bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired state-dependent potentiation of GABAergic synaptic currents triggers seizures in an idiopathic generalized epilepsy model
Authors: Zhang Chun-Qing , Catron Mackenzie A. , Ding Li , Hanna Caitlyn M. , Gallagher Martin J. , Macdonald Robert L. , Zhou Chengwen 
Published: May 2020

AbstractIdiopathic generalized epilepsy(IGE) patients have genetic causes and their seizure onset mechanisms particularly during sleep remain elusive. Here we proposed that sleep-like slow-wave oscillations(0.5 Hz SWOs) potentiated excitatory or inhibitory synaptic currents in layer V cortical pyramidal neurons from wild-type(wt) mouseex vivobrain slices. In contrast, SWOs potentiated excitatory, not inhibitory, currents in cortical neurons from heterozygous(het) knock-in(KI) IGE mice(GABAAreceptor γ2 subunitGabrg2Q390Xmutation), creating an imbalance between evoked excitatory and inhibitory currents to effectively prompt neuronal action potentials. Similarly, more physiologically similar up/down-state(present during slow-wave sleep) induction in cortical neurons could potentiate excitatory synaptic currents within slices from wt/hetGabrg2Q390XKI mice. Consequently, SWOs or up/down-state inductionin vivo(using optogenetic method) could trigger epileptic spike-wave discharges(SWDs) in hetGabrg2Q390XKI mice. To our knowledge, this is the first operative mechanism to explain why epileptic SWDs preferentially happen during non-REM sleep or quiet-wakefulness in human IGE patients.
Machine Learning and Deep Learning challenges for building 2′O site prediction
Authors: Mostavi Milad , Huang Yufei 
Published: May 2020

Abstract2′-O-methylation (2′O) is one of the abundant post-transcriptional RNA modifications which can be found in all types of RNA. Detection and functional analysis of 2′O methylation have become challenging problems for biologists ever since its discovery. This paper addresses computational challenges for building Machine Learning and Deep Learning models for predicting 2′O sites. In particular, the impact of sequence length containing 2′O site, embedding method and the type of predictive model are each investigated separately. 30 different predictive models are built and each showed the impact of the mentioned parameters. The area under the precision-recall and receiving operating characteristics curves are utilized to test imbalanced case scenarios in the real world. By comparing the performance of these models, it is shown that embedding methods are crucial for Machine Learning models. However, they do not improve the performance of Deep Learning models. Furthermore, the best predictive model was further investigated to extract significant nucleotides surrounding 2′O sites. Interestingly, based on the significant score matrix achieved by all 2′O samples, it is depicted that model pays the highest attention at the location that the dominant 2′O motifs exist. Dataset and all of the codes are available athttps://github.com/MMostavi/2_O_Me_sitePred
Object-based attentional selection emerges late in visual cortical hierarchy for objects of varying perceptual strengths
Authors: Al-Janabi Shahd , Strommer Nofar , Gabay Shai , Greenberg Adam S. 
Published: May 2020

AbstractObject-based attention (OBA) can - in addition to acting upon explicit object representations - act upon occluded and illusory objects. It remains unknown, however, whether or not the selection of such object representations is detectable at the same level within visual cortex. This study examined the level within visual cortex (V1-V3, LOC) at which object-based selection is observed for explicit, occluded and illusory objects. During fMRI acquisition, participants identified a target preceded by a predictive arrow cue in the double-rectangle cueing paradigm. We independently localized retinotopically-specific regions of cortex corresponding to all possible target locations to examine neural fluctuations at each level of the visual cortical hierarchy. We found, after cue onset, that activity along visual cortex was not greater for representations of cued than of uncued same object locations. In contrast, we found that activity in V3 was enhanced at retinotopic representations that correspond to uncued same than different object locations. These results, together, support attentional spreading. Additionally, when the target appeared at either the cued or uncued locations, we found higher activation in areas representing uncued same object versus cued locations. This effect emerged along the visual cortical hierarchy. Further, when the target appeared on either the cued or uncued object, we found that activation in V3 transiently increased at uncued same than different object locations. This effect was also detectable upstream in LOC. These results index attentional re-orienting between locations/objects. Effects emerged regardless of object type: explicit or completed. Thus, the gating of object information proceeds completion.Significance StatementWe investigated the level within visual cortex (V1-V3, LOC) that object-based selection is observed for explicit objects and those requiring perceptual completion. We showed that activity along visual cortex was similar for representations of locations on a cued object, which may indicate attention spreads evenly to all locations on an object marked as relevant by the cue. We also showed that activity in late visual areas was greater for representations of uncued same than different object locations, which may indicate that attention enhances the cued object. These findings support the attentional spreading account. Object selection may, thus, be instantiated by even engagement of locations within a cued, and/or suppression of locations within an uncued, object - independent of its type.
A Continuously Active Antimicrobial Coating effective against Human Coronavirus 229E
Authors: Ikner Luisa A. , Torrey Jason R. , Gundy Patricia M. , Gerba Charles P. 
Published: May 2020

AbstractThe disinfection of high-contact surfaces is seen as an infection control practice to prevent the spread of pathogens by fomites. Unfortunately, recontamination of these surfaces can occur any time after the use of common disinfectants. We recently reported on a novel continuously active antimicrobial coating which was shown to reduce the spread of healthcare acquired infections in hospitals. We evaluated a modified coating that demonstrated a residual efficacy against viruses. The coated surfaces were found to be effective against human coronavirus (HCoV) 229E, reducing the concentration of these viruses by greater than 90% in 10 minutes and by greater than 99.9% after two hours of contact. The coating formulation when tested in suspension yielded a greater than 99.99% reduction of HCoV 229E within ten minutes of contact. This outcome presents an opportunity for controlling the transmission of COVID-19 from contaminated fomites.
Processing of a spoken narrative in the human brain is shaped by family cultural background
Authors: Hakonen M. , Ikäheimonen A. , Hultèn A. , Kauttonen J. , Koskinen M. , Lin F-H. , Lowe A. , Sams M. , Jääskelainen I. P. 
Published: May 2020

ABSTRACTUsing neuroimaging, we studied influence of family cultural background on processing of an audiobook in human brain. The audiobook depicted life of two young Finnish men, one with the Finnish and the other with the Russian family background. Shared family cultural background enhanced similarity of narrative processing in the brain at prelexical, word, sentence, and narrative levels. Similarity was also enhanced in brain areas supporting imagery. The cultural background was further reflected as semantic differences in word lists by which the subjects described what had been on their minds when they heard the audiobook during neuroimaging. Strength of social identity shaped word, sentence, and narrative level processing in the brain. These effects might enhance mutual understanding between persons who share family cultural background and social identity and, conversely, deteriorate between-group mutual understanding in modern multicultural societies wherein native speakers of a language may assume highly similar understanding.
In-silico screening of drug candidates for thermoresponsive liposome formulations
Authors: Balouch Martin , Šrejber Martin , Šoltys Marek , Janská Petra , Štěpánek František , Berka Karel 
Published: May 2020

AbstractLiposomal formulations can be advantageous in a number of scenarios such as targeted delivery to reduce the systemic toxicity of highly potent Active Pharmaceutical Ingredients (APIs), to increase drug bioavailability by prolonging systemic circulation, to protect labile APIs from degradation in the gastrointestinal tract, or to improve skin permeation in dermal delivery. However, not all APIs are suitable for encapsulation in liposomes. Some of the issues are too high permeability of the API across the lipid bilayer, which may lead to premature leakage, too low permeability, which may hinder the drug release process, or too strong membrane affinity, which may reduce the overall efficacy of drug release from liposomes. Since the most reliable way to test API encapsulation and release from liposomes so far has been experimental, anin silicomodel capable of predicting API transport across the lipid bilayer might accelerate formulation development. In this work, we demonstrate a newin silicoapproach to compute the temperature dependent permeability of a set of compounds across the bilayer of virtual liposomes constructed by molecular dynamics simulation. To validate this approach, we have conducted a series of experiments confirming the model predictions using a homologous series of fluorescent dyes. Based on the performance of individual molecules, we have defined a set of selection criteria for identifying compatible APIs for stable encapsulation and thermally controlled release from liposomes. To further demonstrate thein silico-based methodology, we have screened the DrugBank database, identified potent drugs suitable for liposome encapsulation and successfully carried out the loading and thermal release of one of them - an antimicrobial compound cycloserine.
Visual stimulus-specific habituation of innate defensive behaviour in mice
Authors: Tafreshiha Azadeh , van den Burg Sven A. , Smits Kato , Blömer Laila A. , Heimel J. Alexander 
Published: May 2020

AbstractInnate defensive responses such as freezing or escape are essential for animal survival. Mice show defensive behaviour to stimuli sweeping overhead, like a bird cruising the sky. Here, we found that mice reduced their defensive freezing after sessions with a stimulus passing overhead repeatedly. This habituation is stimulus-specific, as mice freeze again to a novel shape. This allows us to investigate the invariances in the mouse visual system. The mice generalize over retinotopic location and over size and shape, but distinguish objects when they differ in both size and shape. Innate visual defensive responses are thus strongly influenced by previous experience as mice learn to ignore specific stimuli. This form of learning occurs at the level of a location-independent representation.
ODDPub – a Text-Mining Algorithm to Detect Data Sharing in Biomedical Publications
Authors: Riedel Nico , Kip Miriam , Bobrov Evgeny 
Published: May 2020

AbstractOpen research data are increasingly recognized as a quality indicator and an important resource to increase transparency, robustness and collaboration in science. However, no standardized way of reporting Open Data in publications exists, making it difficult to find shared datasets and assess the prevalence of Open Data in an automated fashion.We developed ODDPub (Open Data Detection in Publications), a text-mining algorithm that screens biomedical publications and detects cases of Open Data. Using English-language original research publications from a single biomedical research institution (n=8689) and randomly selected from PubMed (n=1500) we iteratively developed a set of derived keyword categories. ODDPub can detect data sharing through field-specific repositories, general-purpose repositories or the supplement. Additionally, it can detect shared analysis code (Open Code).To validate ODDPub, we manually screened 792 publications randomly selected from PubMed. On this validation dataset, our algorithm detected Open Data publications with a sensitivity of 0.74 and specificity of 0.97. Open Data was detected for 11.5% (n=91) of publications. Open Code was detected for 1.4% (n=11) of publications with a sensitivity of 0.73 and specificity of 1.00. We compared our results to the linked datasets found in the databases PubMed and Web of Science.Our algorithm can automatically screen large numbers of publications for Open Data. It can thus be used to assess Open Data sharing rates on the level of subject areas, journals, or institutions. It can also identify individual Open Data publications in a larger publication corpus. ODDPub is published as an R package on GitHub.
COTAN: Co-expression Table Analysis for scRNA-seq data
Authors: Galfrè S. G. , Morandin F. , Pietrosanto M. , Cremisi F. , Helmer-Citterich M. 
Published: May 2020

AbstractEstimating co-expression of cell identity factors in single-cell transcriptomes is crucial to decode new mechanisms of cell state transition. Due to the intrinsic low efficiency of single-cell mRNA profiling, novel computational approaches are required to accurately infer gene co-expression in a cell population. We introduce COTAN, a statistical and computational method to analyze the co-expression of gene pairs at single cell level, providing the foundation for single-cell gene interactome analysis.
Ca2+-Dependent Regulation by the Cyclic AMP Pathway of Primary Cilium Length in LLC-PK1 Renal Epithelial Cells
Authors: Scarinci Noelia , Perez Paula L. , del Rocío Cantero María , Cantiello Horacio F. 
Published: May 2020

AbstractThe primary cilium is a sensory organelle projecting from the apical surface of renal epithelial cells. Dysfunctional cilia have been linked to a number of genetic diseases known as ciliopathies, which include autosomal dominant polycystic kidney disease (ADPKD). Previous studies have determined that renal epithelial primary cilia express both the polycystin-2 (PC2, TRPP2) channel and the type-2 vasopressin receptor (V2R), coupled to local cAMP production. However, little is known as to how Ca2+and cAMP signals lead to changes in the length of the primary cilium. Here, we explored how cAMP signals regulate the length of the primary cilium in wild type LLC-PK1 renal epithelial cells. Primary cilia length was determined by immunocytochemical labeling of the ciliary axoneme. Treatment of cells with the cAMP analog 8-Br-cAMP (1 mM) in normal external Ca2+(1.2 mM) produced a 25.3% increase (p < 0.0001) in the length of the primary cilium, a phenomenon also observed in cells exposed to high external Ca2+(6.2 mM). However, exposure of cells to vasopressin (AVP, 10 μM), which also increases cAMP in primary cilia of LLC-PK1 cells, mimicked the effect of 8-Br-cAMP in normal, but not in high Ca2+. Further, specific gene silencing of PC2 expression further increased primary cilium length after 8-Br-cAMP treatment, in normal, but not high Ca2+. The encompassed data indicate a crosstalk between the cAMP and Ca2+signals to modulate the length of the primary cilium, in a phenomenon that implicates the expression of PC2.Significance StatementMorphological changes in primary cilia have been linked to genetic disorders, including autosomal dominant polycystic kidney disease (ADPKD), a major cause of kidney disease. Both cAMP and Ca2+are universal second messengers that regulate polycystin-2 (PC2, TRPP2), a Ca2+permeable non-selective cation channel implicated in ADPKD, and expressed in the primary cilium of renal epithelial cells. Despite current interest, little is known as to how second messenger systems and how aberrant regulation of PC2 may link primary cilium structure with cyst formation in ADPKD. Here we determined that both the cAMP analog 8-Br-cAMP and vasopressin increase the length of the primary cilium in renal epithelial cells. However, this phenomenon depends of external Ca2+andPKD2gene silencing. Proper cAMP signaling may be essential in the control of the primary cilium of renal epithelial cells, and the onset of cyst formation in ADPKD.
A small molecule that binds an RNA repeat expansion stimulates its decay via the exosome complex
Authors: Angelbello Alicia J. , Benhamou Raphael I. , Rzuczek Suzanne G. , Choudhary Shruti , Tang Zhenzhi , Chen Jonathan L. , Roy Madhuparna , Wang Kye Won , Yildirim Ilyas , Jun Albert S. , Thornton Charles A. , Disney Matthew D. 
Published: May 2020

AbstractWe describe the design of a small molecule that binds the structure of a r(CUG) repeat expansion [r(CUG)exp] and reverses molecular defects in two diseases mediated by the RNA - myotonic dystrophy type 1 (DM1) and Fuchs endothelial corneal dystrophy (FECD). Thus, a single structure-specific ligand has potential therapeutic benefit for multiple diseases, in contrast to oligonucleotide-based modalities that are customized for each disease by nature of targeting the gene that harbors the repeat. Indeed, the small molecule binds the target with nanomolar affinity and >100-fold specificity vs. many other RNAs and DNA. Interestingly, the compound’s downstream effects are different in the two diseases, owing to the location of the repeat expansion. In DM1, r(CUG)expis harbored in the 3’ untranslated region (UTR) of and mRNA, and the compound has no effect on the RNA’s abundance. In FECD, however, r(CUG)expis located in an intron, and the small molecule, by binding the repeat expansion, facilitates excision of the intron, which is then degraded by the exosome complex exonuclease, hRRP6. Thus, structure-specific, RNA-targeting small molecules can act disease-specifically to affect biology, either by disabling its gain-of-function mechanism (DM1) or by stimulating quality control pathways to rid a disease-affected cell of a toxic RNA (FECD).Significance statementMany different diseases are caused by toxic structured RNAs. Herein, we designed a lead small molecule that binds a toxic structure and rescues disease biology. We show that a structure-specific small molecule can improve disease-associated defects in two diseases that share the common toxic RNA structure. In one disease, the toxic structure is harbored in an intron and causes its retention. The compound facilitates processing of a retained intron, enabling the disease-affected cell to remove the toxic RNA.
Uptake of monoaromatic hydrocarbons during biodegradation by FadL channel-mediated lateral diffusion
Authors: Somboon Kamolrat , Doble Anne , Bulmer David , Baslé Arnaud , Khalid Syma , van den Berg Bert 
Published: May 2020

AbstractIn modern societies, biodegradation of hydrophobic pollutants generated by industry is important for environmental and human health. In Gram-negative bacteria, biodegradation depends on facilitated diffusion of the pollutant substrates into the cell, mediated by specialised outer membrane (OM) channels. Here we show, via a combined experimental and computational approach, that the uptake of monoaromatic hydrocarbons such as toluene inPseudomonas putidaF1 (PpF1) occurs via lateral diffusion through FadL channels. Contrary to classical diffusion channels via which polar substrates move directly into the periplasmic space, PpF1 TodX and CymD direct their hydrophobic substrates into the OM via a lateral opening in the channel wall, bypassing the polar barrier formed by the lipopolysaccharide leaflet on the cell surface. Our study suggests that lateral diffusion of hydrophobic molecules is themodus operandiof all FadL channels, with potential implications for diverse areas such as biodegradation, quorum sensing and gut biology.
SIRT1 activity orchestrates ECM expression during hESC-chondrogenic differentiation
Authors: Smith Christopher A , Humphreys Paul A , Bates Nicola , Naven Mark A , Cain Stuart A , Dvir-Ginzberg Mona , Kimber Susan J 
Published: May 2020

AbstractEpigenetic modification is a key driver of differentiation and the deacetylase Sirtuin1 (SIRT1) is an established regulator of cell function, ageing and articular cartilage homeostasis. Here we investigate the role of SIRT1 during development of chondrocytes by using human embryonic stem cells (hESCs). HESC-chondroprogenitors were treated with SIRT1 activator; SRT1720, or inhibitor; EX527, at different development stages. Activation of SIRT1 during 3D-pellet culture led to significant increases in expression of ECM genes for type-II collagen (COL2A1) and aggrecan (ACAN), and chondrogenic transcription factorsSOX5andARID5B, with SOX5 ChIP analysis demonstrating enrichment on the ACAN –10 enhancer. Unexpectedly, while ACAN was enhanced, GAG retention in the matrix was reduced when SIRT1 was activated. Significantly,ARID5BandCOL2A1were positively correlated, with Co-IP indicating association of ARID5B with SIRT1 suggesting that COL2A1 expression is promoted by an ARID5B and SIRT1 interaction. In conclusion, SIRT1 activation positively impacts on the expression of the main ECM proteins, whilst altering ECM composition and suppressing GAG content during cartilage development. These results suggest that SIRT1 activity can be beneficial to cartilage development and matrix protein synthesis but tailored by addition of other positive GAG mediators.
Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells: Nafamostat is the most potent antiviral drug candidate
Authors: Ko Meehyun , Jeon Sangeun , Ryu Wang-Shick , Kim Seungtaek 
Published: May 2020

AbstractDrug repositioning represents an effective way to control the current COVID-19 pandemic. Previously, we identified 24 FDA-approved drugs which exhibited substantial antiviral effect against SARS-CoV-2 in Vero cells. Since antiviral efficacy could be altered in different cell lines, we developed an antiviral screening assay with human lung cells, which is more appropriate than Vero cell. Comparative analysis of antiviral activities revealed that nafamostat is the most potent drug in human lung cells (IC50= 0.0022µM).
Expanding theCaenorhabditis elegansauxin-inducible degron system toolkit with internal expression and degradation controls and improved modular constructs for CRISPR/Cas9-mediated genome editing
Authors: Ashley Guinevere , Duong Tam , Levenson Max T. , Martinez Michael A. Q. , Hibshman Jonathan D. , Saeger Hannah N. , Doonan Ryan , Palmisano Nicholas J. , Martinez-Mendez Raquel , Davidson Brittany , Zhang Wan , Ragle James Matthew , Medwig-Kinney Taylor N. , Sirota Sydney S. , Goldstein Bob , Matus David Q. , Dickinson Daniel J. , Reiner David J. , Ward Jordan D. 
Published: May 2020

AbstractThe auxin-inducible degron (AID) system has emerged as a powerful tool to conditionally deplete proteins in a range of organisms and cell-types. Here, we describe a toolkit to augment the use of the AID system inCaenorhabditis elegans. We have generated a set of single-copy, tissue-specific (germline, intestine, neuron, muscle, hypodermis, seam cell, anchor cell) and pan-somaticTIR1-expressing strains carrying an equimolar co-expressed blue fluorescent reporter to enable use of both red and green channels in experiments. We have also constructed a set of plasmids to generate fluorescent protein::AID fusions through CRISPR/Cas9-mediated genome editing. These templates can be produced through frequently used cloning systems (Gibson assembly or SapTrap) or through ribonucleoprotein complex-mediated insertion of PCR-derived, linear repair templates. We have generated a set of sgRNA plasmids carrying modifications shown to boost editing efficiency, targeting standardized transgene insertion sites on chromosomes I and II. Together these reagents should complement existingTIR1strains and facilitate rapid and high-throughput fluorescent protein::AID* tagging of factors of interest. This battery of new TIR1-expressing strains and modular, efficient cloning vectors serves as a platform for facile assembly of CRISPR/Cas9 repair templates for conditional protein depletion.