bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones inDrosophila melanogaster
Authors: Yoshinari Yuto , Kosakamoto Hina , Kamiyama Takumi , Hoshino Ryo , Matsuoka Rena , Kondo Shu , Tanimoto Hiromu , Nakamura Akira , Obata Fumiaki , Niwa Ryusuke 
Published: May 2021

AbstractThe enteroendocrine cell (EEC)-derived incretins play a pivotal role in regulating the secretion of glucagon and insulins in mammals. Although glucagon-like and insulin-like hormones have been found across animal phyla, incretin-like EEC-derived hormones have not yet been characterised in invertebrates. Here, we show that the midgut-derived hormone, Neuropeptide F (NPF), acts as the sugar-responsive, incretin-like hormone in the fruit fly,Drosophila melanogaster. Secreted NPF is received by NPF receptor in the corpora cardiaca and in insulin-producing cells. NPF-NPFR signalling resulted in the suppression of the glucagon-like hormone production and the enhancement of the insulin-like peptide secretion, eventually promoting lipid anabolism. Similar to the loss of incretin function in mammals, loss of midgut NPF led to significant metabolic dysfunction, accompanied by lipodystrophy, hyperphagia, and hypoglycaemia. These results suggest that enteroendocrine hormones regulate sugar-dependent metabolism through glucagon-like and insulin-like hormones not only in mammals but also in insects.
Disrupting the CD177:proteinase 3 membrane complex reduces anti-PR3 antibody-induced neutrophil activation
Authors: Marino Stephen F. , Jerke Uwe , Rolle Susanne , Daumke Oliver , Kettritz Ralph 
Published: May 2021

ABSTRACTCD177 is a neutrophil-specific receptor presenting proteinase 3 (PR3) autoantigen on the neutrophil surface. CD177 expression is restricted to a neutrophil subset resulting in CD177pos/mPR3highand CD177neg/mPR3lowpopulations. The size of the CD177pos/mPR3highsubset has implications for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated autoimmune vasculitis (AAV) where patients harbor PR3-specific ANCA that activate neutrophils. We generated high affinity anti-CD177 monoclonal antibodies, some of which interfered with PR3 binding to CD177 (PR3 “blockers”) as determined by surface plasmon resonance spectroscopy, and used them to test the effect of competing PR3 from the surface of CD177posneutrophils. Because intact anti-CD177 antibodies also caused neutrophil activation, we prepared non-activating Fab fragments of a PR3 blocker and non-blocker that bound specifically to CD177posneutrophils by flow cytometry. We observed that Fab blocker clone 40, but not non-blocker clone 80, dose-dependently reduced anti-PR3 antibody binding to CD177posneutrophils. Importantly, preincubation with clone 40 significantly reduced respiratory burst in primed neutrophils challenged either with monoclonal antibodies to PR3 or PR3-ANCA IgG from AAV patients. After separating the two CD177/mPR3 neutrophil subsets from individual donors by magnetic sorting, we found that PR3-ANCA provoked significantly more superoxide production in CD177pos/mPR3highthan in CD177neg/mPR3lowneutrophils, and that anti-CD177 Fab clone 40 reduced the superoxide production of CD177poscells to the level of the CD177negcells. Our data demonstrate the importance of the CD177:PR3 membrane complex in maintaining a high ANCA epitope density and thereby underscore the contribution of CD177 to the severity of PR3-ANCA diseases.
Synergism between Chromatin Dynamics and Gene Transcription Enhances Robustness and Stability of Epigenetic Cell Memory
Authors: Wang Zihao , Luo Songhao , Chen Meiling , Zhou Tianshou , Zhang Jiajun 
Published: May 2021

AbstractApart from carrying hereditary information inherited from their ancestors and being able to pass on the information to their descendants, cells can also inherit and transmit information that is not stored as changes in their genome sequence. Such epigenetic cell memory, which is particularly important in multicellular organisms, involves multiple biochemical modules mainly including chromatin organization, epigenetic modification and gene transcription. The synergetic mechanism among these three modules remains poorly understood and how they collaboratively affect the robustness and stability of epigenetic memory is unclear either. Here we developed a multiscale model to address these questions. We found that the chromatin organization driven by long-range epigenetic modifications can significantly enhance epigenetic cell memory and its stability in contrast to that driven by local interaction and that chromatin topology and gene activity can promptly and simultaneously respond to changes in nucleosome modifications while maintaining the robustness and stability of epigenetic cell memory over several cell cycles. We concluded that the synergism between chromatin dynamics and gene transcription facilitates the faithful inheritance of epigenetic cell memory across generations.
T Cell Receptor Beta Germline Variability is Revealed by Inference From Repertoire Data
Authors: Omer Aviv , Peres Ayelet , Rodriguez Oscar L , Watson Corey T , Lees William , Polak Pazit , Collins Andrew M , Yaari Gur 
Published: May 2021

AbstractBackgroundT and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of TCRs and BCRs are challenging to decipher due to repetitive elements and undocumented structural variants.MethodsTo confront this challenge, AIRR-seq-based methods have recently been developed for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. However, this approach relies on complete coverage of the receptors’ variable regions, whereas most T cell studies sequence a small fraction of that region. Here, we adapted a B cell pipeline for undocumented alleles, genotype, and haplotype inference for full and partial TCR sequences. The pipeline also deals with gene assignment ambiguities, which is especially important in the analysis of data-sets of partial sequences.ResultsWe identified 39 undocumented polymorphisms in T cell receptor Beta V (TRBV) and 31 undocumented 5’ UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found that a single nucleotide polymorphism differentiating between the two documented T cell receptor Beta D2 (TRBD2) alleles is strongly associated with dramatic changes in the expressed repertoire.ConclusionsWe reveal a rich picture of germline variability, and demonstrate how a single nucleotide polymorphism dramatically affects the composition of the whole repertoire. Our findings provide a basis for annotation of TCR repertoires for future basic and clinical studies.
Navigating Multi-scale Cancer Systems Biology towards Model-driven Personalized Therapeutics
Authors: Gondal Mahnoor Naseer , Chaudhary Safee Ullah 
Published: May 2021

AbstractRapid advancements in high-throughput omics technologies and experimental protocols have led to the generation of vast amounts of biomolecular data on cancer that now populates several online databases and resources. Cancer systems biology models built on top of this data have the potential to provide specific insights into complex multifactorial aberrations underpinning tumor initiation, development, and metastasis. Furthermore, the annotation of these single- or multi-scale models with patient data can additionally assist in designing personalized therapeutic interventions as well as aid in clinical decision-making. Here, we have systematically reviewed the emergence and evolution of (i) repositories with scale-specific and multiscale biomolecular cancer data, (ii) systems biology models developed using this data, (iii) associated simulation software for development of personalized cancer therapeutics, and (iv) translational attempts to pipeline multi-scale panomics data for data-drivenin silicoclinical oncology. The review concludes by highlighting that the absence of a generic, zero-code, panomics-based multi-scale modeling pipeline and associated software framework, impedes the development and seamless deployment of personalizedin silicomulti-scale models in clinical settings.
The time course of molecular acclimation to seawater in a euryhaline fish
Authors: Bonzi Lucrezia C. , Monroe Alison A. , Lehmann Robert , Berumen Michael L. , Ravasi Timothy , Schunter Celia 
Published: May 2021

AbstractThe Arabian pupfish, Aphanius dispar, is a euryhaline fish inhabiting both inland nearly-freshwater desert ponds and highly saline Red Sea coastal lagoons of the Arabian Peninsula. Red Sea populations have been found to receive migrants from desert ponds that are flushed out to sea during flash floods, requiring rapid acclimation to a greater than 40 ppt change in salinity. To investigate the molecular pathways of salinity acclimation during such colonization events, a Red Sea coastal lagoon and a desert pond population were sampled, with the latter exposed to a rapid increase in water salinity. Changes in branchial gene expression were investigated via genome-wide transcriptome measurements over time from 6 hours to 21 days. The two natural populations displayed basal differences in genes related to ion transport, osmoregulation and immune system functions. These mechanisms were also differentially regulated in seawater transferred fish, revealing their crucial role in long-term adaptation. Other processes were only transiently activated shortly after the salinity exposure, including cellular stress response mechanisms, such as molecular chaperone synthesis and apoptosis. Tissue remodeling processes were also identified as transient, but took place later in the timeline, suggesting their importance to long-term acclimation as they likely equip the fish with lasting adaptations to their new environment. The alterations in branchial functional pathways displayed by Arabian pupfish in response to salinity increases are diverse. These reveal a large toolkit of molecular processes important for adaptation to hyperosmolarity that allow for successful colonization to a wide variety of different habitats.
How to describe and measure phenology? An investigation on the diversity of metrics using phenology of births in large herbivores
Authors: Thel Lucie , Chamaillé-Jammes Simon , Bonenfant Christophe 
Published: May 2021

AbstractProposed in 1849 by Charles Morren to depict periodical phenomena governed by seasons, the term “phenology” has spread in many fields of biology. With the wide adoption of the concept of phenology flourished a large number of metrics with different meaning and interpretation. Here, we first a priori classified 52 previously published metrics used to characterise the phenology of births in large herbivores according to four biological characteristics of interest: timing, synchrony, rhythmicity and regularity of births. We then applied each metric retrieved on simulation data, considering normal and non-normal distributions of births, and varying distributions of births in time. We then evaluated the ability of each metric to capture the variation of the four phenology characteristics via a sensitivity analysis. Finally, we scored each metric according to eight criteria we considered important to describe phenology correctly. The high correlation we found among the many metrics we retrieved suggests that such diversity of metrics is unnecessary. We further show that the best metrics are not the most commonly used, and that simpler is often better. Circular statistics with the mean vector orientation and mean vector length seems, respectively, particularly suitable to describe the timing and synchrony of births in a wide range of phenology patterns. Tests designed to compare statistical distributions, like Mood and Kolmogorov-Smirnov tests, allow a first and easy quantification of rhythmicity and regularity of birth phenology respectively. By identifying the most relevant metrics our study should facilitate comparative studies of phenology of births or of any other life-history event. For instance, comparative studies of the phenology of mating or migration dates are particularly important in the context of climate change.
Alcohol Use Disrupts Age-Appropriate Cortical Thinning in Adolescence: A Data Driven Approach
Authors: Sun Delin , Adduru Viraj R. , Phillips Rachel D. , Bouchard Heather C. , Sotiras Aristeidis , Michael Andrew M. , Baker Fiona C. , Tapert Susan F. , Brown Sandra A. , Clark Duncan B. , Goldston David , Nooner Kate B. , Nagel Bonnie J. , Thompson Wesley K. , De Bellis Michael , Morey Rajendra A. 
Published: May 2021

ObjectiveCortical thickness changes dramatically during development and is influenced by adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying heterogeneity from the effects of alcohol.MethodsAdolescents (n=657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) who endorsed little to no alcohol use at baseline were assessed with structural MRI and followed longitudinally at four yearly intervals. Seven unique spatially covarying patterns of cortical thickness were obtained from the baseline scans by applying a novel data-driven method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants’ longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness.ResultsIn most NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts, among moderate drinkers the decline was faster in the younger cohort and slower in the older cohort, among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort (FDR corrected p-values < 0.01).ConclusionsThe NMF method can delineate spatially coordinated patterns of cortical thickness at the vertex level that are unconstrained by anatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers.
The role of Cyp19a1 in female pathway of a freshwater turtle (Mauremys reevesii) with temperature-dependent sex determination
Authors: Wu Peng-fei , Wang Xi-feng , Gao Fei , Du Wei-guo 
Published: May 2021

AbstractThe molecular mechanism of temperature-dependent sex determination (TSD) in reptiles has been drawn great interest from biologists for several decades. However, which genetic factors are essential for TSD remain elusive, especially for the female sex determination process. Cyp19a1, encodes an enzyme of aromatase catalyzing the conversion of testosterone to estrogen, has been confirmed to modulate steroid hormones involved in the sexual differentiation of many species, but whether it has a critical role in determining the gonadal sexual fate in TSD is still to be elucidated. Here, we identified that Cyp19a1 expression exhibited a temperature-dependent, sexually dimorphic expression pattern, preceding gonadal sex differentiation in a TSD turtle Mauremys reevesii. Cyp19a1 expression in gonads increased dramatically when embryos developed at high female-producing temperatures (FPT), but were extremely low throughout embryogenesis at low male-producing temperatures (MPT). Cyp19a1 expression increased rapidly in response to the temperature shift from MPT to FPT in developing gonads. The sexual phenotype of turtles was successfully reversed by aromatase inhibitor treatment at FPT, and by estrogen treatment at MPT, accompanied with the rapid upregulation of Cyp19a1. These results demonstrate that Cyp19a1 is essential for the female sex determination process in M. reevesii, indicating its vital role in the female pathway of TSD.
The 3′ end of the human norovirus antigenomic sequence is required for its genomic RNA synthesis by RNA-dependent RNA polymerase
Authors: Shimoike Takashi , Hayashi Tsuyoshi , Oka Tomoichiro , Muramatsu Masamichi 
Published: May 2021

AbstractNorovirus genome is a single-stranded positive-strand RNA. To reveal the mechanism underlying the initiation of the norovirus genomic RNA synthesis by its RNA-dependent RNA polymerase (RdRp), we used an in vitro assay to detect the complementary RNA synthesis activity. Results showed that the purified recombinant RdRp synthesized the complementary positive-sense RNA from the 100 nt template corresponding to the 3′ end region of the viral antisense genome sequence, but that RdRp did not synthesize the antisense genomic RNA from the 100 nt template, corresponding to the 5′ end region of the positive-sense genome sequence. The 31 nt region at the 3′ end of the RNA antisense template was then predicted to form the stem-loop structure. Its deletion resulted in the loss of complementary RNA synthesis by RdRp. The connection of the 31 nt to the 3′ end of the positive-sense RNA template allowed to be recognized by the RdRp. Similarly, an electrophoretic mobility shift assay further revealed that RdRp bound to the antisense RNA specifically, but the 31 nt deletion at the 3′ end lost the binding to RdRp. Therefore, combining this observation with further deletion and mutation analysis, we concluded that the predicted stem-loop structure in the 31 nt and region close to the antisense viral genomic stem sequences are important for initiating the positive-sense human norovirus genomic RNA synthesis by its RdRp.
Bis(2-nitrophenyl) selenide, bis(2-aminophenyl) selenide and bis(2-aminophenyl) telluride: structural and theoretical analysis
Authors: Saravanan Raju , Singh Harkesh B. , Butcher Ray J. 
Published: May 2021

Three organoselenium and organotellurium compounds containing ortho substitutents, namely, bis(2-nitrophenyl) selenide, C12H8N2O4Se, 2, bis(2-aminophenyl) selenide, C12H12N2Se, 3, and bis(2-aminophenyl) telluride, C12H12N2Te, 7, have been investigated by both structural and theoretical methods. In the structures of all three compounds, there are intramolecular contacts between both Se and Te with the ortho substituents. In the case of 2, this is achieved by rotation of the nitro group from the arene plane. For 3, both amino groups exhibit pyramidal geometry and are involved in intramolecular N—H...Se interactions, with one also participating in intermolecular N—H...N hydrogen bonding. While 3 and 7 are structurally similar, there are some significant differences. In addition to both intramolecular N—H...Te interactions and intermolecular N—H...N hydrogen bonding, 7 also exhibits intramolecular N—H...N hydrogen bonding. In the packing of these molecules, for 2, there are weak intermolecular C—H...O contacts and these, along with the O...N interactions mentioned above, link the molecules into a three-dimensional array. For 3, in addition to the N—H...N and N—H...Se interactions, there are also weak intermolecular C—H...Se interactions, which also link the molecules into a three-dimensional array. On the other hand, 7 shows intermolecular N—H...N interactions linking the molecules into R
2
2(16) centrosymmetric dimers. In the theoretical studies, for compound 2, AIM (atoms in molecules) analysis revealed critical points in the Se...O interactions with values of 0.017 and 0.026 a.u. These values are suggestive of weak interactions present between Se and O atoms. For 3 and 7, the molecular structures displayed intramolecular, as well as intermolecular, hydrogen-bond interactions of the N—H...N type. The strength of this hydrogen-bond interaction was calculated by AIM analysis. Here, the intermolecular (N—H...N) hydrogen bond is stronger than the intramolecular hydrogen bond. This was confirmed by the electron densities for 3 and 7 [ρ(r) = 0.015 and 0.011, respectively].
Accounting and accountability practices in times of crisis: a Foucauldian perspective on the UK government's response to COVID-19 for England
Authors: Ahrens Thomas , Ferry Laurence 
Published: May 2021

PurposeThis paper considers the accounting and accountability practices of the UK government’s response to COVID-19 for England, focussing on the first wave of the pandemic in 2020.Design/methodology/approachBased on a close reading of the news media and official reports from government departments, Parliament select committees and the National Audit Office, among others, this paper frames the UK government's uses of accounting and accountability in its response to COVID-19. This is by using the categories of “apparatuses of security”, Foucault's schematic of government for economising on the uses of state power.FindingsThe paper shows that an important role for accounting is in the process of enabling the government to gauge the extent of the crisis and produce calculations to underpin its response, what Foucault called “normalisation”. This role was unlike statistics and economics. The government relied most on monthly statistical reporting and budgeting flexibilities. By contrast, the multi-year Spending Review and financial reporting were not timely enough. That said, financial reporting fed into financial sustainability projections and enabled audit that could provide potential accountability regarding regularity, probity, value for money and fairness. The authors’ findings suggest that, conceptually, accountability should be added to the object–subject element of Foucault's apparatuses of security because of its significance for governments' ability to pursue crisis objectives that require popular assent.Practical implicationsIn view of the ongoing uncertainty, with the crisis extending over longer budget and financial reporting periods, a Spending Review is becoming ever more necessary for better planning, without limiting, however, the budget flexibilities that have proven so useful for rapid government responses. Moreover, the government should continue its accounting reforms post COVID-19 so that improved accountability and audit can contribute to enhanced future financial resilience.Originality/valueThis is the first paper to apply Foucault's notion of apparatuses of security to an analysis of government accounting and accountability practices.