bluuebunny/crossref_metadata_2025_split huggingface dataset:
JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
Authors: Myers Toshia R. , Amendola Pier Giorgio , Lussi Yvonne C. , Salcini Anna Elisabetta 
Published: February 2018

AbstractPost-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contribution in regulating histone methylation in germ cells has not been fully investigated. Here, we show that jmjd-1.2 is expressed abundantly in the germline where it controls the level of histone 3 lysine 9, lysine 23 and lysine 27 di-methylation (H3K9/K23/K27me2) both in mitotic and meiotic cells. Loss of jmjd-1.2 is not associated with major defects in the germ cells in animals grown under normal conditions or after DNA damage induced by UV or ionizing irradiation. However, jmjd-1.2 mutants are more sensitive to replication stress and the progeny of mutant animals exposed to hydroxyurea show increased embryonic lethality and mutational rate, compared to wild-type. Thus, our results suggest a role for jmjd-1.2 in the maintenance of genome integrity after replication stress and emphasize the relevance of the regulation of histone methylation in genomic stability.
ASC- and caspase-8-dependent apoptotic pathway diverges from the NLRC4 inflammasome in macrophages
Authors: Lee Bettina L. , Mirrashidi Kathleen M. , Stowe Irma B. , Kummerfeld Sarah K. , Watanabe Colin , Haley Benjamin , Cuellar Trinna L. , Reichelt Michael , Kayagaki Nobuhiko 
Published: February 2018

AbstractThe NLRC4 inflammasome recognizes bacterial flagellin and components of the type III secretion apparatus. NLRC4 stimulation leads to caspase-1 activation followed by a rapid lytic cell death known as pyroptosis. NLRC4 is linked to pathogen-free auto-inflammatory diseases, suggesting a role for NLRC4 in sterile inflammation. Here, we show that NLRC4 activates an alternative cell death program morphologically similar to apoptosis in caspase-1-deficient BMDMs. By performing an unbiased genome-wide CRISPR/Cas9 screen with subsequent validation studies in gene-targeted mice, we highlight a critical role for caspase-8 and ASC adaptor in an alternative apoptotic pathway downstream of NLRC4. Furthermore, caspase-1 catalytically dead knock-in (Casp1 C284A KI) BMDMs genetically segregate pyroptosis and apoptosis, and confirm that caspase-1 does not functionally compete with ASC for NLRC4 interactions. We show that NLRC4/caspase-8-mediated apoptotic cells eventually undergo plasma cell membrane damage in vitro, suggesting that this pathway can lead to secondary necrosis. Unexpectedly, we found that DFNA5/GSDME, a member of the pore-forming gasdermin family, is dispensable for the secondary necrosis that follows NLRC4-mediated apoptosis in macrophages. Together, our data confirm the existence of an alternative caspase-8 activation pathway diverging from the NLRC4 inflammasome in primary macrophages.
Absence of Claudin 11 in CNS Myelin Perturbs Behavior and Neurotransmitter Levels in Mice
Authors: Maheras Kathleen J. , Peppi Marcello , Ghoddoussi Farhad , Galloway Matthew P. , Perrine Shane A. , Gow Alexander 
Published: February 2018

AbstractNeuronal origins of behavioral disorders have been examined for decades to construct frameworks for understanding psychiatric diseases and developing useful therapeutic strategies with clinical application. Despite abundant anecdotal evidence for white matter etiologies, including altered tractography in neuroimaging and diminished oligodendrocyte-specific gene expression in autopsy studies, mechanistic data demonstrating that dysfunctional myelin sheaths can cause behavioral deficits and perturb neurotransmitter biochemistry have not been forthcoming. At least in part, this impasse stems from difficulties in identifying model systems free of degenerative pathology to enable unambiguous assessment of neuron biology and behavior in a background of myelin dysfunction. Herein we examine myelin mutant mice lacking expression of the Claudin11 gene in oligodendrocytes and characterize two behavioral endophenotypes: perturbed auditory processing and reduced anxiety/avoidance. Importantly, these behaviors are associated with increased transmission time along myelinated fibers as well as glutamate and GABA neurotransmitter imbalances in auditory brainstem and amygdala, in the absence of neurodegeneration. Thus, our findings broaden the etiology of neuropsychiatric disease to include dysfunctional myelin, and identify a preclinical model for the development of novel disease-modifying therapies.
New thin-film surface electrode array enables brain mapping with high spatial acuity in rodents
Authors: Konerding W. S. , Froriep U. P. , Kral A. , Baumhoff P. 
Published: February 2018

AbstractIn neuroscience, single-shank penetrating multi-electrode arrays are standard for sequentially sampling several cortical sites with high spatial and temporal resolution, with the disadvantage of neuronal damage. Non-penetrating surface grids used in electrocorticography (ECoG) permit simultaneous recording of multiple cortical sites, with limited spatial resolution, due to distance to neuronal tissue, large contact size and high impedances. Here we compared new thin-film parylene C ECoG grids, covering the guinea pig primary auditory cortex, with simultaneous recordings from penetrating electrode array (PEAs), inserted through openings in the grid material. ECoG grid local field potentials (LFP) showed higher response thresholds and amplitudes compared to PEAs. They enabled, however, fast and reliable tonotopic mapping of the auditory cortex (place-frequency slope: 0.7 mm/octave), with tuning widths similar to PEAs. The ECoG signal correlated best with supragranular layers, exponentially decreasing with cortical depth. The grids also enabled recording of multi-unit activity (MUA), yielding several advantages over LFP recordings, including sharper frequency tunings. ECoG first spike latency showed highest similarity to superficial PEA contacts and MUA traces maximally correlated with PEA recordings from the granular layer. These results confirm high quality of the ECoG grid recordings and the possibility to collect LFP and MUA simultaneously.
Associative properties of structural plasticity based on firing rate homeostasis in recurrent neuronal networks
Authors: Gallinaro Júlia V. , Rotter Stefan 
Published: February 2018

AbstractCorrelation-based Hebbian plasticity is thought to shape neuronal connectivity during development and learning, whereas homeostatic plasticity would stabilize network activity. Here we investigate another, new aspect of this dichotomy: Can Hebbian associative properties also emerge as a network effect from a plasticity rule based on homeostatic principles on the neuronal level? To address this question, we simulated a recurrent network of leaky integrate-and-fire neurons, in which excitatory connections are subject to a structural plasticity rule based on firing rate homeostasis. We show that a subgroup of neurons develop stronger within-group connectivity as a consequence of receiving stronger external stimulation. In an experimentally well-documented scenario we show that feature specific connectivity, similar to what has been observed in rodent visual cortex, can emerge from such a plasticity rule. The experience-dependent structural changes triggered by stimulation are long-lasting and decay only slowly when the neurons are exposed again to unspecific external inputs.
Super anticorrosion of aluminized steel by a controlled Mg supply
Authors: Jeong Jae In , Yang Ji Hoon , Jung Jae Hun , Lee Kyung Hwang , Kim Hye Jeong , Jung Yong Hwa , Kim Tae Yeob , Lee Myeong Hoon , Hwang Sung Hwa , Wu Ping , Kim Jae-Hun , Kim Sang Sub 
Published: February 2018

AbstractThe current anticorrosion strategy makes use of coatings to passively protect the steel, which faces increasing challenge due to the tightened environmental regulations and high cost. This paper reports a new method for achieving a super anticorrosion function in Al-Si alloys through Mg nano-metallurgy, which was characterized by real-time synchrotron measurements. The unique function is based on the formation of an amorphous and self-charge-compensated MgAl2O4-SiO2 phase between the grain boundaries to help prevent the penetration of oxygen species through the grain boundaries. Through this, the corrosion resistance of pristine aluminized steel could be improved almost 20 fold. An analysis of the phases, microstructures of the Mg-coated aluminized layer and corrosion products consistently supported the proposed mechanism. This charge-compensated corrosion resistance mechanism provides novel insight into corrosion resistance.
Rapid Detection of Zika Virus in Urine Samples and Infected Mosquitos by Reverse Transcription-Loop-Mediated Isothermal Amplification
Authors: Lamb Laura E. , Bartolone Sarah N. , Tree Maya O. , Conway Michael J. , Rossignol Julien , Smith Christopher P. , Chancellor Michael B. 
Published: February 2018

AbstractInfection with Zika virus (ZIKV) is of growing concern since infection is associated with the development of congenital neurological disease. Quantitative reverse transcription PCR (qRT-PCR) has been the standard for ZIKV detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper testing. Studies have suggested that ZIKV detection in urine is more sensitive and has a longer window of detection compared to serum and saliva. The objective of this study was to develop a urine diagnostic test that could be completed in under 30 minutes. Urine samples spiked with ZIKV or dengue virus were tested using RT-LAMP as well as by conventional quantitative qRT-PCR. These techniques were then validated using crude lysates made from ZIKV infected mosquitoes in addition to urine and serum samples from ZIKV infected patients. RT-LAMP specifically detected ZIKV in urine and serum for ZIKV infected patients and crude mosquito lysates. This test was performed in under 30 minutes and did not require RNA extraction from urine nor mosquitos. This approach could be used for monitoring of exposed individuals, especially pregnant women, couples wanting to conceive, or individuals with suspicious symptoms as well as surveillance of mosquito populations.
The right inferior frontal gyrus processes nested non-local dependencies in music
Authors: Cheung Vincent K. M. , Meyer Lars , Friederici Angela D. , Koelsch Stefan 
Published: February 2018

AbstractComplex auditory sequences known as music have often been described as hierarchically structured. This permits the existence of non-local dependencies, which relate elements of a sequence beyond their temporal sequential order. Previous studies in music have reported differential activity in the inferior frontal gyrus (IFG) when comparing regular and irregular chord-transitions based on theories in Western tonal harmony. However, it is unclear if the observed activity reflects the interpretation of hierarchical structure as the effects are confounded by local irregularity. Using functional magnetic resonance imaging (fMRI), we found that violations to non-local dependencies in nested sequences of three-tone musical motifs in musicians elicited increased activity in the right IFG. This is in contrast to similar studies in language which typically report the left IFG in processing grammatical syntax. Effects of increasing auditory working demands are moreover reflected by distributed activity in frontal and parietal regions. Our study therefore demonstrates the role of the right IFG in processing non-local dependencies in music, and suggests that hierarchical processing in different cognitive domains relies on similar mechanisms that are subserved by domain-selective neuronal subpopulations.
Characterization of Exosomal SLC22A5 (OCTN2) carnitine transporter
Authors: Console Lara , Scalise Mariafrancesca , Tonazzi Annamaria , Giangregorio Nicola , Indiveri Cesare 
Published: February 2018

AbstractExosomes are extracellular vesicles involved in cell-to-cell communication. Previous large scale proteomics revealed that they contain SLC proteins. However, no data on the function of exosomal SLCs is available, so far. An SLC localized in exosomes was here characterized for the first time: the carnitine transporter OCTN2 (SLC22A5). The protein was detected by Western Blot analysis in HEK293 exosomes. To investigate the functional properties of the exosomal OCTN2, the proteins extracted from vesicles were reconstituted into proteolipsomes and the transport function was measured as uptake of 3H-carnitine. Transport was stimulated by sodium and was dependent on pH. 3H-carnitine uptake was inhibited by Acetyl-carnitine, but not by Asn, Gln and Arg thus excluding interference by ATB0,+, an amino acid transporter which also recognizes carnitine. Cardiolipin failed to stimulate transport, excluding the activity of the mitochondrial Carnitine/acylcarnitine transporter. Increased level of exosomal OCTN2 was induced by treatment of HEK293 with the pro-inflammatory cytokine INFγ. All data concurred to demonstrate that OCTN2 present in exosomes is fully functional and is in its native conformation. Functional OCTN2 was detected also in human urinary exosomes, thus suggesting the OCTN2 exosomal protein as a candidate biomarker for inflammation related pathologies.
Evaluation of a Pretargeting Strategy for Molecular Imaging of the Prostate Stem Cell Antigen with a Single Chain Antibody
Authors: Tienken Lena , Drude Natascha , Schau Isabell , Winz Oliver H. , Temme Achim , Weinhold Elmar , Mottaghy Felix M. , Morgenroth Agnieszka 
Published: February 2018

AbstractIn pretargeted radio-immunotherapy, the gradual administration of a non-radioactive tumor antigen-addressing antibody-construct and the subsequent application of a radioactive labeled, low molecular weight substance enable a highly effective and selective targeting of tumor tissue. We evaluated this concept in prostate stem cell antigen (PSCA)-positive cancers using the antigen-specific, biotinylated single chain antibody scFv(AM1)-P-BAP conjugated with tetrameric neutravidin. To visualize the systemic biodistribution, a radiolabeled biotin was injected to interact with scFv(AM1)-P-BAP/neutravidin conjugate. Biotin derivatives conjugated with different chelators for complexation of radioactive metal ions and a polyethylene glycol linker (n = 45) were successfully synthesized and evaluatedin vitroand in a mouse xenograft model.In vivo, the scFv(AM1)-P-BAP showed highly PSCA-specific tumor retention with a PSCA+tumor/PSCA-tumor accumulation ratio of ten. PEGylation of radiolabeled biotin resulted in lower liver uptake improving the tumor to background ratio.
Role of iRhom2 in intestinal ischemia-reperfusion-mediated acute lung injury
Authors: Kim Jee Hyun , Kim Jihye , Chun Jaeyoung , Lee Changhyun , Im Jong Pil , Kim Joo Sung 
Published: February 2018

AbstractIntestinal ischemia-reperfusion (I/R) may cause acute systemic and lung inflammation. However, the detailed mechanism of this inflammatory cascade has not been fully elucidated. Inactive rhomboid protein 2 (iRhom2) is essential for the maturation of TNF-α converting enzyme (TACE), which is required for TNF-α secretion. We evaluated the role of iRhom2 in a mouse model of intestinal I/R using iRhom2 knockout (KO) and wild-type (WT) mice. Lung injury following intestinal I/R was significantly attenuated in iRhom2 KO mice compared with WT mice. After intestinal I/R, lungs from iRhom2 KO mice showed significantly lower myeloperoxidase (MPO) activity and markedly reduced cell apoptosis associated with a decreased level of active caspase 3 and decreased TUNEL staining compared with lungs from WT mice. TNF-α levels were elevated in the serum and lungs of WT mice with intestinal I/R and significantly reduced in iRhom2 KO mice with intestinal I/R. iRhom2 may play a critical role in the pathogenesis of acute lung injury (ALI) after intestinal I/R and thus may be a novel therapeutic target for ALI after intestinal I/R injury.
Simulation of solute transport through heterogeneous networks: analysis using the method of moments and the statistics of local transport characteristics
Authors: Li Min , Qi Tao , Bernabé Yves , Zhao Jinzhou , Wang Ying , Wang Dong , Wang Zheming 
Published: February 2018

AbstractWe used a time domain random walk approach to simulate passive solute transport in networks. In individual pores, solute transport was modeled as a combination of Poiseuille flow and Taylor dispersion. The solute plume data were interpreted via the method of moments. Analysis of the first and second moments showed that the longitudinal dispersivity increased with increasing coefficient of variation of the pore radii CV and decreasing pore coordination number Z. The third moment was negative and its magnitude grew linearly with time, meaning that the simulated dispersion was intrinsically non-Fickian. The statistics of the Eulerian mean fluid velocities $${\hat{{\boldsymbol{u}}}}_{{\boldsymbol{i}}}$$

u
ˆ

i

, the Taylor dispersion coefficients $${\hat{{\boldsymbol{D}}}}_{{\boldsymbol{i}}}$$

D
ˆ

i

and the transit times $${\hat{{\boldsymbol{\tau }}}}_{{\boldsymbol{i}}}$$

τ
ˆ

i

were very complex and strongly affected by CV and Z. In particular, the probability of occurrence of negative velocities grew with increasing CV and decreasing Z. Hence, backward and forward transit times had to be distinguished. The high-τ branch of the transit-times probability curves had a power law form associated to non-Fickian behavior. However, the exponent was insensitive to pore connectivity, although variations of Z affected the third moment growth. Thus, we conclude that both the low- and high-τ branches played a role in generating the observed non-Fickian behavior.
Identification, expression, and endocrine-disruption of three ecdysone-responsive genes in the sentinel species Gammarus fossarum
Authors: Gouveia D. , Bonneton F. , Almunia C. , Armengaud J. , Quéau H. , Degli-Esposti D. , Geffard O. , Chaumot A. 
Published: February 2018

AbstractTaking advantage of a large transcriptomic dataset recently obtained in the sentinel crustacean amphipod Gammarus fossarum, we developed an approach based on sequence similarity and phylogenetic reconstruction to identify key players involved in the endocrine regulation of G. fossarum. Our work identified three genes of interest: the nuclear receptors RXR and E75, and the regulator broad-complex (BR). Their involvement in the regulation of molting and reproduction, along with their sensitivity to chemical contamination were experimentally assessed by studying gene expression during the female reproductive cycle, and after laboratory exposure to model endocrine disrupting compounds (EDCs): pyriproxyfen, tebufenozide and piperonyl butoxide. RXR expression suggested a role of this gene in ecdysis and post-molting processes. E75 presented two expression peaks that suggested a role in vitellogenesis, and molting. BR expression showed no variation during molting/reproductive cycle. After exposure to the three EDCs, a strong inhibition of the inter-molt E75 peak was observed with tebufenozide, and an induction of RXR after exposure to pyriproxyfen and piperonyl butoxide. These results confirm the implication of RXR and E75 in hormonal regulation of female reproductive cycles in G. fossarum and their sensitivity towards EDCs opens the possibility of using them as specific endocrine disruption biomarkers.
Generic approach to access barriers in dehydrogenation reactions
Authors: Yu Liang , Vilella Laia , Abild-Pedersen Frank 
Published: February 2018

AbstractThe introduction of linear energy correlations, which explicitly relate adsorption energies of reaction intermediates and activation energies in heterogeneous catalysis, has proven to be a key component in the computational search for new and promising catalysts. A simple linear approach to estimate activation energies still requires a significant computational effort. To simplify this process and at the same time incorporate the need for enhanced complexity of reaction intermediates, we generalize a recently proposed approach that evaluates transition state energies based entirely on bond-order conservation arguments. We show that similar variation of the local electronic structure along the reaction coordinate introduces a set of general functions that accurately defines the transition state energy and are transferable to other reactions with similar bonding nature. With such an approach, more complex reaction intermediates can be targeted with an insignificant increase in computational effort and without loss of accuracy.
Investigation of a sample of carbon-enhanced metal-poor stars observed with FORS and GMOS
Authors: Caffau E. , Gallagher A. J. , Bonifacio P. , Spite M. , Duffau S. , Spite F. , Monaco L. , Sbordone L. 
Published: February 2018

Aims. Carbon-enhanced metal-poor (CEMP) stars represent a sizeable fraction of all known metal-poor stars in the Galaxy. Their formation and composition remains a significant topic of investigation within the stellar astrophysics community.
Methods. We analysed a sample of low-resolution spectra of 30 dwarf stars, obtained using the visual and near UV FOcal Reducer and low dispersion Spectrograph for the Very Large Telescope (FORS/VLT) of the European Southern Observatory (ESO) and the Gemini Multi-Object Spectrographs (GMOS) at the GEMINI telescope, to derive their metallicity and carbon abundance.
Results. We derived C and Ca from all spectra, and Fe and Ba from the majority of the stars.
Conclusions. We have extended the population statistics of CEMP stars and have confirmed that in general, stars with a high C abundance belonging to the high C band show a high Ba-content (CEMP-s or -r/s), while stars with a normal C abundance or that are C-rich, but belong to the low C band, are normal in Ba (CEMP-no).
Can Elastography Differentiate Isolated Fatty Liver from Nonalcoholic Steatohepatitis?
Authors: Ajmera Veeral , Loomba Rohit 
Published: February 2018

AbstractUltrasound and magnetic resonance (MR)-based elastography have demonstrated excellent performance for noninvasive staging of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD); however, their ability to differentiate isolated fatty liver from nonalcoholic steatohepatitis (NASH) is unclear. In this review, the authors provide background on elastography and review the ability of elastography to discriminate between isolated steatosis and NASH. Studies with available data on the diagnosis of NASH histology are limited to vibration-controlled transient elastography and MR elastography. A wide range of optimal cutoffs for the diagnosis of NASH are reported and likely depend on the prevalence of advanced fibrosis in the study population. MR elastography has good performance characteristics for identifying patients with any fibrosis who are at greatest risk of disease-related morbidity. Currently, neither modality can reliably discriminate NASH from simple steatosis. Novel multiparametric MR imaging and elastography are emerging and may help detect presence of NASH in the future.