bluuebunny/crossref_metadata_2025_split huggingface dataset:
LNCRNA expression landscape and specificity between brain regions
Authors: Adewale Joseph Ogunleye , Ali Umair , Michael Juwon Olufemi 
Published: November 2021

AbstractLong noncoding RNAs (lncRNAs) are transcribed into low potential protein coding RNA molecules, which account for over 70% of mammalian transcriptional products. The role of lncRNAs and their expression is still largely unknown, and the subject of recent investigations. Here, we used bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) project to reveal the occurrence and identify the specificity of lncRNAs in 13 brain regions (1000 samples). We observed that these highly specific lncRNA were co-expressed with previously known mRNA markers for the 13 study regions of the brain. Further investigation revealed that splicing could influence the divergent biogenesis and enrichment of specific lncRNA alleles in different brain regions. Overall, we demonstrate the use of lncRNA as an independent tool for deconvolving brain regions and further highlights its use for cell-type identification from bulk transcriptome data.
The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, are potent BACH1 inhibitors
Authors: Casares Laura , Moreno Rita , Higgins Maureen , Naidu Sharadha Dayalan , Neill Graham , Cassin Lena , Kiib Anders E. , Svenningsen Esben B. , Honda Tadashi , Poulsen Thomas B. , Dinkova-Kostova Albena T. , Olagnier David , de la Vega Laureano 
Published: October 2021

AbstractThe transcription factor BACH1 is a potential target against a variety of chronic conditions linked to oxidative stress and inflammation, and formation of cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2- cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these drugs may have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of CDDO-derivatives, but not CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-derivatives inhibit BACH1, which explains the much higher potency of CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-derivatives inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. Altogether, our study identifies CDDO-derivatives as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs.
GATA2 haploinsufficiency causes an epigenetic feedback mechanism resulting in myeloid and erythroid dysplasi
Authors: Gioacchino Emanuele , Zhang Wei , Koyunlar Cansu , Zink Joke , de Looper Hans , Gussinklo Kirsten J. , Hoogenboezem Remco , Bosch Dennis , Bindels Eric , Touw Ivo P. , de Pater Emma 
Published: October 2021

AbstractThe transcription factor GATA2 has pivotal roles in hematopoiesis. Germline GATA2 mutations in patients result in GATA2 haploinsufficiency syndrome characterized by immunodeficiency, bone marrow failure, and predispositions to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical symptoms in GATA2 patients are diverse and mechanisms driving GATA2 related phenotypes largely unknown. To explore the impact of GATA2 haploinsufficiency on hematopoiesis, we generated a zebrafish model carrying a heterozygous mutation of gata2b (gata2b+/−), an orthologue of GATA2. Morphological analysis revealed myeloid and erythroid dysplasia in gata2b+/−kidney marrow (KM). single nucleus (sn)-ATAC-seq showed that the co-accessibility between the transcription start site (TSS) and a +3.5-4.1kb enhancer was more robust in gata2b+/−zebrafish HSPCs compared to wild type, increasing gata2b expression. This is suggestive of an auto-regulatory feedback mechanism, where gata2b expression remains at sufficient levels after the loss of a single allele to maintain the HSPC pool. As a result, gata2b+/−chromatin is also more accessible in the erythroid and myeloid lineage, causing several defects. scRNA-seq data revealed a differentiation delay in erythroid progenitors, hallmarked by downregulation of intrinsic signals like cytoskeletal transcripts, aberrant proliferative signatures, and downregulation of Gata1a, a master regulator of erythropoiesis, likely preceding erythroid dysplasia. This shows that the cell intrinsic compensatory mechanisms for the maintenance of normal levels of Gata2b to maintain HSPC integrity result in aberrant lineage differentiation and a preleukemia syndrome.
Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism
Authors: Magnotti Flora , Chirita Daria , Dalmon Sarah , Martin Amandine , Bronnec Pauline , Sousa Jeremy , Helynck Olivier , Lee Wonyong , Kastner Daniel , Chae Jae Jin , McDermott Michael F. , Belot Alexandre , Popoff Michel , Sève Pascal , Georgin-Lavialle Sophie , Munier-Lehmann Hélène , Tran Tu Anh , Langhe Ellen De , Wouters Carine , Jamilloux Yvan , Henry Thomas 
Published: October 2021

AbstractThe pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defences against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identified etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step-2 activators. High concentrations of these metabolites fully and rapidly activated pyrin, in a human-specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases (PAAND and FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, displayed increased responses to these metabolites. This study provides a new perspective on pyrin activation, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and explains the “steroid fever” described in the late 1950s, upon steroid injection in humans.
Vocal tract allometry in a mammalian vocal learner
Authors: de Reus Koen , Carlson Daryll , Lowry Alice , Gross Stephanie , Garcia Maxime , Rubio-Garcia Ana , Salazar-Casals Anna , Ravignani Andrea 
Published: October 2021

AbstractAcoustic allometry occurs when features of animal vocalisations can be predicted from body size measurements. Despite this being considered the norm, allometry sometimes breaks, resulting in species sounding smaller or larger than expected for their size. A recent hypothesis suggests that allometry-breaking mammals cluster into two groups: those with anatomical adaptations to their vocal tracts and those capable of learning new sounds (vocal learners). Here we test which mechanism is used to escape from acoustic allometry by probing vocal tract allometry in a proven mammalian vocal learner, the harbour seal (Phoca vitulina). We test whether vocal tract structures and body size scale allometrically in 68 young individuals. We find that both body length and body mass accurately predict vocal tract length and one tracheal dimension. Independently, body length predicts vocal fold length while body mass predicts a second tracheal dimension. All vocal tract measures are larger in weaners than in pups and some structures are sexually dimorphic within age classes. We conclude that harbour seals do comply with anatomical allometric constraints. However, allometry between body size and vocal fold length seems to emerge after puppyhood, suggesting that ontogeny may modulate the anatomy-learning distinction previously hypothesised as clear-cut. We suggest that seals, like other species producing signals that deviate from those expected from their vocal tract dimensions, may break allometry without morphological adaptations. In seals, and potentially other vocal learning mammals, advanced neural control over vocal organs may be the main mechanism for breaking acoustic allometry.
Clamping of DNA shuts the condensin neck gate
Authors: Lee Byung-Gil , Rhodes James , Löwe Jan 
Published: October 2021

ABSTRACTCondensin is a Structural Maintenance of Chromosomes (SMC) complex needed for the compaction of DNA into chromatids during mitosis. Lengthwise DNA compaction by condensin is facilitated by ATPase-driven loop extrusion, a process that is believed to be the fundamental activity of most, if not all SMC complexes. In order to obtain molecular insights, we obtained cryo-EM structures of yeast condensin in the presence of a slowly-hydrolysable ATP analogue and linear, as well as circular DNAs. The DNAs were shown to be “clamped” between the engaged heterodimeric SMC ATPase heads and the Ycs4 subunit, in a manner similar to previously reported DNA-bound SMC complex structures. Ycgl, the other non-SMC subunit was only flexibly bound to the complex, while also binding DNA tightly, and often remaining at a distance from the head module. In the clamped state, the DNA is encircled, or topologically entrapped, by the kleisin Brnl and the two engaged head domains of Smc2 and Smc4, and this tripartite ring is closed at all interfaces, including at the neck of Smc2. We show that the neck gate opens upon head engagement in the absence of DNA, but it remains shut when DNA is present. Our work demonstrates that condensin and other SMC complexes go through similar conformations of the head modules during their ATPase cycle. In contrast, the behaviour of the Ycgl subunit in the condensin complex might indicate differences in the implementation of the extrusion reactions and our findings will constrain further mechanistic models of loop extrusion by SMC complexes.SIGNIFICANCE STATEMENTDNA needs to be compacted dramatically to fit into nuclei and during cell division, when dense chromatids are formed for their mechanical segregation, a process that depends on the protein complex condensin. It forms and enlarges loops in DNA through loop extrusion. Our work resolves the atomic structure of a DNA-bound state of condensin in which ATP has not been hydrolysed. The DNA is clamped within a compartment that has been reported previously in other SMC complexes, including Rad50, cohesin and MukBEF. With the caveat of important differences that we also uncovered, it means that all SMC complexes cycle through at least some similar states and undergo similar conformational changes in their head modules, while hydrolysing ATP and translocating DNA.
Hidden pathway for cytokine receptor activation: Structural insights into a marine sponge-derived lectin that activates the thrombopoietin receptor via recognition of the fucose moiety
Authors: Watari Hiromi , Kageyama Hiromu , Masubuchi Nami , Nakajima Hiroya , Onodera Kako , Focia Pamela J. , Oshiro Takumi , Matsui Takashi , Kodera Yoshio , Ogawa Tomohisa , Yokoyama Takeshi , Hirayama Makoto , Hori Kanji , Freymann Douglas M. , Komatsu Norio , Araki Marito , Tanaka Yoshikazu , Sakai Ryuichi 
Published: October 2021

ABSTRACTN-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that constitutively activates the receptor. However, the molecular basis for this mechanism has not been studied because no external agonists existed. We describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. ThC-induced activation persists due to limited receptor internalization. The strong synergy between ThC and thrombopoietin suggests that ThC catalyzes the formation of receptor dimers on the cell surface. MPL is subject to sugar-mediated activation, where the kinetics differ from those of cytokines. This result suggests the presence of diverse receptor activation pathways in human thrombopoiesis.One-sentence summaryA marine sponge lectin catalyzes thrombopoietin receptor dimerization and activation, exhibiting strong synergy with thrombopoietin, and modulates internalization of the receptor.
Correcting the Hebbian Mistake: Toward a Fully Error-Driven Hippocampus
Authors: Zheng Yicong , Liu Xiaonan L. , Nishiyama Satoru , Ranganath Charan , O’Reilly Randall C. 
Published: October 2021

AbstractThe hippocampus plays a critical role in the rapid learning of new episodic memories. Many computational models propose that the hippocampus is an autoassociator that relies on Hebbian learning (i.e., “cells that fire together, wire together”). However, Hebbian learning is computationally suboptimal as it modifies weights unnecessarily beyond what is actually needed to achieve effective retrieval, causing more interference and resulting in a lower learning capacity. Our previous computational models have utilized a powerful, biologically plausible form of error-driven learning in hippocampal CA1 and entorhinal cortex (EC) (functioning as a sparse autoencoder) by contrasting local activity states at different phases in the theta cycle. Based on specific neural data and a recent abstract computational model, we propose a new model called Theremin (Total Hippocampal ERror MINimization) that extends error-driven learning to area CA3 — the mnemonic heart of the hippocampal system. In the model, CA3 responds to the EC monosynaptic input prior to the EC disynaptic input through dentate gyrus (DG), giving rise to a temporal difference between these two activation states, which drives error-driven learning in the EC→CA3 and CA3↔CA3 projections. In effect, DG serves as a teacher to CA3, correcting its patterns into more pattern-separated ones, thereby reducing interference. Results showed that Theremin, compared with our original model, has significantly increased capacity and learning speed. The model makes several novel predictions that can be tested in future studies.Author SummaryExemplified by the famous case of patient H.M. (Henry Molaison) who had his hippocampus surgically removed, the hippocampus is critical for learning and remembering about everyday events — what is typically called “episodic memory.” The dominant theory for how it learns is based on the intuitive principle stated by Donald Hebb in 1949, that neurons that “fire together, wire together” — when two neurons are active at the same time, the strength of their connection increases. We show in this paper that using a different form of learning based on correcting errors (error-driven learning) results in significantly improved episodic memory function in a biologically-based computational model of the hippocampus. This model also provides a significantly better account of behavioral data on the testing effect, where learning by testing with partial cues is better than learning with the complete set of information.
Chest X-ray Severity and its Association with Outcomes in Patients with COVID-19 Presenting to the Emergency Department
Authors: Kotok Daniel , Robles Jose Rivera , Girard Christine , Shettigar Shruti , Lavina Allen , Gillenwater Samantha , Kim Andrew , Hadeh Anas 
Published: November 2021

AbstractBackgroundSeverity of radiographic abnormalities on chest X-ray (CXR) in patients with COVID-19 has been shown to be associated with worse outcomes, but studies are limited by different scoring systems, sample size, patient age and study duration. Data regarding the longitudinal evolution of radiographic abnormalities and its association with outcomes is scarce. We sought to evaluate these questions using a well-validated scoring system (the Radiographic Assessment of Lung Edema [RALE] score) using data over 6 months from a large, multi-hospital healthcare system.MethodsWe collected clinical and demographic data and quantified radiographic edema on CXRs obtained in the emergency department (ED) as well as on days 1-2 and 3-5 (in those admitted) in patients with a nasopharyngeal swab positive for SARS-CoV-2 PCR visiting the ED for COVID-19-related complaints between March and September 2020. We examined the association of baseline and longitudinal evolution of radiographic edema with severity of hypoxemia and clinical outcomes.Results870 patients were included (median age 53.6, 50.8% female). Inter-rate agreement for RALE scores was excellent (ICC = 0.84, 95% CI 0.82 - 0.87, p < 0.0001). RALE scores correlated with hypoxemia as quantified by SpO2-FiO2 ratio (r = -0.42, p < 0.001). Admitted patients had higher RALE scores than those discharged (6 [2, 11] vs 0 [0, 3], p < 0.001). An increase of RALE score of 4 or more was associated with worse 30-day survival (p < 0.01). Larger increases in the RALE score were associated with worse survival.ConclusionsThe RALE score is reproducible and easily implementable in adult patients presenting to the ED with COVID-19. Its association with physiologic parameters and outcomes at baseline and longitudinally makes it a readily available tool for prognostication and early ICU triage, particularly in patients with worsening radiographic edema.
Two decades of Wikipedia research: a PubMed bibliometric network analysis
Authors: Mostafa Mohamed M. 
Published: November 2021

PurposeThis paper aims to examine the structure and dynamics of scholarly publications dealing with Wikipedia. The research also aims to investigate how such research evolved since its launch in 2001.Design/methodology/approachWikipedia has grown to be the biggest online encyclopedia in terms of comprehensiveness, reach and coverage. Based on 1,040 PubMed Wikipedia documents written by 5,280 authors over two decades (2001–2021), this paper conducts a bibliometric review of the intellectual structure of scholarly publications dealing with Wikipedia.FindingsResults show that annual scholarly publications on Wikipedia growth rate is 13.26. Major outlets publishing Wikipedia’s research arePloS One,the Journal of Medical Internet Research,Nucleic Acids Research,Studies in Health Technology and Informatics,Bioinformaticsandthe International Journal of Medical Informatics. Results also show that the author collaboration network is very sparse, signifying rather negligible collaboration among the authors. Furthermore, results reveal that the Wikipedia research institutions’ collaboration network reflects what is sometimes termed Wikipedia’s “North-South divide,” indicating limited collaboration between rich and poor nations’ institutions. Finally, the multiple correspondence analysis applied to obtain the Wikipedia research conceptual map and its intellectual structure reveals the intellectual thrust and the diversity of the scholarly publications dealing with Wikipedia.Originality/valueTo the best of the author’s knowledge, this research represents the first application of bibliometric methods to investigate two decades of scholarly publications dealing with Wikipedia based on the PubMed database.
Customer helping and advocacy behaviours within dyadic financial service relationships: a gift-giving perspective
Authors: van Tonder Estelle , Saunders Stephen Graham , Mwavita Mwarumba , Kim Sohee 
Published: October 2021

PurposeThis study aims to examine customer helping and advocacy behaviours within dyadic financial service relationships involving customers and fellow customer helpers.Design/methodology/approachThe gift-giving literature was used to propose a customer-to-customer interaction model, which was tested and cross-validated among electronic banking customers in South Africa (n = 404) and Australia (n = 244). Self-administered questionnaires were distributed to respondents who are users of electronic banking services and who previously received help with the service from a fellow customer. Data analysis included multi-group structural equation modelling.FindingsThe findings support the view that selected source credibility dimensions may influence greater affective commitment towards fellow customer helpers at various levels. Subsequently, further altruistic gift-giving in the form of customer helping and advocacy behaviours may result from higher levels of affective commitment. Feeling secure in their relationships with fellow customer helpers, customer recipients of help are likely to further socialise other customers who may share a common interest in the service category (e.g. electronic banking), but do not necessarily support the financial service provider of the customer.Originality/valueThe findings extend the conceptual domain of affective commitment and shed light on the factors contributing to the development of strengthened bonds between customers and fellow customer helpers within dyadic financial service relationships. Additionally, greater financial service socialisation and use may be achieved when the helping and advocacy behaviours of customer helpers are not restricted to a specific service provider. Subsequently, the current investigation advances knowledge of the underlying processes involved in motivating these desired service outcomes and behaviours.
International entrepreneurial startups' location under uncertainty through a heterogeneous multi-layer decision-making approach: evidence and application of an emerging economy
Authors: Razavi Hajiagha Seyed Hossein , Ahmadzadeh Kandi Niloofar , Amoozad Mahdiraji Hannan , Jafari-Sadeghi Vahid , Hashemi Shide Sadat 
Published: October 2021

PurposeScience and technology parks (STPs) have a limited capacity, which can create challenging conditions for applicants. This makes the location selection a multi-criteria decision-making (MCDM) problem to find and apply for the most appropriate STP with the highest accordance with the startup's requirements. This research aims to select the most appropriate STP to locate an international entrepreneurial pharmaceutical startup under uncertainty. Since drugs are generally produced domestically in developing countries such as Iran, the access of pharmaceutical startups to the resources provided by STPs can lead to overcoming competitors and improving the country's health system.Design/methodology/approachIn this research, the factors or attributes effective on startup location were extracted through a two-round Delphi method, which was performed among 15 experts within three groups. Subsequently, the determining factors were used to select the location of a pharmaceutical startup among possible STPs. In this regard, decision-makers were allowed to use different types of numbers to transfer their opinion. Afterward, the heterogeneous weighted aggregated sum product assessment (HWASPAS) method was applied to calculate the score of each alternative and rank them to place the studied startup successfully.FindingsThe results indicated that Tehran STP stands in the first place; however, if the decision was made based on single criterion like cost, some other STPs could be preferable, and many managers would lose this choice. Furthermore, the results of the proposed method were close to other popular heterogeneous MCDM approaches.Originality/valueA heterogeneous WASPAS is developed in this article for the first time to enable international entrepreneurs to imply their opinion with various values and linguistic variables to reduce the emphasis on accurate data in an uncertain environment.