bluuebunny/crossref_metadata_2025_split huggingface dataset:
What determines the FDC polarization and GC size in affinity maturation
Authors: Yan Zishuo , Qi Hai , Lan Yueheng 
Published: September 2020

AbstractGerminal center (GC) is a particular biological structure produced for affinity maturation in the lymphoid follicle during the T-dependent immune response and is an important component of the humoral immune system. However, the impact of morphological features of the GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC including the appearance of two specific zones: the dark zone(DZ) and the light zone (LZ). We find that the development of light and dark zones in GC serves to maintain an effective competition among different cells and promote affinity maturation. On the other hand, by varying the GC size, a phase transition is discovered, which determines a critical GC volume for best performance in both the stochastic and the deterministic model. This critical volume is determined by the distance between the activated B Cell Receptor(BCR) and the target epitope of the antigen. The conclusion is confirmed in both the 2D and the 3D simulations and explains partly the variability in the GC size.Author summaryGerminal center (GC) is an important component of the humoral immune system, which supports antibody affinity maturation and the generation of immunity memory. However, the impact of special morphological features of the GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC. We use the mixing index of different B cells to quantitatively describe the polarization in GC. With the increase of the mixing index, the affinity of plasma cells decreases gradually, even GC might collapse. Therefore, the development of light and dark zones in GC serves to maintain effective competition among different cells and promote affinity maturation. On the other hand, by varying the GC volume, a phase transition is discovered, which determines a critical GC volume for best performance in both the stochastic and the deterministic model. This critical volume is determined by the distance between the activated B Cell Receptor (BCR) and the target epitope of antigen. The conclusion is confirmed in both the 2D and the 3D simulations and explains partly the variability in the GC size.
Aberrant regulation of RNA splicing in sunflower hybrids may underlie intrinsic incompatibilities
Authors: Smith Chris C R , Rieseberg Loren H , Hulke Brent S , Kane Nolan C 
Published: September 2020

AbstractAlternative spicing is an integral part of gene expression in multicellular organisms that allows for diverse mRNA transcripts and proteins to be produced from a single gene. However, most existing analyses have focused on macro-evolution, with only limited research on splice site evolution over shorter term, micro-evolutionary time scales. Here we examine splicing evolution that has occurred during domestication and observe 45 novel splice forms with strongly transgressive isoform compositions, representing 0.24% of analyzed transcripts. We identify loci associated with variation in the levels of these splice forms, finding that many novel transcripts were regulated by multiple alleles with non-additive interactions. A subset of these interactions involved the expression of individual spliceosome components. These overdominant and epistatic interactions often resulted in alteration in the protein-coding regions of the transcripts, resulting in frameshifts and truncations. By associating the splice variation in these genes with size and growth rate measurements, we found that none of the individual splice variants affected these plant traits significantly, but the cumulative expression of all aberrant transcripts did show a significant reduction in growth rate associated with higher proportions of disrupted transcripts. This demonstrates the importance of co-evolution of the different spliceosomal components and their regulators and suggests that these genes may contribute to evolution of reproductive isolation as Bateson-Dobzhansky-Muller incompatibility loci.Author summaryIn multicellular organisms, it is common that segments of pre-mRNA molecules are physically removed, and the remaining segments are spliced back together. Through splicing alternative combinations of segments together, organisms produce various mRNA molecules, and thus multiple proteins, using the information encoded in a single gene. Here, we investigated the RNA of two sunflower genotypes, one wild and one domesticated, as well as the hybrid offspring resulting from a cross between the two genotypes. We found certain mRNA molecules that were spliced exclusively in the hybrids and were absent in the examined parental lines. These unique hybrid mRNAs were predicted to be consequential for the hybrids’ health, and thus represented a malfunction in the mechanisms that regulate splicing. These results improve our understanding of the genetic regulation of alternative splicing and how alternative splice forms evolve. Our findings may lead to further inquiries about how aberrant splicing promotes the formation of new species in nature.
SWATH-MS co-expression profiles reveal paralogue interference in protein complex evolution
Authors: Stalder Luzia , Banaei-Esfahani Amir , Ciuffa Rodolfo , Payne Joshua L , Aebersold Ruedi 
Published: September 2020

AbstractUnderstanding the conservation and evolution of protein complexes is of critical value to decode their function in physiological and pathological processes. One prominent proposal posits gene duplication as a potential mechanism for protein complex evolution. In this study we take advantage of large-scale proteome expression datasets to systematically investigate the role of paralogues, and specifically self-interacting paralogues, in shaping the evolutionary trajectories of protein complexes. First, we show that protein co-expression derived from quantitative proteomic matrices is a good indicator for complex membership and is conserved across species. Second, we suggest that paralogues are commonly strongly co-expressed and that for the subset of paralogues that show diverging co-expression patterns, the divergent co-expression patterns reflect both sequence and functional divergence. Finally, on this basis, we show that homomeric paralogues known to be part of protein complexes display a unique co-expression pattern distribution, with a subset of them being highly diverging. These findings support the idea that homomeric paralogues can avoid cross-interference by diversifying their expression patterns, and corroborates the role of this mechanism as a force shaping protein complex evolution and specialization.
CBP/p300orthologsCBP2andCBP3play distinct roles in planarian stem cell function
Authors: Stelman Clara R. , Smith Britessia M. , Chandra Bidushi , Roberts-Galbraith Rachel H. 
Published: September 2020

AbstractChromatin modifications function as critical regulators of gene expression and cellular identity, especially in the regulation and maintenance of the pluripotent state. However, many studies of chromatin modification in stem cells—and pluripotent stem cells in particular—are performed in mammalian stem cell culture, anin vitrocondition mimicking a very transient state during mammalian development. Thus, new models for study of pluripotent stem cellsin vivocould be helpful for understanding the roles of chromatin modification, for confirming priorin vitrostudies, and for exploring evolution of the pluripotent state. The freshwater flatworm,Schmidtea mediterranea, is an excellent model for studying adult pluripotent stem cells, particularly in the context of robust, whole-body regeneration. To identify chromatin modifying and remodeling enzymes critical for planarian regeneration and stem cell maintenance, we took a candidate approach and screened planarian homologs of 26 genes known to regulate chromatin biology in other organisms. Through our study, we identified six genes with novel functions in planarian homeostasis, regeneration, and behavior. We also identified in our list five planarian homologs of the mammalian CREB-Binding Protein (CBP) family of histone acetyltransferases, representing an expansion of this family in planarians. We find that two planarian CBP family members are required for planarian survival, with knockdown ofSmed-CBP2andSmed-CBP3causing distinct defects in stem cell maintenance or function. Loss of CBP2 causes a quick, dramatic loss of stem cells, while knockdown of CBP3 more narrowly affects stem cells, preferentially decreasing markers of neural progenitors. We propose that the division of labor among a diversified CBP family in planarians presents an opportunity to dissect specific functions of a broadly important histone acetyltransferase family in stem cell biology.
Learning compositional sequences with multiple time scales through a hierarchical network of spiking neurons
Authors: Maes Amadeus , Barahona Mauricio , Clopath Claudia 
Published: September 2020

ABSTRACTSequential behaviour is often compositional and organised across multiple time scales: a set of individual elements developing on short time scales (motifs) are combined to form longer functional sequences (syntax). Such organisation leads to a natural hierarchy that can be used advantageously for learning, since the motifs and the syntax can be acquired independently. Despite mounting experimental evidence for hierarchical structures in neuroscience, models for temporal learning based on neuronal networks have mostly focused on serial methods. Here, we introduce a network model of spiking neurons with a hierarchical organisation aimed at sequence learning on multiple time scales. Using biophysically motivated neuron dynamics and local plasticity rules, the model can learn motifs and syntax independently. Furthermore, the model can relearn sequences efficiently and store multiple sequences. Compared to serial learning, the hierarchical model displays faster learning, more flexible relearning, increased capacity, and higher robustness to perturbations. The hierarchical model redistributes the variability: it achieves high motif fidelity at the cost of higher variability in the between-motif timings.
Highly enriched hiPSC-derived midbrain dopaminergic neurons robustly models Parkinson’s disease
Authors: Virdi Gurvir S , Choi Minee L , Yao Zhi , Evans James R , Athauda Dilan , Melandri Daniela , Sylantyev Sergiy , Abramov Andrey Y , Patani Rickie , Gandhi Sonia 
Published: September 2020

AbstractThe development of human induced pluripotent stem cells (hiPSC) has greatly aided our ability to model neurodegenerative diseases. However, generation of midbrain dopaminergic (mDA) neurons is a major challenge and protocols are variable. Here, we developed a method to differentiate hiPSCs into enriched populations (>80%) of mDA neurons using only small molecules. We confirmed the identity of the mDA neurons using single-cell RNA-sequencing and detection of classical markers. Single-cell live imaging demonstrated neuronal calcium signalling and functional dopamine transport. Electrophysiology measures highlighted the ability to form synapses and networks in culture. Patient-specific hiPSC lines differentiated to produce functional mDA neurons that exhibit the hallmarks of synucleinopathy including: aggregate formation, oxidative stress as well as mitochondrial dysfunction and impaired lysosomal dynamics. In summary, we establish a robust differentiation paradigm to generate enriched mDA neurons from hiPSCs, which can be used to faithfully model key aspects of Parkinson’s disease (PD), providing the potential to further elucidate molecular mechanisms contributing to disease development.
Ly6C defines a subset of memory-like CD27+γδ T cells with inducible cancer-killing function
Authors: Wiesheu Robert , Edwards Sarah C. , Hedley Ann , Kirschner Kristina , Tosolini Marie , Fournie Jean-Jacques , Kilbey Anna , Remak Sarah-Jane , Miller Crispin , Blyth Karen , Coffelt Seth B. 
Published: September 2020

ABSTRACTIn mice, IFNγ-producing γδ T cells that express the co-stimulatory molecule, CD27, play a critical role in host defence and anti-tumour immunity. However, their phenotypic diversity, composition in peripheral and secondary lymphoid organs, similarity to αβ T cells as well as homology with human γδ T cells is poorly understood. Here, using single cell RNA sequencing, we show that CD27+γδ T cells consist of two major clusters, which are distinguished by expression of Ly6C. We demonstrate that CD27+Ly6C—γδ T cells exhibit a naïve T cell-like phenotype, whereas CD27+Ly6C+γδ T cells display a memory-like phenotype, produce several NK cell-related and cytotoxic molecules and are highly similar to both mouse CD8+T cells and mature human γδ T cells. In a breast cancer mouse model, depletion of CD27+γδ T cells failed to affect tumour growth, but these cells could be coerced into killing cancer cells after expansionex vivo. These results identify novel subsets of γδ T cells in mice that are comparable to human γδ T cells, opening new opportunities for γδ T cell-based cancer immunotherapy research.
Effects of prefrontal theta burst stimulation on neuronal activity and subsequent eating behavior: an interleaved rTMS and fNIRS study
Authors: Fatakdawala Idris , Ayaz Hasan , Safati Adrian , Sakib Mohammad Nazmus , Hall Peter A. 
Published: September 2020

AbstractThe dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) are important nodes for self-control and decision-making, but through separable processes (cognitive control versus evaluative processing). This study aimed to examine the effects of excitatory brain stimulation (intermittent theta-burst stimulation; iTBS) targeting the dlPFC and dmPFC on food choice. iTBS was hypothesized to decrease consumption of appetitive snack foods, via enhanced interference control for dlPFC stimulation and reduced delay discounting for dmPFC stimulation. Using a single-blinded, between-subjects design, participants (N= 43) were randomly assigned to of the three conditions: 1) iTBS targeting the left dlPFC, 2) iTBS targeting bilateral dmPFC, or 3) sham. Participants then completed two cognitive tasks (delay discounting (DD) and Flanker), followed by a taste test. fNIRS imaging revealed increases in medial PFC activity were evident in the dmPFC stimulation group during the DD task; likewise, a neural efficiency effect was observed in the dlPFC stimulation group during the Flanker. Gender significantly moderated consumption during the taste test, with females in the dmPFC showing paradoxical increases in food consumption compared to sham. Findings are consistent with possible amplification of positive evaluative processing in the presence of dietary restraint, vis-à-vis excitation of the mPFC.
COVID-19 Transmission Within Danish Households: A Nationwide Study from Lockdown to Reopening
Authors: Lyngse Frederik Plesner , Kirkeby Carsten Thure , Halasa Tariq , Andreasen Viggo , Skov Robert Leo , Møller Frederik Trier , Krause Tyra Grove , Mølbak Kåre 
Published: September 2020

AbstractBackgroundThe Covid-19 pandemic is one of the most serious global public health threats in recent times. Understanding transmission of SARS-CoV-2 is of utmost importance to be able to respond to outbreaks and take action against spread of the disease. Transmission within the household is a concern, especially because infection control is difficult to apply within the household domain.MethodsWe used comprehensive administrative register data from Denmark, comprising the full population and all COVID-19 tests, to estimate household transmission risk and attack rate.ResultsWe studied the testing dynamics for COVID-19 and found that the day after receiving a positive test result within the household, 35% of potential secondary cases were tested and 13% of these were positive. After a primary case in 6,782 households, 82% of potential secondary cases were tested within 14 days, of which 17% tested positive as secondary cases, implying an attack rate of 17%. Among primary cases, those aged 0-24 were underrepresented when compared with the total population. We found an approximately linearly increasing relationship between attack rate and age. We investigated the transmission risk from primary cases by age, and found an increasing risk with age of primary cases for adults, while the risk seems to decrease with age for children.ConclusionsAlthough there is an increasing attack rate and transmission risk of SARS-CoV-2 with age, children are also able to transmit SARS-CoV-2 within the household.
Cofilin1 oxidation links oxidative distress to mitochondrial demise and neuronal cell death
Authors: Hoffmann Lena , Waclawczyk Marcel S. , Hanschmann Eva-Maria , Gellert Manuela , Rust Marco B. , Culmsee Carsten 
Published: September 2020

AbstractMany cell death pathways, including apoptosis, regulated necrosis and ferroptosis are relevant for neuronal cell death and share common mechanisms such as the formation of reactive oxygen species (ROS). However, which molecular signaling pathways contribute to related pathologies and how they are interconnected remains elusive.Here, we present the role of cofilin1 in regulating mitochondrial functions and neuronal impairment. Cofilin1 deletion in neuronal HT22 cells exerted increased mitochondrial resilience, assessed by quantification of mitochondrial ROS production, mitochondrial membrane potential and ATP levels. HT22 cells deficient for cofilin1 exhibited a profound glycolytic shift to meet their energy demand in conditions of erastin and glutamate toxicity, whereas control cells were metabolically impaired and underwent ferroptosis and oxytosis, respectively. Further, cofilin1 was confirmed as a key player in glutamate-mediated excitotoxicity in primary cortical neurons isolated from cofilin1flx/flx, CaMKIIα-Creknock-out mice. Mitochondrial respiration and cell viability were significantly preserved in cofilin1-/-primary neurons under conditions of excitotoxicity.Using isolated mitochondria and recombinant cofilin1, we provide a further link to toxicity-related mitochondrial impairment mediated by oxidized cofilin1. Wildtype cofilin1 directly affected the mitochondrial membrane potential, mitochondrial ROS accumulation and mitochondrial respiration. The detrimental impact of cofilin1 on mitochondria depends on oxidation of cysteine residues at positions 139 and 147.Our findings show that the actin-regulating protein cofilin1 acts as a redox sensor in oxidative cell death pathways of ferroptosis and oxytosis, and also promotes glutamate excitotoxicity. Oxidized cofilin1 links ROS accumulation to mitochondrial demise and neuronal cell death. Protective effects by cofilin1 inhibition are particularly attributed to preserved mitochondrial integrity and function. Thus, interfering with the oxidation and pathological activation of cofilin1 may offer an effective therapeutic strategy in neurodegenerative diseases.
Activity-based work and its implications for the academic work environment
Authors: Muhonen Tuija , Berthelsen Hanne 
Published: September 2020

PurposeThe aim of the current interview study was to investigate how the university staff and their immediate managers perceived the academic work environment after a transition to activity-based workplaces (ABW).Design/methodology/approachInterviews were conducted with 11 university lecturers/researchers and 12 academic middle managers, that is, heads of departments or units in a Swedish university.FindingsThe qualitative content analysis revealed four central themes indicating how the academic environment had been affected: challenges related to decision-making and implementation of ABW, interpersonal relations and communication, consequences for academic identity and issues related to the physical work environment.Research limitations/implicationsThe non-purposive sampling of participants coming from a single university is a limitation of the current study. More studies are needed to deepen the knowledge and to further corroborate the transferability of the findings.Practical implicationsThe savings the universities expect to achieve in terms of reduced costs for premises, when introducing ABW, may lead to other kinds of costs, such as jeopardizing employee performance, comfort and well-being. It is therefore important that the academic staff is empowered and involved during the planning and implementation process of new offices.Originality/valueThe study contributes new knowledge concerning implementation of ABW and its consequences for the academic work environment.
Differences in the influence of aesthetic experience on the innovative behaviors of Thai students and Chinese international students
Authors: Chang Yuan-Cheng , Jaisook Napawan 
Published: September 2020

PurposeThe purpose of this study aims to understand if there are any differences in the influence of aesthetic experience and creative self-efficacy on innovative behaviors of Thai students and Chinese international students and whether creative self-efficacy has a mediating effect between aesthetic experience and innovative behavior.Design/methodology/approachThree Thai universities with Chinese international students were selected through purposive sampling. There were 329 valid responses, consisting of responses from 170 Thai students and 159 Chinese students. The data were analyzed by employing multigroup structural equation modeling.FindingsThe analysis of the differences between the students of the two countries shows that the influence of aesthetic experience on creative self-efficacy, as well as the creative self-efficacy on innovative behavior of Chinese international students, is greater than that of Thai students, while the influence of aesthetic experience on innovative behavior of Thai students is greater than that of Chinese international students.Originality/valueThere are some differences between Thai and Chinese students, which could be attributed to their differing environments, cultures and prior learning experiences.