bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Metric Learning Network using Proxies for Chromosome Classification and Retrieval in Karyotyping Test
Authors: Jung Hwejin , Park Bogyu , Lee Sangmun , Hyun Seungwoo , Lee Jinah , Seo Junseok , Koo Sunyoung , Lee Mina 
Published: May 2020

AbstractIn karyotyping, the classification of chromosomes is a tedious, complicated, and time-consuming process. It requires extremely careful analysis of chromosomes by well-trained cytogeneticists. To assist cytogeneticists in karyotyping, we introduce Proxy-ResNeXt-CBAM which is a metric learning based network using proxies with a convolutional block attention module (CBAM) designed for chromosome classification. RexNeXt-50 is used as a backbone network. To apply metric learning, the fully connected linear layer of the backbone network (ResNeXt-50) is removed and is replaced with CBAM. The similarity between embeddings, which are the outputs of the metric learning network, and proxies are measured for network training.Proxy-ResNeXt-CBAM is validated on a public chromosome image dataset, and it achieves an accuracy of 95.86%, a precision of 95.87%, a recall of 95.9%, and an F-1 score of 95.79%. Proxy-ResNeXt-CBAM which is the metric learning network using proxies outperforms the baseline networks. In addition, the results of our embedding analysis demonstrate the effectiveness of using proxies in metric learning for optimizing deep convolutional neural networks. As the embedding analysis results show, Proxy-ResNeXt-CBAM obtains a 94.78% Recall@1 in image retrieval, and the embeddings of each chromosome are well clustered according to their similarity.
Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells
Authors: Wei Xiaolong , Yang Jiekun , Adair Sara J. , Kuscu Cem , Lee Kyung Yong , Kane William , O’hara Patrick , Liu Denis , Demirlenk Yusuf Mert , Habieb Alaa Hamdi , Yilmaz Ebru , Dutta Anindya , Bauer Todd W. , Adli Mazhar 
Published: May 2020

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancer to treat. Due to the asymptomatic nature of the disease and ineffective drug treatment modalities, the survival rate of PDAC patients remains one of the lowest. The recurrent genetic alterations in PDAC are yet to be targeted; therefore, identifying effective therapeutic combinations is desperately needed. Here, we performed anin vivoCRISPR screening in a clinically relevant patient-derived xenograft (PDX) model system to identify synergistic drug combinations for PDAC treatment. Our approach revealed protein arginine methyltransferase gene 5 (PRMT5) as a promising druggable candidate whose inhibition creates synergistic vulnerability of PDAC cells to gemcitabine. Genetic and pharmacological inhibition results indicate that of PRMT5 depletion results in synergistic cytotoxicity with Gem due to depleted replication protein A (RPA) levels and an impaired non-homology end joining (NHEJ) DNA repair. Thus, the novel combination creates conditional lethality through the accumulation of excessive DNA damage and cell death, bothin vitroandin vivo. The findings demonstrate that unbiased genetic screenings combined with a clinically relevant model system is an effective approach in identifying synthetic lethal drug combinations for cancer treatment.STATEMENT of SIGNIFICANCEIdentify synergistic drug combinations for PDAC is a significant unmet need. Through CRISPR screening, we discovered and validated that PRMT5 depletion creates synergistic vulnerability of PDAC cells to gemcitabine. Mechanistically, the combination impairs DNA repair, synergistic accumulation of DNA damage and cell deathin vitroandin vivo.
Combined Selective Plane Illumination Microscopy and FRAP maps intranuclear diffusion of NLS-GFP
Authors: Hobson Chad M. , O’Brien E. Timothy , Falvo Michael R. , Superfine Richard 
Published: May 2020

AbstractSince its initial development in 1976, fluorescence recovery after photobleaching (FRAP) has been one of the most popular tools for studying diffusion and protein dynamics in living cells. Its popularity is derived from the widespread availability of confocal microscopes and the relative ease of the experiment and analysis. FRAP, however, is limited in its ability to resolve spatial heterogeneity. Here, we combine selective plane illumination microscopy (SPIM) and FRAP to create SPIM-FRAP, wherein we use a sheet of light to bleach a 2D plane and subsequently image the recovery of the same image plane. This provides simultaneous quantification of diffusion or protein recovery for every pixel in a given 2D slice, thus moving FRAP measurements beyond these previous limitations. We demonstrate this technique by mapping intranuclear diffusion of NLS-GFP in live MDA-MB-231 cells; SPIM-FRAP proves to be an order of magnitude faster than fluorescence correlation spectroscopy (FCS) based techniques for such measurements. We observe large length-scale (> ~500 nm) heterogeneity in the recovery times of NLS-GFP, which is validated against simulated data sets. 2D maps of recovery times were correlated with fluorescence images of H2B to address conflicting literature on the role of chromatin in diffusion of small molecules. We observed no correlation between histone density and diffusion. We developed a diffusion simulation for our SPIM-FRAP experiments to compare across techniques; our measured diffusion coefficients are on the order of previously reported results, thus validating the quantitative accuracy of SPIM-FRAP relative to well-established methods. With the recent rise of accessibility of SPIM systems, SPIM-FRAP is set to provide a simple and quick means of quantifying the spatial distribution of protein recovery or diffusion in living cells.Statement of SignificanceWe developed selective plane illumination microscopy combined with fluorescence recovery after photobleaching (SPIM-FRAP) to perform simultaneous FRAP measurements for each pixel in a 2D slice. This technique has the potential to be implemented on almost any light sheet microscope with minimal software development. FRAP studies were previously unable to resolve spatial heterogeneity and FCS techniques require minute-long acquisition times; SPIM-FRAP remedies both of these issues by generating FRAP-based diffusion maps in 4 seconds. This technique can easily be expanded to 3D by photobleaching a single plane and performing light sheet volumetric imaging, which has the benefits of minimal photobleaching and phototoxicity for studying long-term protein turnover. Furthermore, SPIM-FRAP of slowly-recovering structures enables characterization of spatial distortions to measure intracellular stresses.
Visual gene expression reveals a cone to rod developmental progression in deep-sea fishes
Authors: Lupše Nik , Cortesi Fabio , Freese Marko , Marohn Lasse , Pohlman Jan-Dag , Wysujack Klaus , Hanel Reinhold , Musilova Zuzana 
Published: May 2020

AbstractVertebrates use cone cells in the retina for colour vision and rod cells to see in dim light. Many deep-sea fishes have adapted to their environment to have only rod cells in the retina, while both rod and cone genes are still preserved in their genomes. As deep-sea fish larvae start their lives in the shallow, and only later submerge to the depth, they have to cope with diverse environmental conditions during ontogeny. Using a comparative transcriptomic approach in 20 deep-sea fish species from eight teleost orders, we report on a developmental cone-to-rod switch. While adults mostly rely on rod opsin (RH1) for vision in dim light, larvae almost exclusively express middle-wavelength-sensitive (“green”) cone opsins (RH2) in their retinas. The phototransduction cascade genes follow a similar ontogenetic pattern of cone-followed by rod-specific gene expression in most species, except for the pearleye and sabretooth (Aulopiformes), in which the cone cascade remains dominant throughout development. By inspecting the whole genomes of five deep-sea species (four of them sequenced within this study:Idiacanthus fasciola, Chauliodus sloani; Stomiiformes;Coccorella atlantica,andScopelarchus michaelsarsi; Aulopiformes), we found that deep-sea fish possess one or two copies of the rodRH1opsin gene, and up to seven copies of the coneRH2opsin genes in their genomes, while other cone opsin classes have been mostly lost. Our findings hence provide molecular evidence for a limited opsin gene repertoire and a conserved vertebrate pattern whereby cone photoreceptors develop first and rod photoreceptors are added only at later developmental stages.
Neuronal timescales are functionally dynamic and shaped by cortical microarchitecture
Authors: Gao Richard , van den Brink Ruud L. , Pfeffer Thomas , Voytek Bradley 
Published: May 2020

AbstractComplex cognitive functions such as working memory and decision-making require information maintenance over many timescales, from transient sensory stimuli to long-term contextual cues. While theoretical accounts predict the emergence of a corresponding hierarchy of neuronal timescales, direct electrophysiological evidence across the human cortex is lacking. Here, we infer neuronal timescales from invasive intracranial recordings. Timescales increase along the principal sensorimotor-to-association axis across the entire human cortex, and scale with single-unit timescales within macaques. Cortex-wide transcriptomic analysis shows direct alignment between timescales and expression of excitation- and inhibition-related genes, as well as genes specific to voltage-gated transmembrane ion transporters. Finally, neuronal timescales are functionally dynamic: prefrontal cortex timescales expand during working memory maintenance and predict individual performance, while cortex-wide timescales compress with aging. Thus, neuronal timescales follow cytoarchitectonic gradients across the human cortex, and are relevant for cognition in both short- and long-terms, bridging microcircuit physiology with macroscale dynamics and behavior.
Basis of Specificity for a Conserved and Promiscuous Chromatin Remodeling Protein
Authors: Donovan Drake A. , Crandall Johnathan G. , Truong Vi N. , Vaaler Abigail L. , Bailey Thomas B. , Dinwiddie Devin , McKnight Laura E. , McKnight Jeffrey N. 
Published: May 2020

AbstractEukaryotic genomes are organized dynamically through the repositioning of nucleosomes. Isw2 is an enzyme that has been previously defined as a genome-wide, non-specific nucleosome spacing factor. Here, we show that Isw2 instead acts as an obligately targeted nucleosome remodelerin vivothrough physical interactions with sequence-specific factors. We demonstrate that Isw2-recruiting factors use small and previously uncharacterized epitopes, which direct Isw2 activity through highly conserved acidic residues in the Isw2 accessory protein Itc1. This interaction orients Isw2 on target nucleosomes, allowing for precise nucleosome positioning at targeted loci. Finally, we show that these critical acidic residues have been lost in theDrosophilalineage, potentially explaining the inconsistently characterized function of Isw2-like proteins. Altogether, these data suggest an “interacting barrier model” where Isw2 interacts with a sequence-specific factor to accurately and reproducibly position a single, targeted nucleosome to define the precise border of phased chromatin arrays.
Alveolar early progenitors in the aged human lung have increased expression of ACE2 accompanied with genes involved in beta-amyloid clearance: Indication of SARS-CoV-2 also using soluble ACE2 in aged-lungs to enter ACE2-negative cells
Authors: Chaudhri Virendra K. 
Published: May 2020

ABSTRACTCOVID-19 is the current pandemic caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) that uses ACE2 protein on the cell surface. By analyzing publicly available datasets, I uncovered that alveolar early progenitors (AEP), a subset of the type-2 pneumocytes, showed increased ACE2 expression in the older lungs. AEPs co-express TMPRSS2, CTSL. Aged AEP-gene expression signature suggested an active response to beta-amyloid-induced ACE2 shedding, to limit the intercellular beta-amyloid accumulation in otherwise healthy human lungs. Susceptibility of AEP to SARS-CoV2 and ACE2 secretory capacity of these cells makes aged human lung sensitive for rapid-infection, by a possible in-solution ACE2 binding and entry into ACE2-negative cells, thereby increasing the target cell diversity and numbers. Single-cell analysis of COVID19 patients with moderate and severe infections, clearly showed that severe infections showed SARS-CoV-2 transcript in ACE2-negative TMPRSS-negative but CTSL-positive cell types in their bronchoalveolar lavage fluid, validating in-solution ACE2-binding enabling infection.
The fate of SARS-CoV-2 in WWTPs points out the sludge line as a suitable spot for monitoring
Authors: Balboa Sabela , Mauricio-Iglesias Miguel , Rodriguez Santiago , Martínez-Lamas Lucía , Vasallo Francisco J. , Regueiro Benito , Lema Juan M. 
Published: May 2020

AbstractSARS-CoV-2 genetic material is detectable in the faeces of a considerable part of COVID-19 cases and hence, in the urban wastewater. This fact was confirmed early during the spread of the COVID-19 pandemic and prompted several studies that proposed monitoring its incidence by wastewater. This paper studies the fate of SARS-CoV-2 genetic material in wastewater treatment plants using RT-qPCR with a two-fold goal: i) to check the safety of the water effluent and also of the sludge produced and ii) based on the understanding of the virus particles fate, to identify the most suitable spots for detecting the incidence of COVID-19 and monitor its evolution. On the grounds of the affinity of enveloped virus towards biosolids, we hypothesized that the sludge line acts as a concentrator of SARS-CoV-2 genetic material. Sampling several spots in primary, secondary and sludge treatment at the Ourense (Spain) WWTP showed that, in effect, most of SARS-CoV-2 particles cannot be detected in the water effluent as they are retained by the sludge line. We identified the sludge thickener as a suitable spot for detecting SARS-CoV-2 particles thanks to its higher solids concentration (more virus particles) and longer residence time (less sensitive to dilution caused by precipitation). Although more studies will be needed for confirmation, these results contribute to clarify the role of WWTPs in COVID-19 mitigation.
Somatostatin interneurons activated by 5-HT2Areceptor suppress slow oscillations in medial entorhinal cortex
Authors: De Filippo Roberto , Rost Benjamin R. , Stumpf Alexander , Cooper Claire , Tukker John J. , Harms Christoph , Beed Prateep , Schmitz Dietmar 
Published: May 2020

AbstractSerotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical network activity universally present across species. SOs are observed during anesthesia and are considered to be the default cortical activity pattern. We discovered that (±)3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs within the entorhinal cortex (EC) in anesthetized mice. Combining opto- and pharmacogenetic manipulations within vitroelectrophysiological recordings, we uncovered that somatostatin-expressing (Sst) interneurons activated by the 5-HT2Areceptor (5-HT2AR) play an important role in the suppression of SOs. Since 5-HT2AR signaling is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, we propose that the newly discovered link between Sst interneurons and 5-HT will contribute to our understanding of these complex topics.
Investigating the spectral features of the brain meso-scale structure at rest
Authors: Iandolo Riccardo , Semprini Marianna , Sona Diego , Mantini Dante , Avanzino Laura , Chiappalone Michela 
Published: May 2020

AbstractRecent studies provide novel insights into the meso-scale organization of the brain, highlighting the co-occurrence of different structures: classic assortative (modular), disassortative and core-periphery. However, the spectral properties of the brain meso-scale remain mostly unexplored. To fill this knowledge gap, we investigated how the meso-scale structure is organized across the frequency domain. We analyzed the resting state activity of healthy participants with source-localized high-density electroencephalography signals. Then, we inferred the community structure using weighted stochastic block-modelling to capture the landscape of meso-scale structures across the frequency domain. We found that meso-scale modalities were mixed over the frequency spectrum, with a core-periphery structure predominance. Nevertheless, we also highlighted a selective increase of disassortativity in the delta and theta bands, and of assortativity in the low gamma band (30-50 Hz). We further described other features of the meso-scale organization by identifying those brain regions which, at the same time, i) exhibited the highest degree of assortativity, disassortativity and core-peripheriness (i.e. participation), ii) were consistently assigned to the same community, irrespective from the granularity imposed by WSBM (i.e. granularity-invariance). We defined those brain areas as Participation and Granularity Invariant. In conclusion, we observed that the brain spontaneous activity shows frequency-specific meso-scale organization which may support spatially distributed and local information processing.
The impact of daily caffeine intake on nighttime sleep: signs of overnight withdrawal?
Authors: Weibel Janine , Lin Yu-Shiuan , Landolt Hans-Peter , Kistler Joshua , Rehm Sophia , Rentsch Katharina M. , Slawik Helen , Borgwardt Stefan , Cajochen Christian , Reichert Carolin F. 
Published: May 2020

AbstractAcute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 x 150 mg caffeine daily), withdrawal (3 x 150 mg caffeine for eight days, then switch to placebo), and placebo (3 x placebo daily). After nine days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture, nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement (NREM) sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure or subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.Statement of SignificanceCaffeine consumption is highly prevalent worldwide and has been repeatedly shown to acutely disrupt sleep, particularly when consumed after several days of abstinence or close to bedtime. However, commonly, caffeine is consumed daily and during daytime. Our well-controlled laboratory study revealed that this common pattern of intake affects nighttime sleep differently: While slow-wave sleep duration or slow-wave activity were rather similar compared to placebo, caffeine intake surprisingly reduced EEG power density in the sigma frequencies. In the light of earlier studies, this might present early signs of caffeine withdrawal which occurs due to overnight caffeine abstinence. The present findings provide novel insights into the impact of daily presence and nightly abstinence of caffeine on nighttime sleep in regular consumers.
Epidemiological study on foot-and-mouth disease in small ruminants: sero-prevalence and risk factor assessment in Kenya
Authors: Chepkwony Eunice C. , Gitao George C. , Muchemi Gerald M. , Sangula Abraham K. , Kairu-Wanyoike Salome W. 
Published: May 2020

AbstractFoot-and-mouth disease (FMD) is endemic in Kenya affecting cloven-hoofed ruminants. The epidemiology of the disease in small ruminants (SR) is not documented. We carried out a cross-sectional study, the first in Kenya, to estimate the sero-prevalence of FMD in SR and the associated risk factors nationally. Selection of animals to be sampled used a multistage cluster sampling approach. Serum samples totaling 7564 were screened for FMD antibodies of Non-Structural-Proteins using ID Screen®NSP Competition ELISA kit. Data were analysed using Statistical Package for Social Studies Version 20. To identify the risk factors, chi-square and logistic regression analyses were used. The country animal level sero-prevalence was 23.3% (95% CI: 22.3-24.3%) while herd level sero-prevalence was 77.6% (95% CI: 73.9-80.9%). Sero-positivity was significantly higher in the pastoral zone (31.5%) than in the sedentary zone at 14.5% (χ2 =303.2, p<0.05). In the most parsimonious backward fitting logistic multivariable regression, the only risk factors that were significantly positively associated with FMD sero-positivity in SR were multipurpose (OR=1.150; p=0.034) and dairy production types (OR=2.029; p=0.003). Those that were significantly negatively associated with FMD sero-positivity were male sex (OR=0.856; p=0.026), young age (OR=0.601; p=0.037), sedentary production zone (OR=0.471; p<0.001), bringing in of SR (OR=0.838; p=0.004), purchase of SR from market/middlemen (OR=0.877; p=0.049), no interaction with wildlife (OR=0.657; p<0.001), mixed production type (OR=0.701; p=0.016), enclosure of SR day and night (OR=0.515; p=0.001), migratory grazing system (OR=0.807; p=0.047), on-farm watering system (OR=0.724; p=0.002), male-from-another-farm (OR=0.723; p=0.030) and artificial insemination (OR=0.357; p=0.008) breeding methods.This study showed that there is widespread undetected virus circulation in SR indicated by ubiquitous spatial distribution of significant FMD sero-positivity in the country. The risk factors were mainly husbandry related. Strengthening of risk-based FMD surveillance in carrier SR which pose potential risk of virus transmission to other susceptible species is recommended. Adjustment of husbandry practices to control FMD in SR and in-contact species is suggested. Cross-transmission and more risk factors need to be researched.