bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the mitochondrial RNA methyltransferase TRMT61B reveals new therapeutic opportunities in aneuploid cancer cells
Authors: Martín Alberto , Vilaplana-Marti Borja , Macías Rocío IR , Martínez-Ramírez Ángel , Cerezo Ana , Cabezas-Sainz Pablo , Garranzo Asensio Maria , Epifano Carolina , Amarilla Sandra , Gómez-Domínguez Déborah , Hernández Iván , Caleiras Eduardo , Camps Jordi , Barderas Rodrigo , Sánchez Laura , Velasco Susana , de Castro Ignacio Pérez 
Published: April 2021

AbstractChromosomal instability (CIN) is an important source of genetic and phenotypic variation that has been extensively reported as a critical cancer related property that improves tumor cell adaptation and survival. CIN and its immediate consequence, aneuploidy, provoke adverse effects on cellular homeostasis that need to be overcome by developing efficient anti-stress mechanisms. Perturbations in these safeguard responses might be detrimental for cancer cells and represent an important tumor specific Achilles heel since CIN and aneuploidy are very rare events in normal cells. On the other hand, epitranscriptomic marks catalyzed by different RNA modifying enzymes have been found to change under several stress insults. Although CIN and aneuploidy are important intracellular stressors, their biological connection with RNA modifications is pending to be determined. In anin silicosearch for new cancer biomarkers, we have identified TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. In the present work, we study the connection of this molecule with cancer and aneuploidy. First, we show increased protein amounts of TRMT61B in tumor cell lines with imbalanced karyotype as well as in different tumor types compared to unaffected control tissues. In addition, we demonstrate that depletion of TRMT61B in melanoma cells reduces cell proliferation either by fostering apoptosis and inhibiting autophagy in high-aneuploid (ANEhigh) cells or by inducing senescence in the case of low-aneuploid (ANElow) cell lines. Further, TRMT61B elimination compromises mitochondrial function and reduces the expression of several mitochondrial encoded proteins that are part of the electron transport chain. Finally, transwell and xenograft experiments revealed a reduced invasive and tumorigenic capacity upon TRMT61B depletion that strengthen the therapeutic value of this aneuploidy-associated biomarker. These results, which connect tumorigenesis, aneuploidy and mitochondrial RNA methylation, bring to the cancer field a new putative strategy to specifically target high aneuploid tumors.
Control-theoretic immune tradeoffs explain SARS-CoV-2 virulence and transmission variation
Authors: Sarma Anish A. , Sarma Aartik , Csete Marie , Lee Peter P. , Doyle John C. 
Published: April 2021

AbstractDramatic variation in SARS-CoV-2 virulence and transmission between hosts has driven the COVID-19 pandemic. The complexity and dynamics of the immune response present a challenge to understanding variation in SARS-CoV-2 infections. To address this challenge, we apply control theory, a framework used to study complex feedback systems, to establish rigorous mathematical bounds on immune responses. Two mechanisms of SARS-CoV-2 biology are sufficient to create extreme variation between hosts: (1) a sparsely expressed host receptor and (2) potent, but not unique, suppression of interferon. The resulting model unifies disparate and unexplained features of the SARS-CoV-2 pandemic, predicts features of future viruses that threaten to cause pandemics, and identifies potential interventions.
Functional coupling between target selection and acquisition in the superior colliculus
Authors: Essig Jaclyn , Felsen Gidon 
Published: April 2021

AbstractTo survive in unpredictable environments, animals must continuously evaluate their surroundings for behavioral targets, such as food and shelter, and direct their movements to acquire those targets. Although the ability to accurately select and acquire spatial targets depends on a shared network of brain regions, how these processes are linked by neural circuits remains unknown. The superior colliculus (SC) mediates the selection of spatial targets and remains active during orienting movements to acquire targets, which suggests the underexamined possibility that common SC circuits underlie both selection and acquisition processes. Here, we test the hypothesis that SC functional circuitry couples target selection and acquisition using adefault motor plangenerated by selection-related neuronal activity. Single-unit recordings from intermediate and deep layer SC neurons in male mice performing a spatial choice task demonstrated that choice-predictive neurons, including optogenetically identified GABAergic SC neurons whose activity was causally related to target selection, exhibit increased activity during movement to the target. By strategically recording from both rostral and caudal SC neurons, we also revealed an overall caudal-to-rostral shift in activity as targets were acquired. Finally, we used an attractor model to examine how target selection activity in the SC could generate a rostral shift in activity during target acquisition using only intrinsic SC circuitry. Overall, our results suggest a functional coupling between SC circuits that underlie target selection and acquisition, elucidating a key mechanism for goal-directed behavior.Significance StatementThe ability to quickly select and acquire spatial targets is essential to animal survival. Neural circuits underlying these processes are shared in an interconnected network of brain regions, however it is unclear how circuits link decision-making processes with motor commands to execute choices. Here, we examine single-unit activity in the superior colliculus (SC) as mice select and acquire spatial targets to test the hypothesis that choice-related activity promotes target acquisition by generating a default motor plan for orienting movements. By demonstrating that choice-predictive neurons increase their firing rates during movement and capturing the dynamics of SC activity with an attractor model of intrinsic SC circuitry, our results support a role for SC circuits in coupling target selection and acquisition.
Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking
Authors: Schmieder Stefanie S. , Tatituri Raju , Anderson Michael , Kelly Kate , Lencer Wayne I. 
Published: April 2021

AbstractThe complex sphingolipids exhibit a diversity of ceramide acyl chain structures that influence their trafficking and intracellular distributions, but how the cell discerns among the different ceramides to affect such sorting remains unknown. To address mechanism, we synthesized a library of GM1 glycosphingolipids with naturally varied acyl chains and quantitatively assessed their sorting among different endocytic pathways. We found that a stretch of at least 14 saturated carbons extending from C1 at the water-bilayer interface dictated lysosomal sorting by exclusion from endosome sorting tubules. Sorting to the lysosome by the C14*-motif was cholesterol dependent. Perturbations of the C14*-motif by unsaturation enabled GM1 entry into endosomal sorting tubules of the recycling and retrograde pathways independently of cholesterol. Unsaturation occurring beyond the C14*-motif in very long acyl chains rescued lysosomal sorting. These results define a structural motif underlying membrane organization of sphingolipids and implicate cholesterol-sphingolipid nanodomain formation in sorting mechanisms.
Implications of drift and rapid evolution on negative niche construction
Authors: Nguyen Phuong Linh , Costa Manon , Loeuille Nicolas 
Published: April 2021

AbstractOrganisms throughout their lives constantly modify their surrounding environment; such activities are often termed niche construction. An important property of niche construction is that its consequences can persist for a long period of time and several subsequent generations can be affected. This phenomenon is described as a time lag in niche construction, or ecological inheritance.Studies have suggested that time lag in niche construction can help avoiding the tragedy of the commons. In other words, it can lead to evolution of contribution to a common good, which is associated with positive niche construction, or to the limitation of a common bad, which is associated with negative niche construction.In this article, we will study the evolutionary consequences of incorporating time lags in a negative niche construction process: waste production. We consider a population that extrudes waste into its environment as it consumes resources to grow and reproduce. Higher consumption rates can lead to higher waste production. Individuals that adopt this selfish strategy are expected to be selected as toxic effects are equally shared among all individuals.We show that indeed this tragedy of the commons persists in many cases and selfish strategies evolve in general. When evolution is rapid and intragenerational time lag is incorporated, however, selfish strategies are no longer favoured and strategies resulting in less waste production can be selected. Importantly, heavy pollution results in smaller population sizes, so that drift becomes more important than natural selection and limits the evolution of higher waste production.
SIBR-Cas enables host-independent and universal CRISPR genome engineering in bacteria
Authors: Patinios Constantinos , Creutzburg Sjoerd C.A. , Arifah Adini Q. , Pérez Belén A. , Ingham Colin J. , Kengen Servé W.M. , van der Oost John , Staals Raymond H.J. 
Published: April 2021

ABSTRACTCRISPR-Cas is a powerful tool for genome editing in bacteria. However, its efficacy is dependent on host factors (such as DNA repair pathways) and/or exogenous expression of recombinases. In this study, we mitigated these constraints by developing a simple and universal genome engineering tool for bacteria which we termed SIBR-Cas (Self-splicing Intron-Based Riboswitch-Cas). SIBR-Cas was generated from a mutant library of the theophylline-dependent self-splicing T4tdintron that allows for universal and inducible control over CRISPR-Cas counterselection. This control delays CRISPR-Cas counterselection, granting more time for the editing event (e.g., by homologous recombination) to occur. Without the use of exogenous recombinases, SIBR-Cas was successfully applied to knock-out several genes in three bacteria with poor homologous recombination systems. Compared to other genome engineering tools, SIBR-Cas is simple, tightly regulated and widely applicable for most (non-model) bacteria. Furthermore, we propose that SIBR can have a wider application as a universal gene expression and gene regulation control mechanism for any gene or RNA of interest in bacteria.
A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope
Authors: VanBlargan Laura A. , Adams Lucas J. , Liu Zhuoming , Chen Rita E. , Gilchuk Pavlo , Raju Saravanan , Smith Brittany K. , Zhao Haiyan , Case James Brett , Winkler Emma S. , Whitener Bradley M. , Droit Lindsay , Aziati Ishmael D. , Shi Pei-Yong , Creanga Adrian , Pegu Amarendra , Handley Scott A. , Wang David , Boon Adrianus C.M. , Crowe James E. , Whelan Sean P.J. , Fremont Daved H. , Diamond Michael S. 
Published: April 2021

SUMMARYWith the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variantsin vivoand lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.
Assessment of dough rheological characteristics and soft bread roll quality of wheat flour incorporated with seaweed powder
Authors: Mamat Hasmadi Bin , Wan Chen Yeoh , Abdul Hamid Mansoor , Md Haque Akanda Jahurul , Pusiran Arif Kamisan , Zainol Mohamad Khairi 
Published: April 2021

PurposeThis study aims to investigate the effects of incorporating seaweed composite flour on soft roll dough rheological characteristics and quality.Design/methodology/approachIn this study, wheat flour was substituted with seaweed powder obtained from red seaweed (Kappaphycus alvarezii) at varying proportions (100:0; 99:1; 98:2; 97:3; 96:4; 95:5, 94:6, 93:7 and 92:8) and applied in soft roll production. The effects of seaweed composite flour were evaluated in terms of rheological characteristics, proximate composition and physical properties. The sensory characteristics of the soft rolls was evaluated by 40 untrained panellists by using a hedonic scale.FindingsFarinograph analysis of the soft roll doughs showed that the incorporation of seaweed powder promoted an increase in water absorption, development time and mixing tolerance index, whereas it decreased stability time. Analysis of the proximate composition of the soft rolls showed that protein and carbohydrate contents decreased, but moisture, ash and crude fibre contents substantially increased. Dietary fibre increased with the increase in the proportion of seaweed powder added. The specific volume, bulk density and firmness of the soft rolls ranged from 3.01 to 5.48 cm3/g, 0.18 to 0.33 g/cm3 and 1.86 to 20.63 N, respectively. Sensory evaluation results showed that the mean score of sensory attributes decreased as the proportion of seaweed powder added was increased in the formulations. With regard to the overall acceptability, the panellists preferred the soft rolls with the least amount of seaweed powder added. The results of hedonic tests revealed that the panellists' acceptance decreased as higher amounts seaweed powder were added in the formulations.Originality/valueThis study showed that the seaweed powder of K. alvarezii can be utilised as an ingredient to improve the nutrient composition of baked products.
‘I know you shouldn't compare to other people, but I can’t do anything most people can’: Age, family and occupation categorisations in men’s reasoning about their anxiety in an online discussion forum
Authors: Drioli‐Phillips Phoebe G. , Le Couteur Amanda , Oxlad Melissa , Feo Rebecca , Scholz Brett 
Published: April 2021

ABSTRACTDespite its prevalence, men's anxiety is arguably under‐researched and poorly understood. The present study explores the reasoning provided by male posters to an online discussion forum about the source of their anxiety. Posts were collected from an Australian anxiety online discussion forum. This study utilises discursive psychology, informed by principles of membership categorisation analysis, to describe how age, occupation and family‐related identities can be invoked within common sense reasoning about the source of male anxiety. References to various identity categories were routinely employed by male forum posters in their representations of themselves, in order to describe the source of their anxiety in terms of a contrast between how they are, and how they should be. In examining accounts of anxiety and responses to those accounts, we can trace cultural knowledge about issues regarding men, masculinity and anxiety that those accounts make relevant. Findings illustrate how men's descriptions of the source of their anxiety should be understood as culturally bound and related to expectations and obligations associated with their social context and category memberships. By enhancing understandings of how men describe the source of their anxiety, this study offers insight into improving the identification and engagement of men experiencing anxiety in health services.
Splitting Climate Engineering Governance: How Problem Structure Shapes Institutional Design
Authors: Jinnah Sikina , Morrow David , Nicholson Simon 
Published: April 2021

AbstractThis article adds conceptual discipline to a well‐rehearsed but largely intuitive argument within the climate engineering community that carbon dioxide removal (CDR) and solar radiation management (SRM) should be treated separately – ‘split’ rather than ‘lumped’ – in policy discussions. Specifically, we build the first, theoretically derived argument for ‘splitting’. We do this by engaging a set of theoretical insights from the international relations literature, having to do with the relationship between problem structure and institutional design. Centrally, we apply some key elements of problem structure – which allows us to compare policy issues along variables such as geographic scope, costs, and actor number and asymmetries – to the cases of SRM and CDR. By analyzing their problem structures, we demonstrate that SRM and CDR are different in ways that are likely to yield different state preferences for institutional design, and thus policy proposals that split SRM and CDR are more likely to be adopted by states. In short, we construct a theoretical argument for ‘splitting’ SRM and CDR governance in global policy discussions.
Governing Artificial Intelligence in an Age of Inequality
Authors: Gehl Sampath Padmashree 
Published: April 2021

AbstractThis article seeks to position both AI‐based activities, and related policy developments, in the global South in light of a technology industry with desires for continuous expansion and self‐governance. The article proceeds along three themes. First, using field interviews and related information (in an anonymised manner), the article classifies expanding AI activities in several core sectors by businesses, governments and other agencies in the global South into three categories. Next, it reviews the current AI policy priorities and positions in developing countries, showing how the introduction of AI has been punctuated by considerations of digital cannibalization by large firms from the North at the expense of a full‐fledged debate on privacy and data protection. By showing how AI exemplifies structural inequality in the global South, the article identifies four critical departure points in developing countries that make the expanding use of AI a matter of concern. While many of challenges posed by AI are somewhat universal, the article argues that their ramifications can be much worse in the global South. Countering these will require policy frameworks that factor in privacy protection in a more accountable manner. It concludes with suggestions for a more nuanced debate on industrialisation, privacy protection and development.
Productivity Gap and Inward FDI Spillovers: Theory and Evidence from China
Authors: Shen Jim Huangnan , Wang Hao , Lin Steve Chu‐Chia 
Published: April 2021

AbstractThis paper constructs a two‐stage sequential game model to shed light on the spillover effect of inward FDI on the efficiency of domestic firms in host countries. Our model shows that, given an optimal joint‐venture policy made by foreign firms, the impact of the spillover effect of inward FDI is contingent upon the productivity gap between the domestic firms and foreign ones. In particular, we demonstrate that the spillover effect of inward FDI varies negatively with the productivity gap between domestic low‐productivity firms and foreign firms but works in the opposite way for high‐productivity firms. This suggests that once the productivity gap widens, the entry of foreign firms will increase the efficiency of high‐productivity firms but reduce the efficiency of low‐productivity firms. In support of our theoretical model, we provide robust empirical results by using the dataset of annual survey of Chinese industrial enterprises.
Assessing Market Competition in the Chinese Banking Industry Based on a Conjectural Variation Model
Authors: Zhou Xiangyi , Pei Zheng , Qin Botao 
Published: April 2021

AbstractMost literature on market competition in the banking industry neglects to address strategic interaction among banks. This paper studies interaction among Chinese banks by dividing banks into two groups: dominant banks (the “Big 5” state‐owned banks) and small‐ and medium‐sized banks (joint‐stock banks and large city commercial banks). We test an oligopolistic model with conjectural variation developed by Spiller and Favaro (1984). Using data from 2007 to 2016, we find that banking competition is not in the form of Stackelberg competition per se. Some strategic interactions exist between small‐ and medium‐sized banks and the largest state‐owned bank. We also study the effect of interest rate deregulation on oligopolies' strategic interactions. Our results show that interest rate deregulation stimulates banking competition by reducing collusiveness among the dominant state‐owned banks and enhancing the market power of small and medium banks.
“Ex‐vivo” T‐cell depletion in allogeneic hematopoietic stem cell transplantation: New clinical approaches for old challenges
Authors: Diaz Miguel A. , Gasior Mercedes , Molina Blanca , Pérez‐Martínez Antonio , González‐Vicent Marta 
Published: April 2021

AbstractAllogeneic transplantation still remains as standard of care for patients with high‐risk hematological malignancies at diagnosis or after relapse. However, GvHD remains yet as the most relevant clinical complication in the early post‐transplant period. TCD allogeneic transplant is now considered a valid option to reduce severe GvHD and to provide a platform for cellular therapy to prevent relapse disease or to treat opportunistic infections.
Homozygous SCN1B variants causing early infantile epileptic encephalopathy 52 affect voltage‐gated sodium channel function
Authors: Scala Marcello , Efthymiou Stephanie , Sultan Tipu , De Waele Jolien , Panciroli Marta , Salpietro Vincenzo , Maroofian Reza , Striano Pasquale , Van Petegem Filip , Houlden Henry , Bosmans Frank 
Published: April 2021

AbstractWe identified nine patients from four unrelated families harboring three biallelic variants in SCN1B (NM_001037.5: c.136C>T; p.[Arg46Cys], c.178C>T; p.[Arg60Cys], and c.472G>A; p.[Val158Met]). All subjects presented with early infantile epileptic encephalopathy 52 (EIEE52), a rare, severe developmental and epileptic encephalopathy featuring infantile onset refractory seizures followed by developmental stagnation or regression. Because SCN1B influences neuronal excitability through modulation of voltage‐gated sodium (NaV) channel function, we examined the effects of human SCN1BR46C (β1R46C), SCN1BR60C (β1R60C), and SCN1BV158M (β1V158M) on the three predominant brain NaV channel subtypes NaV1.1 (SCN1A), NaV1.2 (SCN2A), and NaV1.6 (SCN8A). We observed a shift toward more depolarizing potentials of conductance–voltage relationships (NaV1.2/β1R46C, NaV1.2/β1R60C, NaV1.6/β1R46C, NaV1.6/β1R60C, and NaV1.6/β1V158M) and channel availability (NaV1.1/β1R46C, NaV1.1/β1V158M, NaV1.2/β1R46C, NaV1.2/β1R60C, and NaV1.6/β1V158M), and detected a slower recovery from fast inactivation for NaV1.1/β1V158M. Combined with modeling data indicating perturbation‐induced structural changes in β1, these results suggest that the SCN1B variants reported here can disrupt normal NaV channel function in the brain, which may contribute to EIEE52.