bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation, phylogenetic relationship and spatial distribution of ‘Candidatus Phytoplasma ulmi’ strains in Germany
Authors: Schneider B. , Hüttel B. , Zübert C. , Kube M. 
Published: December 2020

AbstractA recent survey in Germany revealed the wide presence of ‘Candidatus Phytoplasma ulmi’ in native elm stands. Accessions were studied for their genetic variability and phylogenetic relationship based on the conserved groEL and the variable imp gene. While the groEL sequences revealed a high intraspecific homology of more than 99%, the homology of the imp gene dropped to 71% between distantly related sequences. Twenty-nine groEL and 74 imp genotypes were distinguished based on polymorphic sites. Phylogenetic analysis of the groEL gene clustered all ‘Ca. P. ulmi’ strains and separated them from related phytoplasmas of the 16SrV group. The inferred phylogeny of the imp gene resulted in a different tree topology and separated the ‘Ca. P. ulmi’ genotypes into two clusters, one closely related to the flavescence dorée phytoplasma strain FD-D (16SrV-D), the other affiliated with the flavescence dorée phytoplasma strains FD-C and FD70 and the alder yellows phytoplasma (16SrV-C). In both phylograms, ‘Ca. P. ulmi’ genotypes from Scots elm trees formed a coherent cluster, while genotypes from European white elms and field elms grouped less strictly. The regional distribution pattern was congruent for some of the groEL and imp genotypes, but a strict linkage for all genotypes was not apparent.
Tuning domain wall dynamics by shaping nanowires cross-sections
Authors: Altbir Dora , Fonseca Jakson M. , Chubykalo-Fesenko Oksana , Corona Rosa M. , Moreno Roberto , Carvalho-Santos Vagson L. , Ivanov Yurii P. 
Published: December 2020

AbstractThe understanding of the domain wall (DW) dynamics along magnetic nanowires is crucial for spintronic applications. In this work, we perform a detailed analysis of the transverse DW motion along nanowires with polygonal cross-sections. If the DW displaces under a magnetic field above the Walker limit, the oscillatory motion of the DW is observed. The amplitude, the frequency of oscillations, and the DW velocity depend on the number of sides of the nanowire cross-section, being the DW velocity in a wire with a triangular cross-section one order of magnitude larger than that in a circular nanowire. The decrease in the nanowire cross-section area yields a DW behavior similar to the one presented in a cylindrical nanowire, which is explained using an analytical model based on the general kinetic momentum theorem. Micromagnetic simulations reveal that the oscillatory behavior of the DW comes from energy changes due to deformations of the DW shape during the rotation around the nanowire.
Optoelectronic synapse using monolayer MoS2 field effect transistors
Authors: Islam Molla Manjurul , Dev Durjoy , Krishnaprasad Adithi , Tetard Laurene , Roy Tania 
Published: December 2020

AbstractOptical data sensing, processing and visual memory are fundamental requirements for artificial intelligence and robotics with autonomous navigation. Traditionally, imaging has been kept separate from the pattern recognition circuitry. Optoelectronic synapses hold the special potential of integrating these two fields into a single layer, where a single device can record optical data, convert it into a conductance state and store it for learning and pattern recognition, similar to the optic nerve in human eye. In this work, the trapping and de-trapping of photogenerated carriers in the MoS2/SiO2 interface of a n-channel MoS2 transistor was employed to emulate the optoelectronic synapse characteristics. The monolayer MoS2 field effect transistor (FET) exhibits photo-induced short-term and long-term potentiation, electrically driven long-term depression, paired pulse facilitation (PPF), spike time dependent plasticity, which are necessary synaptic characteristics. Moreover, the device’s ability to retain its conductance state can be modulated by the gate voltage, making the device behave as a photodetector for positive gate voltages and an optoelectronic synapse at negative gate voltages.
Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
Authors: Li Hongzhen , Chaitankar Vijender , Zhu Jianqiong , Chin Kyung , Liu Wenli , Pirooznia Mehdi , Rodgers Griffin P. 
Published: December 2020

AbstractOlfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4’s physiological functions in these cells have not been elucidated. Using single-cell RNA sequencing analysis, we found here that OLFM4 was expressed in multiple stem/progenitor-like cell populations in both the normal prostate epithelium and RWPE1 cells and was frequently co-expressed with KRT13 and LY6D in RWPE1 cells. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of the stem/progenitor-like cell population, shifts stem/progenitor-like cell division to favor symmetric division and differentiated into higher levels PSA expression cells in organoid assays compared with OLFM4-wild RWPE1 cells. Bulk-cell RNA sequencing analysis pinpointed that cMYC expression were enhanced in the OLFM4-knockout RWPE1 cells compared with OLFM4-wild cells. Molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature, as well as that of MYC target genes that regulate multiple biological processes, in OLFM4-knockout RWPE1 cells. These findings indicated that OLFM4 is co-expressed with multiple stem/progenitor cell marker genes in prostate epithelial cells and acts as a novel mediator in prostate stem/progenitor cell proliferation and differentiation.
Variation of the human mu-opioid receptor (OPRM1) gene predicts vulnerability to frustration
Authors: Daniel Alan M. , Rushing Brenda G. , Tapia Menchaca Karla Y. 
Published: December 2020

AbstractUnderstanding the emotional reaction to loss, or frustration, is a critical problem for the field of mental health. Animal models of loss have pointed to the opioid system as a nexus of frustration, physical pain, and substance abuse. However, few attempts have been made to connect the results of animal models of loss to human behavior. Allelic differences in the human mu opioid receptor gene, notably the A118G single nucleotide polymorphism, have been linked to individual differences in pain sensitivity, depressive symptoms, and reward processing. The present study explored the relationship between A118G and behavior in two frustrating tasks in humans. Results showed that carriers of the mutant G-allele were slower to recover behavior following a reward downshift and abandoned a frustrating task earlier than those without the mutation. Additionally, G-carriers were more sensitive to physical pain. These results highlight the overlap between frustration and pain, and suggest that genetic variation in opioid tone may contribute to individual differences in vulnerability and resilience following emotional disturbances.
Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women
Authors: Masala G. , Bendinelli B. , Della Bella C. , Assedi M. , Tapinassi S. , Ermini I. , Occhini D. , Castaldo M. , Saieva C. , Caini S. , D’Elios M. M. , Palli D. 
Published: December 2020

AbstractChronic low-grade inflammation plays a role in the pathogenesis of several chronic diseases including cancer. Physical activity (PA) and diet have been supposed to modulate inflammatory markers. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of pro-inflammatory cytokines, a secondary analysis in the DAMA factorial trial. The 234 study participants (healthy postmenopausal women with high breast density, 50–69 years, non smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Interleukins (IL)-1α, -1β, -6, tumor necrosis factor-α and C-reactive protein were measured at baseline and at the end of the intervention. Intention-to-treat-analyses were carried out using Tobit regression. Although all cytokines tended to increase over time, after 24 months women in the PA intervention (arms 2 + 3) showed lower levels of IL-1α (exp(β) = 0.66; p = 0.04) and IL-6 (exp(β) = 0.70; p = 0.01) in comparison with women in the control group (arms 1 + 4). No effects of the dietary intervention emerged. In healthy postmenopausal women with high breast density a moderate-intensity PA appears to slow the age-related increase of pro-inflammatory cytokines.
Fluorescent ligands for dopamine D2/D3 receptors
Authors: Allikalt Anni , Purkayastha Nirupam , Flad Khajidmaa , Schmidt Maximilian F. , Tabor Alina , Gmeiner Peter , Hübner Harald , Weikert Dorothee 
Published: December 2020

AbstractFluorescent ligands are versatile tools for the study of G protein-coupled receptors. Depending on the fluorophore, they can be used for a range of different applications, including fluorescence microscopy and bioluminescence or fluorescence resonance energy transfer (BRET or FRET) assays. Starting from phenylpiperazines and indanylamines, privileged scaffolds for dopamine D2-like receptors, we developed dansyl-labeled fluorescent ligands that are well accommodated in the binding pockets of D2and D3receptors. These receptors are the target proteins for the therapy for several neurologic and psychiatric disorders, including Parkinson’s disease and schizophrenia. The dansyl-labeled ligands exhibit binding affinities up to 0.44 nM and 0.29 nM at D2R and D3R, respectively. When the dansyl label was exchanged for sterically more demanding xanthene or cyanine dyes, fluorescent ligands 10a-c retained excellent binding properties and, as expected from their indanylamine pharmacophore, acted as agonists at D2R. While the Cy3B-labeled ligand 10b was used to visualize D2R and D3R on the surface of living cells by total internal reflection microscopy, ligand 10a comprising a rhodamine label showed excellent properties in a NanoBRET binding assay at D3R.
Radiologic imaging shows variable accuracy in diagnosing orbital inflammatory disease and assessing its activity
Authors: Lee Min Joung , Hamilton Bronwyn E. , Pettersson David , Ogle Kimberly , Murdock Jennifer , Dailey Roger A. , Ng John D. , Steele Eric A. , Verma Rohan , Planck Stephen R. , Martin Tammy M. , Choi Dongseok , Rosenbaum James T. 
Published: December 2020

AbstractRadiologic orbital imaging provides important information in the diagnosis and management of orbital inflammation. However, the diagnostic value of orbital imaging is not well elucidated. This study aimed to investigate the diagnostic accuracy of orbital imaging to diagnose orbital inflammatory diseases and its ability to detect active inflammation. We collected 75 scans of 52 patients (49 computed tomography (CT) scans; 26 magnetic resonance (MR) imaging scans). Clinical diagnoses included thyroid eye disease (TED) (41 scans, 31 patients), non-specific orbital inflammation (NSOI) (22 scans, 14 patients), sarcoidosis (4 scans, 3 patients), IgG4-related ophthalmic disease (IgG4-ROD) (5 scans, 3 patients), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient). Two experienced neuroradiologists interpreted the scans, offered a most likely diagnosis, and assessed the activity of inflammation, blinded to clinical findings. The accuracy rate of radiological diagnosis compared to each clinical diagnosis was evaluated. Sensitivity and specificity in detecting active inflammation were analyzed for TED and NSOI. The accuracy rate of radiologic diagnosis was 80.0% for IgG4-ROD, 77.3% for NSOI, and 73.2% for TED. Orbital imaging could not diagnose sarcoidosis. Orbital CT had a sensitivity of 50.0% and a specificity of 75.0% to predict active TED using clinical assessment as the gold standard. The sensitivity/specificity of orbital MR was 83.3/16.7% for the detection of active NSOI. In conclusion, orbital imaging is accurate for the diagnosis of IgG4, NSOI, and TED. Further studies with a large number of cases are needed to confirm this finding, especially with regard to uncommon diseases. Orbital CT showed moderate sensitivity and good specificity for identifying active TED.
Gravettian cranial morphology and human group affinities during the European Upper Palaeolithic
Authors: Mounier Aurélien , Heuzé Yann , Samsel Mathilde , Vasilyev Sergey , Klaric Laurent , Villotte Sébastien 
Published: December 2020

AbstractArchaeologically defined Upper Palaeolithic (UP, 45,000–10,000 years ago) “cultures” are often used as proxies to designate fossil populations. While recent genomic studies have partly clarified the complex relationship between European UP “cultures” and past population dynamics, they leave open numerous questions regarding the biological characterization of these human groups, especially regarding the Mid-UP period (MUP, 33,000–24,000 years ago), which encompasses a pan-European cultural mosaic (Gravettian) with several regional facies. Here, we analyse a large database of well-dated and well-preserved UP crania, including MUP specimens from South-West France (SWF) and Moravia, using 3D geometric morphometrics to test for human group affinities. Our results show that the Gravettian makers from these two regions form a remarkably phenetically homogeneous sample which is different from, and more homogeneous than, the Late UP sample. Those results are congruent with genomic studies indicating a genetic continuity within the Gravettian manufacturers and a discontinuity marked by the Last Glacial Maximum (LGM). Moreover, our study expands the geographical range of the MUP phenetic continuity to SWF, for which aDNA data are scarce, and clarifies the post-LGM European population structure in SWF, with a possible dual ancestry stemming from different LGM refugia.
Two-color in-resin CLEM of Epon-embedded cells using osmium resistant green and red fluorescent proteins
Authors: Tanida Isei , Furuta Yoko , Yamaguchi Junji , Kakuta Soichiro , Oliva Trejo Juan Alejandro , Uchiyama Yasuo 
Published: December 2020

AbstractIn-resin CLEM of Epon embedded samples can greatly simplify the correlation of fluorescent images with electron micrographs. The usefulness of this technique is limited at present by the low number of fluorescent proteins that resist CLEM processing. Additionally, no study has reported the possibility of two-color in-resin CLEM of Epon embedded cells. In this study, we screened for monomeric green and red fluorescent proteins that resist CLEM processing. We identified mWasabi, CoGFP variant 0, and mCherry2; two green and one red fluorescent proteins as alternatives for in-resin CLEM. We expressed mitochondria-localized mCherry2 and histone H2B tagged with CoGFP variant 0 in cells. Green and red fluorescence was detected in 100 nm-thin sections of the Epon-embedded cells. In the same thin sections, we correlated the fluorescent signals to mitochondria and the nucleus using a scanning electron microscope. Similar results were obtained when endoplasmic reticulum-localized mCherry2 and histone H2B tagged with CoGFP variant 0 were expressed in the cells. Two-color in-resin CLEM of two cytoplasmic organelles, mitochondria and endoplasmic reticulum, was also achieved using mitochondria-localized mCherry2 and endoplasmic reticulum-localized mWasabi. In summary, we report three new fluorescent protein-alternatives suitable for in-resin CLEM of Epon-embedded samples, and achieved Epon-based two-color in-resin CLEM.
Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression
Authors: Sengupta Debmalya , Bhattacharya Gairika , Ganguli Sayak , Sengupta Mainak 
Published: December 2020

AbstractThe cognate interaction of ROBO1/4 with its ligand SLIT2 is known to be involved in lung cancer progression. However, the precise role of genetic variants, disrupting the molecular interactions is less understood. All cancer-associated missense variants of ROBO1/4 and SLIT2 from COSMIC were screened for their pathogenicity. Homology modelling was done in Modeller 9.17, followed by molecular simulation in GROMACS. Rigid docking was performed for the cognate partners in PatchDock with refinement in HADDOCK server. Post-docking alterations in conformational, stoichiometric, as well as structural parameters, were assessed. The disruptive variants were ranked using a weighted scoring scheme. In silico prioritisation of 825 variants revealed 379 to be potentially pathogenic out of which, about 12% of the variants, i.e. ROBO1 (14), ROBO4 (8), and SLIT2 (23) altered the cognate docking. Six variants of ROBO1 and 5 variants of ROBO4 were identified as "high disruptors" of interactions with SLIT2 wild type. Likewise, 17 and 13 variants of SLIT2 were found to be "high disruptors" of its interaction with ROBO1 and ROBO4, respectively. Our study is the first report on the impact of cancer-associated missense variants on ROBO1/4 and SLIT2 interactions that might be the drivers of lung cancer progression.
A highly sensitive method for the detection of recombinant PERV-A/C env RNA using next generation sequencing technologies
Authors: Kono Ken , Kataoka Kiyoko , Yuan Yuzhe , Yusa Keisuke , Uchida Kazuhisa , Sato Yoji 
Published: December 2020

AbstractSeveral xenogenic cell-based therapeutic products are currently under development around the world for the treatment of human diseases. Porcine islet cell products for treating human diabetes are a typical example. Since porcine cells possess endogenous retrovirus (PERV), which can replicate in human cells in vitro, the potential transmission of PERV has raised concerns in the development of these products. Four subgroups of infectious PERV have been identified, namely PERV-A, -B, -C, and recombinant PERV-A/C. Among them, PERV-A/C shows a high titre and there was a paper reported that an incidence of PERV-A/C viremia was increased in diseased pigs; thus, it would be important to monitor the emergence of PERV-A/C after transplantation of porcine products. In this study, we developed a highly sensitive method for the detection of PERV-A/C using next generation sequencing (NGS) technologies. A model PERV-C spiked with various doses of PERV-A/C were amplified by RT-PCR and the amplicons were analysed by NGS. We found that the NGS analysis allowed the detection of PERV-A/C at the abundance ratios of 1% and 0.1% with true positive rates of 100% and 57%, respectively, indicating that it would be useful for the rapid detection of PERV-A/C emergence after transplantation of porcine products.
Cisplatin induced neurotoxicity is mediated by Sarm1 and calpain activation
Authors: Cetinkaya-Fisgin Aysel , Luan Xinghua , Reed Nicole , Jeong Ye Eun , Oh Byoung Chol , Hoke Ahmet 
Published: December 2020

AbstractCisplatin is a commonly used chemotherapy agent with significant dose-limiting neurotoxicity resulting in peripheral neuropathy. Although it is postulated that formation of DNA-platinum adducts is responsible for both its cytotoxicity in cancer cells and side effects in neurons, downstream mechanisms that lead to distal axonal degeneration are unknown. Here we show that activation of calpains is required for both neurotoxicity and formation of DNA-platinum adduct formation in neurons but not in cancer cells. Furthermore, we show that neurotoxicity of cisplatin requires activation of Sarm1, a key regulator of Wallerian degeneration, as mice lacking the Sarm1 gene do not develop peripheral neuropathy as evaluated by both behavioral or pathological measures. These findings indicate that Sarm1 and/or specific calpain inhibitors could be developed to prevent cisplatin induced peripheral neuropathy.
Efficacy of abdominal trunk muscles-strengthening exercise using an innovative device in treating chronic low back pain: a controlled clinical trial
Authors: Kitagawa Ryo , Kato Satoshi , Demura Satoru , Kurokawa Yuki , Shinmura Kazuya , Yokogawa Noriaki , Yonezawa Noritaka , Shimizu Takaki , Oku Norihiro , Handa Makoto , Annen Ryohei , Tsuchiya Hiroyuki 
Published: December 2020

AbstractExercise is the most common conservative intervention for chronic low back pain (CLBP). We have developed an innovative exercise device for the abdominal trunk muscles that also measures muscle strength in a sitting position. The device, which is easy for patients with CLBP to use, allows for lumbar stabilization exercise under pressure. This study aimed to examine the efficacy of abdominal trunk muscle strengthening using the device in improving CLBP. We conducted a two-group non-randomized controlled clinical trial. CLBP patients were allocated into two groups. The strengthening group underwent a 12-week exercise program that included abdominal trunk muscle strengthening using our device and stretching exercises, while the control group received a 12-week stretching exercise program. The outcome measures included the improvement of the abdominal trunk muscle strength measured by the device, pain intensity of CLBP, physical function, and quality of life (QOL). A total of 40 participants (20 in each group) were analyzed. The strengthening group showed better improvement in the abdominal trunk muscle strength, CLBP, physical function, and QOL than in the control group. In conclusion, the strengthening exercise using the device with easy stretching was effective in improving the strength of the abdominal trunk muscles, pain intensity of CLBP, physical function, and QOL.
Serum metabolites as biomarkers in systemic sclerosis-associated interstitial lung disease
Authors: Meier C. , Freiburghaus K. , Bovet C. , Schniering J. , Allanore Y. , Distler O. , Nakas C. , Maurer B. 
Published: December 2020

AbstractSystemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death. While targeted therapies are emerging, biomarkers for sub-stratifying patients based on individual profiles are lacking. Herein, we investigated how levels of serum metabolites correlated with different stages of SSc and SSc-ILD. Serum samples of patients with SSc without ILD, stable and progressive SSc-ILD as well as of healthy controls (HC) were analysed using liquid targeted tandem mass spectrometry. The best discriminating profile consisted of 4 amino acids (AA) and 3 purine metabolites. l-tyrosine, l-tryptophan, and 1-methyl-adenosine distinguished HC from SSc patients. l-leucine, l-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. In SSc-ILD, both, l-leucine and xanthosine negatively correlated with changes in FVC% predicted. Additionally, xanthosine was negatively correlated with changes in DLco% predicted and positively with the prognostic GAP index. Validation of l-leucine and l-isoleucine by an enzymatic assay confirmed both the sub-stratification of SSc-ILD patients and correlation with lung function and prognosis score. Serum metabolites may have potential as biomarkers for discriminating SSc patients based on the presence and severity of ILD. Confirmation in larger cohorts will be needed to appreciate their value for routine clinical care.