bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-ocular dendritic cells are increased in HLA-B27 associated acute anterior uveitis
Authors: Kasper Maren , Heming Michael , Schafflick David , Li Xiaolin , Lautwein Tobias , zu Horste Melissa Meyer , Bauer Dirk , Walscheid Karoline , Wiendl Heinz , Loser Karin , Heiligenhaus Arnd , zu Horste Gerd Meyer 
Published: February 2021

AbstractUveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. HLA-B27-associated uveitis is a common subtype of uveitis and a prototypical ocular autoimmune disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations.Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27 positive and negative anterior uveitis and an infectious endophthalmitis control by combining single cell RNA-sequencing (scRNA-seq) with flow cytometry and low-input proteomics. Ocular cell infiltrates consisted primarily of lymphocytes in uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured an plasmacytoid and classical dendritic cells (cDC) infiltrate, and of plasma cells. Moreover, cDCs were central in predicted local cell-cell communication.The data suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of particular dendritic cells.
Phase transitions may explain why SARS-CoV-2 spreads so fast and why new variants are spreading faster
Authors: Phillips J. C. , Moret Marcelo , Zebende Gilney F. , Chow Carson C. 
Published: February 2021

AbstractThe novel coronavirus SARS CoV-2 responsible for the COVID-19 pandemic and SARS CoV-1 responsible for the SARS epidemic of 2002-2003 share an ancestor yet evolved to have much different transmissibility and global impact1. A previously developed thermodynamic model of protein conformations predicted that SARS CoV-2 is very close to a thermodynamic critical point, which makes it highly infectious but also easily displaced by a spike-based vaccine because there is a tradeoff between transmissibility and robustness2. The model identified a small cluster of four key mutations of SARS CoV-2 that promotes much stronger viral attachment and viral spreading. Here we apply the model to two new strains (B.1.1.7 and B.1.351)3and predict, using no free parameters, how the new mutations can further enhance infectiousness.
Spatiotemporal heterogeneity of glioblastoma is dictated by microenvironmental interference
Authors: Ravi Vidhya M. , Will Paulina , Kueckelhaus Jan , Sun Na , Joseph Kevin , Salié Henrike , Ehr Jasmin von , Vollmer Lea , Benotmane Jasim K. , Neidert Nicolas , Follo Marie , Scherer Florian , Goeldner Jonathan M , Behringer Simon P. , Franco Pamela , Hofmann Ulrich G. , Fung Christian , Beck Jürgen , Sankowski Roman , Prinz Marco , Killmer Saskia , Bengsch Bertram , Walch Axel Karl , Delev Daniel , Schnell Oliver , Heiland Dieter Henrik 
Published: February 2021

AbstractGlioblastomas are highly malignant tumors of the central nervous system. Evidence suggests that these tumors display large intra- and inter-patient heterogeneity hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies1–3. However, the source for dynamic reorganization of cellular states within their spatial context remains elusive. Here, we in-depth characterized glioblastomas by spatially resolved transcriptomics, metabolomics and proteomics. By deciphering exclusive and shared transcriptional programs across patients, we inferred that glioblastomas develop along defined neural lineages and adapt to inflammatory or metabolic stimuli reminiscent of reactive transformation in mature astrocytes. Metabolic profiling and imaging mass cytometry supported the assumption that tumor heterogeneity is dictated by microenvironmental alterations. Analysis of copy number variation (CNV) revealed a spatially cohesive organization of subclones associated with reactive transcriptional programs, confirming that environmental stress gives rise to selection pressure. Deconvolution of age-dependent transcriptional programs in malignant and non-malignant specimens identified the aging environment as the major driver of inflammatory transformation in GBM, suggesting that tumor cells adopt transcriptional programs similar to inflammatory transformation in astrocytes. Glioblastoma stem cells implanted into human neocortical slices of varying age levels, independently confirmed that the ageing environment dynamically shapes the intratumoral heterogeneity towards reactive transcriptional programs. Our findings provide insights into the spatial architecture of glioblastoma, suggesting that both locally inherent tumor as well as global alterations of the tumor microenvironment shape its transcriptional heterogeneity. Global age-related inflammation in the human brain is driving distinct transcriptional transformation in glioblastomas, which requires an adjustment of the currently prevailing glioma models.
The type and source of reactive oxygen species influences the outcome of oxidative stress in cultured cells
Authors: Goffart Steffi , Tikkanen Petra , Michell Craig , Wilson Trevor , Pohjoismäki Jaakko L.O. 
Published: February 2021

AbstractOxidative stress can be modeled using various different experimental approaches, such as exposing the cells or organisms to oxidative chemicals. However, the actual effects of these chemicals, outside of the immediate measured effect, have attracted relatively little attention. We show here that three commonly used oxidants, menadione, potassium bromate and hydrogen peroxide, while known to function differently, also elicit different types of responses in cultured cells. While cells response to menadione and bromate exposure mainly by an integrated stress response, hydrogen peroxide has more indirect effects. Primary oxidative stress does not induce DNA repair or antioxidant defense mechanisms. However, cells with previous experience of oxidative stress show adaptive changes when the stress is renewed. Our results urge caution when comparing studies using different sources of oxidative stress or generalizing the findings of these studies to different tissue or oxidant types.
Temporal enhancement of cross-adaptation between density and size perception based on the theory of magnitude
Authors: Hisakata Rumi , Kaneko Hirohiko 
Published: February 2021

AbstractThe ability to estimate spatial extent is an important feature of the visual system. A previous study showed that perceived sizes shrank after adaptation to a dense texture and reported that this density–size aftereffect is modulated by the degree of density. In this study, we found that the aftereffect was also modulated by the temporal density of the adapting texture. The test stimuli were two circles, and the adapting stimulus had a dotted texture. The adapting texture refreshed every form 67ms to 500 ms, or not at all (static), during the adaptation. The results showed that the aftereffects from a refreshing stimulus were larger than those under the static condition. On the other hand, density adaptation lacked such enhancement. This result indicates that repetitive presentation of an adapting texture enhanced the density–size cross-aftereffect. The fact that density modulation occurs in both the spatial and temporal domains is consistent with the theory of magnitude, which assumes that the processing of the magnitude estimation of space, time, and numbers share a common cortical basis.
Targeted Memory Reactivation of Face-Name Learning Depends on Ample and Undisturbed Slow-Wave Sleep
Authors: Whitmore Nathan , Bassard Adrianna M. , Paller Ken A. 
Published: February 2021

AbstractFace memory, including the ability to recall the name of a familiar person, is often crucial in social interactions, and like many other memory functions, it may rely on sleep. We investigated whether targeted memory reactivation during sleep could improve associative and perceptual aspects of face memory. Participants studied 80 face-name pairs, and then a subset of spoken names was presented unobtrusively during a daytime nap. This reactivation preferentially improved recall for those face-name pairs, as modulated by two factors related to sleep quality. That is, the memory benefit was positively correlated with the duration of stage N3 sleep (slow-wave sleep) and with the extent to which cues presented during SWS did not produce a sleep disruption indexed by increased alpha-band electroencephalographic activity in the 5 seconds after a cue. Follow-up analyses showed that a memory benefit from presenting spoken names during sleep was evident in participants with high amounts of SWS or with low amounts of sleep disruption. We conclude that sleep reactivation can strengthen memory for specific face-name associations and that the effectiveness of reactivation depends on uninterrupted N3 sleep.
Comparative analysis of Alzheimer’s disease knock-in model brain transcriptomes implies changes to energy metabolism as a causative pathogenic stress
Authors: Barthelson Karissa , Newman Morgan , Lardelli Michael 
Published: February 2021

SummaryEnergy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs such as brains. Here, we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of eleven early-onset familial Alzheimer’s disease (EOfAD)-like and non-EOfAD-like mutations in three zebrafish genes. The one cellular activity consistently predicted as affected by only the EOfAD-like mutations is oxidative phosphorylation that produces most of the brain’s energy. All the mutations were predicted to affect protein synthesis. We extended our analysis to knock-in mouse models ofAPOEalleles and found the same effect for the late onset Alzheimer’s disease risk allele ɛ4. Our results support a common molecular basis for initiation of the pathological processes leading to both early and late onset forms of Alzheimer’s disease and illustrate the utility of both zebrafish and knock-in, single EOfAD mutation models for understanding the causes of this disease.
Evidence for a force favouring GC over AT at short intronic sites inDrosophila simulansandD. melanogaster
Authors: Jackson Ben , Charlesworth Brian 
Published: February 2021

AbstractPopulation genetics studies often make use of a class of nucleotide site free from selective pressures in order to make inferences about population size changes or natural selection at other sites. If such neutral sites can be identified, they offer the opportunity to avoid any confounding effects of selection. Here we investigate evolution at putatively neutrally evolving short intronic sites in natural populations ofDrosophila melanogasterandD. simulans, in order to understand the properties of spontaneous mutations and the extent of GC-biased gene conversion in these species. Use of data on the genetics of natural populations is advantageous because it integrates information from large numbers of individuals over long timescales. In agreement with direct evidence from observations of spontaneous mutations inDrosophila, we find a bias in the spectrum of mutations towards AT basepairs. In addition, we find that this bias is stronger in theD. melanogasterlineage than theD. simulanslineage. The evidence for GC-biased gene conversion inDrosophilahas been equivocal. Here we provide evidence for a weak force favouring GC in both species, which is stronger inD. simulans.Some homologous short intronic sites have diverged in GC content between the two species, which may have been caused by lineage-specific changes in the extent to which different regions of the genome are subject to a GC (or AT)-favouring force.
Toxicity Profile of Artesunate in Rats and Dogs
Authors: Lang Johanna S. 
Published: February 2021

Abstract

OBJECTIVES
The objectives of these studies were to investigate the toxicity, safety
and toxicokinetics of single and multiple doses of artesunate for injection
in rats and dogs.

METHODS
Sprague-Dawley rats and Beagle dogs were treated intravenously or
intramuscularly for 28 consecutive days with doses of up to 30 mg/kg
artesunate, evaluating toxicity, kinetics, genotoxicity, and cardiovascular
and central nervous safety parameters after single and 4-week repeated
administrations. Furthermore, respiratory parameters were evaluated after a
single intravenous administration in rats.

RESULTS
Artesunate was well tolerated with no mortality and only minor effects
on clinical pathology parameters. Following repeated intramuscular
administration, local reactions at the injection site became
evident.

CONCLUSIONS
The results obtained in these studies support the safe use of artesunate
in humans.

Subchronic data for repeated intravenous and intramuscular artesunate in
animals are available in the literature for a maximum duration of 14-days.
Published results of genotoxicity studies in
vitro in bacteria or cells of animal or human origin and
in vivo in animals are equivocal, with a
couple of negative results following oral administration and positive
results in human cells.
With the studies performed in rats and dogs for a treatment period of
28-days including measures of safety pharmacology, toxicokinetic evaluation
and in vivo genotoxicity data, a comparison of
toxicity and exposure of intravenous versus intramuscular artesunate for a
prolonged treatment period is possible, delivering important information,
when a decision between both routes has to be made for use in patients.
Results of the peripheral blood micronucleus assay in rats were positive,
suggesting genotoxic potential for the intravenous route of administration
of artesunate, what is, beside patients, likewise relevant for production
and health care personnel.
Ex vivoanticoagulants affect human blood platelet biomechanics with implications for high-throughput functional mechanophenotyping
Authors: Sachs Laura , Wesche Jan , Lenkeit Lea , Greinacher Andreas , Bender Markus , Otto Oliver , Palankar Raghavendra 
Published: February 2021

AbstractInherited platelet disorders affecting the human platelet cytoskeleton result in increased bleeding risk. However, deciphering their impact on cytoskeleton-dependent intrinsic biomechanics of platelets remains challenging and represents an unmet need from a diagnostic and prognostic perspective. It is currently unclear whetherex vivoanticoagulants used for the collection of peripheral blood impact the mechanophenotype of cellular components of blood. Using unbiased, high-throughput functional mechanophenotyping of single human platelets by deformability cytometry, we found thatex vivoanticoagulants are a critical pre-analytical variable that differentially influences platelet deformation, their size and functional response to agonists by altering the cytoskeleton. We applied our findings to characterize the functional mechanophenotype of platelets from a patient with Myosin Heavy Chain 9 (MYH9) related macrothrombocytopenia. Our data suggest that platelets fromMYH9p.E1841K mutation in humans affecting platelet non-muscle myosin heavy chain IIa (NMMHC-IIA) are biomechanically less deformable in comparison to platelets from healthy individuals.
Defining the Yeast Resistome throughin vitroEvolution and Whole Genome Sequencing
Authors: Ottilie Sabine , Luth Madeline R. , Hellemann Erich , Goldgof Gregory M. , Vigil Eddy , Kumar Prianka , Cheung Andrea L. , Song Miranda , Godinez-Macias Karla P. , Carolino Krypton , Yang Jennifer , Lopez Gisel , Abraham Matthew , Tarsio Maureen , LeBlanc Emmanuelle , Whitesell Luke , Schenken Jake , Gunawan Felicia , Patel Reysha , Smith Joshua , Love Melissa S. , Williams Roy M. , McNamara Case W. , Gerwick William H. , Ideker Trey , Suzuki Yo , Wirth Dyann F. , Lukens Amanda K. , Kane Patricia M. , Cowen Leah E. , Durrant Jacob D. , Winzeler Elizabeth A. 
Published: February 2021

SummaryIn vitroevolution and whole genome analysis were used to comprehensively identify the genetic determinants of chemical resistance in the model microbe,Saccharomyces cerevisiae. Analysis of 355 curated, laboratory-evolved clones, resistant to 80 different compounds, demonstrates differences in the types of mutations that are identified in selected versus neutral evolution and reveals numerous new, compound-target interactions. Through enrichment analysis we further identify a set of 137 genes strongly associated with or conferring drug resistance as indicated by CRISPR-Cas9 engineering. The set of 25 most frequently mutated genes was enriched for transcription factors and for almost 25 percent of the compounds, resistance was mediated by one of 100 independently derived, gain-of-function, single nucleotide variants found in 170-amino-acid domains in two Zn2C6transcription factors,YRR1andYRM1(p < 1x 10−100). This remarkable enrichment for transcription factors as drug resistance genes may explain why it is challenging to develop effective antifungal killing agents and highlights their important role in evolution.
Targeting Mitochondrial Metabolism in Clear Cell Carcinoma of the Ovaries
Authors: Zhang Xianonan , Shetty Mihir , Clemente Valentino , Linder Stig , Bazzaro Martina 
Published: February 2021

SummaryOvarian clear cell carcinoma (OCCC) is a rare but chemorefractory tumor. About 50% of all OCCC patients have inactivating mutations of ARID1A a member of the SWI/SNF chromatin remodeling complex. Members of the SWI/SNF remodeling have emerged as regulators of the energetic metabolism of mammalian cells, however the role of ARID1A as a modulator of the mitochondrial metabolism in OCCCs is yet to be defined. Here we show that ARID1A-loss results in increased mitochondrial metabolism and renders ARID1A-mutated cells increasingly and selectively dependent on it. The increase in mitochondrial activity following ARID1A loss is associated to increase of C-myc and to increased mitochondrial number and reduction of their size consistent with a higher mitochondrial cristae/outer membrane ratio. Significantly, preclinical testing of the complex I mitochondrial inhibitor IACS-010759 extends overall survival in a preclinical model of ARID1A-mutated OCCC. These findings provide the for targeting mitochondrial activity in ARID1A-mutanted OCCCs.
RaptGen: A variational autoencoder with profile hidden Markov model for generative aptamer discovery
Authors: Iwano Natsuki , Adachi Tatsuo , Aoki Kazuteru , Nakamura Yoshikazu , Hamada Michiaki 
Published: February 2021

AbstractNucleic acid aptamers are generated by anin vitromolecular evolution method known as systematic evolution of ligands by exponential enrichment (SELEX). A variety of candidates is limited by actual sequencing data from an experiment. Here, we developed RaptGen, which is a variational autoencoder forin silicoaptamer generation. RaptGen exploits a profile hidden Markov model decoder to represent motif sequences effectively. We showed that RaptGen embedded simulation sequence data into low-dimension latent space dependent on motif information. We also performed sequence embedding using two independent SELEX datasets. RaptGen successfully generated aptamers from the latent space even though they were not included in high-throughput sequencing. RaptGen could also generate a truncated aptamer with a short learning model. We demonstrated that RaptGen could be applied to activity-guided aptamer generation according to Bayesian optimization. We concluded that a generative method by RaptGen and latent representation are useful for aptamer discovery. Codes are available athttps://github.com/hmdlab/raptgen.
Chromosome-level genome assembly of the horned-gall aphid,Schlechtendalia chinensis(Hemiptera: Aphididae: Erisomatinae)
Authors: Wei Hong-Yuan , Ye Yu-Xian , Huang Hai-Jian , Chen Ming-Shun , Yang Zi-Xiang , Chen Xiao-Ming , Zhang Chuan-Xi 
Published: February 2021

AbstractThe horned gall aphidSchlechtendalia chinensis, is an economically important insect that induces galls valuable for medicinal and chemical industries.S. chinensismanipulates its host plant to form well-organized horned galls during feeding. So far, more than twenty aphid genomes have been reported; however, all of those are derived from free-living aphids. Here we generated a high-quality genome assembly ofS. chinensis, representing the first genome sequence of a galling aphid. The final genome assembly was 280.43 Mb, with 97% of the assembled sequences anchored into thirteen chromosomes.S. chinensispresents the smallest aphid genome size among available aphid genomes to date. The contig and scaffold N50 values were 3.39 Mb and 20.58 Mb, respectively. The assembly included 96.4% of conserved arthropod and 97.8% of conserved Hemiptera single-copy orthologous genes based on BUSCO analysis. A total of 13,437 protein-coding genes were predicted. Phylogenomic analysis showed thatS. chinensisformed a single clade between theEriosoma lanigerumclade and the Aphidini+Macrosiphini aphid clades. In addition, salivary proteins were found to be differentially expressed whenS. chinensisunderwent host alternation, indicating their potential roles in gall formation and plant defense suppression. A total of 36 cytochrome P450 genes were identified inS. chinensis, considerably fewer compared to other aphids, probably due to its small host plant range. The high-qualityS. chinensisgenome assembly and annotation provide an essential genetic background for future studies to reveal the mechanism of gall formation and to explore the interaction between aphids and their host plants.
Diversity and Function of Motile Ciliated Cell Types within Ependymal Lineages of the Zebrafish Brain
Authors: D’Gama Percival P. , Qiu Tao , Cosacak Mehmet Ilyas , Chong Yan Ling , Konac Ahsen , Hansen Jan Niklas , Ringers Christa , Hui Subhra P. , Olstad Emilie W. , Peng Ng Chee , Rayamajhi Dheeraj , Wachten Dagmar , Liebl David , Kikuchi Kazu , Kizil Caghan , Yaksi Emre , Roy Sudipto , Jurisch-Yaksi Nathalie 
Published: February 2021

ABSTRACTMotile cilia defects impair cerebrospinal fluid (CSF) flow, and can cause brain and spine disorders. To date, the development of ciliated cells, their impact on CSF flow and their function in brain and axial morphogenesis are not fully understood. Here, we have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricular surface undergoes significant restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs are translationally polarized, co-exist with monociliated cells and generate directional flow patterns. Moreover, these ciliated cells have different developmental origins, and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from specific brain regions or global perturbation of multiciliation does not affect overall brain or spine morphogenesis, but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.