bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma
Authors: Czystowska-Kuzmicz Malgorzata , Sosnowska Anna , Nowis Dominika , Ramji Kavita , Szajnik Marta , Chlebowska-Tuz Justyna , Wolinska Ewa , Gaj Pawel , Grazul Magdalena , Pilch Zofia , Zerrouqi Abdessamad , Graczyk-Jarzynka Agnieszka , Soroczynska Karolina , Cierniak Szczepan , Koktysz Robert , Elishaev Esther , Gruca Slawomir , Stefanowicz Artur , Blaszczyk Roman , Borek Bartlomiej , Gzik Anna , Whiteside Theresa , Golab Jakub 
Published: July 2019

AbstractTumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape from the host immune system. Here, we report that small EVs found in the ascites and plasma of OvCa patients contain ARG1. EVs suppress proliferation of CD4+ and CD8+ T-cells in vitro and in vivo in OvCa mouse models. In mice, ARG1-containing EVs are transported to draining lymph nodes, taken up by dendritic cells and inhibit antigen-specific T-cell proliferation. Increased expression of ARG1 in mouse OvCa cells is associated with accelerated tumor progression that can be blocked by an arginase inhibitor. Altogether, our studies show that tumor cells use EVs as vehicles to carry over long distances and deliver to immune cells a metabolic checkpoint molecule – ARG1, mitigating anti-tumor immune responses.
Cul3 and insomniac are required for rapid ubiquitination of postsynaptic targets and retrograde homeostatic signaling
Authors: Kikuma Koto , Li Xiling , Perry Sarah , Li Qiuling , Goel Pragya , Chen Catherine , Kim Daniel , Stavropoulos Nicholas , Dickman Dion 
Published: July 2019

AbstractAt the Drosophila neuromuscular junction, inhibition of postsynaptic glutamate receptors activates retrograde signaling that precisely increases presynaptic neurotransmitter release to restore baseline synaptic strength. However, the nature of the underlying postsynaptic induction process remains enigmatic. Here, we design a forward genetic screen to discover factors in the postsynaptic compartment necessary to generate retrograde homeostatic signaling. This approach identified insomniac (inc), a putative adaptor for the Cullin-3 (Cul3) ubiquitin ligase complex, which together with Cul3 is essential for normal sleep regulation. Interestingly, we find that Inc and Cul3 rapidly accumulate at postsynaptic compartments following acute receptor inhibition and are required for a local increase in mono-ubiquitination. Finally, we show that Peflin, a Ca2+-regulated Cul3 co-adaptor, is necessary for homeostatic communication, suggesting a relationship between Ca2+ signaling and control of Cul3/Inc activity in the postsynaptic compartment. Our study suggests that Cul3/Inc-dependent mono-ubiquitination, compartmentalized at postsynaptic densities, gates retrograde signaling and provides an intriguing molecular link between the control of sleep and homeostatic plasticity at synapses.
Tailor-made nanostructures bridging chaos and order for highly efficient white organic light-emitting diodes
Authors: Li Yungui , Kovačič Milan , Westphalen Jasper , Oswald Steffen , Ma Zaifei , Hänisch Christian , Will Paul-Anton , Jiang Lihui , Junghaehnel Manuela , Scholz Reinhard , Lenk Simone , Reineke Sebastian 
Published: July 2019

AbstractOrganic light-emitting diodes (OLEDs) suffer from notorious light trapping, resulting in only moderate external quantum efficiencies. Here, we report a facile, scalable, lithography-free method to generate controllable nanostructures with directional randomness and dimensional order, significantly boosting the efficiency of white OLEDs. Mechanical deformations form on the surface of poly(dimethylsiloxane) in response to compressive stress release, initialized by reactive ions etching with periodicity and depth distribution ranging from dozens of nanometers to micrometers. We demonstrate the possibility of independently tuning the average depth and the dominant periodicity. Integrating these nanostructures into a two-unit tandem white organic light-emitting diode, a maximum external quantum efficiency of 76.3% and a luminous efficacy of 95.7 lm W−1 are achieved with extracted substrate modes. The enhancement factor of 1.53 ± 0.12 at 10,000 cd m−2 is obtained. An optical model is built by considering the dipole orientation, emitting wavelength, and the dipole position on the sinusoidal nanotexture.
Clinically-relevant postzygotic mosaicism in parents and children with developmental disorders in trio exome sequencing data
Authors: Wright C. F. , Prigmore E. , Rajan D. , Handsaker J. , McRae J. , Kaplanis J. , Fitzgerald T. W. , FitzPatrick D. R. , Firth H. V. , Hurles M. E. 
Published: July 2019

AbstractMosaic genetic variants can have major clinical impact. We systematically analyse trio exome sequence data from 4,293 probands from the DDD Study with severe developmental disorders for pathogenic postzygotic mosaicism (PZM) in the child or a clinically-unaffected parent, and use ultrahigh-depth sequencing to validate candidate mosaic variants. We observe that levels of mosaicism for small genetic variants are usually equivalent in both saliva and blood and ~3% of causative de novo mutations exhibit PZM; this is an important observation, as the sibling recurrence risk is extremely low. We identify parental PZM in 21 trios (0.5% of trios), resulting in a substantially increased sibling recurrence risk in future pregnancies. Together, these forms of mosaicism account for 40 (1%) diagnoses in our cohort. Likely child-PZM mutations occur equally on both parental haplotypes, and the penetrance of detectable mosaic pathogenic variants overall is likely to be less than half that of constitutive variants.
Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility
Authors: Pandey Nilesh O. , Chauhan Alex V. , Raithatha Nitin S. , Patel Purvi K. , Khandelwal Ronak , Desai Ajesh N. , Choxi Yesha , Kapadia Rutul S. , Jain Neeraj D. 
Published: July 2019

AbstractSingle nucleotide polymorphisms (SNPs) in TLR genes may serve as a crucial marker for early susceptibility of various cancers including cervical cancer. The present study was therefore designed to ascertain the role of TLR4 and TLR9 SNPs and haplotypes to hrHPV infection and cervical cancer susceptibility. The study included 110 cervical cancer biopsies and 141 cervical smears from age-matched healthy controls of Gujarati ethnicity of Western India. hrHPV 16 and 18 were detected using Real-time PCR. Eight SNPs, four each in TLR4 and TLR9 were analyzed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism and Allele-Specific PCR. HPV 16 and 18 were detected in 68% cervical cancer cases. TLR4 rs4986790, rs1927911 and TLR9 rs187084 showed association with HPV 16/18 infection. CC and CT genotypes of TLR4 rs11536889 and rs1927911 respectively, and TC, CC genotypes of TLR9 rs187084, as well as minor alleles of TLR4 rs4986790 and TLR9 rs187084, were associated with the increased risk of cervical cancer. Stage-wise analysis revealed TLR9 rs187084 and rs352140 to be associated with early-stage cancer. TLR4 haplotype GTAC and TLR9 haplotype GATC were associated with the increased risk of cervical cancer while TLR4 haplotype GCAG was associated with the decreased risk. TLR4 haplotype GCAG and TLR9 haplotype GATC showed association with increased susceptibility to hrHPV infection. In conclusion, the present study revealed association of TLR4 and TLR9 polymorphisms and haplotypes with hrHPV infection and cervical cancer risk. Further evaluation of a larger sample size covering diverse ethnic populations globally is warranted.
Graphene-assisted biosensing based on terahertz nanoslot antennas
Authors: Choi Geunchang , Hong Sung Ju , Bahk Young-Mi 
Published: July 2019

AbstractWe report on improvement of sensitivity for molecular detection utilizing terahertz time domain spectroscopy. Based on confining and enhancing electromagnetic field with metallic nanoslot antennas, we additionally employ monolayer graphene sheet whose edge and hydrophobic surface nature lead to increase detecting performance. Terahertz transmittance in monolayer graphene/metallic nanoslot structure exhibits more unambiguous change after lactose molecules are attached, compared to that in metallic nanoslot structure without monolayer graphene. We attribute the prominent change to that more lactose molecules are guided inside/near the metal gap region due to edge and hydrophobic surface nature of monolayer graphene. This monolayer graphene/metallic nanoslot structure can be expanded in other organic or bio-molecular detection.
A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization
Authors: Epp Anna L. , Ebert Sarah N. , Sanchez-Arias Juan C. , Wicki-Stordeur Leigh E. , Boyce Andrew K. J. , Swayne Leigh Anne 
Published: July 2019

AbstractThe Pannexin 1 (Panx1) ion and metabolite channel is expressed in a wide variety of cells where it regulates a number of cell behaviours including proliferation and differentiation. Panx1 is expressed on the cell surface as well as intracellular membranes. Previous work suggests that a region within the proximal Panx1 C-terminus (Panx1CT) regulates cell surface localization. Here we report the discovery of a putative leucine-rich repeat (LRR) motif in the proximal Panx1CT necessary for Panx1 cell surface expression in HEK293T cells. Deletion of the putative LRR motif results in significant loss of Panx1 cell surface distribution. Outcomes of complementary cell surface oligomerization and glycosylation state analyses were consistent with reduced cell surface expression of Panx1 LRR deletion mutants. Of note, the oligomerization analysis revealed the presence of putative dimers and trimers of Panx1 at the cell surface. Expression of Panx1 increased HEK293T cell growth and reduced doubling time, while expression of a Panx1 LRR deletion mutant (highly conserved segment) did not reproduce this effect. In summary, here we discovered the presence of a putative LRR motif in the Panx1CT that impacts on Panx1 cell surface localization. Overall these findings provide new insights into the molecular mechanisms underlying C-terminal regulation of Panx1 trafficking and raise potential new lines of investigation with respect to Panx1 oligomerization and glycosylation.
Comprehensive Metabolomic Analysis of IDH1R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency
Authors: Miyata Satsuki , Tominaga Kaoru , Sakashita Eiji , Urabe Masashi , Onuki Yoshiyuki , Gomi Akira , Yamaguchi Takashi , Mieno Makiko , Mizukami Hiroaki , Kume Akihiro , Ozawa Keiya , Watanabe Eiju , Kawai Kensuke , Endo Hitoshi 
Published: July 2019

AbstractGliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II–IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.
Toxicities of and inflammatory responses to moxifloxacin, cefuroxime, and vancomycin on retinal vascular cells
Authors: Miyake Hitomi , Miyazaki Dai , Shimizu Yumiko , Sasaki Shin-ichi , Baba Takashi , Inoue Yoshitsugu , Matsuura Kazuki 
Published: July 2019

AbstractProphylactic intracameral injection of antibiotics is commonly used to prevent endophthalmitis after cataract surgery. However, devastating visual complications have been reported including hemorrhagic occlusive retinal vasculitis (HORV).To determine the toxic and inflammatory effects of moxifloxacin, cefuroxime, and vancomycin on human retinal vascular cells, human retinal vascular endothelial cells (RVEC) and pericytes were exposed to three antibiotics, and the adverse effects were assessed by membrane damage, loss of intrinsic esterase activity, kinetic cell viability, and inflammatory cytokine secretion. Their retinal toxicity was examined by live/dead assays after an intravitreal injection of the three antibiotics into mice eyes. In vascular cells in culture, membrane damage and loss of esterase activity were induced after exposure to the three antibiotics. The toxic effects were most obvious after moxifloxacin (RVEC, ≥125 μg/mL; pericytes, ≥1000 μg/mL) at 24 h. Cefuroxime also reduced esterase activity and the membrane integrity of vascular cells but were less toxic than moxifloxacin. Kinetic cell viability testing showed that 500 μg/mL of moxifloxacin exposure induced significant decrease (29%) in the viability as early as 1 h. When the inflammatory effects of the antibiotics were examined, a significant induction of IL-8 was observed especially by RVECs after exposure to cefuroxime or vancomycin which was exacerbated by L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP), a NOD1 ligand. Intravitreal injections in mice showed that cefuroxime and vancomycin caused retinal and vascular toxicity extending to the inner nuclear layers. Collectively, moxifloxacin causes immediate damage to retinal vascular cells in vitro, while cefuroxime and vancomycin induced significant inflammatory effects on vascular endothelial cells and caused retinal toxicity. Surgeons need to be cautious of the toxicity when antibiotics are used prophylactically especially by intravitreal administration.
Group A Streptococcus Adsorbed Vaccine: Repeated Intramuscular Dose Toxicity Test in Minipigs
Authors: Postol Edilberto , Sá-Rocha Luiz C. , Sampaio Roney O. , Demarchi Lea M. M. F. , Alencar Raquel E. , Abduch Maria C. D. , Kalil Jorge , Guilherme Luiza 
Published: July 2019

AbstractStreptococcus pyogenesinfection continues to be a worldwide public health problem causing various diseases in humans and plays an important role in the pathogenesis of rheumatic fever and rheumatic heart disease. We developed a vaccine candidate to prevent S. pyogenes infections, identified as StreptInCor, that presented promising results in mouse models. A certified and independent laboratory conducted two repeated intramuscular dose toxicity tests (28 days, four weekly injections). The first test, composed of four experimental groups treated with 0 (vehicle), 50, 100 or 200 µg/500 µL StreptInCor, did not show significant alterations in clinical, hematological, biochemical or anatomopathological parameters related to the administration of StreptInCor. In addition to the parameters mentioned above, we evaluated the cardiac function and valves of animals by echocardiography before and after administration of 200 µg/500 µL StreptInCor versus placebo. We did not observe any changes related to StreptInCor administration, including changes in cardiac function and valves in animals, after receiving the highest dose of this vaccine candidate. The results obtained in the two repeated intramuscular dose toxicity tests showed that this vaccine formulation did not induce harmful effects to the tissues and organs studied, indicating that the candidate vaccine is well tolerated in minipigs.
Origin of the chromospheric three-minute oscillations in sunspot umbrae
Authors: Felipe T. 
Published: July 2019

Context. Sunspot umbrae show a change in the dominant period of their oscillations from five minutes (3.3 mHz) in the photosphere to three minutes (5.5 mHz) in the chromosphere.
Aims. In this paper, we explore the two most popular models proposed to explain the three-minute oscillations: the chromospheric acoustic resonator and the propagation of waves with frequency above the cutoff value directly from lower layers.
Methods. We employ numerical simulations of wave propagation from the solar interior to the corona. Waves are driven by a piston at the bottom boundary. We have performed a parametric study of the measured chromospheric power spectra in a large number of numerical simulations with differences in the driving method, the height of the transition region (or absence of transition region), the strength of the vertical magnetic field, and the value of the radiative cooling time.
Results. We find that both mechanisms require the presence of waves with periods in the three-minute band at the photosphere. These waves propagate upward and their amplitude increases due to the drop of the density. Their amplification is stronger than that of evanescent low-frequency waves. This effect is enough to explain the dominant period observed in chromospheric spectral lines. However, waves are partially trapped between the photosphere and the transition region, forming an acoustic resonator. This chromospheric resonant cavity strongly enhances the power in the three-minute band.
Conclusions. The chromospheric acoustic resonator model and the propagation of waves in the three-minute band directly from the photosphere can explain the observed chromospheric three-minute oscillations. They are both important in different scenarios. Resonances are produced by waves trapped between the temperature minimum and the transition region. Strong magnetic fields and radiative losses remove energy from the waves inside the cavity, resulting in resonances with weaker amplitude.
Les chercheurs innovent sur tous les fronts !
Authors: Brignol Tuy Nga , Marion Sylvie , Attarian Shahram 
Published: July 2019

Du Royaume-Uni à la Belgique en passant par la France, les équipes de recherche rivalisent de talent et d’imagination pour développer des stratégies innovantes qui préfigurent les médicaments de demain. Revue non exhaustive de la session « Thérapies innovantes » lors du congrès Myology 2019, qui s’est déroulé à Bordeaux du 25 au 28 mars.
Vivre avec une ventilation mécanique au quotidien : ergonomie et sécurité au domicile et à l’extérieur
Authors: Delalande Perrine , Wasteels Geert 
Published: July 2019

L’évolution de certaines pathologies neuromusculaires conduit parfois à la nécessité d’une ventilation mécanique. Si l’adaptation de la ventilation est généralement réalisée à l’hôpital, la poursuite du traitement à domicile dans de bonnes conditions nécessite un environnement matériel et humain adapté pour garantir la sécurité et la qualité de vie de la personne.
Outre le ventilateur, le choix et le juste réglage de l’interface et de l’appareil d’humidification contribuent au confort du patient et à la qualité du traitement. La fixation du matériel au fauteuil et au patient contribue à sa sécurité.
À domicile, le patient est accompagné par des aidants familiaux ou professionnels. Il convient de veiller à leur formation afin qu’ils puissent être à l’aise avec le matériel et pour que celui-ci complique le moins possible le quotidien, l’objectif étant que le patient garde la meilleure qualité de vie possible.
En sortie à l’extérieur, le risque potentiel de défaillance du matériel devrait inciter le patient à s’équiper d’un « kit de secours » pour se déplacer en sécurité.
Kombination von Lingualtechnik und skelettaler Verankerung zur Korrektur eines frontal offenen Bisses bei Angle Klasse II/1 mit bialveolärer Protrusion
Authors: Bräutigam Martina , Nienkemper Manuel , Wilmes Benedict , Drescher Dieter 
Published: July 2019

ZusammenfassungDie Behandlung von frontal offenen Bissen ist in der Regel bei erwachsenen Patienten sehr komplex. Neben protrudierten Frontzähnen, die in Infraposition stehen, ist häufig ein persistierendes viszerales Schluckmuster sowie ein Sigmatismus frontalis vorhanden. Zur Korrektur hat sich statt der rezidivanfälligen Extrusion der Frontzähne die Intrusion der Seitenzähne bewährt. Zudem kann mittels Distalisierung der Oberkieferseitenzähne die Frontretrusion ermöglicht und somit auch der offene Biss reduziert werden. Für diese Zahnbewegungen besteht häufig ein maximaler Verankerungsbedarf. Dieser kann mittels skelettal verankerter Apparaturen durch Mini-Implantate im anterioren Gaumen gewährleistet werden.Der Leidensdruck bei erwachsenen Patienten ist häufig groß. Zudem besteht der Wunsch nach wenig sichtbaren Behandlungsapparaturen. Die individualisierten, lingualen Zahnspangen erweisen sich hierbei als gute Behandlungsapparaturen. Durch die Kombination der lingualen Zahnspange mit den skelettal verankerten Distalisierungs- bzw. Intrusionsmechaniken sind die Frontzahnreklination sowie die Bissschließung effizient realisierbar. Anhand zweier Patientenbeispiele sollen die kombinierten Mechaniken sowie das klinische Procedere dargestellt werden.
Hyperthermie bei Fibromyalgie und
Weichteilrheuma
Authors: Wehner Holger 
Published: July 2019

ZusammenfassungIn der aktuellen Literatur wird davon ausgegangen, dass etwa 2 % der Bevölkerung
am Fibromyalgiesyndrom leiden. Die Geschlechterverteilung zeigt, dass Frauen
häufiger als Männer betroffen sind. Neben quälenden Schmerzen aus
unterschiedlichem Anlass und oft ohne direkten Auslöser haben die Patienten
häufig auch das Gefühl, nicht ernst genommen oder einer rein psychosomatischen
Störung zugeordnet zu werden.Die Vielfalt der Symptome erschwert die klare und rasche Diagnosestellung. Die
Schmerzen, deren Ausprägung sehr unterschiedlich sein kann, bilden das
Hauptsymptom. Somit besteht zu Recht eine ständige Suche nach Möglichkeiten, den
Patienten helfen zu können.Die Hyperthermiebehandlung stellt eine wirksame und sichere Behandlungsoption
dar, die nachhaltige Symptomlinderungen erbringen kann, wie in einer
randomisierten, kontrollierten Studie 6
belegt werden konnte.