bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spindle checkpoint signalling in anaphase is prevented by KNL1 release from kinetochores
Authors: Lim-Manley Iona , Gruneberg Ulrike 
Published: May 2023

AbstractCDK1-cyclin B1 kinase is the main driver of mitosis and initiates the morphological changes that characterise mitosis, including mitotic spindle assembly and formation of the outer kinetochore. CDK1-cyclin B1 activity is also critically required for spindle assembly checkpoint (SAC) signalling during mitosis. In particular, CDK1-cyclin B1 promotes the targeting of the principal spindle checkpoint kinase MPS1 to kinetochores, leading to the recruitment of SAC proteins to the outer kinetochore scaffold protein KNL1 and initiation of checkpoint signalling. However, cells expressing kinetochore-tethered MPS1 still require CDK1 activity for SAC signalling, suggesting that CDK1 plays both MPS1-dependent and -independent roles in regulating the SAC. Here we show that the latter is due to CDK1-mediated kinetochore recruitment of KNL1, which is reversed by the PP1 phosphatase at the metaphase-to-anaphase transition. Our findings explain the abrupt and irreversible termination of spindle checkpoint signalling in anaphase, since the drop of CDK1 activity means both MPS1 and the spindle checkpoint scaffold KNL1 are lost from kinetochores.SummaryLim-Manley and Gruneberg investigate MPS1-independent roles of CDK1 in spindle checkpoint signalling. They reveal how PP1 activity following CDK1 inactivation results in the rapid removal of KNL1 from kinetochores at anaphase onset, contributing to prompt spindle checkpoint silencing.
Visualizing and identifying selfish bacteria: a hunting guide
Authors: Reintjes G. , Giljan G. , Fuchs B. M. , Arnosti C. , Amann R. 
Published: May 2023

AbstractPolysaccharides are dominant components of plant biomass, whose degradation is typically mediated by heterotrophic bacteria. These bacteria use extracellular enzymes to hydrolyze polysaccharides to oligosaccharides that are then also available to other bacteria. Recently, a new mechanism of polysaccharide processing – ‘selfish’ uptake – has been recognized, initially among gut-derived bacteria. In ‘selfish’ uptake, polysaccharides are bound at the outer membrane, partially hydrolyzed, and transported into the periplasmic space without loss of hydrolysis products, thus limiting the availability of smaller sugars to the surrounding environment. Selfish uptake is widespread in environments ranging from the ocean’s cool, oxygen-rich, organic carbon-poor waters to the warm, carbon-rich, anoxic environment of the human gut. We provide a detailed guide of how to hunt for selfish bacteria, including how to rapidly visualize selfish uptake in complex bacterial communities, identify selfish organisms, and distinguish the activity of selfish organisms from other members of the community.
Clustering Protein Binding Pockets and Identifying Potential Drug Interactions: A Novel Ligand-based Featurization Method
Authors: Stevenson Garrett A. , Kirshner Dan , Bennion Brian J. , Yang Yue , Zhang Xiaohua , Zemla Adam , Torres Marisa W. , Epstein Aidan , Jones Derek , Kim Hyojin , Bennett W. F. D. , Wong Sergio E. , Allen Jonathan E. , Lightstone Felice C. 
Published: May 2023

AbstractProtein-ligand interactions are essential to drug discovery and drug development efforts. Desirable on-target or multi-target interactions are a first step in finding an effective therapeutic; undesirable off-target interactions are a first step in assessing safety. In this work, we introduce a novel ligand-based featurization and mapping of human protein pockets to identify closely related protein targets, and to project novel drugs into a hybrid protein-ligand feature space to identify their likely protein interactions. Using structure-based template matches from PDB, protein pockets are featurized by the ligands which bind to their best co-complex template matches. The simplicity and interpretability of this approach provides a granular characterization of the human proteome at the protein pocket level instead of the traditional protein-level characterization by family, function, or pathway. We demonstrate the power of this featurization method by clustering a subset of the human proteome and evaluating the predicted cluster associations of over 7,000 compounds.
Evolutionary spread of protein L-(iso)aspartylO-methyltransferases guides the discovery of distinct isoaspartate-containing peptides, pimtides
Authors: Lee Hyunbin , Park Sho Hee , Kim Jiyoon , Lee Jaehak , Koh Min Sun , Lee Jung Ho , Kim Seokhee 
Published: May 2023

ABSTRACTRibosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural products with a distinct biosynthetic logic, the enzymatic modification of genetically encoded precursor peptides. Although their structural and biosynthetic diversity remains largely underexplored, the identification of novel subclasses with unique structural motifs and biosynthetic pathways has been challenging. Here, we report that protein L-(iso)aspartylO-methyltransferases (PIMTs) present in several RiPP subclasses are highly homologous. Importantly, we discovered that the apparent evolutionary transmission of the PIMT gene could serve as a basis to identify a novel RiPP subclass. Biochemical and structural analyses suggest that these homologous PIMTs commonly convert aspartate to isoaspartate via aspartyl-O-methyl ester and aspartimide intermediates, and often require cyclic or hairpin-like structures for modification. By conducting homology-based bioinformatic analysis of PIMTs, we identified over 2,800 biosynthetic gene clusters (BGCs) for known RiPP subclasses in which PIMTs install a secondary modification, and over 1,500 BGCs in which PIMTs function as a primary modification enzyme, thereby defining a new RiPP subclass, named pimtides. Our results suggest that the genome mining of proteins with secondary biosynthetic roles could be an effective strategy for discovering novel biosynthetic pathways of RiPPs.Insert Table of Contents artwork here
De novodistillation of thermodynamic affinity from deep learning regulatory sequence models ofin vivoprotein-DNA binding
Authors: Alexandari Amr M. , Horton Connor A. , Shrikumar Avanti , Shah Nilay , Li Eileen , Weilert Melanie , Pufall Miles A. , Zeitlinger Julia , Fordyce Polly M. , Kundaje Anshul 
Published: May 2023

AbstractTranscription factors (TF) are proteins that bind DNA in a sequence-specific manner to regulate gene transcription. Despite their unique intrinsic sequence preferences,in vivogenomic occupancy profiles of TFs differ across cellular contexts. Hence, deciphering the sequence determinants of TF binding, both intrinsic and context-specific, is essential to understand gene regulation and the impact of regulatory, non-coding genetic variation. Biophysical models trained onin vitroTF binding assays can estimate intrinsic affinity landscapes and predict occupancy based on TF concentration and affinity. However, these models cannot adequately explain context-specific,in vivobinding profiles. Conversely, deep learning models, trained onin vivoTF binding assays, effectively predict and explain genomic occupancy profiles as a function of complex regulatory sequence syntax, albeit without a clear biophysical interpretation. To reconcile these complementary models ofin vitroandin vivoTF binding, we developed Affinity Distillation (AD), a method that extracts thermodynamic affinitiesde-novofrom deep learning models of TF chromatin immunoprecipitation (ChIP) experiments by marginalizing away the influence of genomic sequence context. Applied to neural networks modeling diverse classes of yeast and mammalian TFs, AD predicts energetic impacts of sequence variation within and surrounding motifs on TF binding as measured by diversein vitroassays with superior dynamic range and accuracy compared to motif-based methods. Furthermore, AD can accurately discern affinities of TF paralogs. Our results highlight thermodynamic affinity as a key determinant ofin vivobinding, suggest that deep learning models ofin vivobinding implicitly learn high-resolution affinity landscapes, and show that these affinities can be successfully distilled using AD. This new biophysical interpretation of deep learning models enables high-throughputin silicoexperiments to explore the influence of sequence context and variation on both intrinsic affinity andin vivooccupancy.
Social experiences shape song preference learning independent of developmental exposure to song
Authors: Wall Erin , Woolley Sarah 
Published: May 2023

ABSTRACTCommunication governs the formation and maintenance of social relationships. The interpretation of communication signals depends not only on the signal’s content, but also on a receiver’s individual experience. Experiences throughout life may interact to affect behavioral plasticity, such that a lack of developmental sensory exposure could constrain adult learning, while salient adult social experiences could remedy developmental deficits. We investigated how experiences impact the formation and direction of female auditory preferences in the zebra finch. Zebra finches form long-lasting pair bonds and females learn preferences for their mate’s vocalizations. We found that after two weeks of cohabitation with a male, females formed pair-bonds and learned to prefer their mate’s song regardless of whether they were reared with (“normally-reared”) or without (“song-naïve”) developmental exposure to song. In contrast, females that heard but did not physically interact with a male did not prefer his song. Moreover, even following mating, song-naive females failed to show species-typical preferences for courtship song, hinting that mating is insufficient to ameliorate broader deficits in sensory processing that arise during development. Thus, courtship and mating interactions, but not acoustic-only interactions, strongly influence preference learning regardless of rearing experience, and may dynamically drive auditory plasticity for recognition and preference.
Mapping the MOB proteins’ proximity network reveals a unique interaction between human MOB3C and the RNase P complex
Authors: Elkholi Islam E. , Boulais Jonathan , Thibault Marie-Pier , Phan Hong-Duc , Robert Amélie , Lai Lien B. , Faubert Denis , Smith Matthew J. , Gopalan Venkat , Côté Jean-François 
Published: May 2023

ABSTRACTDistinct functions mediated by members of the monopolar spindle-one-binder (MOB) family of proteins remain elusive beyond the evolutionary conserved and well-established roles of MOB1A and B in regulating the Hippo pathway. Since MOB proteins are adaptors, understanding how they engage in protein-protein interactions and complexes assembly is essential to define the full scope of their biological functions. To address this, we undertook a proximity-dependent biotin identification (BioID) approach to define the interactomes of all seven human MOB proteins in HeLa and HEK293 cell lines. We uncovered > 200 interactions, of which at least 70% are unreported on BioGrid. The generated dataset reliably recalled thebona fideinteractors of the well-studied MOBs. We further defined the common and differential interactome between different MOBs on a subfamily and an individual level. We discovered a unique interaction between MOB3C and 7 out of 10 protein subunits of the RNase P complex, an endonuclease that catalyzes tRNA 5’ maturation. As a proof-of-principle for the robustness of the generated dataset, we validated the specific interaction of MOB3C with catalytically active RNase P by using affinity purification-mass spectrometry and pre-tRNA cleavage assays of MOB3C pulldowns. In summary, our data provide novel insights into the biology of MOB proteins and reveal the first interactors of MOB3C, components of the RNase P complex, and hence an exciting nexus with RNA biology.
Electron transport chain inhibition increases cellular dependence on purine transport and salvage
Authors: Wu Zheng , Bezwada Divya , Harris Robert C , Pan Chunxiao , Nguyen Phong T , Faubert Brandon , Cai Ling , Cai Feng , Vu Hieu S. , Chen Hongli , Sandoval Misty Martin- , Do Duyen , Gu Wen , Zhang Yuannyu , Ko Bookyung , Brooks Bailey , Kelekar Sherwin , Zhang Yuanyuan , Zacharias Lauren G , Oaxaca K. Celeste , Mathews Thomas P , Garcia-Bermudez Javier , Ni Min , DeBerardinis Ralph J. 
Published: May 2023

SUMMARYCancer cells reprogram their metabolism to support cell growth and proliferation in harsh environments. While many studies have documented the importance of mitochondrial oxidative phosphorylation (OXPHOS) in tumor growth, some cancer cells experience conditions of reduced OXPHOS in vivo and induce alternative metabolic pathways to compensate. To assess how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts and plasma from patients with inborn errors of mitochondrial metabolism, and in cancer cells subjected to inhibition of the electron transport chain (ETC). All these analyses revealed extensive perturbations in purine-related metabolites; in non-small cell lung cancer (NSCLC) cells, ETC blockade led to purine metabolite accumulation arising from a reduced cytosolic NAD+/NADH ratio (NADH reductive stress). Stable isotope tracing demonstrated that ETC deficiency suppressed de novo purine nucleotide synthesis while enhancing purine salvage. Analysis of NSCLC patients infused with [U-13C]glucose revealed that tumors with markers of low oxidative mitochondrial metabolism exhibited high expression of the purine salvage enzyme HPRT1 and abundant levels of the HPRT1 product inosine monophosphate (IMP). ETC blockade also induced production of ribose-5’ phosphate (R5P) by the pentose phosphate pathway (PPP) and import of purine nucleobases. Blocking either HPRT1 or nucleoside transporters sensitized cancer cells to ETC inhibition, and overexpressing nucleoside transporters was sufficient to drive growth of NSCLC xenografts. Collectively, this study mechanistically delineates how cells compensate for suppressed purine metabolism in response to ETC blockade, and uncovers a new metabolic vulnerability in tumors experiencing NADH excess.
Systematic Review of Treatment of Beta-Cell Monogenic Diabetes
Authors: Naylor Rochelle N. , Patel Kashyap A. , Kettunen Jarno L.T. , Männistö Jonna M.E. , Støy Julie , Beltrand Jacques , Polak Michel ,   ADA/EASD PMDI, Vilsbøll Tina , Greeley Siri A.W. , Hattersley Andrew T. , Tuomi Tiinamaija 
Published: May 2023

AbstractBackgroundBeta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for precision medicine. We reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A- HNF4A- and HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes.MethodsSystematic reviews with data from PubMed, MEDLINE and Embase were performed for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes.Results147 studies met inclusion criteria with only six experimental studies and the rest being single case reports or cohort studies. Most studies had moderate or serious risk of bias.For GCK-related hyperglycemia, six studies (N=35) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited. While some patients with HNF1B-diabetes (n=301) and MD (n=250) were treated with oral agents, most were on insulin. There was some support for the use of oral agents after relapse in 6q24-TND, and for thiamine improving glycemic control and reducing insulin requirement in SLC19A2-diabetes (less than half achieved insulin-independency).ConclusionThere is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The data supports: no treatment in GCK-related hyperglycemia; SU for HNF1A-diabetes. Further evidence is needed to examine the optimum treatment in monogenic subtypes.
ArchaealS-adenosyl-l-homocysteine hydrolases: structure, function and substrate preferences
Authors: Popadić Désirée , Saleem-Batcha Raspudin , Köppl Lars-Hendrik , Germer Philipp , Andexer Jennifer N. 
Published: May 2023

AbstractS-Adenosyl-l-homocysteine hydrolase (SAHH) reversibly cleavesS-adenosyl-l-homocysteine (SAH), the product ofS-adenosyl-l-methionine (SAM)-dependent methylation reactions. The conversion of SAH into adenosine andl-homocysteine (Hcy) plays an important role in the regulation of the methyl cycle. An alternative metabolic route for SAM regeneration in the extremophilesMethanocaldococcus jannaschiiandThermotoga maritimawas identified with the deamination of SAH toS-inosyl-l-homocysteine (SIH). Herein, we report the first structural characterisation of different archaeal SAHHs together with a biochemical analysis of various SAHHs from all three domains of life. We found that homologues deriving from the Euryarchaeota phylum show a higher conversion rate with SIH compared to SAH. Crystal structures of SAHH originating fromPyrococcus furiosusin complex with SIH and inosine as ligands, show architectural flexibility in the active site and offer deeper insights into the binding mode of hypoxanthine-containing substrates. Altogether, the findings presented in this study support the understanding of an alternative metabolic route for SAM and offer insights into the evolutionary progression and diversification of SAHHs involved in methyl and purine salvage pathways.
Identifying key factors of sustainability practice in financial institutions based on decision-making trial and evaluation laboratory method
Authors: Kuo Yi-Chun , Huang Yueh-Hsia , Sun Lan , Small Garrick , Lin Shih-Jung 
Published: May 2023

PurposeFinancial institutions have a role in harmonising economic purposes with environmental and social purposes through transmission mechanisms whereby the institutions provide channels to promote socially and environmental desirable activities. This study explores the sustainability criteria disclosed at firm-level corporate social responsibility reports for the purpose of providing direction for financial institutions committed to enhancing the contribution to sustainability objectives.Design/methodology/approachThe Delphi Method and the Decision-Making Trial and Evaluation Laboratory (DEMATEL) system have been employed to systematically analyse the opinions of 15 experts regarding the operation of the 7 Taiwanese financial institutions listed on the Dow Jones Sustainability Index in 2019 with respect to the capacity to affect sustainability objectives.FindingsThe findings reveal a high prominence level for corporate governance, law compliance, risk management and occupational safety and health, representing amongst the sustainability criteria considered. This suggests that financial institutions may benefit from focussing resources on these areas, starting with corporate governance, when considering means for enhancing the sustainability performance.Research limitations/implicationsThe study is limited by the small number of financial institutions available in Taiwan which suggests that further research could be directed towards a larger sample of financial institutions, say by international comparison, expanding the range of industries studied or the inclusion for additional sustainability indicators.Practical implicationsOverall, the study has shed light on Taiwan's financial institutions' capacity to contribute to sustainable practices which is an area that has not been extensively investigated. This study may have useful implications for financial institutions in Taiwan.Social implicationsThe authors also recognise other factors that are likely to contribute to social impacts. These include human capacity building and development, information security, green procurement, green building and climate-related financial products.Originality/valueThis study fills the gap by providing useful insights for a better understanding of sustainable development in financial institutions by promoting sustainability practice in general. The authors' analysis will assist decision-makers in identifying and prioritising the driving factors and thus adopting suitable strategies to strengthen sustainability performance.
The great sell-side sell-off: evidence of declining financial analyst coverage
Authors: Hettler Barry , Skomra Justyna , Forst Arno 
Published: May 2023

Purpose
Motivated by significant global developments affecting the sell-side industry, in particular a shift toward passive investments and growing regulation, this study examines whether financial analyst coverage declined over the past decade and if any loss of analyst coverage is associated with a change in forecast accuracy.

Design/methodology/approach
After investigating, and confirming, a general decline in analyst following, the authors calculate the loss of analyst coverage relative to the firm-specific maximum between 2009 and 2013. In multivariate analyses, the authors then examine whether this loss of coverage differs across geographic region, firm size and capital market development, and whether it is associated with consensus analyst accuracy.

Findings
Results indicate that between 2011 and 2021, firm-specific analyst coverage globally declined 17.8%, while the decline in the EU was an even greater, 28.5%. Within the EU, results are most pronounced for small-cap firms. As a consequence of the loss of coverage, the authors observe a global decline in forecast accuracy, with EU small-cap firms and firms domiciled in EU non-developed capital markets faring the worst.

Originality/value
This study is the first to document a concerning global decline in analyst coverage over the past decade. The study results provide broad-based empirical support for anecdotal reports that smaller firms in the EU and those in EU non-developed capital markets bear the brunt of consequences stemming from changes in the sell-side analyst industry.
“Perfectionism is a debacle” how a perfectionist leader hinders in business processes? A multiple mediated model
Authors: Malik Muhammad Faisal 
Published: May 2023

PurposeThe current study highlights the dark side of a perfectionist leader hindering in business processes and also investigates its impact on procrastination through workplace incivility, psychological distress, and psychological detachment by using the tenet of conservation of resource theory. Positivism research philosophy was adopted, followed by a deductive approach.Design/methodology/approachThe survey technique was used to collect the quantitative data from the employees working in public sector organizations. 364 samples were collected and analyzed using SEM-Mplus techniques, where structured and measurement models were produced and interpreted accordingly.FindingsThe results suggested that perfectionist leaders become a source for their followers to involve in procrastination because of depletion of ego and psychological resources. The results supported the chain of mediation and both paths of perfectionist leaders, workplace incivility, psychological detachment, and procrastination and perfectionist leaders, workplace incivility, psychological distress, and procrastination.Originality/valueThe results and dynamics of the current study provided some meaningful managerial and theoretical implications and future research directions for the researchers. The study contributes significantly to the body of literature since it captures and analyzes the overlooked elements in the context of perfectionist leaders.