bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversification of CD1 molecules shapes lipid antigen selectivity
Authors: Paterson Nicole M. , Al-Zubieri Hussein , Barber Matthew F. 
Published: November 2020

AbstractMolecular studies of host-pathogen evolution have largely focused on the consequences of variation at protein-protein interaction surfaces. The potential for other microbe-associated macromolecules to promote arms race dynamics with host factors remains unclear. The cluster of differentiation 1 (CD1) family of vertebrate cell surface receptors plays a crucial role in adaptive immunity through binding and presentation of lipid antigens to T-cells. Although CD1 proteins present a variety of endogenous and microbial lipids to various T-cell types, they are less diverse within vertebrate populations than the related major histocompatibility complex (MHC) molecules. We discovered that CD1 genes exhibit a high level of divergence between simian primate species, altering predicted lipid binding properties and T-cell receptor (TCR) interactions. These findings suggest that lipid-protein conflicts have shaped CD1 genetic variation during primate evolution. Consistent with this hypothesis, multiple primate CD1 family proteins exhibit signatures of repeated positive selection at surfaces impacting antigen presentation, binding pocket morphology, and TCR accessibility. Using a molecular modeling approach, we observe that inter-species variation as well as single mutations at rapidly-evolving sites in CD1a drastically alter predicted lipid binding and structural features of the T-cell recognition surface. We further show that alterations in both endogenous and microbial lipid binding affinities influence the ability of CD1a to undergo antigen swapping required for T-cell activation. Together these findings establish lipid-protein interactions as a critical force of host-pathogen conflict and inform potential strategies for lipid-based vaccine development.
Distinct molecular signatures of fission predict mitochondrial degradation or proliferation
Authors: Kleele Tatjana , Rey Timo , Winter Julius , Zaganelli Sofia , Mahecic Dora , Lambert Hélène Perreten , Ruberto Francesco , Nemir Mohamed , Wai Timothy , Pedrazzini Thierry , Manley Suliana 
Published: November 2020

SUMMARYMitochondrial fission is a highly regulated process which, when disrupted, can alter metabolism, proliferation and apoptosis1–3. The downstream effects have implications for many diseases, from neurodegeneration4–6to cardiovascular disease7,8and cancer9,10. Key components of the fission machinery have been identified: constriction sites are initiated by the endoplasmic reticulum (ER)11and actin12before dynamin-related protein 1 (Drp1)13is recruited to the outer mitochondrial membrane via adaptor proteins14–17, where it drives constriction and scission of the membrane18. In the life cycle of mitochondria, fission is important for the biogenesis of new mitochondria as well as the clearance of dysfunctional mitochondria via mitophagy3,19. Global regulation of fission on the cellular level is insufficient to explain how fate decisions are made at the single organelle level, so it is unknown how those dual functions arise, blocking progress in developing therapies that target mitochondrial activity. However, systematically studying mitochondrial division to uncover fate determinants is challenging, since fission is unpredictable, and mitochondrial morphology is extremely heterogeneous. Furthermore, because their ultrastructure lies below the diffraction limit, the dynamic organization of mitochondria and their interaction partners are hard to study at the single organelle level. We used live-cell structured illumination microscopy (SIM) and instant SIM20for fast multi-colour acquisition of mitochondrial dynamics in Cos-7 cells and mouse cardiomyocytes. We analysed hundreds of fission events, and discovered two functionally and mechanistically distinct types of fission. Mitochondria divide peripherally to shed damaged material into smaller daughter mitochondria that subsequently undergo mitophagy, whereas healthy mitochondria proliferate via midzone division. Both types are Drp1-mediated, but they rely on different membrane adaptors to recruit Drp1, and ER and actin mediated pre-constriction is only involved in midzone fission.
Processing of subjectively and objectively invisible stimuli in human visual cortex
Authors: Stein Timo , Kaiser Daniel , Fahrenfort Johannes J. , van Gaal Simon 
Published: November 2020

AbstractThe study of unconscious processing requires a measure of conscious awareness. Awareness measures can be either subjective (based on participant’s report) or objective (based on perceptual performance). The preferred awareness measure depends on the theoretical position about consciousness, and may influence conclusions about the extent of unconscious processing and about the neural correlates of consciousness. We obtained fMRI measurements from 43 subjects while they viewed masked faces and houses that were either subjectively or objectively invisible. We show that neural representations of objectively invisible faces and houses are limited to visual (shape-related) object properties, while subjectively invisible stimuli are processed up to more abstract, categorical levels of representation. These results demonstrate that the hypothesized extent of unconscious information processing is determined by the measurement approach. Furthermore, our data show that subjective and objective approaches are associated with different neural correlates of consciousness and thus have implications for neural theories of consciousness.
Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R
Authors: Dankovich Tal M. , Kaushik Rahul , Petersen Gabriel Cassinelli , Giro Philipp Emanuel , Hadi Hannah Abdul , Bao Guobin , Beuermann Sabine , Cooper Benjamin H. , Dityatev Alexander , Rizzoli Silvio O. 
Published: November 2020

SummaryThe brain extracellular matrix (ECM) assembles around neurons and synapses, and is thought to change only rarely, through proteolysis and renewed protein synthesis. We report here an alternative ECM remodeling mechanism, based on the recycling of ECM molecules. We found that a key ECM protein, Tenascin-R, is frequently endocytosed, and later resurfaces, preferentially near synapses. The TNR molecules complete this cycle within ∼3 days, in an activity-dependent fashion.
A functional pre-screening platform for identifying points of vulnerability in the cell death map of human melanoma tumors
Authors: Dekel-Bird Naama Pnina , Bialik Shani , Itzhaki Orit , Salame Tomer Meir , Yaeli-Slonim Naama , Levin-Salomon Vered , Dasari Santosh Kumar , Besser Michal , Kimchi Adi 
Published: November 2020

AbstractTargeted drug therapy in melanoma patients carrying theBRAFV600E mutation provides temporary remission, often followed by relapse due to acquired drug resistance. Here we propose a functional approach to circumvent drug resistance by applying a personalized prescreening platform that maps points of vulnerability in each tumor, prior to drug treatment. This platform applies siRNAs targeting 81 apoptosis, autophagy and programmed necrosis genes in patient tumor cell cultures, identifying genes whose targeting maximizes cell killing by short-term BRAF inhibition. Melanoma tumors displayed large heterogeneity in the number and identities of soft-spots, providing different tumor-specific functional death signatures. The soft-spots were targeted by replacing functional siRNAs with small compound inhibitors for long-term treatment in combination with vemurafenib. This strategy reduced the number of drug-tolerant persister cells surviving treatment, and most importantly, the number of drug-resistant foci. Thus, prescreening melanoma tumors for soft-spots within the cell death network may enhance targeted drug therapy before resistance emerges, thereby reducing the odds of developing drug-resistant mutations, and preventing tumor relapse.
Nsp1 of SARS-CoV-2 Stimulates Host Translation Termination
Authors: Shuvalov Alexey , Shuvalova Ekaterina , Biziaev Nikita , Sokolova Elizaveta , Evmenov Konstantin , Egorova Tatiana , Alkalaeva Elena 
Published: November 2020

ABSTRACTThe Nsp1 protein of SARS-CoV-2 regulates the translation of host and viral mRNAs in cells. Nsp1 inhibits host translation initiation by occluding the entry channel of the 40S ribosome subunit. The structural study of SARS-CoV-2 Nsp1-ribosomal complexes reported post-termination 80S complex containing Nsp1 and the eRF1 and ABCE1 proteins. Considering the presence of Nsp1 in the post-termination 80S ribosomal complex simultaneously with eRF1, we hypothesized that Nsp1 may be involved in translation termination. Using a cell-free translation system and reconstitutedin vitrotranslation system, we show that Nsp1 stimulates translation termination in the stop codon recognition stage at all three stop codons. This stimulation targets the release factor 1 (eRF1) and does not affect the release factor 3 (eRF3). The activity of Nsp1 in translation termination is provided by its N-terminal domain and the minimal required part of eRF1 is NM domain. We assume that biological meaning of Nsp1 activity in translation termination is binding with the 80S ribosomes translating host mRNAs and removal them from the pool of the active ribosomes.
Functional and microstructural plasticity following social and interoceptive mental training
Authors: Valk Sofie L , Kanske Philipp , Park Bo-yong , Hong Seok Jun , Böckler Anne , Trautwein Fynn-Mathis , Bernhardt Boris C. , Singer Tania 
Published: November 2020

AbstractThe human brain scaffolds social cognitive functions, including Theory of Mind, empathy and compassion, through its functional and microstructural organization. However, it remains unclear how the learning and refinement of these skills may, in turn, shape brain function and structure. Here we studied if different types of social mental training can lead to plastic changes in brain function and microstructure. We studied a group of 332 healthy adults (197 women, 20-55 years) with repeated multimodal neuroimaging and behavioral testing. Our neuroimaging approach capitalized on the quantification of cortical functional gradients and myelin-sensitive T1 relaxometry, two emerging measures of cortical functional organization and microstructure. Longitudinal analysis indicated marked changes in intrinsic cortical function and microstructure, which varied as a function of social training content. In particular, we observed consistent differential change in function and microstructure between attention-mindfulness and socio-cognitive training in regions functionally associated with attention and interoception, including insular and parietal cortices. Conversely, socio-affective and socio-cognitive training resulted in differential microstructural changes in regions classically implicated in interoceptive and emotional processing, including insular and orbitofrontal areas, but did not result in functional reorganization. Notably, longitudinal changes in cortical function and microstructure were predictive of behavioral change in attention, compassion and perspective-taking, suggesting behavioral relevance. In sum, our work provides evidence for functional and microstructural plasticity after the training of social-interoceptive functions, and provides a causal perspective on the neural basis of behavioral adaptation in human adults.
Force requirements of endocytic vesicle formation
Authors: Abella Marc , Andruck Lynnel , Malengo Gabriele , Skruzny Michal 
Published: November 2020

AbstractMechanical forces are integral to many cellular processes, including clathrin-mediated endocytosis, a principal membrane trafficking route into the cell. During endocytosis, forces provided by endocytic proteins and the polymerizing actin cytoskeleton reshape the plasma membrane into a vesicle. Assessing force requirements of endocytic membrane remodelling is essential for understanding endocytosis. Here, we determined forces applied during endocytosis using FRET-based tension sensors integrated into the major force-transmitting protein Sla2 in yeast. We measured force of approx. 10 pN transmitted over Sla2 molecule, hence a total force of 450-1300 pN required for endocytic vesicle formation. Importantly, decreasing cell turgor pressure and plasma membrane tension reduced force requirements of endocytosis. The measurements in hypotonic conditions and mutants lacking BAR-domain membrane scaffolds then showed the limits of the endocytic force-transmitting machinery. Our study provides force values and force profiles critical for understanding the mechanics of endocytosis and potentially other key cellular membrane-remodelling processes.
Temperature affects the repeatability of evolution in the microbial eukaryoteTetrahymena thermophila
Authors: Tarkington Jason A , Zufall Rebecca 
Published: November 2020

AbstractEvolutionary biologists have long sought to understand what factors affect the repeatability of adaptive outcomes. To better understand the role of temperature in determining the repeatability of adaptive trajectories, we evolved populations of different genotypes of the ciliateTetrahymena thermophilaat low and high temperatures and followed changes in growth rate over 4,000 generations. As expected, growth rate increased with a decelerating rate for all populations; however, there were differences in the patterns of evolution at the two temperatures. The growth rates of the different genotypes converged as evolution proceeded at both temperatures, but this convergence was quicker at the higher temperature. Likewise, we found greater repeatability of evolution, in terms of change in growth rate, among replicates of the same genotype at the higher temperature. Finally, we found no evidence of trade-offs in fitness between temperatures, but did observe asymmetry in the correlated responses, whereby evolution in a high temperature increases growth rate at the lower temperature significantly more than the reverse. These results demonstrate the importance of temperature in determining the repeatability of evolutionary trajectories.
A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity
Authors: McCann Alex , Lou Jieqiong , Moustaqil Mehdi , Blum Ailisa , Fontaine Frank , Liu Hui , Luu Winnie , Koopman Peter , Sierecki Emma , Gambin Yann , Meunier Frédéric A. , Liu Zhe , Hinde Elizabeth , Francois Mathias 
Published: November 2020

AbstractFew genetically dominant mutations involved in human disease have been fully explained at the molecular level. In cases where the mutant gene encodes a transcription factor, the dominant-negative mode of action of the mutant protein is particularly poorly understood. Here, we studied the genome-wide mechanism underlying a dominant-negative form of the SOX18 transcription factor (SOX18RaOp) responsible for both the classical mouse mutant Ragged opossum and the human genetic disorder Hypotrichosis-Lymphedema-Telangiectasia-Renal Syndrome. Combing three single-molecule imaging assays in living cells, we found that SOX18RaOpdisrupts the system through an accumulation of molecular interferences which impair several functional properties of the wild-type SOX18 protein, including its chromatin-binding dynamics. The dominant-negative effect is further amplified by recruiting the interactome of its wild-type counterpart, which perturbs regulatory nodes such as SOX7 and MEF2C. Our findings explain in unprecedented detail the multi-layered process that underpins the molecular etiology of dominant-negative transcription factor function.
Microfluidic guillotine reveals multiple timescales and mechanical modes of wound response inStentor coeruleus
Authors: Zhang Kevin S. , Blauch Lucas R. , Huang Wesley , Marshall Wallace F. , Tang Sindy K. Y. 
Published: November 2020

AbstractBackgroundWound healing is one of the defining features of life and is seen not only in tissues but also within individual cells. Understanding wound response at the single-cell level is critical for determining fundamental cellular functions needed for cell repair and survival. This understanding could also enable the engineering of single-cell wound repair strategies in emerging synthetic cell research. One approach is to examine and adapt self-repair mechanisms from a living system that already demonstrates robust capacity to heal from large wounds. Towards this end,Stentor coeruleus, a single-celled free-living ciliate protozoan, is a unique model because of its robust wound healing capacity. This capacity allows one to perturb the wounding conditions and measure their effect on the repair process without immediately causing cell death, thereby providing a robust platform for probing the self-repair mechanism.ResultsHere we used a microfluidic guillotine and a fluorescence-based assay to probe the timescales and mechanisms of wound repair inStentor. We found thatStentorrequires ∼100 – 1000 s to close bisection wounds, depending on the severity of the wound. This corresponds to a healing rate of ∼8 – 80 μm2/s, faster than most other single cells reported in the literature. Further, we observed and characterized three distinct mechanical modes of wound repair inStentor: contraction, cytoplasm retrieval, and twisting/pulling. Using chemical perturbations, active cilia were found to be important for only the twisting/pulling mode. Contraction of myonemes, a major contractile fiber inStentor, was surprisingly not important for the contraction mode and was of low importance for the others.ConclusionsWhile events local to the wound site have been the focus of many single-cell wound repair studies, our results suggest that large-scale mechanical behaviors may be of greater importance to single-cell wound repair than previously thought. The work here advances our understanding of the wound response inStentor, and will lay the foundation for further investigations into the underlying components and molecular mechanisms involved.
PDO labels and food preferences: results from a sensory analysis
Authors: Savelli Elisabetta , Bravi Laura , Francioni Barbara , Murmura Federica , Pencarelli Tonino 
Published: November 2020

PurposeThe paper aims at investigating whether and how the product designation of origin (PDO) label influences consumers' acceptance, attributes' perception and purchase intention of PDO foods.Design/methodology/approachThe study employs an experimental lab study based on the affective test of acceptance methodology with a nine-point hedonic scale. Three PDO foods are compared with similar non-PDO samples concerning cheese, cured ham and olive oil categories.FindingsThe presence of PDO labels enhances the consumers' acceptance as well as their perception of sensory attributes. A critical role of the brand name as an enhancer of consumer acceptance also emerges, highlighting the relationship between brand-name and PDO label.Research limitations/implicationsThe main limitation is related to the lab study methodology, which employs a small number of participants and occurs far from a “normal” situation of consumption. The acceptance test, moreover, does not provide explanations about motives underlying the differences in consumers' perception and preferences.Practical implicationsPractical implications are suggested for food companies concerning the management of both PDO labels and brand strategies and the product's properties that could improve the sensory perception of consumers and their overall product's acceptance.Originality/valueThe study contributes to the debate on consumer behaviour towards PDO foods by adding evidence about the positive influence of such a certification on individual preferences on the basis of a sensory methodology that has been little employed for studying the domain of product certifications.
Effects of self-affirmation on responses toward graphic cigarette warning labels: testing the mediating role of perceived susceptibility and self-efficacy
Authors: Ma Zexin , Nan Xiaoli , Iles Irina A. , Butler James , Feldman Robert , Wang Min Qi 
Published: November 2020

PurposeThe purpose of this study is to examine the effects of self-affirmation on African American smokers' intentions to quit smoking sooner and desire to stop smoking altogether in response to viewing graphic cigarette warning labels. It also tested the mediating role of perceived susceptibility and self-efficacy in explaining the impact of self-affirmation.Design/methodology/approachAfrican American smokers (N = 158) were recruited to participate in a controlled experiment. Participants first completed a short questionnaire about their demographic background and smoking-related attitudes and behavior. They were then randomly assigned to engage in either a self-affirmation task or a control task and viewed two graphic cigarette warning labels subsequently. Participants then responded to a questionnaire about their perceived susceptibility to smoking-related diseases, perceived self-efficacy to quit smoking, intentions to quit smoking and desire to stop smoking altogether.FindingsResults showed that engaging in self-affirmation prior to exposure to graphic cigarette warning labels increased African American smokers' perceived susceptibility to smoking-related diseases, but decreased their perceived self-efficacy to quit smoking. Furthermore, self-affirmation indirectly enhanced smokers' intentions to quit smoking sooner and desire to stop smoking altogether through increased perceived susceptibility. It also had an unexpected negative indirect effect on intentions to quit smoking sooner through decreased self-efficacy.Originality/valueThis study is one of the few studies that investigates the effect of self-affirmation on African American smokers' responses toward graphic cigarette warning labels.
How and when intragroup relationship conflict leads to knowledge hiding: the roles of envy and trait competitiveness
Authors: Peng He , Bell Chris , Li Yiran 
Published: November 2020

PurposeAlthough studies have demonstrated that knowledge hiding is an important inhibitor of organizational innovation, current research does not clearly address how intragroup relationship conflict influences knowledge hiding. This study aims to identify the underlying mechanism between intra-group relationship conflict and knowledge hiding.Design/methodology/approachDrawing on affective events theory (AET), the authors propose a theoretical model and empirically test it by applying hierarchical regression analysis and a bootstrapping approach to data from a multi-wave survey of 224 employees in China.FindingsConsistent with AET, the empirical results show that envy mediates perceived intragroup relationship conflict and knowledge hiding. As predicted, trait competitiveness moderates the indirect effect of perceived intragroup relationship conflict on knowledge hiding via envy.Originality/valueThe results support an AET perspective whereby knowledge hiding is shaped by relationship conflict, envy and trait competitiveness. This study introduces the novel proposition that relationship conflict and competitiveness influence envy, and consequently knowledge hiding.