bluuebunny/crossref_metadata_2025_split huggingface dataset:
Release from cell cycle arrest with Cdk4/6 inhibitors generates highly synchronised cell cycle progression in human cell culture
Authors: Wendy Trotter Eleanor , Michael Hagan Iain 
Published: July 2020

AbstractEach approach used to synchronise cell cycle progression of human cell lines presents a unique set of challenges. Induction synchrony with agents that transiently block progression through key cell cycle stages are popular, but change stoichiometries of cell cycle regulators, invoke compensatory changes in growth rate and, for DNA replication inhibitors, damage DNA. The production, replacement, or manipulation of a target molecule must be exceptionally rapid if the interpretation of phenotypes in the cycle under study are to remain independent of impacts upon progression through the preceding cycle. We show how these challenges are avoided by exploiting the ability of the Cdk4/6 inhibitors, palbociclib, ribociclib and abemaciclib to arrest cell cycle progression at the natural control point for cell cycle commitment: the restriction point. After previous work found no change in the coupling of growth and division during recovery from CDK4/6 inhibition, we find high degrees of synchrony in cell cycle progression. Although we validate CDK4/6 induction synchronisation with hTERT-RPE-1, THP1 and H1299, it is effective in other lines and avoids the DNA damage that accompanies synchronisation by thymidine block/release. Competence to return to cycle after 72 hours arrest enables out of cycle target induction/manipulation, without impacting upon preceding cycles.
Discrimination of regular and irregular rhythms by accumulation of time differences
Authors: Espinoza-Monroy Marisol , de Lafuente Victor 
Published: July 2020

AbstractPerceiving the temporal regularity in a sequence of repetitive sensory events facilitates the preparation and execution of relevant behaviors with tight temporal constraints. How we estimate temporal regularity from repeating patterns of sensory stimuli is not completely understood. We developed a decision-making task in which participants had to decide whether a train of visual, auditory, or tactile pulses, had a regular or an irregular temporal pattern. We tested the hypothesis that subjects categorize stimuli as irregular by accumulating the time differences between the predicted and observed times of sensory pulses defining a temporal rhythm. Results show that instead of waiting for a single large temporal deviation, participants accumulate timing-error signals and judge a pattern as irregular when the amount of evidence reaches a decision threshold. Model fits of bounded integration showed that this accumulation occurs with negligible leak of evidence. Consistent with previous findings, we show that participants perform better when evaluating the regularity of auditory pulses, as compared with visual or tactile stimuli. Our results suggest that temporal regularity is estimated by comparing expected and measured pulse onset times, and that each prediction error is accumulated towards a threshold to generate a behavioral choice.
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant
Authors: Yurkovetskiy Leonid , Wang Xue , Pascal Kristen E. , Tomkins-Tinch Christopher , Nyalile Thomas , Wang Yetao , Baum Alina , Diehl William E. , Dauphin Ann , Carbone Claudia , Veinotte Kristen , Egri Shawn B. , Schaffner Stephen F. , Lemieux Jacob E. , Munro James , Rafique Ashique , Barve Abhi , Sabeti Pardis C. , Kyratsous Christos A. , Dudkina Natalya , Shen Kuang , Luban Jeremy 
Published: July 2020

SUMMARYThe SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and cells rendered permissive by ectopic expression of various mammalian ACE2 orthologs. Nonetheless, D614G affinity for ACE2 was reduced due to a faster dissociation rate. Assessment of the S protein trimer by cryo-electron microscopy showed that D614G disrupts a critical interprotomer contact and that this dramatically shifts the S protein trimer conformation toward an ACE2-binding and fusion-competent state. Consistent with the more open conformation, neutralization potency of antibodies targeting the S protein receptor-binding domain was not attenuated. These results indicate that D614G adopts conformations that make virion membrane fusion with the target cell membrane more probable but that D614G retains susceptibility to therapies that disrupt interaction of the SARS-CoV-2 S protein with the ACE2 receptor.
Memory destabilization and reconsolidation dynamically regulate the PKMζ maintenance mechanism
Authors: Bernabo Matteo , Nader Karim 
Published: July 2020

AbstractUseful memory must balance between stability and malleability. This puts effective memory storage at odds with plasticity processes like reconsolidation. What becomes of memory maintenance processes during synaptic plasticity is unknown. Here we examined the fate of the memory maintenance protein PKMζ during memory destabilization and reconsolidation. We found that NMDA receptor activation and proteasome activity induced a transient reduction in PKMζ protein following retrieval. During reconsolidation, new PKMζ was synthesized to re-store the memory. Failure to synthesize new PKMζ during reconsolidation impaired memory but uninterrupted PKMζ translation was not necessary for maintenance itself. Finally, NMDA receptor activation was necessary to render memories vulnerable to the amnesic effect of PKMζ-antisense. These findings outline a transient collapse and renewal of the PKMζ memory maintenance mechanism during plasticity. We argue that dynamic changes in PKMζ protein levels can serve as an exemplary model of the molecular changes underlying memory destabilization and reconsolidation.
Antagonistic epistasis of Hnf4α and FoxO1 networks through enhancer interactions in β-cell function
Authors: Kuo Taiyi , Du Wen , Miyachi Yasutaka , Dadi Prasanna K. , Jacobson David A. , Accili Domenico 
Published: July 2020

AbstractGenetic and acquired abnormalities contribute to pancreatic β-cell failure in diabetes. Transcription factors Hnf4α (MODY1) and FoxO1 are respective examples of these two components, and are known to act through β-cell-specific enhancers. However, their relationship is unclear. Here we show by genome-wide interrogation of chromatin modifications that FoxO1 ablation in mature β-cells leads to increased selection of FoxO1 enhancers by Hnf4α. To model the functional significance we generated single and compound knockouts of FoxO1 and Hnf4α in β-cells. Single knockout of either gene impaired insulin secretion in mechanistically distinct fashions. Surprisingly, the defective β-cell secretory function of either single mutant in hyperglycemic clamps and isolated islets treated with various secretagogues, was completely reversed in double mutants. Gene expression analyses revealed the reversal of β-cell dysfunction with an antagonistic network regulating glycolysis, including β-cell “disallowed” genes; and that a synergistic network regulating protocadherins emerged as likely mediators of the functional restoration of insulin secretion. The findings provide evidence of antagonistic epistasis as a model of gene/environment interactions in the pathogenesis of β-cell dysfunction.
Astroglial Calcium Signaling Encodes Sleep Need inDrosophila
Authors: Blum Ian D. , Keleş Mehmet F. , Baz El-Sayed , Han Emily , Park Kristen , Luu Skylar , Issa Habon , Brown Matt , Ho Margaret C.W. , Tabuchi Masashi , Liu Sha , Wu Mark N. 
Published: July 2020

SUMMARYSleep is under homeostatic control, whereby increasing wakefulness generates sleep need and triggers sleep drive. However, the molecular and cellular pathways by which sleep need is encoded are poorly understood. In addition, the mechanisms underlying both how and when sleep need is transformed to sleep drive are unknown. Here, usingex vivoandin vivoimaging, we show inDrosophilathat astroglial Ca2+signaling increases with sleep need. We demonstrate that this signaling is dependent on a specific L-type Ca2+channel and is required for homeostatic sleep rebound. Thermogenetically increasing Ca2+in astrocytes induces persistent sleep behavior, and we exploit this phenotype to conduct a genetic screen for genes required for the homeostatic regulation of sleep. From this large-scale screen, we identify TyrRII, a monoaminergic receptor required in astrocytes for sleep homeostasis. TyrRII levels rise following sleep deprivation in a Ca2+-dependent manner, promoting further increases in astrocytic Ca2+and resulting in a positive-feedback loop. These data suggest that TyrRII acts as a gate to enable the transformation of sleep need to sleep drive at the appropriate time. Moreover, our findings suggest that astrocytes then transmit this sleep need to the R5 sleep drive circuit, by upregulation and release of the interleukin-1 analog Spätzle. These findings define astroglial Ca2+signaling mechanisms encoding sleep need and reveal dynamic properties of the sleep homeostatic control system.
An early cell shape transition drives evolutionary expansion of the human forebrain
Authors: Benito-Kwiecinski Silvia , Giandomenico Stefano L. , Sutcliffe Magdalena , Riis Erlend S. , Freire-Pritchett Paula , Kelava Iva , Wunderlich Stephanie , Martin Ulrich , Wray Greg , Lancaster Madeline A. 
Published: July 2020

AbstractThe human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that the differentiation of neuroepithelial cells to neurogenic radial glia is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition. Temporally resolved RNA-seq from human and gorilla organoids reveals differences in gene expression patterns associated with cell morphogenesis, and in particular highlightsZEB2, a known regulator of epithelial-mesenchymal transition and cell shape. We show, through loss- and gain-of-function experiments, thatZEB2promotes the progression of neuroepithelial differentiation, and its ectopic overexpression in human is sufficient to trigger a premature transition. Thus, by mimicking the nonhuman ape expression in human organoids, we are able to force the acquisition of nonhuman ape architecture, establishing for the first time, an instructive role of neuroepithelial cell shape in human brain expansion.
Cell Type-Specific Chromatin Accessibility Analysis in the Mouse and Human Brain
Authors: Rocks Devin , Jaric Ivana , Tesfa Lydia , Greally John M. , Suzuki Masako , Kundakovic Marija 
Published: July 2020

ABSTRACTThe Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) is becoming increasingly popular in the neuroscience field where chromatin regulation is thought to be involved in neurodevelopment, activity-dependent gene regulation, hormonal and environmental responses, and the pathophysiology of neuropsychiatric disorders. The advantages of using this assay include a small amount of material needed, relatively simple and fast protocol, and the ability to capture a range of gene regulatory elements with a single assay. However, with increasing interest in chromatin research, it is an imperative to have feasible, reliable assays that are compatible with a range of neuroscience study designs in both animals and humans. Here we tested three different protocols for neuronal chromatin accessibility analysis, including a varying brain tissue freezing method followed by fluorescent-activated nuclei sorting (FANS) and the ATAC-seq analysis. Our study shows that the cryopreservation method impacts the number of open chromatin regions that can be identified from frozen brain tissue using the cell-type specific ATAC-seq assay. However, we show that all three protocols generate consistent and robust data and enable the identification of functional regulatory elements, promoters and enhancers, in neuronal cells. Our study also implies that the broad biological interpretation of chromatin accessibility data is not significantly affected by the freezing condition. In comparison to the mouse brain analysis, we reveal the additional challenges of doing chromatin analysis onpost mortemhuman brain tissue. However, we also show that these studies are revealing important cell type-specific information about gene regulation in the human brain. Overall, the ATAC-seq coupled with FANS is a powerful method to capture cell-type specific chromatin accessibility information in the mouse and human brain. Our study provides alternative brain preservation methods that generate high quality ATAC-seq data while fitting in different study designs, and further encourages the use of this method to uncover the role of epigenetic (dys)regulation in healthy and malfunctioning brain.
From spatial value to panopticon: study of organizational changes in riverside areas in Poznań
Authors: Wechta Przemysław 
Published: July 2020

PurposeThe aim of the article is to analyze the process of creating spatial value. The object of the analysis concerns the riverside areas of the city of Poznan. The study focuses on spontaneous practices that are outside the legal regulations, thanks to less-visited places which have gained popularity among residents and disciplinary techniques introduced by government officials in response to such activities.Design/methodology/approachAt the theoretical level, the study is primarily based on Florian Znaniecki's spatial value concept and Michel Foucault's concept of power. The empirical research study includes quantitative (questionnaire-based interviews) and qualitative methods (expert interviews and content analysis).FindingsIdentification of the method of creating spatial value which does not require direct financial outlays; determination of disciplinary techniques used by government officials ultimately led to a reduction in the spatial value.Originality/valueThe article reveals the hidden mechanisms of functioning of the authority that defends itself against the reduction of its powers. It is an alternate way of analyzing and interpreting organizational changes in urban space to the one promoted by the Poznan authorities. The results can be used in various ways. Researchers representing the critical trend of urban research can interpret the process of creating spatial value by residents in terms of community, resistance and alternates to the actions of the authorities. From this point of view, the research study is interventional and exposing in nature. On the other hand, for city decision makers allowing the possibility to consume alcohol in a given area can be an effective, low-cost way of revitalizing it. Research can also be useful in assessing the effectiveness of particular disciplinary techniques by public officers.
Into the wild blueberry (Vaccinium angustifolium) rhizosphere microbiota
Authors: Morvan Simon , Meglouli Hacène , Lounès‐Hadj Sahraoui Anissa , Hijri Mohamed 
Published: July 2020

SummaryThe ability of wild blueberries to adapt to their harsh environment is believed to be closely related to their symbiosis with ericoid mycorrhizal fungi, which produce enzymes capable of organic matter mineralization. Although some of these fungi have been identified and characterized, we still know little about the microbial ecology of wild blueberry. Our study aims to characterize the fungal and bacterial rhizosphere communities of Vaccinium angustifolium (the main species encountered in wild blueberry fields). Our results clearly show that the fungal order Helotiales was the most abundant taxon associated with V. angustifolium. Helotiales contains most of the known ericoid mycorrhizal fungi which are expected to dominate in such a biotope. Furthermore, we found the dominant bacterial order was the nitrogen‐fixing Rhizobiales. The Bradyrhizobium genus, whose members are known to form nodules with legumes, was among the 10 most abundant genera in the bacterial communities. In addition, Bradyrhizobium and Roseiarcus sequences significantly correlated with higher leaf‐nitrogen content. Overall, our data documented fungal and bacterial community structure differences in three wild blueberry production fields.
What is (s)he Worth? Exploring Mechanisms and Boundary Conditions of the Relationship Between CEO Extraversion and Pay
Authors: Malhotra Shavin , Shen Winny , Zhu PengCheng 
Published: July 2020

AbstractIntegrating human capital theories and the status incongruity hypothesis at the upper echelons, we examine for whom extraversion, the personality trait that has been most strongly and consistently implicated in leader success, influences Chief Executive Officer (CEO) pay. To assess the personality traits of CEOs, we used a computerized text analysis approach on the language spoken by CEOs in conference calls. Using a sample of firms listed on the S&P 1500, we find that more extraverted CEOs earned higher pay, indicating that this was a trait valued by boards. Additionally, this relationship was due to enhanced firm performance; specifically, market performance. However, a critical boundary condition is that the relationship between CEO extraversion and pay was weaker for female (vs. male) CEOs, despite the market responding equally positively to extraverted female and male CEOs. Thus, the monetary benefits of higher levels of extraversion did not extend to female CEOs and likely reflects backlash. Supplemental analyses revealed that this devaluation of more extraverted female (vs. male) CEOs was mitigated when the CEO was also the chairperson of the board (i.e., CEO duality) or under conditions of greater female representation on the board of directors.
Make every species count: fastachar software for rapid determination of molecular diagnostic characters to describe species
Authors: Merckelbach Lucas M. , Borges Luísa M. S. 
Published: July 2020

AbstractOnly a fraction of species found so far has been described, particularly cryptic species uncovered by molecular data. The latter might require the use of molecular data for its diagnosis, but it is important to make use of the diagnostic content of the molecular data itself. The molecular character‐based model provides discrete molecular diagnostic characters within DNA sequences that can be used in species descriptions fulfilling the requirement of most codes of nomenclature for a character‐based description of species. Here, we introduce fastachar, a software developed to extract molecular diagnostic characters from one or several taxonomically informative DNA markers of a selected taxon compared with those of other taxa in a single step. The input data consist of a single file with aligned sequences in the fasta format, which can be created using alignment software such as mega or geneious. fastachar is an easy‐to‐use software with a graphical interface. Thus, the software does not require the user to have any knowledge of the underlying programming environment (Python). We hope this software, based on the method proposed by Jörger and Schrödl (Frontiers in Zoology, 10, 59, 2013) to describe cryptic species, will encourage researchers to take the final step in taxonomy: the formal description of species. We propose the use of this method and fastachar also for the inclusion of molecular data in the description of any species. fastachar is released as open‐source software under GNU General Public License V3 and is freely available for all major operating systems from https://github.com/smerckel/FastaChar.
Bee foraging preferences on three willow (Salix) species: Effects of species, plant sex, sampling day and time of day
Authors: Mosseler Alex , Major John , Ostaff Don , Ascher John 
Published: July 2020

AbstractOur objective was to examine how bee foraging preferences on dioecious willows are influenced by plant sex, time of day, by sampling date on multiple sites and across different willow species. In a common garden experiment examining diurnal pollinator visitation patterns of Andrena bees (andrenids), there was a strong preference for male willow plants: 87% of visitations on male plants of Salix eriocephala (ERI) and 71% on males of S. interior (INT). The significant plant sex × time of day interaction was not a result of a change in bee preference for a certain plant sex during a certain part of the day but rather the result of diurnal changes in the magnitude of the preference of andrenid bees for male willow plants. Visits to male flower catkins were highest in the morning and early afternoon, peaking at midday. Visits to female catkins showed a more uniform, lower frequency visitation pattern throughout the day. In a larger field test at a reclaimed former coal mine site, which included S. cordata (COR) as well as ERI and INT, there were no sampling date × plant sex or sampling date × plant sex × willow species interactions. This indicates no plant sex switching behaviour by sampling date for the three willow species. Preference for male plants was greatest on the first sampling day and the proportion of male preference continued to decline until the fourth and final sampling day. On the mine site, 17 of the 25 Apoidea bee species identified were andrenids, and they represented 92% of the 744 individual bees collected while foraging on willow catkins. In addition, the overall number of observed and collected Apoidea bees visiting available flowering willow plants showed that the preference for male plants was 83%, 72% and 91%, for ERI, INT and COR, respectively. We discuss possibilities for promoting populations of native bees to increase commercial fruit and berry crop pollination by using willows as natural sources of pollen and nectar, thereby reducing costs of production associated with the annual importation of commercial bees.
Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity
Authors: Björk Emma , Vinnars Marie‐Therese , Nagaev Ivan , Nagaeva Olga , Lundin Eva , Ottander Ulrika , Mincheva‐Nilsson Lucia 
Published: July 2020

AbstractProblemEndometriosis is a disease characterized by ectopic implantation of endometrium and impaired immune responses. To explore its pathogenic mechanisms, we studied the local and systemic cytokine mRNA profiles and their role in the immunity of patients with endometriosis and healthy controls.Method of StudymRNA for eleven cytokines defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles was characterized locally in endometriotic tissue and endometrium, and systemically in PBMCs from women with endometriosis and healthy controls, using real‐time qRT‐PCR. In addition, immunohistochemical stainings with monoclonal antibodies were performed looking for T regulatory cells in endometriotic lesions.ResultsWe found a downregulation of mRNA for cytokines mediating cytotoxicity and antibody response and an upregulation of inflammatory and T‐regulatory cytokines in the endometriotic tissues and endometrium from the patients with endometriosis, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with those findings, there was an abundancy of T regulatory cells in the endometriotic lesions.ConclusionsThe ectopic implantation seen in endometriosis could be possible as a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression.