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Biology subjects

Xu, B.

Publications and source records attributed to Xu, B..

At least 181 records · Page 10Linked to original sources

Cell cycle arrest explained the observed bulk 3D genomic alterations in response to long term heat shock for mammalian cells

Heat shock is a common environmental stress, while the response of the nucleus to it remains controversial in mammalian cells. Acute reaction and chronic adaptation to environmental stress may have distinct internal rewiring in the gene regulation networks. However, this difference remains largely unexplored. Here, we report that chromatin conformation and chromatin accessibility respond differently in short- and long-term heat shock in human K562 cells. Interestingly, we found that chromatin conformation in K562 cells was largely stable in response to short heat shock, while showed clear and characteristic changes after long-term heat treatment with little alteration in chromatin accessibility during the whole process. We further showed in silico and experimental evidence strongly suggesting that changes in chromatin conformation may largely stem from an accumulation of cells in the M stage of cell cycle in response to heat shock. Our results represent a paradigm shift away from the controversial view of chromatin response to heat shock and emphasize the necessity of cell cycle analysis while when interpreting bulk Hi-C data.

genomics↗

Mapping morphological malformation to genetic dysfunction in blood vessel organoids with 22q11.2 Deletion Syndrome

DiGeorge Syndrome, or 22q11.2 deletion syndrome (22q11.2 DS), is a genetic disorder caused by microdeletions in chromosome 22, impairing the function of endothelial cells (EC) and/or mural cells and leading to deficits in blood vessel development such as abnormal aortic arch morphology, tortuous retinal vessels, and tetralogy of Fallot. The mechanism by which dysfunctional endothelial cells and pericytes contribute to the vasculopathy, however, remains unknown. In this study, we used human blood vessel organoids (VOs) generated from iPSC of 22q11.2 DS patients to model the vascular malformations and genetic dysfunctions. We combined high-resolution lightsheet imaging and single-cell transcriptome analysis to link the genetic profile and vascular phenotype at the single-cell level. We developed a comprehensive analytical methodology by integrating deep learning-mediated blood vessel segmentation, network graph construction, and tessellation analysis for automated morphology characterization. We report that 22q11.2DS VOs demonstrate a smaller size with increased angiogenesis/sprouting, suggesting a less stable vascular network. Overall, clinical presentations of smaller vascular diameter, less connected vasculature, and increased branch points were recapitulated in 22q11.2DS VOs. Single-cell transcriptome profiling showed heterogeneity in both 22q11.2DS and control VOs, but the former demonstrated alterations in endothelial characteristics that are organ-specific and suggest a perturbation in the vascular developmental process. Intercellular communication analysis indicated that the vascular dysfunctions in 22q11.2 deletion were due to a lower cell-cell contact and upregulated extracellular matrix organization involving collagen and fibronectin. Voronoi diagram-based tessellation analysis also indicated that the colocalization of endothelial tubes and mural cells was different between control and 22q11.2 VOs, indicating that alterations in EC and mural interactions might contribute to the deficits in vascular network formation. This study illustrates the utility of VO in revealing the pathogenesis of 22q11.2DS vasculopathy.

bioengineering↗

Effects of perfluoroalkyl and polyfluoroalkyl substances on soil structure and function

Soils are impacted at a global scale by several anthropogenic factors, including chemical pollutants. Among those, perfluoroalkyl and polyfluoroalkyl substances (PFAS) are of concern due to their high environmental persistence, and as they might affect soil health and functions. However, data on impacts of PFASs on soil structure and microbially-driven processes are currently lacking. This study explored the effects of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorobutanesulfonic acid (PFBS) at environmental-relevant nominal concentrations (1 ~ 1000 ng g-1) on soil functions, using a 6-week microcosm experiment. We measured soil respiration, litter decomposition, enzyme and microbial activities, soil aggregates, and bacterial abundance. PFAS (even at 1 ng g-1 for PFBS) significantly increased litter decomposition, associated with positive effects on bacterial abundance, and {beta}-glucosidase activities. This effect increased with PFAS concentrations. Soil respiration was significantly inhibited by PFAS in the 3rd week, while this effect was more variable in week 6. Water-stable aggregates were negatively affected by PFOS and PFOA, possibly related to microbial shifts. The general microbial activities and {beta}-D-cellobiosidase and phosphatase activities were barely affected by PFAS treatments. Our work highlights the potential effects of PFAS on soil health, and we argue that this substance class could be a factor of environmental change of potentially broad relevance in terrestrial ecosystem functioning. SynopsisPFAS are likely to affect soil health. Abstract Art O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/465889v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@88c630org.highwire.dtl.DTLVardef@18b985corg.highwire.dtl.DTLVardef@1bfdc81org.highwire.dtl.DTLVardef@125b09e_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Glucocorticoid signaling delays castration-induced regression in murine models of prostate cancer

Androgen deprivation therapy (ADT) induces regression of recurrent and advanced prostate cancer (PrCa), but many tumors recur. To understand the response to ADT, changes in tumor volume were imaged after castration of murine PrCa models. While mouse (non-tumor) prostate begins to regress within two days of castration, murine PrCa regresses after a delay of 3-14 days in two distinct mouse models. Intra-tumoral androgens are undetectable after castration, but tumor cells proliferate during this period. Intratumoral glucocorticoids and glucocorticoid receptor (GR) protein increase, as does GR mRNA and a set of GR-regulated genes specifically in tumor epithelial cells identified using scRNAseq. A selective GR antagonist (CORT125281, relacorilant), in clinical trials for late-state PrCa, eliminates the delayed regression phenotype in both models. Thus, activated GR signaling and murine tumor proliferation following castration resembles the GR-dependent escape mechanism of castrate resistant PrCa. These results suggest simultaneous inhibition of GR and androgen receptor signaling could improve PrCa therapy. In briefAndrogen deprivation therapy for high risk and recurrent prostate cancers is initially effective, but ultimately fails; better understanding the mechanisms should improve therapy. In two murine prostate cancer models, GR signaling is activated immediately following castration, substituting for the acute reduction in AR signaling, and allowing for continued tumor growth. This continued growth is blocked by relacorilant, selective GR antagonist in clinical trials for late-state PrCa. HighlightsO_LIAndrogen deprivation therapy induces regression of prostate cancer, but tumors recur C_LIO_LIMurine PrCa continues to proliferate for 3-14 days in two distinct mouse prostate cancer models C_LIO_LITumor cells proliferate during this period, and intratumoral glucocorticoids and glucocorticoid receptor (GR) protein increase, as does GR mRNA and a set of GR-regulated genes C_LIO_LIRelacorilant, a selective GR antagonist in clinical trials for late-state PrCa, eliminates the delayed regression C_LI

cancer biology↗

An Attempt to Develop an Aptamer Lateral-Flow Assay (ALFA) for Easy, Rapid, and Sensitive Detection of Lethal Mushroom Toxin α-amanitin

Amatoxins contribute to the majority of mushroom poisoning, most prominently, -amanitin. Since mushroom is a common foodstuff worldwide, an easy, rapid, sensitive test for -amanitin is needed. Several detection methods for -amanitin have been developed, including HPLC, LC-MS, and ELISA, and LFIA. Aptamers have several advantages compared to antibodies: easy development via SELEX, longer shelf life, and higher temperature- and pH-tolerance. Aptamer Lateral Flow Assay (ALFA) is a similar technology compared to LFIA but incorporates aptamers as target-recognizing agents. This study attempted to develop an ALFA test strip for -amanitin using a previously-developed aptamer, however failure of generating a colorimetric readout at the test line is persisted throughout all experiments, even though the concept is fully-proved and the control line functions normally. The failure is attributed to the small size of the molecule, leading to immobilization difficulties on the nitrocellulose membrane to form the test line, and the hindering of effective "surround" mechanism of aptamer-target binding (instead of "adhere", when the target molecule is large, e.g. a protein). It is concluded that ALFAs for small-molecules whose aptamer-target interaction has not yet been studied and modelled in detail remains a challenge, despite ALFAs large potential.

molecular biology↗

STAYGREEN-mediated chlorophyll a catabolism is critical for photosystem stability upon heat stress in ryegrass

Chlorophyll (Chl) loss is one of the most visible symptoms of heat-induced leaf senescence, especially for cool-season grass species. Suppression of the Chl a Me-dechelatase gene, SGR (also named as nye1), blocked the degradation of Chl a and resulted in the stay-green trait during leaf senescence. However, effect of Chl a catabolism on plant tolerance to long-term moderate heat stress (35-40{degrees}C) remains unclear. In this study, we suppressed the expression of Chl a catabolic gene, LpSGR, in both constitutive and inducible manners in perennial ryegrass. Constitutive suppression of LpSGR aggravated heat stress-induced chloroplast structure and photosystem damages, disrupted energy utilization/dissipation during photosynthesis, activated ROS generation with weakened ROS-scavenging enzyme activities. Transcriptome comparison among wildtype (WT) and transgenic RNAi plants under either the optimum or high temperature conditions also emphasized the effect of Chl a catabolism on expression of genes encoding photosynthesis system, ROS-generation and scavenging system, and heat shock transcription factors. Furthermore, making use of a modified ethanol-inducible system, we generated stable transgenic perennial ryegrass to suppress LpSGR in an inducible manner. Without ethanol induction, these transgenic lines exhibited the same growth and heat tolerance traits to WT, while under the induction of ethanol spray, the transgenic lines also showed compromised heat tolerance. Taken together, our data suggest that Chl a catabolism is critical for energy dissipation and electron transfer in photosynthesis, ROS-balancing and chloroplast membrane system stability upon long-term moderate heat stress.

plant biology↗

Rapid visual CRISPR assay: a naked-eye colorimetric detection method for nucleic acids based on CRISPR/Cas12a and convolutional neural network

Rapid diagnosis based on naked-eye colorimetric detection remains challenging, but it could build new capacities for molecular point-of-care testing (POCT). In this study, we evaluated the performance of 16 types of single-stranded DNA-fluorophore-quencher (ssDNA-FQ) reporters for use with CRISPR/Cas12a based visual colorimetric assays. Among them, 9 ssDNA-FQ reporters were found to be suitable for direct visual colorimetric detection, with especially very strong performance using ROX-labeled reporters. We optimized the reaction concentrations of these ssDNA-FQ reporters for naked-eye read-out of assay results (no transducing component required for visualization). Subsequently, we developed a convolutional neural network algorithm standardize and to automate the analytical colorimetric assessment of images and integrated this into the MagicEye mobile phone software. A field-deployable assay platform named RApid VIsual CRISPR (RAVI-CRISPR) based on a ROX-labeled reporter with isothermal amplification and CRISPR/Cas12a targeting was established. We deployed RAVI-CRISPR in a single tube towards an instrument-less colorimetric POCT format that requires only a portable rechargeable hand warmer for incubation. The RAVI-CRISPR was successfully used for the single-copy detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and African swine fever virus (ASFV). Our study demonstrates this novel RAVI-CRISPR system for distinguishing different pathogenic nucleic acid targets with high specificity and sensitivity as the simplest-to-date platform for rapid pen-side testing.

molecular biology↗

Selectively expressing SARS-CoV-2 Spike protein S1 subunit in cardiomyocytes induces cardiac hypertrophy in mice.

Cardiac injury is common in hospitalized COVID-19 patients and portends poorer prognosis and higher mortality. To better understand how SARS-CoV-2 (CoV-2) damages the heart, it is critical to elucidate the biology of CoV-2 encoded proteins, each of which may play multiple pathological roles. For example, CoV-2 Spike glycoprotein (CoV-2-S) not only engages ACE2 to mediate virus infection, but also directly impairs endothelial function and can trigger innate immune responses in cultured murine macrophages. Here we tested the hypothesis that CoV-2-S damages the heart by activating cardiomyocyte (CM) innate immune responses. HCoV-NL63 is another human coronavirus with a Spike protein (NL63-S) that also engages ACE2 for virus entry but is known to only cause moderate respiratory symptoms. We found that CoV-2-S and not NL63-S interacted with Toll-like receptor 4 (TLR4), a crucial pattern recognition receptor that responsible for detecting pathogen and initiating innate immune responses. Our data show that the S1 subunit of CoV-2-S (CoV-2-S1) interacts with the extracellular leucine rich repeats-containing domain of TLR4 and activates NF-kB. To investigate the possible pathological role of CoV-2-S1 in the heart, we generated a construct that expresses membrane-localized CoV-2-S1 (S1-TM). AAV9-mediated, selective expression of the S1-TM in CMs caused heart dysfunction, induced hypertrophic remodeling, and elicited cardiac inflammation. Since CoV-2-S does not interact with murine ACE2, our study presents a novel ACE2-independent pathological role of CoV-2-S, and suggests that the circulating CoV-2-S1 is a TLR4-recognizable alarmin that may harm the CMs by triggering their innate immune responses.

pathology↗

Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response. One Sentence SummaryA herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression

microbiology↗

Chronic opioid treatment arrests neurodevelopment and alters synaptic activity in human midbrain organoids

The impact of long-term opioid exposure on the embryonic brain is crucial to healthcare due to the surging number of pregnant mothers with an opioid dependency. Current studies on the neuronal effects are limited due to human brain inaccessibility and cross-species differences among animal models. Here, we report a model to assess cell-type specific responses to acute and chronic fentanyl treatment, as well as fentanyl withdrawal, using human induced pluripotent stem cell (hiPSC)-derived midbrain organoids. Single cell mRNA sequencing (25,510 single cells in total) results suggest that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters the pathways associated with synaptic activities and neuron projection. Acute fentanyl treatment, however, increases dopamine release but does not induce significant changes in gene expressions of cell lineage development. To date, our study is the first unbiased examination of midbrain transcriptomics with synthetic opioid treatment at the single cell level.

neuroscience↗

CovidExpress: an interactive portal for intuitive investigation on SARS-CoV-2 related transcriptomes

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans could cause coronavirus disease 2019 (COVID-19). Since its first discovery in Dec 2019, SARS-CoV-2 has become a global pandemic and caused 3.3 million direct/indirect deaths (2021 May). Amongst the scientific communitys response to COVID-19, data sharing has emerged as an essential aspect of the combat against SARS-CoV-2. Despite the ever-growing studies about SARS-CoV-2 and COVID-19, to date, only a few databases were curated to enable access to gene expression data. Furthermore, these databases curated only a small set of data and do not provide easy access for investigators without computational skills to perform analyses. To fill this gap and advance open-access to the growing gene expression data on this deadly virus, we collected about 1,500 human bulk RNA-seq datasets from publicly available resources, developed a database and visualization tool, named CovidExpress (https://stjudecab.github.io/covidexpress). This open access database will allow research investigators to examine the gene expression in various tissues, cell lines, and their response to SARS-CoV-2 under different experimental conditions, accelerating the understanding of the etiology of this disease to inform the drug and vaccine development. Our integrative analysis of this big dataset highlights a set of commonly regulated genes in SARS-CoV-2 infected lung and Rhinovirus infected nasal tissues, including OASL that were under-studied in COVID-19 related reports. Our results also suggested a potential FURIN positive feedback loop that might explain the evolutional advantage of SARS-CoV-2.

bioinformatics↗

The pitfalls of using Gaussian Process Regression for normative modeling

Normative modeling, a group of methods used to quantify an individuals deviation from some expected trajectory relative to observed variability around that trajectory, has been used to characterize subject heterogeneity. Gaussian Processes Regression includes an estimate of variable uncertainty across the input domain, which at face value makes it an attractive method to normalize the cohort heterogeneity where the deviation between predicted value and true observation is divided by the derived uncertainty directly from Gaussian Processes Regression. However, we show that the uncertainty directly from Gaussian Processes Regression is irrelevant to the cohort heterogeneity in general.

neuroscience↗

Revealing cell-fate bifurcations from transcriptomic trajectories of hematopoiesis

Inspired by Waddingtons illustration of an epigenetic landscape, cell-fate transitions have been envisioned as bifurcating dynamical systems, wherein the dynamics of an exogenous signal couples to a cells enormously complex signaling and transcriptional machinery, eliciting a qualitative transition in the collective state of a cell - its fate. It remains unclear, however, whether the dynamical systems framework can go beyond a word-based caricature of the system and provide sharp quantitative insights that further our understanding of differentiation. Single-cell RNA sequencing (scRNA-seq), which measures the distributions of possible transcriptional states in large populations of differentiating cells, provides an alternate view, in which development is marked by the individual concentration variations of a myriad of genes. Here, starting from formal mathematical derivations, we challenge these transcriptomic trajectories to a rigorous statistical evaluation of whether they display signatures consistent with bifurcations. After pinpointing bifurcations along transcriptomic trajectories of the neutrophil branch of hematopoeitic differentiation we are able to further leverage the primitive features of a linear instability to identify the single-direction in gene expression space along which the bifurcation unfolds and identify possible gene contributors. This scheme identifies transcription factors long viewed to play a crucial role in the process of neutrophil differentiation in addition to identifying a host of other novel genetic players. Most broadly speaking, we provide evidence that, though very high-dimensional, a bifurcating dynamical systems formalism might be appropriate for the process of cellular differentiation and that it can be leveraged to provide insights. Ambitiously, our work attempts to take a step beyond data-analysis and towards the construction of falsifiable mathematical models that describe the dynamics of the entire transcriptome.

biophysics↗

Interaction of the Causal Agent of Apricot bud gall Acalitus phloeocoptes (Nalepa) with Apricot: Implications in Infested Tissues

Apricot bud gall mite, Acalitus phloeocoptes (Nalepa), is a destructive arthropod pest that causes significant economic losses to apricot trees worldwide. Infested bud examination revealed that the starch granules in the bud axon were extended at the onset of the attack. During the later stages of the attack, the cytoplasm was distributed in apricot. The results also demonstrated that the accumulation of large amounts of cytokinin (zeatin, ZT) and auxin (indoleacetic acid, IAA) led to rapid bud proliferation during the rapid growth period. Abscisic acid (ABA) controls the development of gall buds and plays a vital role in gall bud maturity. The reduction of gibberellic acid (GA3) content led to rapid lignification at the later phase of bud development. Our results reveal the mechanism underlying the interaction of apricot bud gall with its parasite and provide reliable information for designing valuable breeding programs. This study will be quite useful for pest management and will provide a comprehensive evaluation of ecology-based cost-effective control, life history and demographic parameters of A. phloeocoptes.

microbiology↗

Cypripedium wardii (Orchidaceae) employs pseudopollen with both reward and deception to attract both flis and bees as pollinators

O_LIFlowering plants always attract animals providing rewards or deceptive signals to gain reproductive success. However, there is no well-documented reporting about a pollination mechanism with both rewards and deceptive signals by a same object. We found Cypripedium wardii flowers seem to attract visitors by the white pseudopollenlike trichomes on labella in our preliminary field observation. C_LIO_LITo explore the pollination mechanism of Cypripedium wardii, especially, the ecological function of the pseudopollen-like trichomes, we conducted field observations, analyses of the traits of visitors and flowers, and breeding system experiments. C_LIO_LIThe white trichomes composed by multicellular moniliform hairs on the floral labella played a crucial role to attract pollinators, causing a high natural fruit set ratio in C. wardii. We established the direct connection of the white trichomes and real pollen. C_LIO_LIWe propose that flowers of C. wardii provide pseudopollen to attract suitable bees and hoverflies as pollinators. And our evidence indicate that the pseudopollen owns both deceptive and rewarding ecological functions. Our study provide a clear pollination mechanism with both rewards and deceptive signals by a same object in angiosperm for the first time. However, an inbreeding depression seem to be caused by this strategy. And we speculated that the pollen mimicry strategy with both rewarding and deceptive functions in C. wardii may be an adaptation to the habitat fragmentation of this species to gain a reproductive assurance. C_LI

plant biology↗

Maxent modeling for predicting the potential distribution of global talaromycosis

Talaromycosis, an invasive mycosis caused by Talaromyces marneffei (Tm), has rapidly increased in recent years, becoming an emerging pathogenic fungal disease. However, The driving factors and potential distribution of global talaromycosis is still unclear. Here, we developed maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic to forecast ecological niche of talaromycosis worldwhile, as well as Identify the drivering factors. The constructed model had excellent performance with the area under the curve (AUC) of the receiver operating curve (ROC) of 0.997 in training data and 0.991 in testing data. Our model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting talaromycosis distribution. In addition to traditional talaromycosis epidemic areas (South of the Yangtze River in China, Southeast Asian and North and Northeast India), our model also identified other potential epidemic regions, inculding parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Our findings has redefined global talaromycosis, discovered hidden high-risk areas and prorvided insights about driving factors of talaromycosis distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against Tm infections. Author SummaryOur study aims to explore the spatial ecology of talaromycosis worldwhile. The diseases burden of Talaromycosis, a neglected zoonotic disease, is continuously rising in recent years because of the sheer size of susceptible population in the setting of increased globalization, rising HIV prevalence, and emerging iatrogenic immunodeficiency conditions. Here, we used historic reported talaromycosis cases from 1964 to 2017, combined with environmental factors, Rhizomys distribution and HIV/AIDS epidemic to build an maxent ecology model to define the ecological niche of talaromycosis, then predicting the potential distribution of the disease. The ecological niche of talaromycosis is characterized by a concentrated distribution, which can be cognitively divided into two regions: traditional talaromycosis epidemic areas (South of the Yangtze River in China, Southeast Asian and North and Northeast India), while other potential epidemic regions were predicted in parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Our model also identified 5 driving factors affecting talaromycosis distribution. These findings will help demonstrate the global distribution of talaromycosis, discover hidden high-risk areas, and improve the effectiveness of public health interventions against Tm infections.

ecology↗

The Dynamic Continuum of Nanoscale Peptide Assemblies Facilitates Endocytosis and Endosomal Escape

Considerable number of works have reported alkaline phosphatase (ALP) enabled intracellular targeting by peptide assemblies, but little is known how these substrates of ALP enters cells. Here we show that the nanoscale assemblies of phosphopeptides, as a dynamic continuum, cluster ALP to enable caveolae mediated endocytosis (CME) and eventual endosomal escape. Specifically, fluorescent phosphopeptides, as substrates of tissue nonspecific alkaline phosphatase (TNAP), undergo enzyme catalyzed self-assembly to form nanofibers. As shown by live cell imaging, the nanoparticles of phosphopeptides, being incubated with HEK293 cells overexpressing red fluorescent protein-tagged TNAP (TNAP-RFP), cluster TNAP-RFP in lipid rafts to enable CME, further dephosphorylation of the phosphopeptides form the peptide nanofibers for endosomal escape inside cells. Inhibiting TNAP, cleaving the membrane anchored TNAP, or disrupting lipid rafts abolishes the endocytosis. Moreover, decreasing the formation of peptide nanofibers prevents the endosomal escape. As the first study establishing a dynamic continuum of supramolecular assemblies for cellular uptake, this work not only illustrates an effective design for enzyme responsive supramolecular therapeutics, but also provides mechanism insights for understanding the dynamics of cellular uptakes of proteins or exogenous peptide aggregates at nanoscale.

biochemistry↗

A low-cost, long-term underwater camera trap network coupled with deep residual learning image analysis

AO_SCPLOWBSTRACTC_SCPLOWO_LIUnderstanding long-term trends in marine ecosystems requires accurate and repeatable counts of fishes and other aquatic organisms on spatial and temporal scales that are difficult or impossible to achieve with diver-based surveys. Long-term, spatially distributed cameras, like those used in terrestrial camera trapping, have not been successfully applied in marine systems due to limitations of the aquatic environment. C_LIO_LIHere, we develop methodology for a system of low-cost, long-term camera traps (Dispersed Environment Aquatic Cameras), deployable over large spatial scales in remote marine environments. We use machine learning to classify the large volume of images collected by the cameras. We present a case study of these combined techniques use by addressing fish movement and feeding behavior related to grazing halos, a well-documented benthic pattern in shallow tropical reefscapes. C_LIO_LICameras proved able to function continuously underwater at deployed depths (up to 7 m, with later versions deployed to 40 m) with no maintenance or monitoring for over five months, and collected time-lapse images during daylight hours for a total of over 100,000 images. Our ResNet-50-based deep learning model achieved 92.5% overall accuracy in sorting images with and without fish, and diver surveys revealed that the camera images accurately represented local fish communities. C_LIO_LIThe cameras and machine learning classification represent the first successful method for broad-scale underwater camera trap deployment, and our case study demonstrates the cameras potential for addressing questions of marine animal behavior, distributions, and large-scale spatial patterns. C_LI

ecology↗