Biology subjects

Song, S.

Publications and source records attributed to Song, S..

At least 145 records · Page 8Linked to original sources

bioRxiv2021

Machine Learning to Summarize and Provide Context for Sleep and Eating Schedules.

The relative timing of sleep and of eating within the circadian day is important for human health. Despite much data on sleep, and a growing data set for eating, there remains a need for an interpretative framework for the understanding of this data for health decisions. This study provides a new statistical and machine learning analysis of more than 500 participants in the Daily24 project. From their data, and the analysis, we propose a framework for determining the classification of participants into different chronotypes and with that the ability to realize the potential impact of daily circadian habits on health. We propose that our resulting distribution curves could be used, similar to NHANES (National Health and Nutrition Examination Survey) data for pediatric growth, as a measure for circadian misalignment and used to help guide re-entrainment schedules. Author summaryDaily habits can be positive, negative or neutral for human health. Generally sleep and eating schedules are assumed without thought for their potential to help or interfere with health. In this study we propose a framework, based on data from more than 500 participants, for evaluating the relative timing of meals and sleep schedules. This evaluation, similar to pediatric growth charts, can guide clinical suggestions for those at the extremes, while helping others to realize that they are unusual relative to the population average

bioinformatics↗

bioRxiv2020

Aberrant peripheral immune responses in acute Kawasaki disease with single-cell sequencing

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although diverse immune aberrance was reported, a global understanding of immune responses underlying acute KD was lacking. Based on single-cell sequencing, we profiled peripheral blood mononuclear cells from patients with acute KD before and after intravenous immunoglobulin therapy and from healthy controls. Most differentially expressed genes were derived from monocytes, with upregulation of immunoglobulin receptors, complement and receptors and downregulation of MHC class II receptors before therapy. The percentage of B cells was significantly increased before therapy and rapidly returned to normal after therapy. There was also an increased abundance of B-cell receptors with IGHA and IGHG after therapy, accompanied by massive oligoclonal expansion. The percentage of CD8 T cells was remarkably decreased during acute KD, especially the subset of effector memory CD8 T cells. All lymphocyte compartments were characterized by underexpressed interferon response pathways before therapy. The identification of unique innate and adaptive immune responses suggests potential mechanisms underlying pathogenesis and progression of KD.

immunology↗

bioRxiv2020

Loss of a plant receptor kinase recruits beneficial rhizosphere-associated Pseudomonas

Maintaining microbiome structure is critical for the health of both plants1 and animals2. In plants, enrichment of beneficial bacteria is associated with advantageous outcomes including protection from biotic and abiotic stress3,4. However, the genetic and molecular mechanisms by which plants enrich for specific beneficial microbes without general dysbiosis have remained elusive. Here we show that through regulation of NADPH oxidase, FERONIA kinase negatively regulates beneficial Pseudomonas fluorescens in the Arabidopsis rhizosphere microbiome. By rescreening a collection of Arabidopsis mutants that affect root immunity under gnotobiotic conditions, followed by microbiome sequencing in natural soil, we identified a FERONIA mutant (fer-8) with a rhizosphere microbiome enriched in P. fluorescens without phylum-level dysbiosis. Using microbiome transplant experiments, we found that the fer-8 microbiome was beneficial and promoted plant growth. The effect of FER on rhizosphere Pseudomonads was independent of its immune coreceptor function, role in development, and jasmonic acid autoimmunity. We found that the fer-8 mutant has reduced basal levels of reactive oxygen species (ROS) in roots and that mutants deficient in NADPH oxidase showed elevated rhizosphere Pseudomonad levels. Overexpression of the ROP2 gene (encoding a client of FER and positive regulator of NADPH oxidase5) in fer-8 plants suppressed Pseudomonad overgrowth. This work shows that FER-mediated ROS production regulates levels of beneficial Pseudomonads in the rhizosphere microbiome.

plant biology↗

bioRxiv2020

Ancestry Inference Using Reference Labeled Clusters of Haplotypes

We present ARCHes, a fast and accurate haplotype-based approach for inferring an individuals ancestry composition. Our approach works by modeling haplotype diversity from a large, admixed cohort of hundreds of thousands, then annotating those models with population information from reference panels of known ancestry. The running time of ARCHes does not depend on the size of a reference panel because training and testing are separate processes, and the inferred population-annotated haplotype models can be written to disk and reused to label large test sets in parallel (in our experiments, it averages less than one minute to assign ancestry from 32 populations to 1,001 sections of a genotype using 10 CPU). We test ARCHes on public data from the 1,000 Genomes Project and HGDP as well as simulated examples of known admixture. Our results demonstrate that ARCHes outperforms RFMix at correctly assigning both global and local ancestry at finer population scales regardless of the amount of population admixture. Author SummaryHuman DNA is inherited from ancestors that come from different populations across the globe and across time. Being able to identify which of those populations make up an individuals DNA, how much they contribute, and on which chromosomes, is currently an important open research problem with many applications in the study of human diversity and history. As DNA sequencing and genotyping technology has developed, we have greater and greater amounts of data, which allows for the development of new sophisticated machine learning methods to approach this problem, and presents a need to process large amounts of data efficiently. These methods learn from examples of DNA data from known populations, and must be robust to differences in size and diversity among those reference populations. We present a new approach to this problem called ARCHes (Ancestry inference using Reference labeled Clusters of Haplotypes), that models the global diversity of small segments of human DNA sequence ("haplotypes"), and the extent to which these haplotypes are associated with each of a set of population reference panels. It then computes the most likely population assignments and the points along the genome where the populations change. Our experiments show that ARCHes has superior accuracy compared to a state-of-the-art method in identifying source populations and their locations on the genome, regardless of the number of different populations present in the genome, how closely related those populations are. ARCHes is also able to model populations despite having a small amount of population reference DNA data.

genomics↗

bioRxiv2020

A key linear epitope for a potent neutralizing antibody to SARS-CoV-2 S-RBD

The spread of SARS-CoV-2 confers a serious threat to the public health without effective intervention strategies1-3. Its variant carrying mutated Spike (S) protein D614G (SD614G) has become the most prevalent form in the current global pandemic4,5. We have identified a large panel of potential neutralizing antibodies (NAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 S6. Here, we focused on the top 20 potential NAbs for the mechanism study. Of them, the top 4 NAbs could individually neutralize both authentic SARS-CoV-2 and SD614G pseudovirus efficiently. Our epitope mapping revealed that 16/20 potent NAbs overlapped the same steric epitope. Excitingly, we found that one of these potent NAbs (58G6) exclusively bound to a linear epitope on S-RBD (termed as 58G6e), and the interaction of 58G6e and the recombinant ACE2 could be blocked by 58G6. We confirmed that 58G6e represented a key site of vulnerability on S-RBD and it could positively react with COVID-19 convalescent patients plasma. We are the first, as far as we know, to provide direct evidences of a linear epitope that can be recognized by a potent NAb against SARS-CoV-2 S-RBD. This study paves the way for the applications of these NAbs and the potential safe and effective vaccine design.

immunology↗

bioRxiv2020

The global landscape of SARS-CoV-2 genomes, variants, and haplotypes in 2019nCoVR

On 22 January 2020, the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), created the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access SARS-CoV-2 information resource. 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by our in-house automated pipeline. Of particular note, 2019nCoVR performs systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. It also generates visualization of the spatiotemporal change for each variant and yields historical viral haplotype network maps for the course of the outbreak from all complete and high-quality genomes. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on COVID-19 (Coronavirus Disease 2019), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB-NGDC, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with National Center for Biotechnology Information. Collectively, all SARS-CoV-2 genome sequences, variants, haplotypes and literature are updated daily to provide timely information, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

genomics↗

bioRxiv2020

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades

COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months and a global fight against both is still going on. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code, to molecular mechanisms based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on replicase-transcriptase complex. Our analysis starts with primary sequence information and identity-based phylogeny based on 22,051 SARS-CoV-2 genome sequences and evaluation of sequence variation patterns as mutation spectrum and its 12 permutations among organized clades tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings include: (1) The most dominant mutation is C-to-U permutation whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity albeit assumed most slightly deleterious. (2) The second abundance group includes: three negative-strand mutations U-to-C, A-to-G, G-to-A and a positive-strand mutation G-to-U generated through an identical mechanism as C-to-U. (3) A clade-associated and biased mutation trend is found attributable to elevated level of the negative-sense strand synthesis. (4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes. These findings demand a bioinformatics platform where emerging mutations are mapped on to mostly subtle but fast-adjusting viral proteomes and transcriptomes to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications. Such thoughts and actions are in desperate need, especially in the middle of the War against COVID-19.

microbiology↗

bioRxiv2020

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

Neutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.

immunology↗

bioRxiv2020

Deep reinforcement learning for modeling human locomotion control in neuromechanical simulation

Modeling human motor control and predicting how humans will move in novel environments is a grand scientific challenge. Despite advances in neuroscience techniques, it is still difficult to measure and interpret the activity of the millions of neurons involved in motor control. Thus, researchers in the fields of biomechanics and motor control have proposed and evaluated motor control models via neuromechanical simulations, which produce physically correct motions of a musculoskeletal model. Typically, researchers have developed control models that encode physiologically plausible motor control hypotheses and compared the resulting simulation behaviors to measurable human motion data. While such plausible control models were able to simulate and explain many basic locomotion behaviors (e.g. walking, running, and climbing stairs), modeling higher layer controls (e.g. processing environment cues, planning long-term motion strategies, and coordinating basic motor skills to navigate in dynamic and complex environments) remains a challenge. Recent advances in deep reinforcement learning lay a foundation for modeling these complex control processes and controlling a diverse repertoire of human movement; however, reinforcement learning has been rarely applied in neuromechanical simulation to model human control. In this paper, we review the current state of neuromechanical simulations, along with the fundamentals of reinforcement learning, as it applies to human locomotion. We also present a scientific competition and accompanying software platform, which we have organized to accelerate the use of reinforcement learning in neuromechanical simulations. This "Learn to Move" competition, which we have run annually since 2017 at the NeurIPS conference, has attracted over 1300 teams from around the world. Top teams adapted state-of-art deep reinforcement learning techniques to produce complex motions, such as quick turning and walk-to-stand transitions, that have not been demonstrated before in neuromechanical simulations without utilizing reference motion data. We close with a discussion of future opportunities at the intersection of human movement simulation and reinforcement learning and our plans to extend the Learn to Move competition to further facilitate interdisciplinary collaboration in modeling human motor control for biomechanics and rehabilitation research.

bioengineering↗

bioRxiv2020

KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype

Cellular senescence restrains the expansion of neoplastic cells through several layers of regulation, including epigenetic decoration of chromatin structure and functional modulation of bioactive components. Here we report that expression of the histone H3-specific demethylase KDM4 is upregulated in human stromal cells upon cellular senescence. In clinical oncology, upregulated KDM4 and diminished H3K9/H3K36 methylation are correlated with adverse survival of cancer patients post-chemotherapy. Global chromatin accessibility mapping via ATAC-seq and expression profiling through RNA-seq reveal extensive reorganization of chromosomes and spatiotemporal reprogramming of the transcriptomic landscape, events responsible for development of the senescence-associated secretory phenotype (SASP). Selectively targeting KDM4 dampens the SASP of senescent stromal cells and enhances the apoptotic index of cancer cells in the treatment-damaged tumor microenvironment (TME), together prolonging overall survival of experimental animals. Our study supports the dynamic change of H3K9/H3K36 methylation marks during cellular senescence, identifies an unusually permissive chromatin state, unmasks KDM4 as a key modulator of the SASP, and presents a novel therapeutic avenue to manipulate cellular senescence and curtail age-related pathologies.

cell biology↗

bioRxiv2020

Production of diverse beauveriolide analogs in closely related fungi: a rare case of fungal chemodiversity

Fungal chemodiversity is well known in part due to the production of diverse analogous compounds by a single biosynthetic gene cluster (BGCs). Usually, similar metabolites are produced by closely related fungal species. Here we report a rare case of the production of the cyclodepsipeptide beauveriolides (BVDs) in three insect pathogenic fungi. We found that the more closely-related fungi Beauveria bassiana and B. brongniartii produce structurally distinct analogs of BVDs whereas the rather divergently evolved species B. brongniartii and Cordyceps militaris produce structural analogs in a similar pattern. It was verified that a conserved BGC containing four genes is responsible for BVD biosynthesis in three fungi including a polyketide synthase (PKS) for the production of 3-hydroxy fatty acids (FAs) with chain length variations. In contrast to BVD production patterns, phylogenetic analysis of the BGC enzymes or enzyme domains largely resulted in the congruence relationship with fungal speciation. Feeding assays demonstrated that a FA with a chain length of eight carbon atoms was preferentially utilized whereas a FA with a chain longer than 10 carbon atoms could not be used as a substrate for BVD biosynthesis. We also found that addition of D-type amino acids could not enable B. bassiana to produce those analogs biosynthesized by other two fungi. Insect survival assays suggested that the contribution of BVD to fungal virulence might be associated with the susceptibility of insect species. The results of this study enrich the knowledge of fungal secondary metabolic diversity. IMPORTANCEFungal chemotaxonomy is an approach to classify fungi based on fungal production of natural compounds especially the secondary metabolites. We found an atypical example that could question chemical classification of fungi in this study: the more closely-related entomopathogenic species Beauveria bassiana and B. brongniartii produce structurally different analogs of the cyclodepsipeptide beauveriolides whereas the rather divergent species B. brongniartii and Cordyceps militaris biosynthesize similar analogs under the same growth condition. The conserved BGC containing four genes is present in each species and responsible for beauveriolide production. In contrast to the compound formation profiles, the phylogenies of biosynthetic enzymes or enzymatic domains show associations with fungal speciation relationship. Dependent on insect species, production of beauveriolides may contribute to fungal virulence against insect. The findings in this study augment the diversity of fungal secondary metabolisms.

microbiology↗

bioRxiv2020

Combination of favorable gene haplotypes plays an important role in rice hybrid grain quality traits based on genome-wide association analysis

Yield level and grain quality determine the commercial potential of rice (Oryza sativa L.) varieties. Mining and using genes that control important rice grain quality characteristics are major tasks for plant breeders. Here, a genome-wide association study was conducted to determine the genetic bases of 12 rice grain quality traits in 113 varieties and 565 testcross hybrids. A total of 56 significant SNPs were associated with 9 of the traits in variety phenotypic, general combining ability, testcross hybrid phenotypic and mid-parental heterotic datasets, from which 45 novel loci were identified. The cumulative effects of superior alleles or favorable haplotypes of genes closest to significant quality trait-associated loci were found in the four datasets. Additionally, the favorable gene haplotypes performed better than those of superior alleles in the variety and testcross hybrid datasets. Pyramiding the favorable haplotypes of five cloned rice grain quality genes resulted in a very low amylose content and high yield in the latter. These testcross hybrids had rice grain qualities similar to their parental lines but with much higher yields. The amylose content, grain width and grain length predictions for potential hybrids among the 113 varieties using genomic selection based on the BayesB method revealed a performance trend similar to those the testcross hybrids in our study. Thus, the selection of combination of favorable rice quality-related gene haplotypes is recommended to breed hybrids with high yields and elite grain qualities.

genetics↗

bioRxiv2020

Transcriptional and epigenetic characterization of early striosomes identifies Foxf2 and Olig2 as factors required for development of striatal compartmentation and neuronal phenotypic differentiation

The basal ganglia, best known for processing information required for multiple aspects of movement, is also part of a network which regulates reward and cognition. The major output nucleus of the basal ganglia is the striatum, and its functions are dependent on neuronal compartmentation, including striosomes and matrix, which are selectively affected in disease. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), all of which share basic molecular signatures but are subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating terminal neuronal differentiation following migration are largely unidentified. We performed RNA- and ATAC-seq on sorted murine striosome and matrix cells at postnatal day 3. Focusing on the striosomal compartment, we validated the localization and role of transcription factors and their regulator(s), previously not known to be associated with striatal development, including Irx1, Foxf2, Olig2 and Stat1/2. In addition, we validated the enhancer function of a striosome-specific open chromatin region located 15Kb downstream of the Olig2 gene. These data and data bases provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation and thus provide new approaches to establishing MSN subtypes from human iPSCs for disease modeling and drug discovery.

neuroscience↗

bioRxiv2020

Gene expression and chromatin accessibility during progressive EMT and MET linked to dynamic CTCF engagement

BackgroundEpithelial-mesenchymal transition (EMT) facilitates cellular movements critical for proper development; however, in a carcinoma, EMT promotes metastatic dissemination. Stable intermediate states (partial-EMT) are increasingly implicated in metastatic dissemination while reversal of EMT, termed mesenchymal-epithelial transition (MET), is increasingly implicated in metastatic colonization. To understand the partial and reversible nature of EMT, we characterized chromatin accessibility dynamics, transcriptome changes, protein expression patterns, as well as E-cadherin expression, localization, and gene-level dynamics in mammary epithelial cells undergoing stepwise reversible EMT. ResultsWhile shorter EMT induction induced internalization of E-cadherin protein, surface expression was recovered upon MET without loss of transcript or bulk protein. Conversely, a longer EMT induced stable repression of E-cadherin indicated by loss of chromatin accessibility and induced global expansion of accessible sites across the genome, facilitated by increased engagement of multiple transcription factor families, including AP-1 and SMAD. We observe enrichment for binding sites for the insulator proteins CTCF and BORIS was significantly diminished in both stemness-enriched partial-EMT and partial-MET states and determined that CTCF repression imparts alterations in some histone covalent modifications concomitant with those observed during TGF{beta}-induced EMT. ConclusionsThese findings are indicative of a major role for chromatin looping and reorganization in plasticity, stemness, and partial EMT phenotypes.

cell biology↗

bioRxiv2020

Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A

The epithelial-mesenchymal transition (EMT) imparts properties of cancer stem-like cells, including resistance to frequently used chemotherapy, necessitating the identification of molecules that induce cell death specifically in stem-like cells with EMT properties. Herein, we demonstrate that breast cancer cells enriched for EMT features are more sensitive to cytotoxicity induced by ophiobolin A (OpA), a sesterterpenoid natural product. Using a model of experimentally induced EMT in human mammary epithelial (HMLE) cells, we show that EMT is both necessary and sufficient for OpA sensitivity. Moreover, prolonged, sub-cytotoxic exposure to OpA is sufficient to reduce migration, sphere formation, and resistance to doxorubicin. OpA is well-tolerated in mice and treatment with OpA alone reduces tumor burden. These data identify a driver of EMT-driven cytotoxicity with significant potential for use either in combination with standard chemotherapy or for tumors enriched for EMT features.

cancer biology↗

bioRxiv2020

Abortion and various associated risk factors in dairy cow and sheep in Ili, China

We studied livestock abortion and various associated risk factors in the Ili region of northwest China. Livestock abortion prevalence was estimated and correlated with infections (Brucellosis, Salmonellosis, Mycoplasma and Chlamydia seropositivity) and management (farming type and contact with other herds/flocks) risk factors. The prevalence of cow and sheep abortion induced by Brucella was 76.8% (P<0.0001) and 84.1% (P<0.0001), and Mycoplasma caused an estimated 15.5% (P=0.025) and 17.6% (P<0.001) abortions, respectively. Abortion-related risk factors included mixed farming (cow P=0.001, sheep P<0.001), contact with other flocks (cow P=0.007, sheep P=0.003), brucellosis positivity (cow P<0.001, sheep P<0.001) and Mycoplasma positivity (cow P=0.031, sheep P<0.001). A total of 2996 serum samples (1402 cow, 1594 sheep) were identified by RBPT (Rose Bengal Plate Test), and they showed the seroprevalence of brucellosis in X county was cow 7.1%, sheep 9.1%; in H county was cow 11.7%, sheep 10.7%; and in Q county was cow 4.2%, sheep 9.1%. The seroprevalence of Mycoplasma in X county was cow 3.4%, sheep 7.9%; in H county was cow 5.3%, sheep 9.9%; and in Q county was cow 2.1%, sheep 4.3%. A total of 54 samples, including aborted cow (22), sheep (30) fetuses and milk samples (2), were identified as Brucella melitensis (B. melitensis) positive. A total of 38 Brucella were isolated from 16 aborted cow, 20 sheep fetuses and 2 milk samples. All of these isolates were identified, and confirmed, as B. melitensis. A phylogenetic tree showed that the Brucella isolates closely matched the B. melitensis biovar 3 isolated in Inner Mongolia, China, and B. melitensis isolated from Norway and India. These results suggest that B. melitensis biovar 3 is the main pathogen responsible for cow and sheep abortion and also pose a human health risk. Additionally, livestock reproduction can also be influenced by Mycoplasma infection and managerial factors (farming type and contact with other herds/flocks), especially in remote areas.View Full Text

zoology↗

bioRxiv2020

The evolution of red colour vision is linked to coordinated rhodopsin tuning in lycaenid butterflies

Colour vision is largely mediated by changes in number, expression, and spectral properties of rhodopsins, but the genetic mechanisms underlying adaptive shifts in spectral sensitivity remain largely unexplored. Using in vivo photochemistry, optophysiology, and in vitro functional assays, we link variation in eye spectral sensitivity at long wavelengths to species-specific absorbance spectra for LW opsins in lycaenid butterflies. In addition to loci specifying an ancestral green-absorbing rhodopsin with maximum spectral sensitivity ({lambda}max) at 520-530 nm in Callophrys sheridanii and Celastrina ladon, we find a novel form of red-shifted LW rhodopsin at {lambda}max = 565-570 nm in Arhopala japonica and Eumaeus atala. Furthermore, we show that Ca. sheridanii and Ce. ladon exhibit a smaller bathochromic shift at BRh2 (480-489 nm), and with the ancestral LW rhodopsin, cannot perceive visible red light beyond 600 nm. In contrast, molecular variation at the LW opsin in A. japonica and E. atala is coordinated with tuning of the blue opsin that also shifts sensitivity to longer wavelengths enabling colour discrimination up to 617 nm. We then use E. atala as a model to examine the interplay between red and blue spectral sensitivity. Owing to blue duplicate expression, the spatial distribution of opsin mRNAs within an ommatidium defines an expanded retinal stochastic mosaic of at least six opsin-based photoreceptor classes. Our mutagenesis in vitro assays with BRh1 ({lambda}max = 435 nm) chimeric blue rhodopsins reveal four main residues contributing to the 65 nm bathochromic shift towards BRh2 ({lambda}max = 500 nm). Adaptations in this four-opsin visual system are relevant for discrimination of conspecific reflectance spectra in E. atala. Together, these findings illustrate how functional changes at multiple rhodopsins contribute to the evolution of a broader spectral sensitivity and adaptation in visual performance. Significance StatementRhodopsins are photosensitive protein molecules that absorb specific wavelengths of incoming light and convey colour information in the visual system. We show that molecular evolution in a green insect opsin gene resulted in a shift in its maximal absorbance peak, enabling some lycaenid butterflies to use spectral energy of longer wavelengths (LW) to discriminate colours in the red spectrum better than relatives bearing ancestral green LW rhodopsins. Lycaenids also evolved a duplicate blue opsin gene, and we illustrate an example where species equipped with red LW rhodopsins shifted their blue sensitivity peak to longer wavelengths due to changes in several blue-tuning residues that have evolved repeatedly in different insect lineages. We demonstrate how changes at multiple vision genes in the insect eye effectively create a coordinated mechanism expanding spectral sensitivity for visually guided behaviours such as selecting host plants and mates.

evolutionary biology↗

bioRxiv2020

Potent human neutralizing antibodies elicited by SARS-CoV-2 infection

The pandemic caused by emerging coronavirus SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. SARS-CoV-2 cellular entry depends on binding between the viral Spike protein receptor-binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) target cell receptor. Here, we report on the isolation and characterization of 206 RBD-specific monoclonal antibodies (mAbs) derived from single B cells of eight SARS-CoV-2 infected individuals. These mAbs come from diverse families of antibody heavy and light chains without apparent enrichment for particular families in the repertoire. In samples from one patient selected for further analyses, we found coexistence of germline and germline divergent clones. Both clone types demonstrated impressive binding and neutralizing activity against pseudovirus and live SARS-CoV-2. However, the antibody neutralizing potency is determined by competition with ACE2 receptor for RBD binding. Surprisingly, none of the SARS-CoV-2 antibodies nor the infected plasma cross-reacted with RBDs from either SARS-CoV or MERS-CoV although substantial plasma cross-reactivity to the trimeric Spike proteins from SARS-CoV and MERS-CoV was found. These results suggest that antibody response to RBDs is viral species-specific while that cross-recognition target regions outside the RBD. The specificity and neutralizing characteristics of this plasma cross-reactivity requires further investigation. Nevertheless, the diverse and potent neutralizing antibodies identified here are promising candidates for prophylactic and therapeutic SARS-CoV-2 interventions.

immunology↗