bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposing dominance within a color gene block underpins hybrid plumage signal discordance
Authors: de Zwaan Devin R. , Mackenzie Jacqueline , Mikklesen Else , Wood Chris , Wang Silu 
Published: February 2021

AbstractThe divergence of plumage color genes is increasingly recognized as important for speciation in songbirds through its influence on social signaling. However, the behavioral mechanisms underlying the eco-evolutionary feedback that acts across species boundaries is poorly understood. The hybrid zone betweenSetophaga occidentalis(SOCC) andS. townsendi(STOW) in the Cascade Mountain range provides a natural observatory to test the interplay between genetics, plumage signals, and territoriality in maintaining nascent species boundaries. Recently, we found that selection within a gene block underpinning color variation (ASIP-RALY) has maintained a stable and narrow hybrid zone. Here we investigated the roles of cheek darkness and flank streaking as plumage signals during simulated territorial intrusion, two melanin-based traits underpinned by ASIP-RALY that reflect opposing dominance of SOCC and STOW alleles. We found that both plumage traits act as honest signals of body size in the territorial sex (i.e., males). The opposing dominance effects of ASIP-RALY resulted in plumage signal discordance for heterozygotes, which in turn was associated with reduced territorial performance, a fitness proxy quantified by vocal and physical responses to a decoy intruder. Taken together, this study highlights a behavioral mechanism underlying selection acting on a simple genetic architecture that shapes species boundary despite gene flow.
The possible fidelity-speed-proofreading cost trade-offs in DNA replication due to the exonuclease proofreading
Authors: Li Qiu-Shi , Shu Yao-Gen , Fu Wen-Bo , Ou-Yang Zhong-Can , Li Ming 
Published: February 2021

DNA replication is a high-fidelity information-copying processes which is realized by DNA polymerase (DNAP). The high fidelity was explained on the basis of the well-known kinetic-proofreading mechanism (KPR), under which the so-called fidelity-speed trade-off was studied theoretically. However, numerous biochemical experiments have shown that the high fidelity of DNA replication is achieved due to the initial discrimination of polymerase domain of DNAP, as well as the proofreading of the exonuclease domain of DNAP. This exonuclease-proofreading mechanism (EPR) is totally different from KPR. So the trade-off issues are worth being re-examined under EPR. In this paper, we use the first-passage method recently proposed by us to discuss the possible trade-offs in DNA replication under EPR. We show that there could be no fidelity-speed trade-off under EPR, i.e., the fidelity and the speed can be simultaneously enhanced by EPR in a large range of kinetic parameters. This provides a new perspective to understand the experimental data of the exonuclease activity of T7 DNAP and T4 DNAP. We also show that there exists the fidelity-proofreading cost trade-off, i.e., the fidelity is enhanced at the cost of increasing the futile hydrolysis of dNTP. A possible way to avoid this trade-off is to regulate the rate of DNAP translocation: slowing down the forward translocation (in the presence of the terminal mismatch) can enhance the fidelity without changing the speed and the proofreading cost. Our theoretical analysis offers deeper insights on the kinetics-function relation of DNAP.PACS numbers: 82.39.-k, 87.15.Rn, 87.16.A-
Modelling the visual world of a velvet worm
Authors: Ljungholm Mikael , Nilsson Dan-E. 
Published: February 2021

AbstractIn many animal phyla, eyes are small and provide only low-resolution vision for general orientation in the environment. Because these primitive eyes rarely have a defined image plane, traditional visual-optics principles cannot be applied. To assess the functional capacity of such eyes we have developed modelling principles based on ray tracing in 3D reconstructions of eye morphology, were refraction on the way to the photoreceptors and absorption in the photopigment are calculated incrementally for ray bundles from all angles withing the visual field. From the ray tracing, we calculate the complete angular acceptance function of each photoreceptor in the eye, revealing the visual acuity for all parts of the visual field. We then use this information to generate visual filters that can be applied to high resolution images or videos to convert them to accurate representations of the spatial information seen by the animal. The method is here applied to the 0.1 mm eyes of the velvet wormEuperipatoides rowelli(Onychophora). These eyes of these terrestrial invertebrates consist of a curved cornea covering an irregular but optically homogeneous lens directly joining a retina packed with photoreceptive rhabdomeres. 3D reconstruction from histological sections revealed an asymmetric eye, where the retina is deeper in the forward-pointing direction. The calculated visual acuity also reveals performance differences across the visual field, with a maximum acuity of about 0.11 cycles/deg in the forward direction despite laterally pointing eyes. The results agree with previous behavioural measurements of visual acuity, and suggest that velvet worm vision is adequate for orientation and positioning within the habitat.Author summaryIt is difficult to understand the roles that vision may have in animals with visual performance very different to our own. Many invertebrates such as flatworms, polychaetes, onychophorans, gastropod molluscs and numerous arthropods have tiny eyes with unknown visual abilities. At best, behavioural experiments can reveal visual performance limits for specific behaviours but they will not give general information about what is visible to the animal, which is crucial for understanding the roles vision may have. Here we use ray tracing applied to accurate anatomical/optical models of the eyes of a velvet worm to reconstruct the visual acuity in all parts of the visual field. We also use the calculated visual performance to closely simulate what animals would see in their natural habitat. The method can be applied to any (preferably small) eye and offers an alternative strategy that may yield information about the visual capacity that is otherwise hard to obtain.
Retrograde Control of Cytosolic Translation Targets Synthesis of Plastid Proteins and Nuclear Responses for High-Light Acclimation
Authors: Moore Marten , Smith Aaron B. , Wegener Melanie , Wesemann Corinna , Schmidtpott Sonja , Farooq Muhammad Ansar , Ganguly Diep Ray , Seidel Thorsten , Pogson Barry J. , Dietz Karl-Josef 
Published: February 2021

AbstractCanonical retrograde signalling comprises information transmission from organelles to the nucleus and in particular controls gene expression for organellar proteins. The need to re-assess this paradigm was suggested by discrepancies between de novo protein synthesis and transcript abundance in response to excess light. Here we uncover major components of a translation-dependent retrograde signalling pathway that first impacts translation and then transcription. The response realization depends on the kinases Mitogen-activated protein kinase 6 (MPK6) and Sucrose non-fermenting 1-related kinase (SnRK1) subunit, AKIN10. Global ribosome foot-printing revealed differential ribosome association of 951 transcripts within 10 min after transfer from low to high light. Despite predominant translational repression, 15 % of transcripts were increased in translation and enriched for chloroplast-localized photosynthetic proteins. About one third of these transcripts, including Stress associated proteins (SAP) 2 and 3, share regulatory motifs in their 5′-UTR that act as binding sites for glyceraldehyde-3-phosphate dehydrogenase (GAPC) and light responsive RNA binding proteins (RBPs). SAP2 and 3 are both translationally regulated and interact with the calcium sensor Calmodulin-like 49 (CML49), which promotes relocation to the nucleus inducing a translation-dependent nuclear stress response. Thus, translation-dependent retrograde signalling bifurcates to directly regulate a translational circuit of chloroplast proteins and simultaneously initiate a nuclear circuit synchronizing retrograde and anterograde response pathways, serving as a rapid mechanism for functional acclimation of the chloroplast.
Fast A-type currents shape a rapidly adapting form of delayed short latency firing of excitatory superficial dorsal horn neurons that express the NPY Y1 receptor
Authors: Sinha Ghanshyam P. , Prasoon Pranav , Smith Bret N. , Taylor Bradley K. 
Published: February 2021

ABSTRACTNeuroanatomical and behavioral evidence indicates that neuropeptide Y Y1 receptor-expressing interneurons (Y1-INs) in the superficial dorsal horn (SDH) are predominantly excitatory and contribute to chronic pain. Using an adultex vivospinal cord slice preparation from Y1eGFP reporter mice, we characterized firing patterns in response to steady state depolarizing current injection of GFP-positive cells in lamina II, the great majority of which expressed Y1 mRNA (88%). Randomly sampled and Y1eGFP neurons exhibited five firing patterns: tonic (TF), initial burst (IBF), phasic (PF), delayed short-latency <180 ms (DSLF), and delayed long-latency >180 ms (DLLF). When studied at resting membrane potential, most RS neurons exhibited delayed firing, while most Y1eGFP neurons exhibited phasic firing and not delayed firing. A preconditioning membrane hyperpolarization produced only subtle changes in the firing patterns of randomly sampled neurons, but dramatically shifted Y1eGFP neurons to DSLF (46%) and DLLF (24%). In contrast to randomly sampled DSLF neurons which rarely exhibited spike frequency adaptation, Y1eGFP DSLF neurons were almost always rapidly adapting, a characteristic of nociceptive-responsive SDH neurons. Rebound spiking was more prevalent in Y1eGFP neurons (6% RS vs 32% Y1eGFP), indicating enrichment of T-type calcium currents. Y1eGFP DSLF neurons exhibited fast A-type potassium currents that are known to delay or limit action potential firing, and these were of smaller current density as compared to randomly sampled DSLF neurons. Our results inspire future studies to determine whether tissue or nerve injury downregulates channels that contribute to A-currents, thus potentially unmasking T-type calcium channel activity and membrane hyperexcitability in Y1-INs, leading to persistent pain.KEYPOINTSNeuropeptide Y Y1 receptor-expressing neurons in the dorsal horn of the spinal cord contribute to chronic pain.For the first time, we characterized the firing patterns of Y1-expressing neurons in Y1eGFP reporter mice.Under hyperpolarized conditions, most Y1eGFP neurons exhibited fast A-type potassium currents and delayed, short-latency firing (DSLF).Y1eGFP DSLF neurons were almost always rapidly adapting and often exhibited rebound spiking, characteristics of spinal pain neurons under the control of T-type calcium channels.These results inspire future studies to determine whether tissue or nerve injury downregulates the channels that underlie A-currents, thus unmasking membrane hyperexcitability in Y1- expressing dorsal horn neurons, leading to persistent pain
Intracellular NASPM allows an unambiguous functional measure of GluA2-lacking calcium-permeable AMPA receptor prevalence
Authors: Coombs Ian D. , Bats Cécile , Sexton Craig A. , Cull-Candy Stuart G. , Farrant Mark 
Published: February 2021

AbstractCalcium-permeable AMPA-type glutamate receptors (CP-AMPARs) contribute to many forms of synaptic plasticity and pathology. They can be distinguished from GluA2-containing calcium-impermeable AMPARs by the inward rectification of their currents, which reflects voltage-dependent block by intracellular spermine. However, the efficacy of this weakly permeant blocker is differentially altered by the presence of AMPAR auxiliary subunits – including transmembrane AMPAR regulatory proteins, cornichons and GSG1L – that are widely expressed in neurons and glia. This complicates the interpretation of rectification as a measure of CP-AMPAR expression. Here we show that inclusion of the spider toxin analogue 1-naphthylacetyl spermine (NASPM) in the intracellular recording solution results in complete block of GluA1-mediated outward currents irrespective of the type of associated auxiliary subunit. In neurons from GluA2-knockout mice expressing only CP-AMPARs, intracellular NASPM, unlike spermine, blocks all outward synaptic current. Thus, our results identify an unambiguous functional measure, sensitive solely to changes in CP-AMPAR prevalence.
Invasive atypical non-typhoidalSalmonellaserovars in The Gambia
Authors: Kanteh Abdoulie , Sesay Abdul Karim , Alikhan Nabil-Fareed , Ikumapayi Usman Nurudeen , Salaudeen Rasheed , Manneh Jarra , Olatunji Yekini , Page Andrew J , Mackenzie Grant 
Published: February 2021

AbstractBackgroundInvasive non-typhoidalSalmonella(iNTS) disease continues to be a significant public health problem in sub-Saharan Africa. Common clinical misdiagnosis, antimicrobial resistance, high case fatality and lack of a vaccine make iNTS a priority for global health research. Using whole genome sequence analysis of 164 invasiveSalmonellaisolates obtained through population-based surveillance between 2008 and 2016, we conducted genomic analysis of the serovars causing invasiveSalmonelladiseases in rural Gambia.ResultsThe incidence of iNTS varied over time. The proportion of atypical serovars causing disease increased over time from 40% to 65% compared to the typical serovars Enteritidis and Typhimurium decreasing from 30% to 12%. Overall iNTS case fatality was 10% with 10% fatality in cases of atypical iNTS. Genetic virulence factors were identified in 14/70 (20%) typical serovars and 45/68 (66%) of the atypical serovars and were associated with: invasion, proliferation and/or translocation (Clade A); and host colonization and immune modulation (Clade G). Among Enteritidis isolates, 33/40 were resistant to ≥4 the antimicrobials tested, except for ciprofloxacin, to which all isolates were susceptible. Resistance was low in Typhimurium isolates, however, all16 isolates were resistant to gentamicin.ConclusionThe increase in incidence and proportion of iNTS disease caused by atypical serovars is concerning. The increased proportion of atypical serovars and the high associated case fatality may be related to acquisition of specific genetic virulence factors. These factors may provide a selective advantage to the atypical serovars. Investigations should be conducted elsewhere in Africa to identify potential changes in the distribution iNTS serovars and the extent of these virulence elements.
Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2
Authors: Fischhoff Ilya R. , Castellanos Adrian A. , Rodrigues João P.G.L.M. , Varsani Arvind , Han Barbara A. 
Published: February 2021

AbstractBack and forth transmission of SARS-CoV-2 between humans and animals may lead to wild reservoirs of virus that can endanger efforts toward long-term control of COVID-19 in people, and protecting vulnerable animal populations that are particularly susceptible to lethal disease. Predicting high risk host species is key to targeting field surveillance and lab experiments that validate host zoonotic potential. A major bottleneck to predicting animal hosts is the small number of species with available molecular information about the structure of ACE2, a key cellular receptor required for viral cell entry. We overcome this bottleneck by combining species’ ecological and biological traits with 3D modeling of virus and host cell protein interactions using machine learning methods. This approach enables predictions about the zoonotic capacity of SARS-CoV-2 for over 5,000 mammals — an order of magnitude more species than previously possible. The high accuracy predictions achieved by this approach are strongly corroborated byin vivoempirical studies. We identify numerous common mammal species whose predicted zoonotic capacity and close proximity to humans may further enhance the risk of spillover and spillback transmission of SARS-CoV-2. Our results reveal high priority areas of geographic overlap between global COVID-19 hotspots and potential new mammal hosts of SARS-CoV-2. With molecular sequence data available for only a small fraction of potential host species, predictive modeling integrating data across multiple biological scales offers a conceptual advance that may expand our predictive capacity for zoonotic viruses with similarly unknown and potentially broad host ranges.
Pregnancy and weaning regulate human maternal liver size and function
Authors: Bartlett Alexandra Q , Vesco Kimberly K , Purnell Jonathan Q , Francisco Melanie , Goddard Erica , DeBarber Andrea , Leo Michael C , Baetscher Eric , Rooney William , Naugler Willscott , Guimaraes Alex , Catalano Patrick , Schedin Pepper 
Published: February 2021

AbstractBACKGROUNDDuring pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a pro-metastatic niche. These data suggest a mechanism for increased liver metastasis in postpartum breast cancer patients.OBJECTIVESInvestigate if the human liver changes in size and function during pregnancy and weaning.METHODSAbdominal imaging was obtained in healthy women at early and late pregnancy, and post-wean. During pregnancy time points, endogenous glucose production was measured and fasting blood taken to measure bile acids.RESULTSIndependent of weight gain, most women’s livers increased in size with pregnancy, returning to baseline post-wean. Putative roles for bile acids in liver growth were observed in pregnant women and rodents.CONCLUSIONSThe human liver is regulated by reproductive state with growth during pregnancy and volume loss post-wean. These findings may have broad implications for sex-specific liver diseases and cancer.
Analysis of Structural Variation Among Inbred Mouse Strains Identifies Genetic Factors for Autism-Related Traits
Authors: Arslan Ahmed , Fang Zhuoqing , Wang Meiyue , Cheng Zhuanfen , Yoo Boyoung , Bejerano Gill , Peltz Gary 
Published: February 2021

AbstractThe genomes of six inbred strains were analyzed using long read (LR) sequencing. The results revealed that structural variants (SV) were very abundant within the genome of inbred mouse strains (4.8 per gene), which indicates that they could impact genetic traits. Analysis of the relationship between SNP and SV alleles across 53 inbred strains indicated that we have a very limited ability to infer whether SV are present using short read sequence data, even when nearby SNP alleles are known. The benefit of having a more complete map of the pattern of genetic variation was demonstrated by identifying at least three genetic factors that could underlie the unique neuroanatomic and behavioral features of BTBR mice that resemble human Autism Spectrum Disorder (ASD). Similar to the genetic findings in human ASD cohorts, the identified BTBR-unique alleles are very rare, and they cause high impact changes in genes that play a role in neurodevelopment and brain function.
neurolib: a simulation framework for whole-brain neural mass modeling
Authors: Cakan Caglar , Jajcay Nikola , Obermayer Klaus 
Published: February 2021

ABSTRACTneurolibis a computational framework for whole-brain modeling written in Python. It provides a set of neural mass models that represent the average activity of a brain region on a mesoscopic scale. In a whole-brain network model, brain regions are connected with each other based on biologically informed structural connectivity, i.e. the connectome of the brain.neurolibcan load structural and functional datasets, set up a whole-brain model, manage its parameters, simulate it, and organize its outputs for later analysis. The activity of each brain region can be converted into a simulated BOLD signal in order to calibrate the model against empirical data from functional magnetic resonance imaging (fMRI). Extensive model analysis is possible using a parameter exploration module, which allows one to characterize the model’s behavior given a set of changing parameters. An optimization module can fit a model to multimodal empirical data using an evolutionary algorithm.neurolibis designed to be extendable such that custom neural mass models can be implemented easily, offering a versatile platform for computational neuroscientists for prototyping models, managing large numerical experiments, studying the structure-function relationship of brain networks, and for performing in-silico optimization of whole-brain models.
scMM: Mixture-of-experts multimodal deep generative model for single-cell multiomics data analysis
Authors: Minoura Kodai , Abe Ko , Nam Hyunha , Nishikawa Hiroyoshi , Shimamura Teppei 
Published: February 2021

AbstractThe recent development in single-cell multiomics analysis has enabled simultaneous detection of multiple traits at the single-cell level, thus providing deeper insights into the cellular phenotypes and functions in diverse tissues. However, currently, it is challenging to infer the joint representations and learn relationships among multiple modalities from complex multimodal single-cell data. Herein, we present scMM, a novel deep generative model-based framework for the extraction of interpretable joint representations and cross-modal generation. scMM addresses the complexity of data by leveraging a mixture-of-experts multimodal variational autoencoder. The pseudocell generation strategy of scMM compensates for the limited interpretability of deep learning models and discovered multimodal regulatory programs associated with latent dimensions. Analysis of recently produced datasets validated that scMM facilitates high-resolution clustering with rich interpretability. Furthermore, we show that cross-modal generation by scMM leads to more precise prediction and data integration compared with the state-of-the-art and conventional approaches.
BREVIPEDICELLUS and ERECTA mediate expression ofAtPRX17in preventing Arabidopsis callus retardation and browning
Authors: Xie Junyan , Qi Bin , Wu Yuanyuan , Mou Chenghong , Wang Lihua , Jiao Yuwei , Dou Yanhui , Zheng Huiqiong 
Published: February 2021

ABSTRACTEfficient in vitro callus generation is fundamental to tissue culture propagation, a process required for plant regeneration and transgenic breeding for desired phenotypes. Identifying genes and regulatory elements that prevent callus retardation and browning is essential to facilitate the development of vitro callus systems. Here we show thatBREVIPEDICELLUS(BP) andERECTA(ER) pathways inArabidopsiscallus are converged to prevent callus browning and positively regulate an isoperoxidase gene AtPRX17expression in the rapid growth callus. Loss of functions in bothBPandERresulted in markedly increasing callus browning. Transgenic lines withpro35S::AtPRX17in thebp-5 er105double mutant background fully rescued this phenotypic abnormality. Using plantin vitroDNA-binding assays, we observed that BP protein bound directly to the upstream sequence ofAtPRX17to promote its transcription during callus growth. ER is a universally presenting factor required for cell proliferation and growth, we show thatERpositively regulates expression of a transcription factorWRKY6, which also directly binds to an additional site of the AtPRX17promoter for its high expression. Our data reveals an important molecular mechanism in regulating expression of peroxidase isozyme to reduce Arabidopsis callus browning.HighlightBREVIPEDICELLUSandERECTAare involved in regulating Arabidopsis callus browning by controlling expression ofAtPRX17.