenario, the proper direction of male genitalia is critical for successful mating. Here, we tested this hypothesis using a Drosophila Myosin31DF (Myo31DF) mutant, in which the rotation of the male genitalia terminates prematurely, resulting in various deviations in genitalia direction. We found that the proper dorsoventral direction of the male genitalia was a prerequisite for successful copulation, but it did not affect the other courtship behaviors. Therefore, our results suggested that the male genitalia rotation and mating position evolved cooperatively in Drosophila.
One- and two-stage surgical revision of infected shoulder prostheses following arthroplasty surgery: A systematic review and meta-analysis
Authors: Kunutsor Setor K. , Wylde Vikki , Beswick Andrew D. , Whitehouse Michael R. , Blom Ashley W. 
Published: January 2019

AbstractPeriprosthetic joint infection (PJI) is a catastrophic complication of shoulder arthroplasty. Commonly used surgical treatments include one- or two-stage revision, but their effectiveness in controlling infection is uncertain. We aimed to compare re-infection (recurrent and new infections) rates; clinical measures of function and pain; and noninfection complication rates of one- and two-stage revision surgery for shoulder PJI using a systematic review and meta-analysis. We searched MEDLINE, Embase, Web of Science, and The Cochrane Library to February 2018. Longitudinal studies conducted in patients with shoulder PJI treated exclusively by one- or two-stage revision were eligible. No clinical trials were identified. Re-infection rates were meta-analysed using random-effect models after arcsine transformation. The re-infection rate (95% CI) in pooled analysis of eight one-stage studies (147 participants) was 5.3% (1.4–10.6). The corresponding rate for 27 two-stage studies (351 participants) was 11.5% (6.0–18.1). Postoperative clinical measures of function and pain were not significantly different between the two revision strategies. The pooled noninfection complication rate (95% CI) for one-stage and two-stage revision was 12.1% (6.1–19.5) and 18.9% (8.4–31.9) respectively. New evidence suggests one-stage revision is at least equally as effective as the two-stage in controlling infection, maintaining joint function, and improving complications in shoulder PJI.
Body sway reflects joint emotional expression in music ensemble performance
Authors: Chang Andrew , Kragness Haley E. , Livingstone Steven R. , Bosnyak Dan J. , Trainor Laurel J. 
Published: January 2019

AbstractJoint action is essential in daily life, as humans often must coordinate with others to accomplish shared goals. Previous studies have mainly focused on sensorimotor aspects of joint action, with measurements reflecting event-to-event precision of interpersonal sensorimotor coordination (e.g., tapping). However, while emotional factors are often closely tied to joint actions, they are rarely studied, as event-to-event measurements are insufficient to capture higher-order aspects of joint action such as emotional expression. To quantify joint emotional expression, we used motion capture to simultaneously measure the body sway of each musician in a trio (piano, violin, cello) during performances. Excerpts were performed with or without emotional expression. Granger causality was used to analyze body sway movement time series amongst musicians, which reflects information flow. Results showed that the total Granger-coupling of body sway in the ensemble was higher when performing pieces with emotional expression than without. Granger-coupling further correlated with the emotional intensity as rated by both the ensemble members themselves and by musician judges, based on the audio recordings alone. Together, our findings suggest that Granger-coupling of co-actors’ body sways reflects joint emotional expression in a music ensemble, and thus provide a novel approach to studying joint emotional expression.
A near infrared light emitting electrochemical cell with a 2.3 V turn-on voltage
Authors: Nemati Bideh Babak , Shahroosvand Hashem , Sousaraei Ahmad , Cabanillas-Gonzalez Juan 
Published: January 2019

AbstractWe report on an organic electroluminescent device with simplified geometry and emission in the red to near infrared (NIR) spectral region which, has the lowest turn-on voltage value, 2.3 V, among light emitting electrochemical cells (LEECs). We have synthesized and characterized three novel ruthenium π-extended phenanthroimidazoles which differ on their N^N ligands. The use of dimethyl electron donating groups along with the π-extended phenanthroimidazole moiety promotes ambipolar transport thereby avoiding the use of additional charge transport layers. Furthermore, a facile cathode deposition method based on transfer of a molten alloy (Ga:In) on top of the active layer is deployed, thus avoiding high vacuum thermal deposition which adds versatile assets to our approach. We combine ambipolar charge transport organic complex design and a simple ambient cathode deposition to achieve a potentially cost effective red to NIR emitting device with outstanding performance, opening new avenues towards the development of simplified light emitting sources through device optimization.
In utero and lactational exposure to the Selective Serotonin Reuptake Inhibitor fluoxetine compromises pup bones at weaning
Authors: Weaver Samantha R. , Xie Cynthia , Charles Julia F. , Hernandez Laura L. 
Published: January 2019

AbstractSelective Serotonin Reuptake Inhibitors (SSRIs) such as fluoxetine are widely prescribed to pregnant and breastfeeding women, yet the effects of peripartum SSRI exposure on neonatal bone are not known. In adult populations, SSRI use is associated with compromised bone health, and infants exposed to in utero SSRIs have a smaller head circumference and are shorter, suggesting possible effects on longitudinal growth. Yet no study to date has examined the effects of peripartum SSRIs on long bone growth or mass. We used microCT to determine the outcomes of in utero and lactational SSRI exposure on C57BL6 pup bone microarchitecture. We found that peripartum exposure to 20 mg/kg fluoxetine reduced femoral bone mineral density and bone volume fraction, negatively impacted trabecular and cortical parameters, and resulted in shorter femurs on postnatal day 21. Although SSRIs are considered the first-choice antidepressant for pregnant and lactating women due to a low side effect profile, SSRI exposure may compromise fetal and neonatal bone development.
Klebsiella pneumoniae prevents spore germination and hyphal development of Aspergillus species
Authors: Nogueira M. F. , Pereira L. , Jenull S. , Kuchler K. , Lion T. 
Published: January 2019

AbstractDifferent bacteria and fungi live as commensal organisms as part of the human microbiota, but shifts to a pathogenic state potentially leading to septic infections commonly occur in immunocompromised individuals. Several studies have reported synergistic or antagonistic interactions between individual bacteria and fungi which might be of clinical relevance. Here, we present first evidence for the interaction between Klebsiella pneumoniae and several Aspergillus species including A. fumigatus, A. terreus, A. niger and A. flavus which cohabit in the lungs and the intestines. Microbiological and molecular methods were employed to investigate the interaction in vitro, and the results indicate that Klebsiella pneumoniae is able to prevent Aspergillus spp. spore germination and hyphal development. The inhibitory effect is reversible, as demonstrated by growth recovery of Aspergillus spp. upon inhibition or elimination of the bacteria, and is apparently dependent on the physical interaction with metabolically active bacteria. Molecular analysis of Klebsiella-Aspergillus interaction has shown upregulation of Aspergillus cell wall-related genes and downregulation of hyphae-related genes, suggesting that Klebsiella induces cell wall stress response mechanisms and suppresses filamentous growth. Characterization of polymicrobial interactions may provide the basis for improved clinical management of mixed infections by setting the stage for appropriate diagnostics and ultimately for optimized treatment strategies.
Anomalous acoustic phonons as the physical mechanism behind the adiabatic barocaloric effect on graphene
Authors: Ma Ning , Reis Mario S. 
Published: January 2019

AbstractA graphene sheet is able to either heat up or cool down due to a mechanical strain: this is the adiabatic barocaloric effect. In order to understand the physical mechanism behind this effect, we have explored the adiabatic temperature change of the graphene and, for this purpose, we considered two contributions to the total entropy: a lattice entropy (depending on the transversal, longitudinal and anomalous out-of-plane acoustic phonons) and a strain entropy. We found that the adiabatic barocaloric effect only depends on the strain energy and the anomalous acoustic phonons, without terms due to the transversal and longitudinal acoustic phonons.
Sediment fluxes rather than oxic methanogenesis explain diffusive CH4 emissions from lakes and reservoirs
Authors: Peeters Frank , Encinas Fernandez Jorge , Hofmann Hilmar 
Published: January 2019

AbstractMethane emissions from lakes and reservoirs are a major natural source in the global budget of atmospheric CH4. A large fraction of these emissions are due to diffusive transport of CH4 from surface waters to the atmosphere. It was suggested recently that CH4 production in the oxic surface waters is required to compensate for diffusive CH4 emissions from lakes. In contrast, we demonstrate here that typical diffusive CH4-fluxes from sediments in shallow water zones, Fsed,S, suffice to explain CH4 emissions to the atmosphere. Our analysis is based on the combination of an exceptional data set on surface concentrations of CH4 with a mass balance model of CH4 that is focused on the surface mixed layer and considers CH4-fluxes from sediments, lateral transport, gas exchange with the atmosphere, and includes temperature dependencies of sediment fluxes and gas exchange. Fsed,S not only explains observed surface CH4 concentrations but also concentration differences between shallow and open water zones, and the seasonal variability of emissions and lateral concentration distributions. Hence, our results support the hypothesis that diffusive fluxes from shallow sediments and not oxic methanogenesis are the main source of the CH4 in the surface waters and the CH4 emitted from lakes and reservoirs.
Tribological and mechanical investigation of multi-directional forged nickel
Authors: Djavanroodi Faramarz , Ebrahimi Mahmoud , Nayfeh Jamal F. 
Published: January 2019

AbstractTailoring material properties to specific application requirements is one of the major challenges in materials engineering. Grain size is a key factor affecting physical and mechanical properties of polycrystals materials, the presented work enables insight into how the pure nickel properties are affected by application of multi-directional forging (MDF) as a well-known severe plastic deformation method. It is demonstrated that the hardness and wear rate are improved by imposing MDF process. The rate of enhancement is reduced at the higher pass numbers. It is also shown that the application of MDF process changed the mechanism of wear. Non-MDF sample’s surface shows spalling and delamination, while the dominated wear mechanism of final pass sample is peeling with a slight of adhesion. The change of wear mechanism can be associated with the reduction of friction coefficient of the deformed sample. By considering the linear correlation between the hardness and wear rate, a simple and fast procedure is proposed to estimate the wear rate of sample after the different MDF pass numbers using the corresponding hardness magnitude. Additionally, the attained microstructure of the final pass sample shows a combination of ultrafine grains and micro shear bands.
Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT
Authors: Safee Zaitulhusna M. , Baark Friedrich , Waters Edward C. T. , Veronese Mattia , Pell Victoria R. , Clark James E. , Mota Filipa , Livieratos Lefteris , Eykyn Thomas R. , Blower Philip J. , Southworth Richard 
Published: January 2019

AbstractBy the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-detection apparatus to characterize the pharmacokinetics of 99mTc-sestamibi and 99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced 99mTc-sestamibi washout; hypoxia from 24.9 ± 2.6% ID to 0.4 ± 6.2%, CCCP from 22.8 ± 2.5% ID to −3.5 ± 3.1%, and doxorubicin from 23.0 ± 2.2% ID to 17.8 ± 0.7, p < 0.05. Cardiac 99mTc-NOET retention (34.0 ± 8.0% ID) was unaffected in all cases. Translating to an in vivo rat model, 2 weeks after bolus doxorubicin injection, there was a dose-dependent loss of cardiac 99mTc-sestamibi retention (from 2.3 ± 0.3 to 0.9 ± 0.2 ID/g with 10 mg/kg (p < 0.05)), while 99mTc-NOET retention (0.93 ± 0.16 ID/g) was unaffected. 99mTc-NOET therefore traps in myocardium independently of the mitochondrial perturbations that induce 99mTc-sestamibi washout, demonstrating proof-of-concept for an imaging approach to detect evolving cardiotoxicity.
Claudin-3-deficient C57BL/6J mice display intact brain barriers
Authors: Castro Dias Mariana , Coisne Caroline , Lazarevic Ivana , Baden Pascale , Hata Masaki , Iwamoto Noriko , Francisco David Miguel Ferreira , Vanlandewijck Michael , He Liqun , Baier Felix A. , Stroka Deborah , Bruggmann Rémy , Lyck Ruth , Enzmann Gaby , Deutsch Urban , Betsholtz Christer , Furuse Mikio , Tsukita Shoichiro , Engelhardt Britta 
Published: January 2019

AbstractThe tight junction protein claudin-3 has been identified as a transcriptional target of the Wnt/β-catenin signaling pathway regulating blood-brain barrier (BBB) maturation. In neurological disorders loss of claudin-3 immunostaining is observed at the compromised BBB and blood-cerebrospinal fluid barrier (BCSFB). Although these observations support a central role of claudin-3 in regulating brain barriers’ tight junction integrity, expression of claudin-3 at the brain barriers has remained a matter of debate. This prompted us to establish claudin-3−/−C57BL/6J mice to study the role of claudin-3 in brain barrier integrity in health and neuroinflammation. Bulk and single cell RNA sequencing and direct comparative qRT-PCR analysis of brain microvascular samples from WT and claudin-3−/−mice show beyond doubt that brain endothelial cells do not express claudin-3 mRNA. Detection of claudin-3 protein at the BBBin vivoandin vitrois rather due to junctional reactivity of anti-claudin-3 antibodies to an unknown antigen still detected in claudin-3−/−brain endothelium. We confirm expression and junctional localization of claudin-3 at the BCSFB of the choroid plexus. Our study clarifies that claudin-3 is not expressed at the BBB and shows that absence of claudin-3 does not impair brain barrier function during health and neuroinflammation in C57BL/6J mice.