bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Mortality During Holidays and the COVID-19 Pandemic in Israel
Authors: Rasnic Roni , Klinger Danielle , Ofer Dan , Comay Yoav , Linial Michal , Bachmat Eitan 
Published: July 2020

AbstractEvidence suggests varied trends in mortality surrounding the holiday period. Most studies support an association between increased mortality rates and holidays. We compare the effect of the number of holiday days per week on the overall mortality rate in the Israeli population. Between 2000-2020, we see significantly reduced mortality rates in weeks containing national holidays. We observed the same trend in all-cause mortality during the 3-weeks COVID-19 pandemic lockdown. As the Israeli health care system, and hospitals especially, function near peak capacity year-round, we propose that reduced medical service utilization during holidays and the COVID-19 lockdown period might underlie the lower mortality rates.
Long-read-sequenced reference genomes of the seven major lineages of enterotoxigenicEscherichia coli(ETEC) circulating in modern time
Authors: von Mentzer Astrid , Blackwell Grace A. , Pickard Derek , Boinett Christine J. , Joffré Enrique , Page Andrew J , Svennerholm Ann-Mari , Dougan Gordon , Sjöling Åsa 
Published: July 2020

AbstractBackgroundEnterotoxigenicEscherichia coli(ETEC) is an enteric pathogen responsible for the majority of diarrheal cases worldwide. ETEC infections are estimated to cause 80,000 fatalities per year, with the highest rates of burden, ca 75 million cases per year, amongst children under five years of age in resource-poor countries. It is also the leading cause of diarrhoea in travellers. Previous large-scale sequencing studies have found seven major ETEC lineages currently in circulation worldwide.ResultsWe used PacBio long-read sequencing combined with Illumina sequencing to create high-quality complete reference genomes for each of the major lineages with manually curated chromosomes and plasmids. The plasmids carrying ETEC virulence genes were compared to other available long-read sequenced ETEC strains using blastn. The ETEC reference strains harbour between two and five plasmids, including virulence, antibiotic resistance and phage-plasmids. The virulence plasmids carrying the colonisation factors are highly conserved as shown by comparison with plasmids with other ETEC strains and confirm that the plasmids and chromosomes of ETEC are both crucial for ETEC virulence and success as pathogens.ConclusionWe confirm that the major ETEC lineages all harbour conserved plasmids that have been associated with their respective background genomes for decades. The in-depth analysis of gene content, synteny and correct annotations of plasmids will elucidate other plasmids with and without virulence factors in related bacterial species. These reference genomes allow for fast and accurate comparison between different ETEC strains, and these data will form the foundation of ETEC genomics research for years to come.
Immature dendritic cells promote high-avidity tuning of vaccine T cell response
Authors: Kumbhari Adarsh , Egelston Colt A. , Lee Peter P. , Kim Peter S. 
Published: July 2020

ABSTRACTTherapeutic vaccines can elicit tumor-specific cytotoxic T lymphocytes (CTLs), but durable reductions in tumor burden require vaccines that stimulate high-avidity CTLs. Recent advances in immunotherapy responses have led to renewed interest in vaccine approaches, including dendritic cell vaccine strategies. However, dendritic cell requirements for vaccines that generate potent anti-tumor T-cell responses are unclear. Here we use mathematical modeling to show that counterintuitively, increasing levels of immature dendritic cells may lead to selective expansion of high-avidity CTLs. This finding contrasts with traditional dendritic cell vaccine approaches that have sought to harness ex vivo generated mature dendritic cells. We show that the injection of vaccine antigens in the context of increased numbers of immature dendritic cells results in a decreased overall peptide:MHC complex load that favors high-avidity CTL activation and expansion. Overall, our results provide a firm basis for further development of this approach, both alone and in combination with other immunotherapies such as checkpoint blockade.
Characterizing the diverse cells that associate with the developing commissures of the zebrafish forebrain
Authors: Schnabl J. , Litz M.P.H. , Schneider C. , PenkoffLidbeck N. , Bashiruddin S. , Schwartz M.S. , Alligood K. , Barresi M.J.F. 
Published: July 2020

AbstractDuring embryonic development of bilateral organisms, neurons send axons across the midline at specific points to connect the two halves of the nervous system with a commissure. Little is known about the cells at the midline that facilitate this tightly regulated process. We exploit the con served process of vertebrate embryonic development in the zebrafish model system to elucidate the identity of cells at the midline that may facilitate postoptic (POC) and anterior commissure (AC) development. We have discovered that three differentgfap+ astroglialcell morphologies persist in contact with pathfinding axons throughout commissure formation. Similarly,olig2+progenitor cells occupy delineated portions of the postoptic and anterior commissures. These earlyolig2+progenitors demonstrate glial-like morphologies despite the lack of a myelination marker. Moreover, we conclude that both thegfap+andolig2+progenitor cells give rise to neuronal populations in both the telencephalon and diencephalon. Interestingly, these varied cell populations showed significant developmental heterochrony between the telencephalon and diencephalon. Lastly, we also showed thatfli1a+mesenchymal cells migrate along the presumptive commissure regions before and during midline axon crossing. Furthermore, following commissure maturation, specific blood vessels formed at the midline of the POC and immediately ventral and parallel to the AC. This comprehensive account of the cellular populations that correlate with the timing and position of commissural axon pathfinding has supported the conceptual modeling and identification of the early forebrain architecture that may be necessary for proper commissure development.
Cytoplasmic aggregation of uranium in human dopaminergic cells after continuous exposure to soluble uranyl at non-cytotoxic concentrations
Authors: Carmona Asuncion , Porcaro Francesco , Somogyi Andrea , Roudeau Stéphane , Domart Florelle , Medjoubi Kadda , Aubert Michel , Isnard Hélène , Nonell Anthony , Rincel Anaïs , Paredes Eduardo , Vidaud Claude , Malard Véronique , Bresson Carole , Ortega Richard 
Published: July 2020

ABSTRACTUranium exposure can lead to neurobehavioral alterations in particular of the monoaminergic system, even at non-cytotoxic concentrations. However, the mechanisms of uranium neurotoxicity after non-cytotoxic exposure are still poorly understood. In particular, imaging uranium in neurons at low intracellular concentration is still very challenging. We investigated uranium intracellular localization by means of synchrotron X-ray fluorescence imaging with high spatial resolution (< 300 nm) and high analytical sensitivity (< 1 μg.g-1per 300 nm pixel). Neuron-like SH-SY5Y human cells differentiated into a dopaminergic phenotype were continuously exposed, for seven days, to a non-cytotoxic concentration (10 μM) of soluble natural uranyl. Cytoplasmic submicron uranium aggregates were observed accounting on average for 62% of the intracellular uranium content. In some aggregates, uranium and iron were co-localized suggesting common metabolic pathways between uranium and iron storage. Uranium aggregates contained no calcium or phosphorous indicating that detoxification mechanisms in neuron-like cells are different from those described in bone or kidney cells. Uranium intracellular distribution was compared to fluorescently labeled organelles (lysosomes, early and late endosomes) and to fetuin-A, a high affinity uranium-binding protein. A strict correlation could not be evidenced between uranium and the labelled organelles, or with vesicles containing fetuin-A. Our results indicate a new mechanism of uranium cytoplasmic aggregation after non-cytotoxic uranyl exposure that could be involved in neuronal defense through uranium sequestration into less reactive species. The remaining soluble fraction of uranium would be responsible for protein binding and the resulting neurotoxic effects.
Targeted intragenic demethylation initiates chromatin rewiring for gene activation
Authors: Liu Yanjing V. , Bassal Mahmoud A. , Jayasinghe Migara Kavishka , Lin Quy Xiao Xuan , Wu Chan-Shuo , Tang Jing Ping , Kwon Junsu , Zhou Qiling , Tan Hong Kee , Ebralidze Alexander K. , Le Minh T.N. , Chai Li , Benoukraf Touati , Ruscio Annalisa Di , Tenen Daniel G. 
Published: July 2020

AbstractAberrant DNA methylation in the region surrounding the transcription start site is a hallmark of gene silencing in cancer. Currently approved demethylating agents lack specificity and exhibit high toxicity. Herein we show, using thep16gene as an example, that targeted demethylation of the promoter-exon 1-intron 1 (PrExI) region initiates an epigenetic wave of local chromatin remodeling and distal long-range interactions, culminating in gene-locus specific activation. Through development of CRISPR-DiR (DNMT1-interacting RNA), in which ad hoc edited guides block methyltransferase activity in a locus-specific fashion, we demonstrate that demethylation is coupled to epigenetic and topological changes. These results suggest the existence of a specialized “demethylation firing center (DFC)” which can be switched on by an adaptable and selective RNA-mediated approach for locus-specific transcriptional activation.One Sentence SummaryLocus demethylation via CRISPR-DiR reshapes chromatin structure and specifically reactivates its cognate gene.
Query to reference single-cell integration with transfer learning
Authors: Lotfollahi Mohammad , Naghipourfar Mohsen , Luecken Malte D. , Khajavi Matin , Büttner Maren , Avsec Ziga , Misharin Alexander V. , Theis Fabian J. 
Published: July 2020

AbstractLarge single-cell atlases are now routinely generated with the aim of serving as reference to analyse future smaller-scale studies. Yet, learning from reference data is complicated by batch effects between datasets, limited availability of computational resources, and sharing restrictions on raw data. Leveraging advances in machine learning, we propose a deep learning strategy to map query datasets on top of a reference calledsingle-cell architectural surgery(scArches,https://github.com/theislab/scarches). It uses transfer learning and parameter optimization to enable efficient, decentralized, iterative reference building, and the contextualization of new datasets with existing references without sharing raw data. Using examples from mouse brain, pancreas, and whole organism atlases, we showcase that scArches preserves nuanced biological state information while removing batch effects in the data, despite using four orders of magnitude fewer parameters compared tode novointegration. To demonstrate mapping disease variation, we show that scArches preserves detailed COVID-19 disease variation upon reference mapping, enabling discovery of new cell identities that are unseen during training. We envision our method to facilitate collaborative projects by enabling the iterative construction, updating, sharing, and efficient use of reference atlases.
Flavoceraceomyces(NOM. PROV.) (Irpicaceae, Basidiomycota), encompassingCeraceomyces serpensandCeriporia sulphuricola, and a new resupinate species,F. damiettense, found onPhoenix dactylifera(date palm) trunks in the Nile Delta of Egypt
Authors: El-Gharabawy Hoda M. , Leal-Dutra Caio A. , Griffith Gareth W. 
Published: July 2020

AbstractThe taxonomy of Polyporales is complicated by the variability in key morphological characters across families and genera, now being gradually resolved through molecular phylogenetic analyses. Here a new resupinate species,Flavoceraceomyces damiettense(NOM. PROV.) found on the decayed trunks of date palm (Phoenix dactylifera) trees in the fruit orchards of the Nile Delta region of Egypt is reported. Multigene phylogenetic analyses based on ITS, LSU, EF1α, RPB1 and RPB2 loci place this species in Irpicaceae, and forming a distinct clade withCeraceomyces serpensandCeriporia sulphuricolor, which we also incorporate into a new genusFlavoceraceomyces(NOM. PROV.). The honey-yellow basidiomes with white margins and presence of crystal-encrusted hyphae in the hymenium and subiculum are distinctive features ofFlavoceraceomyces(NOM. PROV.), despite variability in hymenium morphology and presence of clamp connections and cystidia, as noted for other genera within Irpicacae.F. damiettenseis hitherto consistently associated with date palms killed by the red palm weevilRhynchophorus ferrugineus, a highly damaging and invasive pest, recently spread to the Mediterranean region.F. damiettensecauses rapid wood decay by a potentially unusual white-rot mechanism and may play a role in the damage caused byR. ferrugineus.
Automatic Integration of Gender Information during Phrase Processing: ERP Evidence
Authors: Alekseeva Maria , Myachykov Andriy , Margaretto Beatriz Bermudez , Shtyrov Yury 
Published: July 2020

AbstractBoth linguistic (e.g., words, syntax) and extralinguistic (e.g., voice quality) information needs to be considered by interlocutors during linguistic communication. The effects of extralinguistic information on neural sentence processing are particularly poorly understood. Here, we used EEG and passive non-attend design with visual distraction in order to investigate how extralinguistic information affects brain activity during syntactic processing. We collected ERPs while participants listened to Russian pronoun-verb phrases recorded in either male or female voice. We manipulated congruency between the grammatical gender signaled by the verb’s ending and the speaker’s apparent gender. We registered both early and late phrase processing signatures in the incongruent conditions including ELAN (peaking at ∼150 ms) and N400. Our data suggest a high degree of automaticity in integrating extralinguistic information during syntactic processing indicating existence of a rapid automatic syntactic integration mechanism sensitive to both linguistic and extralinguistic information.
New genes involved in Angelman syndrome-like: expanding the genetic spectrum
Authors: Aguilera Cinthia , Gabau Elisabeth , Ramirez-Mallafré Ariadna , Brun-Gasca Carme , Dominguez-Carral Jana , Delgadillo Veronica , Laurie Steve , Derdak Sophia , Padilla Natàlia , de la Cruz Xavier , Capdevila Núria , Spataro Nino , Baena Neus , Guitart Miriam , Ruiz Anna 
Published: July 2020

AbstractAngelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with absence of speech, happy disposition, frequent laughter, hyperactivity, stereotypies, ataxia and seizures with specific EEG abnormalities. There is a 10-15% of patients with an AS phenotype whose genetic cause remains unknown (Angelman-like syndrome, AS-like). Whole-exome sequencing (WES) was performed on a cohort of 14 patients with clinical features of AS and no molecular diagnosis. As a result, we identified 10de novoand 1 X-linked pathogenic/likely pathogenic variants in 10 neurodevelopmental genes (SYNGAP1, VAMP2, TBL1XR1, ASXL3, SATB2, SMARCE1, SPTAN1, KCNQ3, SLC6A1andLAS1L) and one deleteriousde novovariant in a candidate gene (HSF2). Our results highlight the wide genetic heterogeneity in AS-like patients and expands the differential diagnosis. New AS-like genes do not interact directly withUBE3Agene product but are involved in synapsis and neuron system development.
Sample pooling methods for efficient pathogen screening: Practical implications
Authors: Furstenau Tara N. , Cocking Jill H. , Hepp Crystal M. , Fofanov Viacheslav Y. 
Published: July 2020

AbstractDue to the large number of negative tests, individually screening large populations for rare pathogens can be wasteful and expensive. Sample pooling methods improve the efficiency of large-scale pathogen screening campaigns by reducing the number of tests and reagents required to accurately categorize positive and negative individuals. Such methods rely on group testing theory which mainly focuses on minimizing the total number of tests; however, many other practical concerns and tradeoffs must be considered when choosing an appropriate method for a given set of circumstances. Here we use computational simulations to determine how several theoretical approaches compare in terms of (a) the number of tests, to minimize costs and save reagents, (b) the number of sequential steps, to reduce the time it takes to complete the assay, (c) the number of samples per pool, to avoid the limits of detection, (d) simplicity, to reduce the risk of human error, and (e) robustness, to poor estimates of the number of positive samples. We found that established methods often perform very well in one area but very poorly in others. Therefore, we introduce and validate a new method which performs fairly well across each of the above criteria making it a good general use approach.
Selected reaction monitoring for the quantification ofEscherichia coliribosomal proteins
Authors: Kosaka Yuishin , Aoki Wataru , Mori Megumi , Aburaya Shunsuke , Ohtani Yuta , Minakuchi Hiroyoshi , Ueda Mitsuyoshi 
Published: July 2020

AbstractRibosomes are the sophisticated machinery that is responsible for protein synthesis in a cell. Recently, quantitative mass spectrometry (qMS) based on data-dependent acquisition (DDA) have been widely used to understand the biogenesis and function of ribosomes. However, DDA-based qMS sometimes does not provide the reproducible and quantitatively reliable analysis that is needed for high-throughput hypothesis testing. To overcome this problem, we developed a highly sensitive, specific, and accurate method to quantify all ribosomal proteins (r-proteins) by combining selected reaction monitoring (SRM) and isotope labeling. We optimized the SRM methods using purified ribosomes andEscherichia colilysates, and verified this approach as a high-throughput analytical tool by detecting 41 of the 54 r-proteins separately synthesized inE. coliS30 extracts. The SRM methods will enable us to utilize qMS as a high-throughput hypothesis testing tool in the research ofE. coliribosomes, and they have potential to accelerate the understanding of ribosome biogenesis, function, and the development of engineered ribosomes with additional functions.
Inhibition of p-glycoprotein does not increase the efficacy of proteasome inhibitors in multiple myeloma cells
Authors: Mynott Rachel L. , Wallington-Beddoe Craig T. 
Published: July 2020

AbstractThe aim of this study is to determine whether manipulation of the drug transporter P-glycoprotein improves the efficacy of proteasome inhibitors in multiple myeloma cells. P-glycoprotein is a well-known drug transporter that is associated with chemotherapy resistance in a number of cancers but its role in modulating the efficacy of proteasome inhibitors in multiple myeloma is not well understood. Research has shown that the second generation proteasome inhibitor carfilzomib is a substrate of P-glycoprotein and as such its efficacy may correlate with P-glycoprotein activity. In contrast to carfilzomib, research concerning the first-in-class proteasome inhibitor bortezomib is inconsistent with some reports suggesting that inhibition of P-glycoprotein increases bortezomib cytotoxicity in multiple myeloma cells whereas others have shown no effect. Through the mining of publicly available gene expression microarrays of patient bone marrow, we show that P-glycoprotein gene expression increases with the disease stages leading to multiple myeloma. However, RNA-seq on LP-1 cells treated with bortezomib or carfilzomib demonstrated minimal basal P-glycoprotein expression which did not increase with treatment. Moreover, only one (KMS-18) of nine multiple myeloma cell lines expressed P-glycoprotein, including RPMI-8226 cells that are resistant to bortezomib or carfilzomib. We hypothesised that by inhibiting P-glycoprotein, multiple myeloma cell sensitivity to proteasome inhibitors would increase, thus providing a potential approach to improving responses and reversing resistance to these agents. However, the sensitivity of multiple myeloma cells lines to proteasome inhibition was not enhanced by inhibition of P-glycoprotein with the specific inhibitor tariquidar. In addition, targeting glucosylceramide synthase with eliglustat did not inhibit P-glycoprotein activity and also did not improve proteasome inhibitor efficacy except at a high concentration. We conclude that P-glycoprotein is poorly expressed in multiple myeloma cells, its inhibition does not enhance the efficacy of proteasome inhibitors, and it is unlikely to be a useful avenue for further translational research.
Chemical and technological characteristics of sugarcane as a function of pelletized organomineral fertilizer with filter cake or sewage sludge sources
Authors: Gonçalves Carlos André , de Camargo Reginaldo , de Sousa Robson Thiago Xavier , Soares Narcisa Silva , de Oliveira Roberta Camargos , Stanger Mayara Cristina , Quintão Lana Regina Maria , Lemes Ernane Miranda 
Published: July 2020

AbstractSugarcane is one of the major alternatives for the biofuel sector and its large production has considerable environmental impacts. Organomineral fertilizers formulated with environmental liabilities such as filter cake and sewage sludge positively affect parameters of plant growth and development. The objective of this study was to evaluate the chemical and technological characteristics of sugarcane fertilized with pelletized organomineral fertilizers based on filter cake and sewage sludge. Eight field treatments were studied, being three levels of organomineral (50, 100, 150%) of two organic matter sources (filter cake, sewage sludge), plus a control with 100% of the recommended fertilization via mineral fertilizer and no fertilization control (0%). Sugarcane was evaluated during two consecutive harvest, and the amount of stalks per hectare (ton ha−1), the sugarcane productivity (ton ha−1), the quantity of sugar per hectare (TSH, ton ha−1), and the chemical and technological analysis of the sugarcane juice: pol (%), brix (%), purity (%) and fiber (%) were evaluated. None of the organomineral sources or doses differed from the exclusive mineral fertilization. The analysis of both harvests indicated that the first cut was the most productive since the responses of the first harvest were superior or similar to the second harvest. The recommended organomineral dose to obtaining maximum quantitative and qualitative sugarcane results was between 102 and 109% of the regular recommendation for mineral fertilization, regardless of the organic source in the first sugarcane harvest. In the second sugarcane harvest, sewage sludge source increase by 4.68 and 4.19% the total amount of sugar per hectare and the quantity of sugarcane compared to the sugarcane filter cake source. Sewage sludge and sugarcane filter cake as sources for organominerals are viable alternatives and advantageous in economic and environmental terms for the cultivation of sugarcane.