bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronatine is more potent than jasmonates in regulating Arabidopsis circadian clock
Authors: Gao Min , Zhang Chong , Lu Hua 
Published: July 2020

AbstractRecent studies establish a crucial role of the circadian clock in regulating plant defense against pathogens. Whether pathogens modulate host circadian clock as a potential strategy to suppress host innate immunity is not well understood. Coronatine is a toxin produced by the bacterial pathogen Pseudomonas syringae that is known to counteract Arabidopsis defense through mimicking defense signaling molecules, jasmonates (JAs). We report here that COR preferentially suppresses expression of clock-related genes in high throughput gene expression studies, compared with the plant-derived JA molecule methyl jasmonate (MJ). COR treatment dampens the amplitude and lengthens the period of all four reporters tested while MJ and another JA agonist JA-isoleucine (JA-Ile) only affect some reporters. COR, MJ, and JA-Ile act through the canonical JA receptor COI1 in clock regulation. These data support a stronger role of the pathogen-derived molecule COR than plant-derived JA molecules in regulating Arabidopsis clock. Further study shall reveal mechanisms underlying COR regulation of host circadian clock.
Parallel residual projection: a new paradigm for solving linear inverse problems
Authors: Miao Wei , Narayanan Vignesh , Li Jr-Shin 
Published: July 2020

AbstractA grand challenge to solve a large-scale linear inverse problem (LIP) is to retain computational efficiency and accuracy regardless of the growth of the problem size. Despite the plenitude of methods available for solving LIPs, various challenges have emerged in recent times due to the sheer volume of data, inadequate computational resources to handle an oversized problem, security and privacy concerns, and the interest in the associated incremental or decremental problems. Removing these barriers requires a holistic upgrade of the existing methods to be computationally efficient, tractable, and equipped with scalable features. We, therefore, develop the parallel residual projection (PRP), a parallel computational framework involving the decomposition of a large-scale LIP into sub-problems of low complexity and the fusion of the sub-problem solutions to form the solution to the original LIP. We analyze the convergence properties of the PRP and accentuate its benefits through its application to complex problems of network inference and gravimetric survey. We show that any existing algorithm for solving an LIP can be integrated into the PRP framework and used to solve the sub-problems while handling the prevailing challenges.
In vitro selection for adhesion of Plasmodium falciparum-infected erythrocytes to ABO antigens does not affect PfEMP1 and RIFIN expression
Authors: van der Puije William , Wang Christian W. , Sudharson Srinidhi , Hempel Casper , Olsen Rebecca W. , Dalgaard Nanna , Ofori Michael F. , Hviid Lars , Kurtzhals Jørgen A. L. , Staalsoe Trine 
Published: July 2020

AbstractPlasmodium falciparum causes the most severe form of malaria in humans. The adhesion of the infected erythrocytes (IEs) to endothelial receptors (sequestration) and to uninfected erythrocytes (rosetting) are considered major elements in the pathogenesis of the disease. Both sequestration and rosetting appear to involve particular members of several IE variant surface antigens (VSAs) as ligands, interacting with multiple vascular host receptors, including the ABO blood group antigens. In this study, we subjected genetically distinct P. falciparum parasites to in vitro selection for increased IE adhesion to ABO antigens in the absence of potentially confounding receptors. The selection resulted in IEs that adhered stronger to pure ABO antigens, to erythrocytes, and to various human cell lines than their unselected counterparts. However, selection did not result in marked qualitative changes in transcript levels of the genes encoding the best-described VSA families, PfEMP1 and RIFIN. Rather, overall transcription of both gene families tended to decline following selection. Furthermore, selection-induced increases in the adhesion to ABO occurred in the absence of marked changes in immune IgG recognition of IE surface antigens, generally assumed to target mainly VSAs. Our study sheds new light on our understanding of the processes and molecules involved in IE sequestration and rosetting.
System wide channel network analysis reveals hotspots of morphological change in anthropogenically modified regions of the Ganges Delta
Authors: Jarriel Teresa , Isikdogan Leo F. , Bovik Alan , Passalacqua Paola 
Published: July 2020

AbstractThe Ganges Brahmaputra Meghna Delta (GBMD) is a large and complex coastal system whose channel network is vulnerable to morphological changes caused by sea level rise, subsidence, anthropogenic modifications, and changes to water and sediment loads. Locating and characterizing change is particularly challenging because of the wide range of forcings acting on the GBMD and because of the large range of scales over which these forcings act. In this study, we examine the spatial variability of change in the GBMD channel network. We quantify the relative magnitudes and directions of change across multiple scales and relate the spatial distribution of change to the spatial distribution of a variety of known system forcings. We quantify how the channelization varies by computing the Channelized Response Variance (CRV) on 30 years of remotely sensed imagery of the entire delta extent. The CRV analysis reveals hotspots of morphological change across the delta. We find that the magnitude of these hotspots are related to the spatial distribution of the dominant physiographic forcings in the system (tidal and fluvial influence levels, channel connectivity, and anthropogenic interference levels). We find that the anthropogenically modified embanked regions have much higher levels of geomorphic change than the adjacent natural Sundarban forest and that this change is primarily due to channel infilling and increased rates of channel migration. Having a better understanding of how anthropogenic changes affect delta channel networks over human timescales will help to inform policy decisions affecting the human and ecological presences on deltas around the world.
Congruent geographic variation in saccular otolith shape across multiple species of African cichlids
Authors: Bose Aneesh P. H. , Zimmermann Holger , Winkler Georg , Kaufmann Alexandra , Strohmeier Thomas , Koblmüller Stephan , Sefc Kristina M. 
Published: July 2020

AbstractThe otoliths of teleost fishes exhibit a great deal of inter- and intra-species shape variation. The ecomorphology of the saccular otolith is often studied by comparing its shape across species and populations inhabiting a range of environments. However, formal tests are often lacking to examine how closely variation in otolith shape follows the genetic drift of a neutral trait. Here, we examine patterns of saccular otolith shape variation in four species of African cichlid fishes, each sampled from three field sites. All four species showed the greatest level of otolith shape variation along two principal component axes, one pertaining to otolith height and another to the prominence of an anterior notch. Fish collected from the same site possessed similarities in saccular otolith shape relative to fish from other sites, and these ‘site-difference’ signatures were consistent across species and observable in both sexes. Sex-differences in saccular otolith shape differed in magnitude from site to site. Population differences in saccular otolith shape did not covary with neutral genetic differentiation between those populations. Otolith height, in particular, displayed large site similarities across species, weak correlation with neutral genetic variation, and strong sex differences, collectively suggesting that otolith shape represents a selectively non-neutral trait.
Fluorescence-assisted sequential insertion of transgenes (FASIT): an approach for increasing specific productivity in mammalian cells
Authors: Bravo Felipe E. , Parra Natalie C. , Camacho Frank , Acosta Jannel , González Alaín , Toledo Jorge R. , Sanchez Oliberto 
Published: July 2020

AbstractCurrently, the generation of cell lines for the production of recombinant proteins has the limitation of unstable gene expression due to the repeat-induced gene silencing or the loss of transgene copies resulting from recombination events. In this work, we developed a new strategy based on the sequential insertion of transgenes for generating stable clones producing high levels of a chimeric human follicle-stimulating hormone (hscFSH). Gene insertion was done by transducing HEK-293 cells with a lentiviral vector containing a bicistronic transcriptional unit for expressing hscFSH and GFP genes. Clone selection was performed by flow cytometry coupled to cell sorting, and the GFP gene was further removed by CRE-mediated site-specific recombination. High-producing clones of hscFSH were obtained after three rounds of lentiviral transduction. Expression levels increased in a step-wise manner from 7 to 23 pg/cell/day, with a relatively constant rate of 7 pg/cell/day in each round of transduction. The GFP gene was successfully removed from the cell genome without disturbing the hscFSH gene expression. Clones generated using this approach showed stable expression levels for more than two years. This is the first report describing the sequential insertion of transgenes as an alternative for increasing the expression levels of transformed cell lines. The methodology described here could notably impact on biotechnological industry by improving the capacity of mammalian cells to produce biopharmaceuticals.
Check point to get adequate weight loss within 6-months after laparoscopic sleeve gastrectomy for morbid obesity in Asian population
Authors: Chen Chung-Yen , Lee Cheng-Hung , Lee Hui-Ming , Yin Wen-Yao , Chin Wei-Leng , Lee Ming-Hsien , Chen Jian-Han 
Published: July 2020

AbstractPurpose of this study is to develope a scoring system to predict the likelihood of excess body weight loss (EBWL) ≥ 50% 6-months after laparoscopic sleeve gastrectomy (LSG). From April 2016 to September 2018, data was collected from 160 patients (BMI ≥ 32) who underwent primary LSG with at least 6-months follow-up. They were separated into score generation (operated by one surgeon, n = 122) and validation groups (operated by 3 different surgeons, n = 38). EBWL at 6-months ≥ 50% was considered adequate weight loss. Independent variables including age, gender, initial body mass index (BMI), comorbidities, life-style habits, percentage of EBWL and percentage of total body weight loss at 1-week, 1-month, and 3-months were analyzed with mutivariate logistic regression to generate the scoring system. The system was applied to internal and external validation groups to determine efficacy. As results, between the score generation and internal validation groups, the only significant difference in patient characteristics was in exercise participation. EBWL at 1-month > 19.5% (1 point) and EBWL at 3-months > 37.7% (2 points) were identified as independent factors to predict EBWL at 6-months ≥ 50%. When scores were > 1, the system had 94.03% positive predictive value (PPV) and 81.82% negative predictive value (NPV) (AUC: 0.923). Internal validation scores > 1 had a 95.83% PPV and 85.71% NPV (AUC: 0.975). External validation results showed 88.59% PPV and 72.00% NPV (AUC: 0.802). We concluded that this scoring system provides a reliable, objective prediction of EBWL at 6-months ≥ 50%. Patients requiring more aggressive clinical follow-up and intervention can be detected as early as 1- to 3-months after LSG.
Long-term administration of recombinant canstatin prevents adverse cardiac remodeling after myocardial infarction
Authors: Sugiyama Akira , Ito Rumi , Okada Muneyoshi , Yamawaki Hideyuki 
Published: July 2020

AbstractMyocardial infarction (MI) still remains a leading cause of mortality throughout the world. An adverse cardiac remodeling, such as hypertrophy and fibrosis, in non-infarcted area leads to uncompensated heart failure with cardiac dysfunction. We previously demonstrated that canstatin, a C-terminus fragment of type IV collagen α2 chain, exerted anti-remodeling effect against isoproterenol-induced cardiac hypertrophy model rats. In the present study, we examined whether a long-term administration of recombinant canstatin exhibits a cardioprotective effect against the adverse cardiac remodeling in MI model rats. Left anterior descending artery of male Wistar rats was ligated and recombinant mouse canstatin (20 μg/kg/day) was intraperitoneally injected for 28 days. Long-term administration of canstatin improved survival rate and significantly inhibited left ventricular dilatation and dysfunction after MI. Canstatin significantly inhibited scar thinning in the infarcted area and significantly suppressed cardiac hypertrophy, nuclear translocation of nuclear factor of activated T-cells, interstitial fibrosis and increase of myofibroblasts in the non-infarcted area. Canstatin significantly inhibited transforming growth factor-β1-induced differentiation of rat cardiac fibroblasts into myofibroblasts. The present study for the first time demonstrated that long-term administration of recombinant canstatin exerts cardioprotective effects against adverse cardiac remodeling in MI model rats.
Isoform-specific characterization of class I histone deacetylases and their therapeutic modulation in pulmonary hypertension
Authors: Chelladurai Prakash , Dabral Swati , Basineni Sobha Rani , Chen Chien-Nien , Schmoranzer Mario , Bender Nina , Feld Christine , Nötzold René Reiner , Dobreva Gergana , Wilhelm Jochen , Jungblut Benno , Zhao Lan , Bauer Uta-Maria , Seeger Werner , Pullamsetti Soni Savai 
Published: July 2020

AbstractPharmacological modulation of class I histone deacetylases (HDAC) has been evaluated as a therapeutic strategy for pulmonary hypertension (PH) in experimental models of PH. However, information of their expression, regulation and transcriptional targets in human PH and the therapeutic potential of isoform-selective enzyme modulation are lacking. Comprehensive analysis of expression and regulation of class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC8) was performed in cardiopulmonary tissues and adventitial fibroblasts isolated from pulmonary arteries (PAAF) of idiopathic pulmonary arterial hypertension (IPAH) patients and healthy donors. Cellular functions and transcriptional targets of HDAC enzymes were investigated. Therapeutic effects of pan-HDAC (Vorinostat), class-selective (VPA) and isoform-selective (CAY10398, Romidepsin, PCI34051) HDAC inhibitors were evaluated ex vivo (IPAH-PAAF, IPAH-PASMC) and in vivo (rat chronic hypoxia-induced PH and zebrafish angiogenesis). Our screening identifies dysregulation of class I HDAC isoforms in IPAH. Particularly, HDAC1 and HDAC8 were consistently increased in IPAH-PAs and IPAH-PAAFs, whereas HDAC2 and HDAC8 showed predominant localization with ACTA2-expressing cells in extensively remodeled IPAH-PAs. Hypoxia not only significantly modulated protein levels of deacetylase (HDAC8), but also significantly caused dynamic changes in the global histone lysine acetylation levels (H3K4ac, H3K9/K14ac and H3K27ac). Importantly, isoform-specific RNA-interference revealed that HDAC isoforms regulate distinct subset of transcriptome in IPAH-PAAFs. Reduced transcript levels of KLF2 in IPAH-PAAFs was augmented by HDAC8 siRNA and HDAC inhibitors, which also attenuated IPAH-associated hyperproliferation and apoptosis-resistance ex vivo, and mitigated chronic hypoxia-induced established PH in vivo, at variable degree. Class I HDAC isoforms are significantly dysregulated in human PAH. Isoform-selective HDAC inhibition is a viable approach to circumvent off-target effects.
Clinical and neuroimaging factors associated with aphasia severity in stroke patients: diffusion tensor imaging study
Authors: Lee Sekwang , Na Yoonhye , Tae Woo-Suk , Pyun Sung-Bom 
Published: July 2020

AbstractThis study investigated factors associated with aphasia severity at both 2 weeks and 3 months after stroke using demographic and clinical variables, brain diffusion tensor imaging (DTI) parameters, and lesion volume measurements. Patients with left hemisphere stroke were assessed at 2 weeks (n = 68) and at 3 months (n = 20) after stroke. Demographic, clinical, and neuroimaging data were collected; language functions were assessed using the Western Aphasia Battery. For neuroimaging, DTI parameters, including the laterality index (LI) of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, mean diffusivity and fibre density (FD) of the arcuate fasciculus (AF), and lesion volume, were measured. Lesion volume, cortical involvement, and the National Institutes of Health Stroke Scale score significantly predicted aphasia severity at 2 weeks after stroke, whereas the aphasia quotient and presence of depression during the early subacute stage were significant predictors at 3 months after stroke. According to Pearson correlation, LI-AD and LI-FD were significantly correlated with the aphasia quotient 2 weeks after ischaemic stroke, and the LI-FA was significantly correlated with the aphasia quotient 2 weeks after haemorrhagic stroke, suggesting that the extent and mechanism of AF injuries differ between ischaemic and haemorrhagic strokes. These differences may contribute to aphasia severity.
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization
Authors: Dominguez-Meijide Antonio , Vasili Eftychia , König Annekatrin , Cima-Omori Maria-Sol , Ibáñez de Opakua Alain , Leonov Andrei , Ryazanov Sergey , Zweckstetter Markus , Griesinger Christian , Outeiro Tiago F. 
Published: July 2020

AbstractParkinson's disease (PD) and Alzheimer's disease (AD) are common neurodegenerative disorders of the elderly and, therefore, affect a growing number of patients worldwide. Both diseases share, as a common hallmark, the accumulation of characteristic protein aggregates, known as Lewy bodies (LB) in PD, and neurofibrillary tangles in AD. LBs are primarily composed of misfolded α-synuclein (aSyn), and neurofibrillary tangles are primarily composed of tau protein. Importantly, upon pathological evaluation, most AD and PD/Lewy body dementia cases exhibit mixed pathology, with the co-occurrence of both LB and neurofibrillary tangles, among other protein inclusions. Recent studies suggest that both aSyn and tau pathology can spread and propagate through neuronal connections. Therefore, it is important to investigate the mechanisms underlying aggregation and propagation of these proteins for the development of novel therapeutic strategies. Here, we assessed the effects of different pharmacological interventions on the aggregation and internalization of tau and aSyn. We found that anle138b and fulvic acid decrease aSyn and tau aggregation, that epigallocatechin gallate decreases aSyn aggregation, and that dynasore reduces tau internalization. Establishing the effects of small molecules with different chemical properties on the aggregation and spreading of aSyn and tau will be important for the development of future therapeutic interventions.
Successful mating and hybridisation in two closely related flatworm species despite significant differences in reproductive morphology and behaviour
Authors: Singh Pragya , Ballmer Daniel N. , Laubscher Max , Schärer Lukas 
Published: July 2020

AbstractReproductive traits are some of the fastest diverging characters and can serve as reproductive barriers. The free-living flatworm Macrostomum lignano, and its congener M. janickei are closely related, but differ substantially in their male intromittent organ (stylet) morphology. Here, we examine whether these morphological differences are accompanied by differences in behavioural traits, and whether these could represent barriers to successful mating and hybridization between the two species. Our data shows that the two species differ in many aspects of their mating behaviour. Despite these differences, the species mate readily with each other in heterospecific pairings. Although both species have similar fecundity in conspecific pairings, the heterospecific pairings revealed clear postmating barriers, as few heterospecific pairings produced F1 hybrids. These hybrids had a stylet morphology that was intermediate between that of the parental species, and they were fertile. Finally, using a mate choice experiment, we show that the nearly two-fold higher mating rate of M. lignano caused it to mate more with conspecifics, leading to assortative mating, while M. janickei ended up mating more with heterospecifics. Thus, while the two species can hybridize, the mating rate differences could possibly lead to higher fitness costs for M. janickei compared to M. lignano.
Postmarketing safety surveillance data reveals antidepressant effects of botulinum toxin across various indications and injection sites
Authors: Makunts Tigran , Wollmer Marc Axel , Abagyan Ruben 
Published: July 2020

AbstractThe World Health Organization estimates the number of people suffering from depression to be over 264 million. Current monoamine transmission modulating therapeutics, even with proper adherence and acceptable tolerability, are not effective for nearly one third of the patients, leading clinicians to explore other therapeutic options such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine infusions, and, more recently, glabellar botulinum toxin, BoNT, injections. The scale and mechanism of antidepressant action of BoNT is unclear and maybe hypothetically attributed to the disruption of proprioceptive facial feedback reinforcing negative emotions. Here we verify the antidepressant effect of botulinum toxin by analysis of over 40 thousand BoNT treatment reports out of thirteen million postmarketing safety reports in the FDA Adverse Event Reporting System, FAERS. The results of the analysis indicate that patients who received BoNT injections to treat hyperhidrosis, facial wrinkles, migraine prophylaxis, spasticity, and spasms, had a significantly lower number of depression reports when compared to patients undergoing different treatments for the same conditions. These findings suggest that the antidepressant effect of BoNT is significant, and, surprisingly, is observed for a broad range of injection sites.
Mismatch negativity indices and functional outcomes in unipolar and bipolar depression
Authors: Kim Sungkean , Baek Ji Hyun , Shim Se-hoon , Kwon Young Joon , Lee Hwa Young , Yoo Jae Hyun , Kim Ji Sun 
Published: July 2020

AbstractThe aim of the study was to explore the association between functional outcomes and mismatch negativity (MMN) activity in participants with mood disorders. The study participants were 27 subjects with major depressive disorder (MDD), 29 subjects with bipolar disorder (BD), and 33 healthy controls who performed a passive auditory oddball paradigm while electroencephalography (EEG) was recorded. Peak amplitudes and source activity of the MMN were compared across groups. Mood and anxiety symptoms were evaluated. The functional levels were the lowest in the BD group, followed by the MDD and healthy control groups. The subjects with BD had significantly lower MMN amplitudes at the frontal and frontocentral electrodes than the healthy controls. The source activity of the MMN from the left anterior cingulate cortex, inferior frontal gyrus, and middle frontal gyrus was significantly increased in the BD group compared to the MDD group. Significant correlations were detected between the functional outcomes and MMN amplitudes at frontal and frontocentral sites. The functional outcome was significantly correlated with left frontal regions. In conclusion, MMN activity appears to be a promising candidate as an evaluation tool for functional outcomes in mood disorders.