bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-temperature thermal stability driven by magnetization dilution in CoFeB free layers for spin-transfer-torque magnetic random access memory
Authors: Iwata-Harms Jodi M. , Jan Guenole , Liu Huanlong , Serrano-Guisan Santiago , Zhu Jian , Thomas Luc , Tong Ru-Ying , Sundar Vignesh , Wang Po-Kang 
Published: September 2018

AbstractSpin-transfer-torque magnetic random access memory (STT-MRAM) is the most promising emerging non-volatile embedded memory. For most applications, a wide range of operating temperatures is required, for example −40 °C to +150 °C for automotive applications. This presents a challenge for STT-MRAM, because the magnetic anisotropy responsible for data retention decreases rapidly with temperature. In order to compensate for the loss of thermal stability at high temperature, the anisotropy of the devices must be increased. This in turn leads to larger write currents at lower temperatures, thus reducing the efficiency of the memory. Despite the importance of high-temperature performance of STT-MRAM for energy efficient design, thorough physical understanding of the key parameters driving its behavior is still lacking. Here we report on CoFeB free layers diluted with state-of-the-art non-magnetic metallic impurities. By varying the impurity material and concentration to modulate the magnetization, we demonstrate that the magnetization is the primary factor driving the temperature dependence of the anisotropy and thermal stability. We use this understanding to develop a simple model allowing for the prediction of thermal stability of STT-MRAM devices from blanket film properties, and find good agreement with direct measurements of patterned devices.
Surveying the genome and constructing a high-density genetic map of napiergrass (Cenchrus purpureus Schumach)
Authors: Paudel Dev , Kannan Baskaran , Yang Xiping , Harris-Shultz Karen , Thudi Mahendar , Varshney Rajeev K. , Altpeter Fredy , Wang Jianping 
Published: September 2018

AbstractNapiergrass (Cenchrus purpureus Schumach) is a tropical forage grass and a promising lignocellulosic biofuel feedstock due to its high biomass yield, persistence, and nutritive value. However, its utilization for breeding has lagged behind other crops due to limited genetic and genomic resources. In this study, next-generation sequencing was first used to survey the genome of napiergrass. Napiergrass sequences displayed high synteny to the pearl millet genome and showed expansions in the pearl millet genome along with genomic rearrangements between the two genomes. An average repeat content of 27.5% was observed in napiergrass including 5,339 simple sequence repeats (SSRs). Furthermore, to construct a high-density genetic map of napiergrass, genotyping-by-sequencing (GBS) was employed in a bi-parental population of 185 F1 hybrids. A total of 512 million high quality reads were generated and 287,093 SNPs were called by using multiple de-novo and reference-based SNP callers. Single dose SNPs were used to construct the first high-density linkage map that resulted in 1,913 SNPs mapped to 14 linkage groups, spanning a length of 1,410 cM and a density of 1 marker per 0.73 cM. This map can be used for many further genetic and genomic studies in napiergrass and related species.
A short isoform of ATG7 fails to lipidate LC3/GABARAP
Authors: Ogmundsdottir M. H. , Fock V. , Sooman L. , Pogenberg V. , Dilshat R. , Bindesbøll C. , Ogmundsdottir H. M. , Simonsen A. , Wilmanns M. , Steingrimsson E. 
Published: September 2018

AbstractAutophagy is a degradation pathway important for cellular homeostasis. The E1-like enzyme ATG7 is a key component of the autophagy machinery, with the main function of mediating the lipidation of LC3/GABARAP during autophagosome formation. By analysing mRNA-sequencing data we found that in addition to the full-length ATG7 isoform, various tissues express a shorter isoform lacking an exon of 27 amino acids in the C-terminal part of the protein, termed ATG7(2). We further show that ATG7(2) does not bind LC3B and fails to mediate the lipidation of members of the LC3/GABARAP family. We have thus identified an isoform of ATG7 that is unable to carry out the best characterized function of the protein during the autophagic response. This short isoform will have to be taken into consideration when further studying the role of ATG7.
Fecal microbiota profile in a group of myasthenia gravis patients
Authors: Moris German , Arboleya Silvia , Mancabelli Leonardo , Milani Christian , Ventura Marco , de los Reyes-Gavilán Clara G. , Gueimonde Miguel 
Published: September 2018

AbstractThe intestinal microbiota plays a key role in the maintenance of human health. Alterations in this microbiota have been described in several autoimmune diseases, including nervous system diseases. Nevertheless, the information regarding neuromuscular conditions is still limited. In this study, we aimed at characterizing the intestinal microbiota composition in myasthenia gravis patients (MG). To this end fecal samples were taken from ten patients, with antibodies against the acetylcholine receptor, and ten age and sex matched controls from the same population (Asturias region, Spain). Fecal samples were submitted to microbiota analyses by 16S rRNA gene profiling, bifidobacterial ITS-region profiling and qPCR. The fecal levels of short chain fatty acids were determined by gas chromatography. MG patients were found to harbor lower relative proportions of Verrucomicrobiaceae and Bifidobacteriaceae, among others, and increased of the phylum Bacteroidetes and the family Desulfovibrionaceae. The increase of these latter microbial groups was also confirmed at quantitative level by qPCR. In contrast, no statistically significant differences were found between MG patients and the control group in the bifidobacterial population at the species level or in short chain fatty acids profiles. Our data indicates an altered fecal microbiota pattern in MG patients and point out at specific microbiota targets for intervention in this population.
Impact of Age and Diastolic Function on Novel, 4D flow CMR Biomarkers of Left Ventricular Blood Flow Kinetic Energy
Authors: Crandon Saul , Westenberg Jos J. M. , Swoboda Peter P. , Fent Graham J. , Foley James R. J. , Chew Pei G. , Brown Louise A. E. , Saunderson Christopher , Al-Mohammad Abdallah , Greenwood John P. , van der Geest Rob J. , Dall’Armellina Erica , Plein Sven , Garg Pankaj 
Published: September 2018

AbstractTwo-dimensional (2D) methods of assessing mitral inflow velocities are pre-load dependent, limiting their reliability for evaluating diastolic function. Left ventricular (LV) blood flow kinetic energy (KE) derived from four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) may offer improvements. It remains unclear whether 4D LV blood flow KE parameters are associated with physiological factors, such as age when compared to 2D mitral inflow velocities. Fifty-three healthy volunteers underwent standard CMR, plus 4D flow acquisition. LV blood flow KE parameters demonstrated good reproducibility with mean coefficient of variation of 6 ± 2% and an accuracy of 99% with a precision of 97%. The LV blood flow KEiEDV E/A ratio demonstrated good association to the 2D mitral inflow E/A ratio (r = 0.77, P < 0.01), with both decreasing progressively with advancing age (P < 0.01). Furthermore, peak E-wave KEiEDV and A-wave KEiEDV displayed a stronger association to age than the corresponding 2D metrics, peak E-wave and A-wave velocity (r = −0.51 vs −0.17 and r = 0.65 vs 0.46). Peak E-wave KEiEDV decreases whilst peak A-wave KEiEDV increases with advancing age. This study presents values for various LV blood flow KE parameters in health, as well as demonstrating that they show stronger and independent correlations to age than standard diastolic metrics.
Micro-computed tomography and histology to explore internal morphology in decapod larvae
Authors: Castejón Diego , Alba-Tercedor Javier , Rotllant Guiomar , Ribes Enric , Durfort Mercè , Guerao Guillermo 
Published: September 2018

AbstractTraditionally, the internal morphology of crustacean larvae has been studied using destructive techniques such as dissection and microscopy. The present study combines advances in micro-computed tomography (micro-CT) and histology to study the internal morphology of decapod larvae, using the common spider crab (Maja brachydactylaBalss, 1922) as a model and resolving the individual limitations of these techniques. The synergy of micro-CT and histology allows the organs to be easily identified, revealing simultaneously the gross morphology (shape, size, and location) and histological organization (tissue arrangement and cell identification). Micro-CT shows mainly the exoskeleton, musculature, digestive and nervous systems, and secondarily the circulatory and respiratory systems, while histology distinguishes several cell types and confirms the organ identity. Micro-CT resolves a discrepancy in the literature regarding the nervous system of crab larvae. The major changes occur in the metamorphosis to the megalopa stage, specifically the formation of the gastric mill, the shortening of the abdominal nerve cord, the curving of the abdomen beneath the cephalothorax, and the development of functional pereiopods, pleopods, and lamellate gills. The combination of micro-CT and histology provides better results than either one alone.
Comparison of immunogenicity and vaccine efficacy between heat-shock proteins, HSP70 and GrpE, in the DnaK operon of Mycobacterium tuberculosis
Authors: Kim Woo Sik , Kim Jong-Seok , Kim Hong Min , Kwon Kee Woong , Eum Seok-Yong , Shin Sung Jae 
Published: September 2018

AbstractAntigens (Ags) in Mycobacterium tuberculosis (Mtb) that are constitutively expressed, overexpressed during growth, essential for survival, and highly conserved may be good vaccine targets if they induce the appropriate anti-Mtb Th1 immune response. In this context, stress response-related antigens of Mtb might serve as attractive targets for vaccine development as they are rapidly expressed and are up-regulated during Mtb infection in vivo. Our group recently demonstrated that GrpE, encoded by rv0351 as a cofactor of heat-shock protein 70 (HSP70) in the DnaK operon, is a novel immune activator that interacts with DCs to generate Th1-biased memory T cells in an antigen-specific manner. In this study, GrpE was evaluated as a subunit vaccine in comparison with the well-known HSP70 against the hyper-virulent Mtb Beijing K-strain. Both HSP70- and GrpE-specific effector/memory T cells expanded to a similar extent as those stimulated with ESAT-6 in the lung and spleen of Mtb-infected mice, but GrpE only produced a similar level of IFN-γ to that produced by ESAT-6 stimulation during the late phase and the early phase of Mtb K infection, indicating that GrpE is highly-well recognised by the host immune system as a T cell antigen. Mice immunised with the GrpE subunit vaccine displayed enhanced antigen-specific IFN-γ and serum IgG2c responses along with antigen-specific effector/memory T cell expansion in the lungs. In addition, GrpE-immunisation markedly induced multifunctional Th1-type CD4+ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs of Mtb K-infected mice, whereas HSP70-immunisation induced mixed Th1/Th2 immune responses. GrpE-immunisation conferred a more significant protective effect than that of HSP70-immunisation in terms of bacterial reduction and improved inflammation, accompanied by the remarkable persistence of GrpE-specific multifunctional CD4+ T cells. These results suggest that GrpE is an excellent vaccine antigen component for the development of a multi-antigenic Mtb subunit vaccine by generating Th1-biased memory T cells with multifunctional capacity, and confers durable protection against the highly virulent Mtb K.
ERK activating peptide, AES16-2M promotes wound healing through accelerating migration of keratinocytes
Authors: Lee Sora , Kim Myun Soo , Jung Su-Jin , Kim Daejin , Park Hyun Jeong , Cho Daeho 
Published: September 2018

AbstractWound healing is an important issue that influences quality of life, and the need for products associated with wound healing is growing annually. New materials and therapies for skin wounds are being continuously researched and developed in order to increase treatment efficacy. Here, we show that the peptide AES16-2M comprised of five short amino acid sequences (REGRT) demonstrates efficacy in wound healing. AES16-2M exerted more effective healing than the control in an acute wound model, and tissue regeneration was similar to that of normal tissue in AES16-2M-treated skin. We found that the increase in re-epithelialization by AES16-2M early in wound development was due to migration of keratinocytes; a scratch assay using a human keratinocyte cell line (HaCaT) also demonstrated effective wound closure by AES16-2M. The migration of keratinocytes effected by AES16-2M was promoted through ERK phosphorylation and blocked with U0126, an ERK inhibitor. Moreover, AES16-2M treatment stimulated human dermal fibroblast (HDF) migration as well as keratinocyte. Taken together, these results suggest that AES16-2M can be an effective therapeutic agent for wound healing by promoting migration of keratinocytes and fibroblasts via ERK phosphorylation.
Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate
Authors: Luu Maik , Weigand Katharina , Wedi Fatana , Breidenbend Carina , Leister Hanna , Pautz Sabine , Adhikary Till , Visekruna Alexander 
Published: September 2018

AbstractThe gut microbiota produces metabolites such as short-chain fatty acids (SCFAs) that regulate the energy homeostasis and impact on immune cell function of the host. Recently, innovative approaches based on the oral administration of SCFAs have been discussed for therapeutic modification of inflammatory immune responses in autoimmune diseases. So far, most studies have investigated the SCFA-mediated effects on CD4+ T cells and antigen presenting cells. Here we show that butyrate and, to a lesser degree, propionate directly modulate the gene expression of CD8+ cytotoxic T lymphocytes (CTLs) and Tc17 cells. Increased IFN-γ and granzyme B expression by CTLs as well as the molecular switch of Tc17 cells towards the CTL phenotype was mediated by butyrate independently of its interaction with specific SCFA-receptors GPR41 and GPR43. Our results indicate that butyrate strongly inhibited histone-deacetylases (HDACs) in CD8+ T cells thereby affecting the gene expression of effector molecules. Accordingly, the pan-HDAC inhibitors trichostatin A (TSA) and sodium valproate exerted similar influence on CD8+ T cells. Furthermore, higher acetate concentrations were also able to increase IFN-γ production in CD8+ T lymphocytes by modulating cellular metabolism and mTOR activity. These findings might have significant implications in adoptive immunotherapy of cancers and in anti-viral immunity.
Deletion of BmoR affects the expression of genes related to thiol/disulfide balance in Bacteroides fragilis
Authors: Teixeira Felipe L. , Pauer Heidi , Costa Scarlathe B. , Smith C. Jeffrey , Domingues Regina M. C. P. , Rocha Edson R. , Lobo Leandro A. 
Published: September 2018

AbstractBacteroides fragilis, an opportunistic pathogen and commensal bacterium in the gut, is one the most aerotolerant species among strict anaerobes. However, the mechanisms that control gene regulation in response to oxidative stress are not completely understood. In this study, we show that the MarR type regulator, BmoR, regulates the expression of genes involved in the homeostasis of intracellular redox state. Transcriptome analysis showed that absence of BmoR leads to altered expression in total of 167 genes. Sixteen of these genes had a 2-fold or greater change in their expression. Most of these genes are related to LPS biosynthesis and carbohydrates metabolism, but there was a significant increase in the expression of genes related to the redox balance inside the cell. A pyridine nucleotide-disulfide oxidoreductase located directly upstream of bmoR was shown to be repressed by direct binding of BmoR to the promoter region. The expression of two other genes, coding for a thiosulphate:quinone-oxidoreductase and a thioredoxin, are indirectly affected by bmoR mutation during oxygen exposure. Phenotypic assays showed that BmoR is important to maintain the thiol/disulfide balance in the cell, confirming its relevance to B. fragilis response to oxidative stress.
Three new species of Cucullanus (Nematoda: Cucullanidae) from marine fishes off New Caledonia, with a key to species of Cucullanus from Anguilliformes
Authors: Moravec František , Justine Jean-Lou 
Published: September 2018

Based on light and scanning electron microscopical studies of nematode specimens from the digestive tract of some rarely collected anguilliform and perciform fishes off New Caledonia, three new species of Cucullanus Müller, 1777 (Cucullanidae) are described: C. austropacificus n. sp. from the longfin African conger Conger cinereus (Congridae), C. gymnothoracis n. sp. from the lipspot moray Gymnothorax chilospilus (Muraenidae), and C. incognitus n. sp. from the seabream Dentex fourmanoiri (Sparidae). Cucullanus austropacificus n. sp. is characterized by the presence of cervical alae, ventral sucker, alate spicules 1.30–1.65 mm long, conspicuous outgrowths of the anterior and posterior cloacal lips and by elongate-oval eggs measuring 89–108 × 48–57 μm; C. gymnothoracis n. sp. is similar to the foregoing species, but differs from it in the absence of cervical alae and the posterior cloacal outgrowth, in the shape and size of the anterior cloacal outgrowth and somewhat shorter spicules 1.12 mm long; C. incognitus n. sp. (based on female morphology) differs from other congeneric species parasitic in the Sparidae mainly in possessing cervical alae, the postequatorial vulva, phasmids situated at the mid-length of the tail and in the size of the eggs (75–84 × 45–66 μm). A key to species of Cucullanus parasitizing anguilliform fishes is provided.
Comparing Schizophrenia Patients With a Predicted High/Low
Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A
Randomized-Controlled Study
Authors: Schennach Rebecca , Riedel Michael , Spellmann Ilja , Musil Richard , Obermeier Michael , Jäger Markus , Bottlender Roland , Schmauss Max , Laux Gerd , Möller Hans-Jürgen 
Published: September 2018

Abstract
Introduction The aim of this double-blind randomized study was to
evaluate the response to antipsychotic treatment in schizophrenia patients
with predicted high/low risk of nonresponse identified by applying a
set of well-established scales and predictors of outcome and to compare
efficacy between ziprasidone and haloperidol.
Methods One hundred twelve schizophrenia patients (ziprasidone:
n=54; haloperidol: n=58) were rated weekly on the Positive
and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment
of Functioning Scale (GAF), the Social and Occupational Functioning Scale
(SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale
(HAS).
Results Ninety-two patients (82%) were predicted to have a
high risk of nonresponse. No significant difference regarding PANSS
improvement in this subsample was found comparing ziprasidone and
haloperidol (p=0.563). Also, for the total patient sample, no
significant difference was found regarding the course of the PANSS total
score, GAF (p=0.921), and SOFAS (p=0.658) between
ziprasidone and haloperidol. Haloperidol resulted in higher scores on the
SAS (p=0.001) and HAS (p=0.011).
Discussion An alarmingly high number of patients were at high risk of
nonresponse to antipsychotic treatment.
Metastatic Phaeochromocytoma: Spinning Towards More Promising Treatment Options
Authors: Nölting Svenja , Grossman Ashley , Pacak Karel 
Published: September 2018

AbstractPhaeochromocytomas (PCC) and paragangliomas (PGL) are rare tumours arising from the chromaffin cells of the adrenal medulla (PCC) or the paraganglia located outside the adrenal gland (PGL). However, their incidence is likely to be underestimated; around 10% of all PCC/PGL are metastatic, with higher metastatic potential of PGLs compared to PCCs. If benign, surgery is the treatment of choice, but if metastatic, therapy is challenging. Here we review the currently existing therapy options for metastatic PCCs/PGLs including conventional chemotherapy (the original Averbuch scheme, but updated), radiopharmaceutical treatments (131I-MIBG, 90Y- and 177Lu-DOTATATE) and novel targeted therapies (anti-angiogenic tyrosine kinase inhibitors and mTORC1 inhibitors), emphasising future therapeutic approaches (HIF-2α and PARP inhibitors, temozolomide alone, metronomic temozolomide, somatostatin analogues) based on the oncogenic signalling pathways related to three different clusters comprising more than 20 well-characterised PCC/PGL susceptibility genes. We suggest that targeted combination therapies including repurposed agents may offer more effective future options worthy of exploration.
Pro-Angiogenic Effects of Latent Heparanase and Thrombin Receptor-Mediated Pathways—Do They Share a Common Ground in Melanoma Cells?
Authors: Hoß Sebastian , Grundmann Manuel , Benkel Tobias , Gockel Lukas , Schwarz Svenja , Kostenis Evi , Schlesinger Martin , Ilan Neta , Vlodavsky Israel , Bendas Gerd 
Published: September 2018

AbstractHeparanase (HPSE) is an endo-β-D-glucuronidase that cleaves heparan sulphate (HS) chains of proteoglycans (HSPGs). Besides a remodelling of the extracellular matrix, HPSE increases the bioavailability of pro-angiogenic mediators, such as HS-associated vascular endothelial growth factor (VEGF), thereby contributing to metastatic niche formation. Notably, HPSE also induces release of VEGF from tumour cells independent of its enzymatic activity, but the underlying molecular mechanisms remain unresolved. We found that exogenous addition of latent HPSE stimulates VEGF release from human MV3 melanoma cells. The same effect was noted upon direct stimulation of thrombin receptor (protease-activated receptor 1 [PAR-1]) by Thrombin Receptor Activator Peptide 6 (TRAP-6). The matricellular ligand cysteine-rich 61 protein (Cyr61) was identified as pathway component since Cyr61 knockdown in MV3 cells abolished the VEGF release by TRAP-6 and HPSE. Since both TRAP-6 and HPSE mediated an up-regulation of phosphorylated focal adhesion kinase, which could be blocked by antagonizing PAR-1, we postulated a crosstalk between latent HPSE and PAR-1 in promoting pro-angiogenic pathways. To test this hypothesis at a molecular level, we applied dynamic mass redistribution (DMR) technique measuring intracellular mass relocation as consequence of direct receptor activation. Indeed, latent HPSE evoked a concentration-dependent DMR signal in MV3 cells as TRAP-6 did. Both could be modulated by targeting G-protein receptor signalling in general or by the PAR-1 inhibitor RWJ 56110. Using cells devoid of cell surface HS synthesis, we could confirm HPSE effects on PAR-1, independent of HSPG involvement. These data indicate, for the first time, a crosstalk between latent HPSE, thrombin receptor activation and G-protein signalling in general.