bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline deletion of Cdyl causes teratozoospermia and progressive infertility in male mice
Authors: Xia Xiaoyu , Zhou Xiaowei , Quan Yanmei , Hu Yanqin , Xing Fengying , Li Zhengzheng , Xu Bufang , Xu Chen , Zhang Aijun 
Published: March 2019

AbstractChromodomain Y(CDY) is one of the candidate genes for male dyszoospermia related to Y chromosome microdeletion (YCM). However, the function of CDY in regulating spermatogenesis has not been completely determined. The mouseCdyl (CDY-like)gene is the homolog of humanCDY. In the present study, we generated a germline conditional knockout (cKO) model of mouseCdyl. Significantly, theCdylcKOmale mice suffered from the defects in spermatogonia maintenance and spermatozoon morphogenesis, demonstrating teratozoospermia and a progressive infertility phenotype in early adulthood. Importantly, patterns of specific histone methylation and acetylation were extensively changed, which disturbed the transcriptome inCdylcKOtestis. Our findings indicated thatCdylis crucial for spermatogenesis and male fertility, which provides novel insights into the function of CDY gene, as well as the pathogenesis of YCM-related reproductive failure.
Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice
Authors: Qiu Dongze , Chu Xun , Hua Laiqing , Yang Yunke , Li Keyong , Han Yi , Yin Jun , Zhu Ming , Mu Sucheng , Sun Zhan , Tong Chaoyang , Song Zhenju 
Published: March 2019

AbstractG protein-coupled receptor 174 (GPR174) is mainly expressed in thymus, spleen, lymph nodes, and leukocytes, and genetic variation in GPR174 is associated with susceptibility to autoimmune diseases, indicating that GPR174 is involved in the immune response. However, the function of GPR174 in regulating inflammatory responses against bacterial infection in sepsis remains unclear. In this study, we investigated the role of GPR174 in regulating suppressive function of regulatory T cells (Treg cells) and the underlying mechanism of Gpr174-deficient Treg cells in controlling cytokine storm of sepsis. We showed that Gpr174-dedicient mice were resistant to inflammatory shock induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). Moreover, Gpr174 was highly expressed in Treg cells, and its deficiency in mice promoted the expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and interleukin (IL)−10 in Treg cells. By using the LPS-induced sepsis model, we demonstrated that anti-inflammatory macrophages (M2 macrophages) induction was Treg cell-dependent and Gpr174-deficient Treg cells protected mice against sepsis-induced lung damage through prompting M2 macrophages polarization. In vitro, Gpr174-deficient Treg cells also promoted the polarization of macrophages toward M2 cells and dampened the secretions of pro-inflammatory cytokines (IL-6 and tumor necrosis factor-α (TNF-α)) in macrophages. In conclusion, these findings suggested that GPR174 plays an important role in the initial period of sepsis through the regulation of macrophage polarization and pro- and anti-inflammatory cytokine secretions. Therefore, GPR174 may be a promising target for therapeutic agents to regulate inflammatory disorders.
Spinon confinement and a sharp longitudinal mode in Yb2Pt2Pb in magnetic fields
Authors: Gannon W. J. , Zaliznyak I. A. , Wu L. S. , Feiguin A. E. , Tsvelik A. M. , Demmel F. , Qiu Y. , Copley J. R. D. , Kim M. S. , Aronson M. C. 
Published: March 2019

AbstractThe fundamental excitations in an antiferromagnetic chain of spins-1/2 are spinons, de-confined fractional quasiparticles that when combined in pairs, form a triplet excitation continuum. In an Ising-like spin chain the continuum is gapped and the ground state is Néel ordered. Here, we report high resolution neutron scattering experiments, which reveal how a magnetic field closes this gap and drives the spin chains in Yb2Pt2Pb to a critical, disordered Luttinger-liquid state. In Yb2Pt2Pb the effective spins-1/2 describe the dynamics of large, Ising-like Yb magnetic moments, ensuring that the measured excitations are exclusively longitudinal, which we find to be well described by time-dependent density matrix renormalization group calculations. The inter-chain coupling leads to the confinement of spinons, a condensed matter analog of quark confinement in quantum chromodynamics. Insensitive to transverse fluctuations, our measurements show how a gapless, dispersive longitudinal mode arises from confinement and evolves with magnetic order.
CRISPR-Cas9 genome editing induces megabase-scale chromosomal truncations
Authors: Cullot Grégoire , Boutin Julian , Toutain Jérôme , Prat Florence , Pennamen Perrine , Rooryck Caroline , Teichmann Martin , Rousseau Emilie , Lamrissi-Garcia Isabelle , Guyonnet-Duperat Véronique , Bibeyran Alice , Lalanne Magalie , Prouzet-Mauléon Valérie , Turcq Béatrice , Ged Cécile , Blouin Jean-Marc , Richard Emmanuel , Dabernat Sandrine , Moreau-Gaudry François , Bedel Aurélie 
Published: March 2019

AbstractCRISPR-Cas9 is a promising technology for genome editing. Here we use Cas9 nuclease-induced double-strand break DNA (DSB) at the UROS locus to model and correct congenital erythropoietic porphyria. We demonstrate that homology-directed repair is rare compared with NHEJ pathway leading to on-target indels and causing unwanted dysfunctional protein. Moreover, we describe unexpected chromosomal truncations resulting from only one Cas9 nuclease-induced DSB in cell lines and primary cells by a p53-dependent mechanism. Altogether, these side effects may limit the promising perspectives of the CRISPR-Cas9 nuclease system for disease modeling and gene therapy. We show that the single nickase approach could be safer since it prevents on- and off-target indels and chromosomal truncations. These results demonstrate that the single nickase and not the nuclease approach is preferable, not only for modeling disease but also and more importantly for the safe management of future CRISPR-Cas9-mediated gene therapies.
In-host evolution of Staphylococcus epidermidis in a pacemaker-associated endocarditis resulting in increased antibiotic tolerance
Authors: Dengler Haunreiter Vanina , Boumasmoud Mathilde , Häffner Nicola , Wipfli Dennis , Leimer Nadja , Rachmühl Carole , Kühnert Denise , Achermann Yvonne , Zbinden Reinhard , Benussi Stefano , Vulin Clement , Zinkernagel Annelies S. 
Published: March 2019

AbstractTreatment failure in biofilm-associated bacterial infections is an important healthcare issue. In vitro studies and mouse models suggest that bacteria enter a slow-growing/non-growing state that results in transient tolerance to antibiotics in the absence of a specific resistance mechanism. However, little clinical confirmation of antibiotic tolerant bacteria in patients exists. In this study we investigate a Staphylococcus epidermidis pacemaker-associated endocarditis, in a patient who developed a break-through bacteremia despite taking antibiotics to which the S. epidermidis isolate is fully susceptible in vitro. Characterization of the clinical S. epidermidis isolates reveals in-host evolution over the 16-week infection period, resulting in increased antibiotic tolerance of the entire population due to a prolonged lag time until growth resumption and a reduced growth rate. Furthermore, we observe adaptation towards an increased biofilm formation capacity and genetic diversification of the S. epidermidis isolates within the patient.
Targeting of dermal myofibroblasts through death receptor 5 arrests fibrosis in mouse models of scleroderma
Authors: Park Jong-Sung , Oh Yumin , Park Yong Joo , Park Ogyi , Yang Hoseong , Slania Stephanie , Hummers Laura K. , Shah Ami A. , An Hyoung-Tae , Jang Jiyeon , Horton Maureen R. , Shin Joseph , Dietz Harry C. , Song Eric , Na Dong Hee , Park Eun Ji , Kim Kwangmeyung , Lee Kang Choon , Roschke Viktor V. , Hanes Justin , Pomper Martin G. , Lee Seulki 
Published: March 2019

AbstractScleroderma is an autoimmune rheumatic disorder accompanied by severe fibrosis in skin and other internal organs. During scleroderma progression, resident fibroblasts undergo activation and convert to α-smooth muscle actin (α-SMA) expressing myofibroblasts (MFBs) with increased capacity to synthesize collagens and fibrogenic components. Accordingly, MFBs are a major therapeutic target for fibrosis in scleroderma and treatment with blocking MFBs could produce anti-fibrotic effects. TLY012 is an engineered human TNF-related apoptosis-inducing ligand (TRAIL) which induces selective apoptosis in transformed cells expressing its cognate death receptors (DRs). Here we report that TLY012 selectively blocks activation of dermal fibroblasts and induces DR-mediated apoptosis in α-SMA+ MFBs through upregulated DR5 during its activation. In vivo, TLY012 reverses established skin fibrosis to near-normal skin architecture in mouse models of scleroderma. Thus, the TRAIL pathway plays a critical role in tissue remodeling and targeting upregulated DR5 in α-SMA+ MFBs is a viable therapy for fibrosis in scleroderma.
Small contact resistance and high-frequency operation of flexible low-voltage inverted coplanar organic transistors
Authors: Borchert James W. , Peng Boyu , Letzkus Florian , Burghartz Joachim N. , Chan Paddy K. L. , Zojer Karin , Ludwigs Sabine , Klauk Hagen 
Published: March 2019

AbstractThe contact resistance in organic thin-film transistors (TFTs) is the limiting factor in the development of high-frequency organic TFTs. In devices fabricated in the inverted (bottom-gate) device architecture, staggered (top-contact) organic TFTs have usually shown or are predicted to show lower contact resistance than coplanar (bottom-contact) organic TFTs. However, through comparison of organic TFTs with different gate-dielectric thicknesses based on the small-molecule organic semiconductor 2,9-diphenyl-dinaphtho[2,3-b:2’,3’-f]thieno[3,2-b]thiophene, we show the potential for bottom-contact TFTs to have lower contact resistance than top-contact TFTs, provided the gate dielectric is sufficiently thin and an interface layer such as pentafluorobenzenethiol is used to treat the surface of the source and drain contacts. We demonstrate bottom-contact TFTs fabricated on flexible plastic substrates with record-low contact resistance (29 Ωcm), record subthreshold swing (62 mV/decade), and signal-propagation delays in 11-stage unipolar ring oscillators as short as 138 ns per stage, all at operating voltages of about 3 V.
Enterovirus particles expel capsid pentamers to enable genome release
Authors: Buchta David , Füzik Tibor , Hrebík Dominik , Levdansky Yevgen , Sukeník Lukáš , Mukhamedova Liya , Moravcová Jana , Vácha Robert , Plevka Pavel 
Published: March 2019

AbstractViruses from the genus Enterovirus are important human pathogens. Receptor binding or exposure to acidic pH in endosomes converts enterovirus particles to an activated state that is required for genome release. However, the mechanism of enterovirus uncoating is not well understood. Here, we use cryo-electron microscopy to visualize virions of human echovirus 18 in the process of genome release. We discover that the exit of the RNA from the particle of echovirus 18 results in a loss of one, two, or three adjacent capsid-protein pentamers. The opening in the capsid, which is more than 120 Å in diameter, enables the release of the genome without the need to unwind its putative double-stranded RNA segments. We also detect capsids lacking pentamers during genome release from echovirus 30. Thus, our findings uncover a mechanism of enterovirus genome release that could become target for antiviral drugs.
Terrain uplift due to natural hydrologic overpressure in karstic conduits
Authors: Braitenberg Carla , Pivetta Tommaso , Barbolla Dora Francesca , Gabrovšek Franci , Devoti Roberto , Nagy Ildikó 
Published: March 2019

AbstractWater supply from karst sources is a worldwide natural resource and the exploitation is tied to the knowledge of the positions of the hydrologic channels. We show that surface deformation induced by flood events in karst conduits is observable, and consists in uplift and outward movement from the hydraulic channel. Precipitation events produce the natural occurrence of subsurface hydraulic overpressure up to 1 MPa. Numerical modeling shows that the stresses are so strong to uplift and dislocate the surface by several mm and induce tilts in the order of microradians. The naturally induced deformation is compatible with a transient internal pressure loading of a channel. The results can be used to find new channels with dense GNSS networks. Sea water incursion and channels accessed for tourism could be monitored. Seismicity has been shown to have a seasonal variation in some areas, which could be explained by the subsurface stresses induced by the natural subsurface overpressure. The pressure induced deformation is expected to be observed in all karstic systems worldwide.
Black carbon and other light-absorbing impurities in snow in the Chilean Andes
Authors: Rowe Penny M. , Cordero Raul R. , Warren Stephen G. , Stewart Emily , Doherty Sarah J. , Pankow Alec , Schrempf Michael , Casassa Gino , Carrasco Jorge , Pizarro Jaime , MacDonell Shelley , Damiani Alessandro , Lambert Fabrice , Rondanelli Roberto , Huneeus Nicolas , Fernandoy Francisco , Neshyba Steven 
Published: March 2019

AbstractVertical profiles of black carbon (BC) and other light-absorbing impurities were measured in seasonal snow and permanent snowfields in the Chilean Andes during Austral winters 2015 and 2016, at 22 sites between latitudes 18°S and 41°S. The samples were analyzed for spectrally-resolved visible light absorption. For surface snow, the average mass mixing ratio of BC was 15 ng/g in northern Chile (18–33°S), 28 ng/g near Santiago (a major city near latitude 33°S, where urban pollution plays a significant role), and 13 ng/g in southern Chile (33–41°S). The regional average vertically-integrated loading of BC was 207 µg/m2 in the north, 780 µg/m2 near Santiago, and 2500 µg/m2 in the south, where the snow season was longer and the snow was deeper. For samples collected at locations where there had been no new snowfall for a week or more, the BC concentration in surface snow was high (~10–100 ng/g) and the sub-surface snow was comparatively clean, indicating the dominance of dry deposition of BC. Mean albedo reductions due to light-absorbing impurities were 0.0150, 0.0160, and 0.0077 for snow grain radii of 100 µm for northern Chile, the region near Santiago, and southern Chile; respective mean radiative forcings for the winter months were 2.8, 1.4, and 0.6 W/m2. In northern Chile, our measurements indicate that light-absorption by impurities in snow was dominated by dust rather than BC.
Coevolution of visual behaviour, the material world and social complexity, depicted by the eye-tracking of archaeological objects in humans
Authors: Criado-Boado Felipe , Alonso-Pablos Diego , Blanco Manuel J. , Porto Yolanda , Rodríguez-Paz Anxo , Cabrejas Elena , del Barrio-Álvarez Elena , Martínez Luis M. 
Published: March 2019

AbstractWe live in a cluttered visual world that is overflowing with information, the continuous processing of which would be a truly daunting task. Nevertheless, our brains have evolved to select which part of a visual scene is to be prioritized and analysed in detail, and which parts can be discarded or analysed at a later stage. This selection is in part determined by the visual stimuli themselves, and is known as “selective attention”, which, in turn, determines how we explore and interact with our environment, including the distinct human artefacts produced in different socio-cultural contexts. Here we hypothesize that visual responses and material objects should therefore co-evolve to reflect changes in social complexity and culture throughout history. Using eye-tracking, we analysed the eye scan paths in response to prehistoric pottery ranging from the Neolithic through to the Iron Age (ca 6000–2000 BP), finding that each ceramic style caused a particular pattern of visual exploration. Horizontal movements become dominant in earlier periods, while vertical movements are more frequent in later periods that were marked by greater social complexity.
Fusion proteins consisting of Bet v 1 and Phl p 5 form IgE-reactive aggregates with reduced allergenic activity
Authors: Najafi N. , Hofer G. , Gattinger P. , Smiljkovic D. , Blatt K. , Selb R. , Stoecklinger A. , Keller W. , Valent P. , Niederberger V. , Thalhamer J. , Valenta R. , Flicker S. 
Published: March 2019

AbstractThe cross-linking of effector cell-bound IgE antibodies by allergens induces the release of inflammatory mediators which are responsible for the symptoms of allergy. We demonstrate that a recombinant hybrid molecule consisting of the major birch (Bet v 1) and grass (Phl p 5) pollen allergen exhibited reduced allergenic activity as compared to equimolar mixes of the isolated allergens in basophil activation experiments. The reduced allergenic activity of the hybrid was not due to reduced IgE reactivity as demonstrated by IgE binding experiments using sera from allergic patients. Physicochemical characterization of the hybrid by size exclusion chromatography, dynamic light scattering, negative-stain electron microscopy and circular dichroism showed that the hybrid occurred as folded aggregate whereas the isolated allergens were folded monomeric proteins. IgG antibodies raised in rabbits against epitopes of Bet v 1 and Phl p 5 showed reduced reactivity with the hybrid compared to the monomeric allergens. Our results thus demonstrate that aggregation can induce changes in the conformation of allergens and lead to the reduction of allergenic activity. This is a new mechanism for reducing the allergenic activity of allergens which may be important for modifying allergens to exhibit reduced side effects when used for allergen-specific immunotherapy.
Lifespan Changes of the Human Brain In Alzheimer’s Disease
Authors: Coupé Pierrick , Manjón José Vicente , Lanuza Enrique , Catheline Gwenaelle 
Published: March 2019

AbstractBrain imaging studies have shown that slow and progressive cerebral atrophy characterized the development of Alzheimer’s Disease (AD). Despite a large number of studies dedicated to AD, key questions about the lifespan evolution of AD biomarkers remain open. When does the AD model diverge from the normal aging model? What is the lifespan trajectory of imaging biomarkers for AD? How do the trajectories of biomarkers in AD differ from normal aging? To answer these questions, we proposed an innovative way by inferring brain structure model across the entire lifespan using a massive number of MRI (N = 4329). We compared the normal model based on 2944 control subjects with the pathological model based on 3262 patients (AD + Mild cognitive Impaired subjects) older than 55 years and controls younger than 55 years. Our study provides evidences of early divergence of the AD models from the normal aging trajectory before 40 years for the hippocampus, followed by the lateral ventricles and the amygdala around 40 years. Moreover, our lifespan model reveals the evolution of these biomarkers and suggests close abnormality evolution for the hippocampus and the amygdala, whereas trajectory of ventricular enlargement appears to follow an inverted U-shape. Finally, our models indicate that medial temporal lobe atrophy and ventricular enlargement are two mid-life physiopathological events characterizing AD brain.
Exploration of the Structure and Recognition of a G-quadruplex in the her2 Proto-oncogene Promoter and Its Transcriptional Regulation
Authors: Cui Xiaojie , Chen Han , Zhang Qiang , Xu Ming , Yuan Gu , Zhou Jiang 
Published: March 2019

AbstractG-quadruplexes in oncogene promoters provide putative targets for transcriptional regulation. The structure of a putative G-quadruplex sequence (S1: GGAGAAGGAGGAGGTGGAGGAGGAGGG) in potassium solution in the her2 promoter has been resolved mainly through nuclear magnetic resonance (NMR) spectroscopy. By application of various NMR spectra, we proved the formation of a four-layer G-quadruplex composing of two G-tetrads and two G/A-mixed planes with a four-residues loop (A3-G4-A5-A6). Further evidence from a luciferase reporter assay, Q-RT-PCR and Western blotting indicates that S1 G-quadruplex formation can repress her2 promoter activity, and a selected G-quadruplex ligand cβ can enhance the repression by down regulating her2 transcription and expression. These findings provide a G-quadruplex target and perspective implications in her2 transcriptional regulation.
Vibration induced refrigeration using ferroelectric materials
Authors: Kumar Anuruddh , Chauhan Aditya , Patel Satyanarayan , Novak Nikola , Kumar Rajeev , Vaish Rahul 
Published: March 2019

AbstractThis article aims to propose a cantilever based cooling device employing non-axis symmetric placement of bulk ferroelectric patches. Ambient mechanical vibrations produce large stresses in cantilevers resulting in elastocaloric effect associated with ferroelectrics. Further, design allows cascading of several cantilevers to achieve large cooling response. A finite element analysis of the system was performed using material properties of bulk 0.50Ba(Zr0.2Ti0.8)O3−0.50(Ba0.7Ca0.3)TiO3. An individual element could produce a peak elastocaloric effect of 0.02 K (324 K); whereas the proposed system could achieve a temperature drop of 0.2 K within 50 seconds (10 elements, 1.5 Hz). Furthermore, net cooling can be further improved about ~2 K (using 10 cantilevers) for a starting temperature of 358 K. This study shows that elastocaloric effect in ferroelectric materials is capable of converting waste mechanical vibration into refrigeration effect which is not reported so far.
Parasitoid envenomation alters the Galleria mellonella midgut microbiota and immunity, thereby promoting fungal infection
Authors: Polenogova Olga V. , Kabilov Marsel R. , Tyurin Maksim V. , Rotskaya Ulyana N. , Krivopalov Anton V. , Morozova Vera V. , Mozhaitseva Kseniya , Kryukova Nataliya A. , Alikina Tatyana , Kryukov Vadim Yu. , Glupov Viktor V. 
Published: March 2019

AbstractGut bacteria influence the development of different pathologies caused by bacteria, fungi and parasitoids in insects. Wax moth larvae became more susceptible to fungal infections after envenomation by the ectoparasitoid Habrobracon hebetor. In addition, spontaneous bacterioses occurred more often in envenomated larvae. We analyzed alterations in the midgut microbiota and immunity of the wax moth in response to H. hebetor envenomation and topical fungal infection (Beauveria bassiana) alone or in combination using 16S rRNA sequencing, an analysis of cultivable bacteria and a qPCR analysis of immunity- and stress-related genes. Envenomation led to a predominance shift from enterococci to enterobacteria, an increase in CFUs and the upregulation of AMPs in wax moth midguts. Furthermore, mycosis nonsignificantly increased the abundance of enterobacteria and the expression of AMPs in the midgut. Combined treatment led to a significant increase in the abundance of Serratia and a greater upregulation of gloverin. The oral administration of predominant bacteria (Enterococcus faecalis, Enterobacter sp. and Serratia marcescens) to wax moth larvae synergistically increased fungal susceptibility. Thus, the activation of midgut immunity might prevent the bacterial decomposition of envenomated larvae, thus permitting the development of fungal infections. Moreover, changes in the midgut bacterial community may promote fungal killing.