Biology subjects

Wong, A.

Publications and source records attributed to Wong, A..

At least 73 records · Page 4Linked to original sources

bioRxiv2020

ExoNet Database: Wearable Camera Images of Human Locomotion Environments

Advances in computer vision and artificial intelligence are allowing researchers to develop environment recognition systems for powered lower-limb exoskeletons and prostheses. However, small-scale and private training datasets have impeded the widespread development and dissemination of image classification algorithms for classifying human walking environments. To address these limitations, we developed ExoNet - the first open-source, large-scale hierarchical database of high-resolution wearable camera images of human locomotion environments. Unparalleled in scale and diversity, ExoNet contains over 5.6 million RGB images of different indoor and outdoor real-world walking environments, which were collected using a lightweight wearable camera system throughout the summer, fall, and winter seasons. Approximately 923,000 images in ExoNet were human-annotated using a 12-class hierarchical labelling architecture. Available publicly through IEEE DataPort, ExoNet offers an unprecedented communal platform to train, develop, and compare next-generation image classification algorithms for human locomotion environment recognition. Besides the control of powered lower-limb exoskeletons and prostheses, applications of ExoNet could extend to humanoids and autonomous legged robots.

bioengineering↗

bioRxiv2020

Arginine citrullination of proteins as a specific response mechanism in Arabidopsis thaliana

Arginine deamination, also referred to as citrullination of proteins by peptidyl-arginine deiminases, is a post-translational modification affecting histone modifications, epigenetic transcriptional regulation and proteolysis in animals, but has not been reported in higher plants. Here we report, firstly, that Arabidopsis thaliana proteome contains proteins with a specific citrullination signature and that many of the citrullinated proteins have nucleotide-binding regulatory functions. Secondly, we show that changes in the citrullinome occur in response to cold stress, and thirdly, we identify an Arabidopsis thaliana protein with calcium-dependent arginine deiminase activity. Taken together, these findings establish this post-translational modification as a hitherto neglected component of cellular reprogramming during stress responses.

plant biology↗

bioRxiv2020

Mutagenicity of folic acid deficiency and supplementation is tissue-specific and results in distinct mutation profiles

Cancer incidence varies by tissue due to differences in environmental risk factor exposure, gene variant inheritance, and lifetime number of stem cell divisions in a tissue. Folate deficiency is associated with increased risk for colorectal cancer (CRC) and acute lymphocytic leukemia. Conversely, high folic acid (FA) intake has been associated with higher CRC risk. However, the mutagenic potential of FA intake in different tissues has not been characterized. Here we quantified mutations in folate-susceptible somatic tissues, namely bone marrow and colon, from the same MutaMouse mice and determined the FA-induced mutation profiles of both tissues using next generation sequencing. FA-induced mutagenesis was tissue- and dose-specific: FA deficiency increased mutant frequency (MF) in bone marrow while FA supplementation increased MF in colon. Analyses of mutation profiles suggested that FA interacted with mutagenic mechanisms that are unique to each tissue. These data illuminate potential mechanisms underpinning differences in susceptibility to FA-related cancers.

genetics↗

bioRxiv2020

Factors influencing riverine utilization patterns in two sympatric macaques

Many species of terrestrial animals, including primates, live in varied association with the aquatic (e.g., riverine or coastal) environment. However, the benefits that each species receive from the aquatic environment are thought to vary depending on their social and ecological characteristics, and thus, elucidating those benefits to each species is important for understanding the principles of wild animal behaviour. In the present study, to gain a more complete picture of aquatic environment use, including social and ecological factors in primates, factors affecting riverine habitat utilization of two macaque species (Macaca nemestrina and M. fascicularis) were identified and qualitative comparisons were made with sympatric proboscis monkeys (Nasalis larvatus), which have different social and ecological characteristics. Temporal variation in sighting frequency of macaques at the riverbanks was positively related to the fruit availability of a dominant riparian plant species and negatively related to the river water level which affects the extent of predation pressure. Riverine utilization of macaques was greatly influenced by distribution and abundance of food (especially fruit) resources, possibly in association with predation pressure. Additionally, qualitative ecological comparisons with sympatric proboscis monkeys suggest that the drivers of riverine utilization depend on the feeding niches of the species, and different anti-predator strategies resulting from their differing social structures.

ecology↗

bioRxiv2020

A bimodular PKS platform that expands the biological design space

Traditionally engineered to produce novel bioactive molecules, Type I modular polyketide synthases (PKSs) could be engineered as a new biosynthetic platform for the production of de novo fuels, commodity chemicals, and specialty chemicals. Previously, our investigations manipulated the first module of the lipomycin PKS to produce short chain ketones, 3-hydroxy acids, and saturated, branched carboxylic acids. Building upon this work, we have expanded to multi-modular systems by engineering the first two modules of lipomycin to generate unnatural polyketides as potential biofuels and specialty chemicals in Streptomyces albus. First, we produce 20.6 mg/L of the ethyl ketone, 4,6 dimethylheptanone through a reductive loop exchange in LipPKS1 and a ketoreductase knockouts in LipPKS2. We then show that an AT swap in LipPKS1 and a reductive loop exchange in LipPKS2 can produce the potential fragrance 3-isopropyl-6-methyltetrahydropyranone. Highlighting the challenge of maintaining product fidelity, in both bimodular systems we observed side products from premature hydrolysis in the engineered first module and stalled dehydration in reductive loop exchanges. Collectively, our work expands the biological design space and moves the field closer to the production of “designer” biomolecules.HighlightsEngineered lipomycin module 1 and module 2 to produce unnatural polyketides as valuable bio-based chemicalsA reductive loop swap and ketoreductase knockout used to produce 20 mg/mL of a novel ethyl ketone, a gasoline replacementAn acyltransferase swap and reductive loop swap successfully produced δ-lactone, a potential fragrant compoundIncomplete reduction and premature hydrolysis observed in engineered modulesCompeting Interest StatementJ.D.K. has a financial interest in Amyris, Lygos, Demetrix, Napigen, Maple Bio, Berkeley Brewing Sciences, Ansa Biotech and Apertor Labs.View Full Text

synthetic biology↗

bioRxiv2020

Spatial Transcriptional Mapping of the Human Nephrogenic Program

Congenital abnormalities of the kidney and urinary tract are amongst the most common birth defects affecting 3% of newborns. The human kidney develops over a 30-week period in which a nephron progenitor pool gives rise to around a million nephrons. To establish a framework for human nephrogenesis, we spatially resolved a stereotypical process by which equipotent nephron progenitors generate a nephron anlagen, then applied data-driven approaches to construct three-dimensional protein maps on anatomical models of the nephrogenic program. Single cell RNA sequencing identified novel progenitor states which were spatially mapped to the nephron anatomy enabling the generation of functional gene-networks predicting interactions within and between nephron cell-types. Network mining identified known developmental disease genes and predicts new targets of interest. The spatially resolved nephrogenic program made available through the Human Nephrogenesis Atlas (https://sckidney.flatironinstitute.org/) will facilitate an understanding of kidney development and disease, and enhance efforts to generate new kidney structures.

cell biology↗

bioRxiv2020

Chromosomal-level reference genome of the incense tree Aquilaria sinensis

Trees in the genus Aquilaria (Thymelaeaceae) are known as lign aloes, and are native to the forests of southeast Asia. Lign aloes produce agarwood as an antimicrobial defence. Agarwood has a long history of cultural and medicinal use, and is of considerable commercial value. However, due to habitat destruction and over collection, lign aloes are threatened in the wild. We present a chromosomal-level assembly for Aquilaria sinensis, a lign aloe endemic to China known as the incense tree, based on Illumina short-read, 10X Genomics linked-read, and Hi-C sequencing data. Our 783.8Mbp A. sinensis genome assembly is of high physical contiguity, with a scaffold N50 of 87.6Mbp, and high completeness, with a 95.8% BUSCO score for eudicotyledon genes. We include 17 transcriptomes from various plant tissues, providing a total of 35,965 gene models. We reveal the first complete set of genes involved in sesquiterpenoid production, plant defence, and agarwood production for the genus Aquilaria, including genes involved in the biosynthesis of sesquiterpenoids via the mevalonic acid (MVA), 1-deoxy-D-xylulose-5-phosphate (DXP), and methylerythritol phosphate (MEP) pathways. We perform a detailed repeat content analysis, revealing that transposable elements account for [~]61% of the genome, with major contributions from gypsy-like and copia-like LTR retroelements. We also provide a comparative analysis of repeat content across sequenced species in the order Malvales. Our study reveals the first chromosomal-level genome assembly for a tree in the genus Aquilaria and provides an unprecedented opportunity to address a variety of applied, genomic and evolutionary questions in the Thymelaeaceae more widely.

genomics↗

bioRxiv2020

Millipede genomes reveal unique adaptation of genes and microRNAs during myriapod evolution

The Myriapoda including millipedes and centipedes is of major importance in terrestrial ecology and nutrient recycling. Here, we sequenced and assembled two chromosomal-scale genomes of millipedes Helicorthomorpha holstii (182 Mb, N50 18.11 Mb mainly on 8 pseudomolecules) and Trigoniulus corallinus (449 Mb, N50 26.78 Mb mainly on 15 pseudomolecules). Unique defense systems, genomic features, and patterns of gene regulation in millipedes, not observed in other arthropods, are revealed. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules in centipedes. Sets of genes associated with anti-microbial activity are identified with proteomics, suggesting that the ozadene gland is not primarily an antipredator adaptation (at least in T. corallinus). Macro-synteny analyses revealed highly conserved genomic blocks between centipede and the two millipedes. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute proteins for loading small RNAs are duplicated in both millipedes, but unlike insects, an argonaute duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs, including species-specific microRNA arm switching that provide differential gene regulation is also obtained. Millipede genomes reveal a series of unique genomic adaptations and microRNA regulation mechanisms have occurred in this major lineage of arthropod diversity. Collectively, the two millipede genomes shed new light on this fascinating but poorly understood branch of life, with a highly unusual body plan and novel adaptations to their environment.

evolutionary biology↗

bioRxiv2019

Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection

Glaucoma surgeries, such as trabeculectomy, are performed to lower the intraocular pressure to reduce the risk of vision loss. The surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. However, the current knowledge of these ocular surface lymphatics remains limited. Here, we characterized the biology and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed by a primary lymphatic vessel that grows out from the nasal-side medial canthus region at the time of birth. This primary lymphatic vessel immediately branches out and invades the limbus and conjunctiva, and then simultaneously encircles the cornea in a bidirectional manner. As a result, the distribution of the ocular lymphatic is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic spouts are mainly produced from the nasal-side limbal lymphatics, posing the nasal side of the eye more responsive to fluid drainage and inflammatory stimuli. Consistently, when a fluorescent tracer was injected, fluid clearance was much more efficient in the nasal side than the temporal side of the eyes. In comparison, blood vessels are evenly distributed on the front surface of the eyes. We found that these distinct vascular distribution patterns were also conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a surgical site for glaucoma surgeries to improve the fluid drainage.

developmental biology↗

bioRxiv2019

Data-driven inference of crosstalk in the tumor microenvironment

Signaling between cancer and nonmalignant (stromal) cells in the tumor microenvironment (TME) is key to tumorigenesis yet challenging to decipher from tumor transcriptomes. Here, we report an unbiased, data-driven approach to deconvolute bulk tumor transcriptomes and predict crosstalk between ligands and receptors on cancer and stromal cells in the TME of 20 solid tumor types. Our approach recovers known transcriptional hallmarks of cancer and stromal cells and is concordant with single-cell and immunohistochemistry data, underlining its robustness. Pan-cancer analysis reveals previously unrecognized features of cancer-stromal crosstalk. We find that autocrine cancer cell cross-talk varied between tissues but often converged on known cancer signaling pathways. In contrast, many stromal cross-talk interactions were highly conserved across tumor types. Interestingly, the immune checkpoint ligand PD-L1 was overexpressed in stromal rather than cancer cells across all tumor types. Moreover, we predicted and experimentally validated aberrant ligand and receptor expression in cancer cells of basal and luminal breast cancer, respectively. Collectively, our findings validate a data-driven method for tumor transcriptome deconvolution and establishes a new resource for hypothesis generation and downstream functional interrogation of the TME in tumorigenesis and disease progression.

cancer biology↗

bioRxiv2019

Chemoinformatic-guided engineering of polyketide synthases

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge in PKS design is engineering a partially reductive module to produce a saturated {beta}-carbon through a reductive loop exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, could provide a viable strategy to reductive loop exchanges. We first introduced a set of donor reductive loops of diverse genetic origin and chemical substrate structures into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with atom pair chemical similarity between the substrate of the donor reductive loops and recipient LipPKS1, reaching a titer of 165 mg/L of short chain fatty acids produced by Streptomyces albus J1074 harboring these engineered PKSs. Expanding this method to larger intermediates requiring bimodular communication, we introduced reductive loops of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products.

biochemistry↗

bioRxiv2019

IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival

BackgroundBreast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ER and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity.\n\nMethodsWe performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR- BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) to identify signaling pathways encoded by our RNA-seq data set.\n\nResultsWe identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines.\n\nConclusionsOur 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

cancer biology↗

bioRxiv2019

A general approach to engineer positive-going eFRET voltage indicators

We engineered electrochromic fluorescence resonance energy transfer (eFRET) genetically encoded voltage indicators (GEVIs) with \"positive-going\" fluorescence response to membrane depolarization through rational manipulation of the native proton transport pathway in microbial rhodopsins. We transformed the state-of-the-art eFRET GEVI Voltron into Positron, with kinetics and sensitivity equivalent to Voltron but flipped fluorescence signal polarity. We further applied this general approach to GEVIs containing different voltage sensitive rhodopsin domains and various fluorescent dye and fluorescent protein reporters.

neuroscience↗

bioRxiv2019

The Arabidopsis Diacylglycerol Kinase 4 is involved in nitric oxide-dependent pollen tube guidance and fertilization

Nitric oxide (NO) is a key signaling molecule that regulates diverse biological processes in both animals and plants. In animals, NO regulates vascular wall tone, neurotransmission and immune response while in plants, NO is essential for development and responses to biotic and abiotic stresses [1-3]. Interestingly, NO is involved in the sexual reproduction of both animals and plants mediating physiological events related to the male gamete [2, 4]. In animals, NO stimulates sperm motility [4] and binding to the plasma membrane of oocytes [5] while in plants, NO mediates pollen-stigma interactions and pollen tube guidance [6, 7]. NO generation in pollen tubes (PTs) has been demonstrated [8] and intracellular responses to NO include cytosolic Ca2+ elevation, actin organization, vesicle trafficking and cell wall deposition [7, 9]. However, the NO-responsive proteins that mediate these responses are still elusive. Here we show that PTs of Arabidopsis lacking the pollen-specific Diacylglycerol Kinase 4 (DGK4) grow slower and become insensitive to NO-dependent growth inhibition and re-orientation responses. Recombinant DGK4 protein yields NO-responsive spectral and catalytic changes in vitro which are compatible with a role in NO perception and signaling in PTs. NO is a fast, diffusible gas and, based on our results, we hypothesize it could serve in long range signaling and/or rapid cell-cell communication functions mediated by DGK4 downstream signaling during the progamic phase of angiosperm reproduction.

plant biology↗

bioRxiv2019

Identifying TCDD-resistance genes via murine and rat comparative genomics and transcriptomics

The aryl hydrocarbon receptor (AHR) mediates many of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the AHR alone is insufficient to explain the widely different outcomes among organisms. Attempts to identify unknown factor(s) have been confounded by genetic variability of model organisms. Here, we evaluated three transgenic mouse lines, each expressing a different rat AHR isoform (rWT, DEL, and INS), as well as C57BL/6 and DBA/2 mice. We supplement these with whole-genome sequencing and transcriptomic analyses of the corresponding rat models: Long-Evans (L-E) and Han/Wistar (H/W) rats. These integrated multi-species genomic and transcriptomic data were used to identify genes associated with TCDD-response phenotypes.\n\nWe identified several genes that show consistent transcriptional changes in both transgenic mice and rats. Hepatic Pxdc1 was significantly repressed by TCDD in C57BL/6, rWT mice, and in L-E rat. Three genes demonstrated different AHRE-1 (full) motif occurrences within their promoter regions: Cxxc5 had fewer occurrences in H/W, as compared with L-E; Sugp1 and Hgfac (in either L-E or H/W respectively). These genes also showed different patterns of mRNA abundance across strains.\n\nThe AHR isoform explains much of the transcriptional variability: up to 50% of genes with altered mRNA abundance following TCDD exposure are associated with a single AHR isoform (30% and 10% unique to DEL and rWT respectively following 500 g/kg TCDD). Genomic and transcriptomic evidence allowed identification of genes potentially involved in phenotypic outcomes: Pxdc1 had differential mRNA abundance by phenotype; Cxxc5 had altered AHR binding sites and differential mRNA abundance.\n\nAuthor SummaryEnvironmental contaminants such as dioxins cause many toxic responses, anything from chloracne (common in humans) to death. These toxic responses are mostly regulated by the Ahr, a ligand-activated transcription factor with roles in drug metabolism and immune responses, however other contributing factors remain unclear. Studies are complicated by the underlying genetic heterogeneity of model organisms. Our team evaluated a number of mouse and rat models, including two strains of mouse, two strains of rat and three transgenic mouse lines which differ only at the Ahr locus, that present widely different sensitivities to the most potent dioxin: 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). We identified a number of changes to gene expression that were associated with different toxic responses. We then contrasted these findings with results from whole-genome sequencing of the H/W and L-E rats and found some key genes, such as Cxxc5 and Mafb, which might contribute to TCDD toxicity. These transcriptomic and genomic datasets will provide a valuable resource for future studies into the mechanisms of dioxin toxicities.

genomics↗

bioRxiv2019

Integrative analysis of Hydra head regeneration reveals activation of distal enhancer-like elements

The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role of cis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.

genomics↗

bioRxiv2018

Altered protein quality control contributes to noise-induced hearing loss

Exposure to damaging levels of noise is the most common cause of hearing loss and impairs high frequency hearing in more than 15 % of adult Americans. Using mice exposed to increasing levels of noise in combination with quantitative proteomics, we tested how noise insults remodel the cochlear proteome both acutely and after a two-week recovery period. We used ABR & DPOAE recordings to define the intensity of noise exposure necessary to produce temporary or permanent threshold shifts (TTS, PTS) in young adult mice and found noise at 94 and 105 dB SPL levels for 30 minutes elicits TTS and PTS, respectively. We quantified thousands of proteins and found that noise insults cause a rapid increase rather than a decrease in the levels of many proteins involved with protein homeostasis, myelin, cytoskeletal structures, and cell junctions such as the synapse. The vast majority of proteins with increased levels immediately after noise exposure showed normal levels after two weeks of recovery. However, several proteins involved in oxidative stress and neuroprotection had significantly increased levels only after the recovery period suggesting they play in important role in regeneration. Interestingly, a small panel of mitochondrial proteins were significantly altered only in PTS conditions suggesting potential discrete protein mechanisms. Our discovery-based proteomic analysis extends the recent description of noise-induced cochlear synaptopathy and shows that noise insults drive a robust proteostasis response. These data provide a new understanding of noise sensitive proteins and may inform the development of effective preventiative strategies or therapies for NIHL.

neuroscience↗

bioRxiv2018

High-performance GFP-based calcium indicators for imaging activity in neuronal populations and microcompartments

Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics, and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and tracking large populations of neurons using 2-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

neuroscience↗