bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel method for clarifying faster interstitial flow in the intimal side of the aorta under intraluminal pressurization
Authors: Fukui Wataru , Yoshihiro Ujihara , Nakamura Masanori , Sugita Shukei 
Published: July 2021

AbstractHypertension causes aortic thickening, especially on the intimal side. Although the production of the extracellular matrix is observed, the type of mechanical stress that produces this response remains unclear. In this study, we hypothesize that the interstitial flow causes the thickening. To validate this claim, we proposed a novel method to measure the velocity distribution in the radial direction in the aorta, which has been unclear. A fluorescent dye was introduced in the lumen of the mouse thoracic aorta ex vivo, intraluminal pressure was applied, and a time-lapse image in the radial-circumferential plane was acquired under a two-photon microscope. The flow of the fluorescent dye from the intimal to the adventitial sides in the aorta was successfully observed. The acquired image was converted to a radial-time image (i.e., kymograph), and the flow velocity was quantified by applying the one-dimensional advection-diffusion equation to the fluorescent images. The results revealed a higher interstitial flow velocity in the aortic walls under higher intraluminal pressure and a higher velocity on the more intimal side. Thus, the interstitial flow is a candidate for the mechanical stress causing hyperplasia of the aorta under hypertension.
Tn5 transposase-based epigenomic profiling methods are prone to open chromatin bias
Authors: Wang Meng , Zhang Yi 
Published: July 2021

AbstractEpigenetic studies of rare biological samples like mammalian oocytes and preimplantation embryos require low input or even single cell epigenomic profiling methods. To reduce sample loss and avoid inefficient immunoprecipitation, several chromatin immuno-cleavage-based methods using Tn5 transposase fused with Protein A/G have been developed to profile histone modifications and transcription factor bindings using small number of cells. The Tn5 transposase-based epigenomic profiling methods are featured with simple library construction steps in the same tube, by taking advantage of Tn5 transposase’s capability of simultaneous DNA fragmentation and adaptor ligation. However, the Tn5 transposase prefers to cut open chromatin regions. Our comparative analysis shows that Tn5 transposase-based profiling methods are prone to open chromatin bias. The high false positive signals due to biased cleavage in open chromatin could cause misinterpretation of signal distributions and dynamics. Rigorous validation is needed when employing and interpreting results from Tn5 transposase-based epigenomic profiling methods.
Divergent assembly trajectories: a comparison of the plant and soil microbiome with plant communities in a glacier forefield
Authors: Junker Robert R. , He Xie , Otto Jan-Christoph , Ruiz-Hernández Victoria , Hanusch Maximilian 
Published: July 2021

AbstractCommunity assembly is a result of dispersal, abiotic and biotic characteristics of the habitat as well as stochasticity. A direct comparison between the assembly of microbial and ‘macrobial’ organisms is hampered by the sampling of these communities in different studies, at different sites, or on different scales. In a glacier forefield in the Austrian Alps, we recorded the soil and plant microbiome (bacteria and fungi) and plants that occurred in the same landscape and in close proximity in the same plots. We tested five predictions deduced from assembly processes and revealed deviating patterns of assembly in these community types. In short, microbes appeared to be less dispersal limited than plants, soil microbes and plants strongly responded to abiotic factors whereas the leaf microbiome was plant species-specific and well buffered from environmental conditions. The observed differences in community assembly processes may be attributed to the organisms’ dispersal abilities, the exposure of the habitats to airborne propagules, and habitat characteristics. The finding that assembly is conditional to the characteristics of the organisms, the habitat, and the spatial scale under consideration is thus central for our understanding about the establishment and the maintenance of biodiversity.
Quantitative characterisation of low abundant yeast mitochondrial proteins reveals compensation for haplo-insufficiency in different environments
Authors: Manousaki Alkisti , Bagnall James , Spiller David , Balarezo-Cisneros Laura Natalia , White Michael , Delneri Daniela 
Published: July 2021

AbstractQuantification of low abundant membrane-binding proteins such as transcriptional factors and chaperones has been proved difficult even with the most sophisticated analytical technologies. Here we exploit and optimise the non-invasive Fluorescence Correlation Spectroscopy (FCS) for quantitation of low abundance proteins and as proof of principle we choose two interacting proteins involved in fission of mitochondria in yeast, Fis1p and Mdv1p. In Saccharomyces cerevisiae the recruitment of Fis1p and Mdv1p to mitochondria is essential for the scission of the organelles and the retention of functional mitochondrial structures in the cell. We used FCS in single, GFP-labelled live yeast cells to quantify the protein abundance in homozygote and heterozygote cells, and to investigate the impact of the environments on protein copy number, bound/unbound protein state and mobility kinetics. Both proteins were observed to localise predominantly at mitochondrial structures with the Mdv1p bound state increasing significantly in a strictly respiratory environment. Moreover, a compensatory mechanism which controls Fis1p abundance upon deletion of one allele was observed in Fis1p but not in Mdv1p, suggesting differential regulation of Fis1p and Mdv1p protein expression.
BERTax: taxonomic classification of DNA sequences with Deep Neural Networks
Authors: Mock Florian , Kretschmer Fleming , Kriese Anton , Böcker Sebastian , Marz Manja 
Published: July 2021

AbstractTaxonomic classification, i.e., the identification and assignment to groups of biological organisms with the same origin and characteristics, is a common task in genetics. Nowadays, taxonomic classification is mainly based on genome similarity search to large genome databases. In this process, the classification quality depends heavily on the database since representative relatives have to be known already. Many genomic sequences cannot be classified at all or only with a high misclassification rate.Here we presentBERTax, a program that uses a deep neural network to pre-cisely classify the superkingdom, phylum, and genus of DNA sequences taxonomically without the need for a known representative relative from a database. For this,BERTaxuses the natural language processing model BERT trained to represent DNA. We showBERTaxto be at least on par with the state-of-the-art approaches when taxonomically similar species are part of the training data. In case of an entirely novel organism, however,BERTaxclearly outperforms any existing approach. Finally, we show thatBERTaxcan also be combined with database approaches to further increase the prediction quality.SinceBERTaxis not based on homologous entries in databases, it allows precise taxonomic classification of a broader range of genomic sequences. This leads to a higher number of correctly classified sequences and thus increases the overall information gain.
Neural excitation/inhibition imbalance and the treatment of severe depression
Authors: ten Doesschate Freek , Bruin Willem , Zeidman Peter , Abbott Christopher C. , Argyelan Miklos , Dols Annemieke , Emsell Louise , van Eijndhoven Philip F.P. , van Exel Eric , Mulders Peter C.R. , Narr Katherine , Tendolkar Indira , Rhebergen Didi , Sienaert Pascal , Vandenbulcke Mathieu , Verdijk Joey , van Verseveld Mike , Bartsch Hauke , Oltedal Leif , van Waarde Jeroen A. , van Wingen Guido A. 
Published: July 2021

AbstractAn influential hypothesis holds that depression is related to a neural excitation/inhibition imbalance, but its role in the treatment of depression remains unclear. Here, we show that unmedicated patients with severe depression demonstrated reduced inhibition of brain-wide resting-state networks relative to healthy controls. Patients using antidepressants showed inhibition that was higher than unmedicated patients and comparable to controls, but they still suffered from severe depression. Subsequent treatment with electroconvulsive therapy (ECT) reduced depressive symptoms, but its effectiveness did not depend on changes in network inhibition. Concomitant pharmacotherapy increased the effectiveness of ECT, but only when the strength of neural inhibition before ECT was within the normal range and not when inhibition was excessive. These findings suggest that reversing the excitation/inhibition imbalance may not be sufficient nor necessary for the effective treatment of severe depression, and that brain-state informed pharmacotherapy management may enhance the effectiveness of ECT.
Development and Validation Molecular Docking Analysis of Human serum albumin (HSA)
Authors: Ferrari Ivan Vito , Patrizio Paolo 
Published: July 2021

AbstractBackgroundHAS (Human Serum Albumin) is a highly water-soluble globular plasma protein, with a relative molecular weight (g/mol) of 67 KDa, consisting of 585 amino acid residues. In this study, we have investigated the interaction of the Crystal structures complexed in human serum albumin at resolutions of 2.8 to 2.0: Camptothecin, 9-amino-camptothecin, Etoposide, Teniposide, Bicalutamide and Idarubicin, using a bioinformatic approach, estimated by Pyrx Virtual Screen Tool and AMDock (AMDock, Assisted Molecular Docking). We have analyzed a validated protocol, studying several parameters, as Binding Affinity, RMSD value, Ligand Efficiency, and Inhibition constant (Ki value).MethodsHuman Serum Albumin protein preparation was characterized with several programs, as Chimera, MGLTools 1.5.6, Swiss PDB Viewer Software to perform docking analysis by Autodock Vina estimated with Pyrx Software.ResultsIn this work, we have found crystalized camptothecin, crystalized 9-amino-camptothecin and crystalized teniposide, gave excellent results for Binding Affinity, (kcal/mol), RMSD value (A°), inhibition constant Ki value (nM): -Binding Affinity of 9-amino-camptothecin (ca.−10 kcal/mol), camptothecin (−9 kcal/mol) and teniposide (−11 kcal/mol, -RMSD Value of 9 -amino-camptothecin (ca.1.8 Å), camptothecin (ca.2.2 Å) and teniposide (ca. 3.6 Å), - Ki Value: 9 -amino-camptothecin (ca 59 nM), camptothecin (ca 183 nM) and teniposide (ca 9 nM), -Ligand efficiency: of 9 -amino-camptothecin(ca −0.35 kcal/mol), camptothecin (ca −0.34 kcal/mol) and teniposide (ca −0.24 kcal/molConclusionsWe explored the best three crystallized ligand in Human Serum Albumin. Moreover, we observe a complete overlap, during the re-docking analysis phase, estimated by chimera Software. Therefore we have concluded that ID PDB Crystal 4L8U human serum albumin-Crystallised 9 -amino Camptothecin; ID PDB Crystal 4L9K human serum albumin-Crystallised Camptothecin and ID PDB Crystal 4L9Q human serum albumin-crystallized teniposide be used as a possible as a reference template protein to be compared with the target protein, by Docking molecular analysis.
Rapid divergence in vegetative morphology of a wind-pollinated plant between populations at contrasting densities
Authors: Tonnabel Jeanne , David Patrice , Pannell John 
Published: July 2021

AbstractPlant sexual dimorphism is thought to evolve in response to sex-specific selection associated with competition for access to mates or resources, both of which will often be density-dependent. In wind-pollinated plants in particular, vegetative traits can have an important influence on both resource acquisition and the pollen dispersal and receipt, with potential conflict between these two components of fitness. We evaluated the role of plant density in shaping plant traits by measuring evolutionary responses in experimental populations of the sexually dimorphic wind-pollinated plant Mercurialis annua. After three generations of evolution, we observed divergence between high- and low-density populations in several vegetative traits, whereas there was no divergence for reproductive traits. A reversal in the direction of sexually dimorphic traits expressed in young plants evolved in both low- and high-density populations compared to the original population (stored as seeds). Compared to the source population, males at high density evolved to be taller when young, whereas at low density young females tended to become smaller. These results demonstrate that a simple change in plant density can induce rapid, age-dependent and sex-specific evolution in the ontogeny of vegetative organs, and illustrates the power of experimental evolution for investigating plant trait evolution.
One-week escitalopram intake shifts excitation-inhibition balance in the healthy female brain
Authors: Zsido Rachel G. , Molloy Eóin N. , Cesnaite Elena , Zheleva Gergana , Beinhölzl Nathalie , Scharrer Ulrike , Piecha Fabian A. , Regenthal Ralf , Villringer Arno , Nikulin Vadim V. , Sacher Julia 
Published: July 2021

AbstractNeural health relies on cortical excitation-inhibition balance (EIB), with disrupted EIB underlying circuit dysfunction in several neuropsychiatric disorders. Previous research suggests links between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. To this end, we assessed changes in EIB following longitudinal escitalopram-intake. In a randomized, double-blind study protocol, a sample of 59 healthy female individuals on oral contraceptives underwent three resting-state electroencephalography recordings after daily administration of 20 mg escitalopram (n = 28) or placebo (n = 31) at baseline, after single dose, and after 1 week (steady state). We assessed 1/f slope of the power spectrum, a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram-intake associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after single dose of escitalopram predicted 1/f slope at steady state. Higher plasma escitalopram levels at single dose associated with better maintenance of these EIB changes throughout the drug administration week. Characterizing changes in 1/f slope during longitudinal SSRI-intake in healthy female individuals, we show that escitalopram shifted EIB in favor of excitation. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the neuroimaging lens by testing an interventional psychopharmacological design in a clearly-defined endocrinological state.
Community composition exceeds area as a predictor of long-term conservation value
Authors: O’Sullivan Jacob D. , Terry J. Christopher D. , Wilson Ramesh , Rossberg Axel G. 
Published: July 2021

AbstractConserving biodiversity often requires deciding which sites to prioritise for protection. Predicting the impact of habitat loss is a major challenge, however, since impacts can be distant from the perturbation in both space and time. Here we study the long-term impacts of habitat loss in a mechanistic metacommunity model in terms of both immediate extinctions and secondary species losses. We find that biomass-at-site, closely related to site area, is a poor predictor of long-term regional species losses following site removal. Knowledge of the compositional distinctness (average between-site Bray-Curtis dissimilarity) of the removed community can markedly improve the prediction of impacts at the regional scale, even when biotic responses play out at substantial spatial or temporal distance from the removed site. Fitting our model to empirical species-by-site tables describing Andean diatoms and Brazilian lichen-fungi, we show that compositional distinctness surpasses area as a predictor of long-term species losses in the empirically relevant parameter range. Our results robustly demonstrate that site area alone is not sufficient to gauge conservation priorities; analysis of compositional distinctness permits improved prioritisation at low cost.
HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells
Authors: Woodfield Sarah E. , Mistretta Brandon J. , Patel Roma H. , Ibarra Aryana M. , Fisher Kevin E. , Sarabia Stephen F. , Gandhi Ilavarasi , Reuther Jacquelyn , Starosolski Zbigniew , Badachhape Andrew , Shah Aayushi P. , Larson Samuel R. , Srivastava Rohit K. , Shi Yan , Whitlock Richard S. , Holloway Kimberly , Roy Angshumoy , Ghaghada Ketan B. , Lopez-Terrada Dolores , Gunaratne Preethi H. , Vasudevan Sanjeev A. 
Published: July 2021

AbstractHepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs). HepT1 cells were injected into the livers or tail veins of mice, and tumor growth was monitored with magnetic resonance and bioluminescent imaging. Blood was analyzed with fluorescence activated cell sorting to identify CTCs. Intra- and extra-hepatic tumor samples were harvested for immunohistochemistry and RNA and DNA sequencing. Cell lines were grown from tumor samples and profiled with RNA sequencing. With intrahepatic injection of HepT1 cells, 100% of animals grew liver tumors and showed vascular invasion, metastasis, and CTCs. Mutation profiling revealed genetic alterations in seven cancer-related genes, while transcriptomic analyses showed changes in gene expression with cells that invade vessels. Tail vein injection of HepT1 cells resulted in multifocal, metastatic disease. These unique models will facilitate further meaningful studies of high-risk HB.Summary StatementIn this work, we developed and thoroughly characterized several unique models of hepatoblastoma derived from the HepT1 cell line that show high-risk features.
De novo whole-genome assembly ofChrysanthemum makinoi, a key wild ancestor to hexaploid Chrysanthemum
Authors: van Lieshout N. , van Kaauwen M. , Kodde L. , Arens P. , Smulders M.J.M. , Visser R.G.F. , Finkers R. 
Published: July 2021

ABSTRACTChrysanthemum is among the top ten cut, potted and perennial garden flowers in the world. Despite this, to date, only the genomes of two wild diploid chrysanthemums have been sequenced and assembled. Here we present the most complete and contiguous chrysanthemumde novoassembly published so far, as well as a correspondingab initioannotation. The wild diploidChrysanthemum makinoiis thought to be one of the ancestors of the cultivated hexaploid varieties which are currently grown all around the world. Using a combination of Oxford Nanopore long reads, Pacific Biosciences long reads, Illumina short reads, Dovetail sequences and a genetic map, we assembled 3.1 Gb of its sequence into 9 pseudochromosomes, with an N50 of 330 Mb and BUSCO complete score of 92.1%. Ourab initioannotation pipeline predicted 95 074 genes and marked 80.0% of the genome as repetitive. This genome assembly ofC. makinoiprovides an important step forward in understanding the chrysanthemum genome, evolution and history.
Sleep Medicine Knowledge Among Graduating Medical Students in Lebanon During an Economic and Political Crisis
Authors: Aoun Raissa , Zibara Victor , Costanian Christy , Attarian Hrayr , Bahous Sola Aoun 
Published: July 2021

AbstractObjectivesSleep disorders are prevalent and underrecognized during both economic and political crises. They are a major reason for poor overall health and decreased quality of life. Sleep medicine education is limited at most medical schools, resulting in limited awareness of this important aspect of healthcare. The aim of the study is to assess sleep medicine knowledge of graduating medical students in Lebanon and to assess their readiness to tackle sleep health issues in a country during an unprecedented crisis.MethodsFinal-year medical students at 7 medical schools in Lebanon were invited to fill a survey between January 2020 and March 2021. The Assessment of Sleep Knowledge in Medical Education survey was used to assess their knowledge in sleep medicine. The curriculum organizers at the medical schools were also surveyed. Student’s t-test was used for analysis.Results158 and 58 students completed the survey during 2020 and 2021, with a mean overall score on sleep knowledge of was 17.5 and 15.9 /30, respectively. There was no difference in mean knowledge scores by gender, age, American versus European medical school systems, and between medical schools that included sleep medicine in their curriculum versus those that did not.ConclusionsPresence of sleep medicine education in the curriculum was associated with higher scores on ASKME among graduating Lebanese medical students. Overall, the new crop of physicians in Lebanon possesses a relatively good knowledge base in sleep medicine. Nevertheless, more effort should be made to uniformly maintain this level of sleep education.
Antisense oligonucleotides targeting UBE3A-ATS restore expression of UBE3A by relieving transcriptional interference
Authors: Germain Noelle D. , Gorka Dea , Drennan Ryan , Jafar-nejad Paymaan , Whipple Amanda , Core Leighton , Levine Eric S. , Rigo Frank , Chamberlain Stormy J. 
Published: July 2021

AbstractAngelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A allele. In neurons, the paternal allele of UBE3A is silenced in cis by the long noncoding RNA, UBE3A-ATS. Unsilencing paternal UBE3A by reducing UBE3A-ATS is a promising therapeutic approach for the treatment of AS. Here we show that targeted cleavage of UBE3A-ATS using antisense oligonucleotides (ASOs) restores UBE3A and rescues electrophysiological phenotypes in human AS neurons. We demonstrate that cleavage of UBE3A-ATS results in termination of its transcription by displacement of RNA Polymerase II. Reduced transcription of UBE3A-ATS allows transcription of UBE3A to proceed to completion, providing definitive evidence for the transcriptional interference model of paternal UBE3A silencing. These insights into the mechanism by which ASOs restore UBE3A inform the future development of nucleotide-based approaches for the treatment of AS, including alternative strategies for cleaving UBE3A-ATS that can be developed for long-term restoration of UBE3A function.