bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-κB p65/Hif-1α Signaling Pathway
Authors: Liu Rui , Liao Xin-Yu , Pan Meng-Xian , Tang Jun-Chun , Chen Song-Feng , Zhang Ya , Lu Pei-Xin , Lu Long J. , Zou Ying-Ying , Qin Xing-Ping , Bu Li-Hong , Wan Qi 
Published: February 2019

Abstract
Glycine is a simple nonessential amino acid known to have neuroprotective properties. Treatment with glycine results in reduced infarct volume of the brain, neurologic function scores, and neuronal and microglial death in ischemic stroke injury. Neuroinflammation has been considered a major contributor to cerebral ischemia–induced brain damage. However, the role of glycine in neuroinflammation following ischemic stroke is unclear. The present study aimed to determine whether neuroinflammation is involved in the neuroprotective effects of glycine in cerebral ischemia injury. Ischemic stroke promotes M1 microglial polarization. Interestingly, we found that the injection of glycine in rats after injury can inhibit ischemia-induced inflammation and promote M2 microglial polarization in vivo (Sprague–Dawley rats) and in vitro (cortical microglia and BV-2 cells). We show that glycine suppresses Hif-1α by inhibiting the upregulation of NF-κB p65 after ischemia-reperfusion injury, resulting in the inhibition of proinflammatory activity. The activation of AKT mediates the inhibition of NF-κB p65/Hif-1α signaling by glycine. Moreover, we confirm that glycine-regulated AKT activation is mediated by the inhibition of PTEN in a PTEN depletion cell line, U251 cells. Glycine modulates microglial polarization after ischemic stroke, which indirectly inhibits ischemia-induced neuronal death and functional recovery. Taken together, our findings provide a new understanding of glycine in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing NF-κB p65/Hif-1α signaling.
Histone Methylation Directs Myeloid TLR4 Expression and Regulates Wound Healing following Cutaneous Tissue Injury
Authors: Davis Frank M. , Kimball Andrew , denDekker Aaron , Joshi Amrita D. , Boniakowski Anna E. , Nysz Dylan , Allen Ronald M. , Obi Andrea , Singer Kanakadurga , Henke Peter K. , Moore Bethany B. , Kunkel Steven L. , Gallagher Katherine A. 
Published: February 2019

Abstract
Myeloid cells are critical for orchestrating regulated inflammation during wound healing. TLRs, particularly TLR4, and its downstream-signaling MyD88 pathway play an important role in regulating myeloid-mediated inflammation. Because an initial inflammatory phase is vital for tissue repair, we investigated the role of TLR4-regulated, myeloid-mediated inflammation in wound healing. In a cutaneous tissue injury murine model, we found that TLR4 expression is dynamic in wound myeloid cells during the course of normal wound healing. We identified that changes in myeloid TLR4 during tissue repair correlated with increased expression of the histone methyltransferase, mixed-lineage leukemia 1 (MLL1), which specifically trimethylates the histone 3 lysine 4 (H3K4me3) position of the TLR4 promoter. Furthermore, we used a myeloid-specific Mll1 knockout (Mll1f/fLyz2Cre+) to determine MLL1 drives Tlr4 expression during wound healing. To understand the critical role of myeloid-specific TLR4 signaling, we used mice deficient in Tlr4 (Tlr4−/−), Myd88 (Myd88−/−), and myeloid-specific Tlr4 (Tlr4f/fLyz2Cre+) to demonstrate delayed wound healing at early time points postinjury. Furthermore, in vivo wound myeloid cells isolated from Tlr4−/− and Myd88−/− wounds demonstrated decreased inflammatory cytokine production. Importantly, adoptive transfer of monocyte/macrophages from wild-type mice trafficked to wounds with restoration of normal healing and myeloid cell function in Tlr4-deficient mice. These results define a role for myeloid-specific, MyD88-dependent TLR4 signaling in the inflammatory response following cutaneous tissue injury and suggest that MLL1 regulates TLR4 expression in wound myeloid cells.
Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution
Authors: Arruda Lucas C. M. , Gaballa Ahmed , Uhlin Michael 
Published: February 2019

Abstract
Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft γδ TCR repertoire on clinical outcomes following HSCT. Using a high-throughput sequencing platform, we sought to analyze the TCR γ-chain (TRG) repertoire of γδ T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV+/−. The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT. In all samples, TRG repertoire showed a reduced diversity and displayed overrepresented clones. This was more prominent in grafts from CMV+ donors, which presented a more private repertoire, lower diversity, skewed distribution, and reduced usage of the V9-JP pairing. Grafts given to nonrelapse patients presented a more public repertoire and increased presence of long sequence clonotypes. Variable-joining gene segment usage was not associated with aGvHD development, but a higher usage of V2-JP1 pairing and lower usage of V4-J2/V5-J2/V8-JP2 were observed in grafts given to nonrelapse patients. Our work identified five private overrepresented and one public CDR3 sequence (CATWDGPYYKKLF) associated with CMV infection, in addition to 12 highly frequent public sequences present exclusively in grafts given to nonrelapse patients. Our findings show that, despite CMV infection reshaping the TRG repertoire, TRG composition is not associated with aGvHD development, and several public sequences are associated with clinical remission.
MEK2 Negatively Regulates Lipopolysaccharide-Mediated IL-1β Production through HIF-1α Expression
Authors: Talwar Harvinder , Bouhamdan Mohamad , Bauerfeld Christian , Talreja Jaya , Aoidi Rifdat , Houde Nicolas , Charron Jean , Samavati Lobelia 
Published: February 2019

Abstract
LPS-activated macrophages require metabolic reprogramming and glucose uptake mediated by hypoxia-inducible factor (HIF)–1 α and glucose transporter 1 (Glut1) expression for proinflammatory cytokine production, especially IL-1β. This process is tightly regulated through activation of MAPK kinases, including the MEK/ERK pathway as well as several transcription factors including HIF-1α. Although MAPK kinase (MEK) 2 deficiency had no significant effect on NO, TNF-α, or IL-12 production in response to LPS challenge, MEK2-deficient murine bone marrow–derived macrophages (BMDMs) exhibited lower IL-10 production. Importantly, MEK2-deficient BMDMs exhibited a preserved ERK1/2 phosphorylation, higher HIF-1α and Glut1 levels, and substantially increased IL-1β as well as IL-6 production in response to LPS stimulation. Knockdown of HIF-1α expression via short interference RNA decreased the level of HIF-1α expression in MEK2-deficient BMDMs and decreased IL-1β production in response to LPS treatment. Furthermore, we performed gain of function experiments by overexpressing MEK2 protein in RAW264.7 cells. LPS stimulation of MEK2 overexpressed in RAW264.7 cells led to a marked decreased IL-1β production. Finally, we investigated the role of Mek1 and Mek2 double and triple mutation on ERK phosphorylation, HIF-1α expression, and IL-1β production. We found that MEK2 is the major kinase, which inversely proportionally regulates HIF-1α and IL-1β expression independent of ERK activation. Our findings demonstrate a novel regulatory function for MEK2 in response to TLR4 activation in IL-1β production through modulating HIF-1α expression.
dc Talk’s Jesus Freak
Authors: Stockton Will , Gilson D. 
Published: February 2019

Late in the Reagan years, three young men at Jerry Falwell's Liberty University formed the Christian rap group dc Talk. The trio put out a series of records that quickly secured their place at the forefront of contemporary Christian music. But, with their fourth studio album Jesus Freak (1995), dc Talk staked a powerful claim on the worldly market of alternative music, becoming an evangelical group with secular selling power.
This book sets out to study this mid-90s crossover phenomenon—a moment of cultural convergence between Christian and secular music and an era of particular political importance for American evangelicalism. Written by two queer scholars with evangelical pasts, Jesus Freak explores the importance of a multifarious album with complex ideas about race, sexuality, gender, and politics—an album where dc Talk wonders, “What will people do when they hear that I’m a Jesus freak?” and evangelical fans stake a claim for Christ-like coolness in a secular musical world
More severe hydrological drought events emerge at different warming levels over the Wudinghe watershed in northern China
Authors: Jiao Yang , Yuan Xing 
Published: February 2019

Abstract. Assessment of changes in hydrological droughts at specific warming levels is
important for an adaptive water resources management with consideration of
the 2015 Paris Agreement. However, most studies focused on the response of
drought frequency to the warming and neglected other drought characteristics,
including severity. By using a semiarid watershed in northern China (i.e.,
Wudinghe) as an example, here we show less frequent but more severe
hydrological drought events emerge at 1.5, 2 and 3 ∘C warming levels.
We used meteorological forcings from eight Coupled Model Intercomparison
Project Phase 5 climate models under four representative concentration
pathways, to drive a newly developed land surface hydrological model to
simulate streamflow, and analyzed historical and future hydrological drought
characteristics based on the standardized streamflow index. The Wudinghe
watershed will reach the 1.5, 2 and 3 ∘C warming levels around
2015–2034, 2032–2051 and 2060–2079, with an increase in precipitation of
8 %, 9 % and 18 % and runoff of 27 %, 19 % and 44 %, and a drop
in hydrological drought frequency of 11 %, 26 % and 23 % as compared to the
baseline period (1986–2005). However, the drought severity will rise
dramatically by 184 %, 116 % and 184 %, which is mainly caused by the
increased variability in precipitation and evapotranspiration. The climate
models and the land surface hydrological model contribute to more than 80 %
of total uncertainties in the future projection of precipitation and
hydrological droughts. This study suggests that different aspects of
hydrological droughts should be carefully investigated when assessing the
impact of 1.5, 2 and 3 ∘C global warming.
Safe Zones for Anterior Acetabular Retractor Placement in Direct Anterior Total Hip Arthroplasty: A Cadaveric Study
Authors: Sullivan Connor W. , Banerjee Samik , Desai Khusboo , Smith Michael , Roberts Jared T. 
Published: February 2019

Introduction:
There is paucity of literature evaluating anterior acetabular retractor proximity to the femoral nerve and external iliac vessels during total hip arthroplasty through the direct anterior approach. In this cadaveric study, we evaluated three retractor locations to identify optimal positioning of anterior retractors.

Methods:
A direct anterior approach was performed in 22 hips of 15 cadavers. Anterior acetabular retractors were placed over the anterior acetabular wall in-line with the femoral neck (12-o'clock or middle position). The anterior neurovascular structures were identified through the ilioinguinal approach. Retractors were reinserted at 10-o'clock (right hip; superior) and 2-o'clock (right hip; inferior) locations marked using K-wires. Horizontal and vertical distances from retractor tip positions to neurovascular structures were measured with a digital caliper.

Results:
Retractor tips moved significantly from lateral to the femoral nerve when placed in the superior position (mean, 2.8 mm) to medial to the femoral nerve in the middle (mean, −2.3 mm) and inferior (mean, −4.8 mm) locations. Retractor tips moved significantly medial toward the external iliac artery when retractors were moved from superior (mean, 15.3 mm) to inferior (mean, 6.6 mm) positions placing the retractor tip closer to the vessels.

Conclusion:
As retractor placements moved inferior, retractor tips moved medial to neurovascular structures. Inferior retractor positioning placed the femoral nerve and external iliac artery at the risk of injury during the initial retractor placement or adjustment. Retractors should be placed in a relative safe zone superior to the 12-o'clock position to avoid damage to neurovascular structures.

Level of Evidence:
IV
Hoop voor langdurig rechteloos verblijvende 1F’ers
Authors: Terlouw A.B. , Bruin R.J.A. 
Published: February 2019

Hoop voor langdurig rechteloos verblijvende 1F’ers. Noot bij HvJ 2 mei 2018, gevoegde zaken C-331/16, K, en C-366/16, H.F., ECLI:EU:C:2018:296
Het Hof van Justitie geeft in deze uitspraak uitleg aan het begrip openbare orde in de artikelen 27 en 28 van Richtlijn 2004/38. Het oordeelt dat maatregelen die het recht van bewegingsvrijheid beperken alleen kunnen worden gerechtvaardigd als zij voldoen aan het beginsel van proportionaliteit. Als een persoon is uitgesloten van vluchtelingrechtelijke bescherming omdat hem in het verleden artikel 1 F van het Vluchtelingenverdrag is tegengeworpen, betekent dit niet automatisch dat zijn enkele aanwezigheid op het grondgebied van de gaststaat een werkelijke, actuele en voldoende serieuze bedreiging oplevert. De uitspraak van het Hof kan bredere betekenis hebben dan alleen voor Unieburgers en hun gezinsleden.HvJ 2 mei 2018, gevoegde zaken C-331/16, K, en C-366/16, H.F., ECLI:EU:C:2018:296.
Over arbeidstijden en cabotage in het goederenvervoer over de weg: ‘dubbel klutsen’ door het Hof van Justitie
Authors: Sevinga K. 
Published: February 2019

Over arbeidstijden en cabotage in het goederenvervoer over de weg: ‘dubbel klutsen’ door het Hof van Justitie
In twee recente arresten heeft het Hof van Justitie zich uitgesproken over een aantal actuele vraagstukken inzake het vervoer over de weg. In de zaak Vaditrans gaat het om rijtijden en, in dit geval vooral, rusttijden. In de zaak Commissie/Denemarken gaat het om de voorwaarden waaronder cabotage mag worden verricht. In beide gevallen gaat het om verordeningen die nadere uitvoering behoeven. Beide zaken worden hier in samenhang besproken, mede in het licht van het zogenoemde ‘mobiliteitspakket’.HvJ 20 december 2017, zaak C-102/16, Vaditrans, ECLI:EU:C:2017:1012; HvJ 12 april 22018, zaak 541/16, Commissie/Denemarken, ECLI:EU:C:2018:251.
Orientation Regulation of Tin‐Based Reduced‐Dimensional Perovskites for Highly Efficient and Stable Photovoltaics
Authors: Xu Hongyu , Jiang Yuanzhi , He Tingwei , Li Saisai , Wang Huanhua , Chen Yu , Yuan Mingjian , Chen Jun 
Published: February 2019

AbstractTin‐based perovskites have exhibited high potential for efficient photovoltaics application due to their outstanding optoelectrical properties. However, the extremely undesired instabilities significantly hinders their development and further commercialization process. A novel tin‐based reduced‐dimensional (quasi‐2D) perovskites is reported here by using 5‐ammoniumvaleric acid (5‐AVA+) as the organic spacer. It is demonstrated that by introducing appropriate amount of ammonium chloride (NH4Cl) as additive, highly vertically oriented tin‐based quasi‐2D perovskite films are obtained, which is proved through the grazing incidence wide‐angle X‐ray scattering characterization. In particular, this approach is confirmed to be a universal method to deliver highly vertically oriented tin‐based quasi‐2D perovskites with various spacers. The highly ordered vertically oriented perovskite films significantly improve the charge collection efficiency between two electrodes. With the optimized NH4Cl concentration, the solar cells employing quasi‐2D perovskite, AVA2FAn−1SnnI3n+1 (<n> = 5), as light absorbers deliver a power conversion efficiency up to 8.71%. The work paves the way for further employing highly vertically oriented tin‐based quasi‐2D perovskite films for highly efficient and stable photovoltaics.
Motile Piezoelectric Nanoeels for Targeted Drug Delivery
Authors: Mushtaq Fajer , Torlakcik Harun , Hoop Marcus , Jang Bumjin , Carlson Franklin , Grunow Tim , Läubli Nino , Ferreira Antoine , Chen Xiang‐Zhong , Nelson Bradley J. , Pané Salvador 
Published: February 2019

AbstractThe field of small‐scale robotics is undergoing a paradigm shift toward the use of soft smart materials. The integration of soft smart components in micro‐ and nanorobotic platforms not only allows for more sophisticated locomotion mechanisms, but also more closely mimicks the functioning of biological systems. A soft hybrid nanorobot that mimics an electric eel, a knifefish with an elongated cylindrical body that is able to generate electricity during its motion, is presented here. These nanoeels consist of a flexible piezoelectric tail composed of a polyvinylidene fluoride–based copolymer, linked to a polypyrrole nanowire, which is decorated with nickel rings for magnetic actuation. Upon the application of rotating magnetic fields, the piezoelectric soft tail is deformed causing changes in its electric polarization. Capitalizing on this magnetically coupled piezoelectric effect, electrostatically enhanced on‐demand release of therapeutic cargo loaded on the surface of the piezoelectric tail is demonstrated. It is also shown that this approach allows for a pulsatile release of payloads. Interestingly, the driving magnetic parameters can be selected to provide the nanoeel with translational motion or to control the discharge kinetics of the drug.
Iron‐Free Cathode Catalysts for Proton‐Exchange‐Membrane Fuel Cells: Cobalt Catalysts and the Peroxide Mitigation Approach
Authors: Wang Xiao Xia , Prabhakaran Venkateshkumar , He Yanghua , Shao Yuyan , Wu Gang 
Published: February 2019

AbstractHigh‐performance and inexpensive platinum‐group‐metal (PGM)‐free catalysts for the oxygen reduction reaction (ORR) in challenging acidic media are crucial for proton‐exchange‐membrane fuel cells (PEMFCs). Catalysts based on Fe and N codoped carbon (Fe–N–C) have demonstrated promising activity and stability. However, a serious concern is the Fenton reactions between Fe2+ and H2O2 generating active free radicals, which likely cause degradation of the catalysts, organic ionomers within electrodes, and polymer membranes used in PEMFCs. Alternatively, Co–N–C catalysts with mitigated Fenton reactions have been explored as a promising replacement for Fe and PGM catalysts. Therefore, herein, the focus is on Co–N–C catalysts for the ORR relevant to PEMFC applications. Catalyst synthesis, structure/morphology, activity and stability improvement, and reaction mechanisms are discussed in detail. Combining experimental and theoretical understanding, the aim is to elucidate the structure–property correlations and provide guidance for rational design of advanced Co catalysts with a special emphasis on atomically dispersed single‐metal‐site catalysts. In the meantime, to reduce H2O2 generation during the ORR on the Co catalysts, potential strategies are outlined to minimize the detrimental effect on fuel cell durability.
Bioinspired Stable and Photoluminescent Assemblies for Power Generation
Authors: Tao Kai , Hu Wen , Xue Bin , Chovan Drahomir , Brown Noam , Shimon Linda J. W. , Maraba Oguzhan , Cao Yi , Tofail Syed A. M. , Thompson Damien , Li Junbai , Yang Rusen , Gazit Ehud 
Published: February 2019

AbstractPeptide assemblies are ideal components for eco‐friendly optoelectronic energy harvesting devices due to their intrinsic biocompatibility, ease of fabrication, and flexible functionalization. However, to date, their practical applications have been limited due to the difficulty in obtaining stable, high‐performance devices. Here, it is shown that the tryptophan‐based simplest peptide cyclo‐glycine‐tryptophan (cyclo‐GW) forms mechanically robust (elastic modulus up to 24.0 GPa) and thermally stable up to 370 °C monoclinic crystals, due to a supramolecular packing combining dense parallel β‐sheet hydrogen bonding and herringbone edge‐to‐face aromatic interactions. The directional and extensive driving forces further confer unique optical properties, including aggregation‐induced blue emission and unusual stable photoluminescence. Moreover, the crystals produce a high and sustained open‐circuit voltage (1.2 V) due to a high piezoelectric coefficient of 14.1 pC N−1. These findings demonstrate the feasibility of utilizing self‐assembling peptides for fabrication of biointegrated microdevices that combine high structural stability, tailored optoelectronics, and significant energy harvesting properties.
Electric Field Induced Room Temperature Null to High Spin State Switching: A Computational Prediction
Authors: Amorim Carlos O. , Amaral João S. , Gonçalves João N. , Amaral Vítor S. 
Published: February 2019

AbstractBaTiO3 is a well‐known ferroelectric material, with an electric field‐induced coupled electrical/structural transition from a cubic to a tetragonal lattice above room temperature. Via DFT calculations, the magnetic properties of an Fe monolayer sandwiched between bulk‐like BaTiO3 are explored, showing how the magnetic moment of each Fe atom is switched from a null spin to a high spin (2 μB per Fe) state when the BaTiO3 structure changes from cubic to tetragonal. This effect occurs in an optimized range of interatomic distances at the interface, allowing the design of an above‐room temperature binary, electric field write/magnetic read device.
Embryonic Stem Cells‐Derived Exosomes Endowed with Targeting Properties as Chemotherapeutics Delivery Vehicles for Glioblastoma Therapy
Authors: Zhu Qingwei , Ling Xiaozheng , Yang Yunlong , Zhang Juntao , Li Qing , Niu Xin , Hu Guowen , Chen Bi , Li Haiyan , Wang Yang , Deng Zhifeng 
Published: February 2019

AbstractExosomes are nanosized membrane vesicles (30–100 nm) that can easily penetrate the blood–brain barrier, safely deliver therapeutic drugs, and be modified with target ligands. Embryonic stem cells (ESCs) provide abundant exosome sources for clinical application due to their almost unlimited self‐renewal. Previous studies show that exosomes secreted by ESCs (ESC‐exos) have antitumor properties. However, it is not known whether ESC‐exos inhibit glioblastoma (GBM) growth. In this study, the anti‐GBM effect of ESC‐exos is confirmed and then c(RGDyK)‐modified and paclitaxel (PTX)‐loaded ESC‐exos, named cRGD‐Exo‐PTX are prepared. It is then investigated whether the engineered exosomes deliver more efficiently to GBM cells versus free drug alone and drug‐loaded ESC‐exos using an in vitro GBM model and in vivo subcutaneous and orthotopic xenografts model. The results show that cRGD‐Exo‐PTX significantly improves the curative effects of PTX in GBM via enhanced targeting. These data indicate that ESC‐exos are potentially powerful therapeutic carriers for GBM and could have utility in many other diseases.
Advances in optical assays for detecting telomerase activity
Authors: Yang Bing , Shi Lu , Lei Jing , Li Baoxin , Jin Yan 
Published: February 2019

AbstractTelomerase uses its RNA as template and its protein unit as reverse transcriptase to synthesize TTAGGG repeats at the ends of the eukaryotic chromosome to maintain the lengths of telomeres. Telomerase activity up‐regulates in about 85% of human tumors compared with somatic cells, which indicates that telomerase is a tumor biomarker. Reliable assay of telomerase activity is thus essential in diagnosis and management of malignant tumors. In this review, recent developed optical assays are summarized based on the readout signal, including chemiluminescence assay, colorimetric assay, and fluorescence assay.