bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic identification of players in the flavonoid biosynthesis with application on the biomedicinal plantCroton tiglium
Authors: Pucker Boas , Reiher Franziska , Schilbert Hanna Marie 
Published: June 2020

AbstractThe flavonoid biosynthesis is a well characterised model system for specialised metabolism and transcriptional regulation in plants. Flavonoids have numerous biological functions like UV protection and pollinator attraction, but also biotechnological potential. Here, we present Knowledge-based Identification of Pathway Enzymes (KIPEs) as an automatic approach for the identification of players in the flavonoid biosynthesis. KIPEs combines comprehensive sequence similarity analyses with the inspection of functionally relevant amino acid residues and domains in subjected peptide sequences. Comprehensive sequence sets of flavonoid biosynthesis enzymes and knowledge about functionally relevant amino acids were collected. As a proof of concept, KIPEs was applied to investigate the flavonoid biosynthesis of the medicinal plantCroton tigliumbased on a transcriptome assembly. Enzyme candidates for all steps in the biosynthesis network were identified and matched to previous reports of corresponding metabolites inCrotonspecies.
A Time Series Analysis of Trends in Medicare Utilization and Reimbursement for Cancer Immunotherapy Drugs: 2012-2017
Authors: Puri Pranav , Cortese Denis , Baliga Sujith 
Published: June 2020

AbstractThe adoption of immunotherapy has dramatically transformed the landscape of oncology, and improved the prognosis of patients diagnosed with metastatic malignancies. Fee-for-service (FFS) Medicare is the largest payer in the U.S, and pays for physician-administered oncolytics through its medical Part B benefit. However, to the best of our knowledge, trends in Medicare utilization and expenditures for cancer immunotherapy have yet to be described. The aim of this study was to describe trends in Medicare immunotherapy reimbursement. We utilized the public Drugs@FDA database to identify all immunotherapy drugs that were approved by the FDA for solid and hematological cancers in adults as of December 31, 2017. The Medicare Physician Supplier and Other Provider Public Use File (POSPUF) provides reimbursement and utilization data on all services and procedures provided to Medicare fee-for-service beneficiaries. Using the Medicare POSPUF, we aggregated the volume of services, average Medicare reimbursement, and the number of distinct patients receiving each immunotherapy drug from January 2012 to December 2017. The number of Medicare reimbursed cancer immunotherapy drugs increased from 3 in 2012 to 12 in 2017. Over this time period, the number of patients receiving immunotherapy administrations increased 88% from 59,506 to 111,577. Similarly, the number of drug administrations increased by 2,412% from 2,338,691 to 58,752,804. From 2012 to 2017, total Medicare expenditure on cancer immunotherapy drugs increased 154% from $771,434,031 to $1,962,279,164. Medicare expenditure on cancer immunotherapy drugs accounted for 26% of the increase in total Medicare Part B drug expenditures over this time period.
Quantitative occupancy of myriad transcription factors from one DNase experiment enables efficient comparisons across conditions
Authors: Luo Kaixuan , Zhong Jianling , Safi Alexias , Hong Linda K. , Tewari Alok K. , Song Lingyun , Reddy Timothy E. , Ma Li , Crawford Gregory E. , Hartemink Alexander J. 
Published: June 2020

AbstractOver a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the TF occupancy landscape, let alone quantify how it changes across conditions. We developed TOP, a Bayesian hierarchical regression framework, to profile genome-wide quantitative occupancy of numerous TFs using data from a single DNase-seq experiment. TOP is supervised, and its hierarchical structure allows it to predict the occupancy of any sequence-specific TF, even those never assayed with ChIP. We used TOP to profile the quantitative occupancy of nearly 1500 human TF motifs, and examined how their occupancies changed genome-wide in multiple contexts: across 178 cell types, over 12 hours of exposure to different hormones, and across the genetic backgrounds of 70 individuals. TOP enables cost-effective exploration of quantitative changes in the landscape of TF binding.
Post-ictal generalized EEG suppression and seizure-induced mortality are reduced by enhancing dorsal raphe serotonergic neurotransmission
Authors: Petrucci Alexandra N. , Joyal Katelyn G. , Chou Jonathan W. , Li Rui , Vencer Kimberly M. , Buchanan Gordon F. 
Published: June 2020

AbstractSudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. A proposed risk marker for SUDEP is the duration of post-ictal generalized EEG suppression (PGES). The mechanisms underlying PGES are unknown. Serotonin (5-HT) has been implicated in SUDEP pathophysiology. Seizures suppress activity of 5-HT neurons in the dorsal raphe nucleus (DRN). We hypothesized that suppression of DRN 5-HT neuron activity contributes to PGES and increasing 5-HT neurotransmission or stimulating the DRN before a seizure would decrease PGES duration. Adult C57BL/6 andPet1-Cremice received EEG/EMG electrodes, a bipolar stimulating/recording electrode in the right basolateral amygdala, and either a microdialysis guide cannula or an injection of adeno-associated virus (AAV) allowing expression of channelrhodopsin2 plus an optic fiber into the DRN. Systemic application of the selective 5-HT reuptake inhibitor citalopram (20 mg/kg) decreased PGES duration from seizures induced during wake (n = 23) and NREM sleep (n = 13) whereas fluoxetine (20 mg/kg) pretreatment decreased PGES duration following seizures induced from wake (n = 11), but not NREM sleep (n = 9). Focal chemical (n = 6) or optogenetic (n = 8) stimulation of the DRN reduced PGES duration following kindled seizures and reduced morality following maximal electroshock seizures (n = 6) induced during wake. During PGES, animals exhibited immobility and suppression of EEG activity that was reduced by citalopram pretreatment. These results indicate that 5-HT and the DRN may regulate PGES and seizure-induced mortality.Highlights-PGES consistently follows seizures induced by amygdala stimulation in amygdala-kindled mice.-Seizure-induced dysregulation of 5-HT neurotransmission from the dorsal raphe nucleus may contribute to PGES.-Systemic administration of 5-HT enhancing drugs and stimulation of the DRN reduces PGES duration.-PGES is associated with post-ictal immobility in kindled mice that can be reduced by pretreatment with citalopram.-Recovery of EEG frequencies to baseline occurs in a stepwise manner with the lowest frequencies recovering first.
Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020
Authors: Lazar Mihaela , Popovici Odette , Mühlemann Barbara , Durfee Tim , Stan Razvan 
Published: June 2020

AbstractImpact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.
Assembly of 23 Plastid Genomes Provides the Chloroplast View onMiscanthusOrigins
Authors: Evans Dyfed Lloyd 
Published: June 2020

AbstractDespite its economic importance as a new biofuel resource, little work has been done on the large-scale phylogenetics ofMiscanthus. Twenty-three completeMiscanthuschloroplasts were assembled and annotated. A phylogeny was performed with these assemblies, which shows the relationships between the mainMiscanthusspecies and sub-species. The phylogeny demonstrates that there is no meaningful distinction betweenMiscanthus floridulusandMiscanthus transmorrisonensisas the accessions are not distinct. However, at the crown of the tree there is a clear distinction betweenM. sinensis malepartusandM. sinensis condensatussubspecies. The phylogeny reaveals that the female parent ofMiscanthus xgiganteusisMiscanthus lutarioripariusrather thanMiscanthus sacchariflorus. The phylogeny also shows a novel hybrid betweenMiscanthus oligostachyusandMiscanthus sinensis, a grouping to whichMiscanthus sinensisvar Purpurascens belongs. This hybrid form is namedMiscanthus×oligostachyus.
Nested Stochastic Block Models Applied to the Analysis of Single Cell Data
Authors: Morelli Leonardo , Giansanti Valentina , Cittaro Davide 
Published: June 2020

AbstractSingle cell profiling has been proven to be a powerful tool in molecular biology to understand the complex behaviours of heterogeneous system. The definition of the properties of single cells is the primary endpoint of such analysis, cells are typically clustered to underpin the common determinants that can be used to describe functional properties of the cell mixture under investigation. Several approaches have been proposed to identify cell clusters; while this is matter of active research, one popular approach is based on community detection in neighbourhood graphs by optimisation of modularity. In this paper we propose an alternative and principled solution to this problem, based on Stochastic Block Models. We show that such approach not only is suitable for identification of cell groups, it also provides a solid framework to perform other relevant tasks in single cell analysis, such as label transfer. To encourage the use of Stochastic Block Models, we developed a python library,schist, that is compatible with the popularscanpyframework.
Shotgun scanning glycomutagenesis: a simple and efficient strategy for constructing and characterizing neoglycoproteins
Authors: Li Mingji , Zheng Xiaolu , Shanker Sudhanshu , Jaroentomeechai Thapakorn , Moeller Tyler D. , Hulbert Sophia W. , Koçer Ilkay , Byrne Josef , Cox Emily C. , Fu Qin , Zhang Sheng , Labonte Jason W. , Gray Jeffrey J. , DeLisa Matthew P. 
Published: June 2020

AbstractAs a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins. However, the routine use of glycosylation at naïve sites as a strategy for engineering proteins with advantageous properties is currently limited by our inability to construct large collections of glycoproteins for interrogating the structural and functional consequences of glycan installation. To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis (SSGM) in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein. Moreover, the resulting neoglycoproteins can be readily subjected to available medium- to high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone. The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and a human anti-HER2 single-chain Fv antibody, all of which were found to tolerateN-glycan attachment at a large number of positions and with relatively high efficiency. The stability and activity of many glycovariants was measurably altered by theN-linked glycan in a manner that critically depended on the precise location of the modification. Importantly, we anticipate that our workflow for creating and characterizing large ensembles of neoglycoproteins should provide access to unexplored regions of glycoprotein structural space and to custom-made glycoproteins with desirable properties.
Feature Frequency Profile-based phylogenies are inaccurate
Authors: Li Yuanning , David Kyle T. , Shen Xing-Xing , Steenwyk Jacob L. , Halanych Kenneth M. , Rokas Antonis 
Published: June 2020

AbstractChoi and Kim (PNAS, 117: 3678-3686; first published February 4, 2020;https://doi.org/10.1073/pnas.1915766117) used the alignment-free Feature Frequency Profile (FFP) method to reconstruct a broad sketch of the tree of life based on proteome data from 4,023 taxa. The FFP-based reconstruction reports many relationships that strongly contradict the current consensus view of the tree of life and its accuracy has not been tested. Comparison of FFP with current standard approaches, such as concatenation and coalescence, using simulation analyses shows that FFP performs poorly. We conclude that the phylogeny of the tree of life reconstructed by Choi and Kim is suspect based on methodology as well as prior phylogenetic evidence.
Weight and organ specific immune cell profiling of Sleeve Gastrectomy
Authors: Harris David A. , Subramaniam Renuka , Brenner Todd , Tavakkoli Ali , Sheu Eric G. 
Published: June 2020

AbstractSleeve gastrectomy (SG) has profound, immediate weight-loss independent effects on obesity related diabetes (T2D). Our prior studies have shown that immunologic remodeling may play a part in this metabolic improvement. However, to date, little is known about how the major immune cell populations change following SG. Using mass cytometry with time of flight analysis (CyTOF) we aimed to broadly explore the organ-specific immune cell repertoire induced by SG. Surgery was performed on obese, insulin resistant and lean mice in order to understand surgery-specific phenotypes. We identified a shift within the splenic B cell compartment with a reduction in follicular and an increase in innate-like B cell subsets in SG animals. There was a concomitant increase in multiple circulating immunoglobulin classes. Further, SG animals had a conserved increase in splenic neutrophils and a tendency toward M2 macrophage polarization. Others have shown that these, weight-loss independent, surgery-specific changes are linked to improved glucose metabolism and thus, may be a major contributor to post SG physiology. Characterizing the complex immune milieu following SG is an important step toward understanding the physiology of SG and the potential therapies therein.
Visualizing active viral infection reveals diverse cell fates in synchronized algal bloom demise
Authors: Vincent Flora , Sheyn Uri , Porat Ziv , Vardi Assaf 
Published: June 2020

SummaryMarine viruses are considered as major evolutionary and biogeochemical drivers of microbial life, through metabolic reprogramming of their host and cell lysis that modulates nutrient cycling1, primary production and carbon export in the oceans2. Despite the fact that viruses are the most abundant biological entities in the marine environment, we still lack mechanistic and quantitative approaches to assess their impact on the marine food webs. Here, we provide the first quantification of active viral infection, during bloom succession of the cosmopolitan coccolithophoreEmiliania huxleyi, by subcellular visualization of both virus and host transcripts on a single cell resolution across thousands of cells. Using this novel method, that we coined Virocell-FISH, we revealed that distinct transcriptional states co-exist during the infection dynamics, and that viral infection reached only a quarter of theE. huxleyipopulation although the bloom demised in a synchronized manner. Through a detailed laboratory time-course infection ofE. huxleyiby its lytic large virus EhV, we quantitatively show that metabolically active infected cells chronically release viral particles, and that viral-induced lysis is not systematically accompanied by virion increase, thus challenging major assumptions regarding the life cycle of giant lytic viruses. Using Virocell-FISH, we could further assess in a new resolution, the level of viral infection in cell aggregates, a key ecosystem process that can facilitate carbon export to the deep ocean3. We project that our approach can be applied to diverse marine microbial systems, opening a mechanistic dimension to the study of host-pathogen interactions in the ocean.One Sentence SummaryQuantifying active viral infection in algal blooms
Distinct genetic architectures underlie divergent thorax, leg, and wing pigmentation betweenDrosophila elegansandD. gunungcola
Authors: Massey Jonathan H. , Li Jun , Stern David L. , Wittkopp Patricia J. 
Published: June 2020

AbstractUnderstanding the genetic basis of species differences is a major goal in evolutionary biology. Pigmentation divergence betweenDrosophilaspecies often involves genetic changes in pigmentation candidate genes that pattern the body and wings, but it remains unclear how these changes affect pigmentation evolution in multiple body parts between the same diverging species.Drosophila elegansandD. gunungcolashow pigmentation differences in the thorax, legs, and wings, withD. elegansexhibiting male-specific wing spots andD. gunungcolalacking wing spots with intensely dark thoraces and legs. Here, we performed QTL mapping to identify the genetic architecture of these differences. We find a large effect QTL on the X chromosome for all three body parts. QTL on Muller Element E were found for thorax pigmentation in both backcrosses but were only marginally significant in one backcross for the legs and wings. Consistent with this observation, we isolated the effects of the Muller Element E QTL by introgressingD. gunungcolaalleles into aD. elegansgenetic background and found thatD. gunungcolaalleles linked near the pigmentation candidate geneebonycaused intense darkening of the thorax, minimal darkening of legs, and minimal shrinking of wing spots.D. elegans ebonymutants showed changes in pigmentation consistent with Ebony having different effects on pigmentation in different tissues. Our results suggest that multiple genes have evolved differential effects on pigmentation levels in different body regions.
Vertical Stratification in Urban Green Space Aerobiomes
Authors: Robinson Jake M. , Cando-Dumancela Christian , Liddicoat Craig , Weinstein Philip , Cameron Ross , Breed Martin F. 
Published: June 2020

AbstractExposure to a diverse environmental microbiome is thought to play an important role in ‘educating’ the immune system and facilitating competitive exclusion of pathogens to maintain human health. Vegetation and soil are known to be key sources of airborne microbiota––theaerobiome. Only a limited number of studies have attempted to characterise the dynamics of the aerobiome, and no studies to date have investigated these dynamics from a vertical perspective simulating human exposure. Studies of pollution and allergenic pollen show vertical stratification at various scales, and present an expectation that such vertical stratification may also be present in the aerobiome. Such stratification could have important implications for public health and for the design, engineering and management of urban green spaces. For example, do children receive the same exposure to airborne microbiota as taller adults, and what are the downstream implications for health? In this study, we combine an innovative columnar sampling method at soil level, 0.0, 0.5, 1.0, and 2.0 m together with high-throughput sequencing of the bacterial 16S rRNA gene to assess whether significant vertical stratification of the aerobiome occurred in a parkland habitat in Adelaide, South Australia. Our results provide evidence of vertical stratification in both alpha and beta (compositional) diversity of airborne bacterial communities, with diversity increasing roughly with height. We also found significant vertical stratification in known pathogenic and beneficial bacterial taxa, suggesting potentially different exposure attributes between adults and children. These results could have important implications for public health and urban planning, potentially informing ways to optimise the design and management of health-promoting urban green spaces.
Dynamic changes in β-cell electrical activity and [Ca2+] regulates NFATc3 activation and downstream gene transcription
Authors: Miranda Jose G. , Schleicher Wolfgang E , Ramirez David G. , Landgrave Samantha P , Benninger Richard KP 
Published: June 2020

AbstractDiabetes results from insufficient insulin secretion as a result of dysfunction to β-cells within the islet of Langerhans. Elevated glucose causes β-cell membrane depolarization and action potential generation, voltage gated Ca2+channel activation and oscillations in free-Ca2+activity ([Ca2+]), triggering insulin release. Nuclear Factor of Activated T-cell (NFAT) is a transcription factor that is regulated by increases in [Ca2+] and calceineurin (CaN) activation. NFAT regulation links cell activity with gene transcription in many systems, and within the β-cell regulates proliferation and insulin granule biogenesis. However the link between the regulation of β-cell electrical activity and oscillatory [Ca2+], with NFAT activation and downstream transcription is poorly understood. In this study we tested whether dynamic changes to β-cell electrical activity and [Ca2+] regulates NFAT activation and downstream transcription. In cell lines, mouse islets and human islets, including those from donors with type2 diabetes, we applied both agonists/antagonists of ion channels together with optogenetics to modulate β-cell electrical activity. Both glucose-induced membrane depolarization and optogenetic-stimulation triggered NFAT activation, and increased transcription of NFAT targets and intermediate early genes (IEGs). Importantly only conditions in which slow sustained [Ca2+] oscillations were generated led to NFAT activation and downstream transcription. In contrast in human islets from donors with type2 diabetes NFAT activation by glucose was diminished, but rescued upon pharmacological stimulation of electrical activity. Thus, we gain insight into the specific patterns of electrical activity that regulate NFAT activation and gene transcription and how this is disrupted in diabetes.