Biology subjects

Song, S.

Publications and source records attributed to Song, S..

At least 163 records · Page 9Linked to original sources

bioRxiv2020

Opposing neural signals of CaV1-encoded peptides are tuned by C-terminus mediated inhibition

L-type calcium (CaV1) channels regulate gene expressions via the cascade of excitation-transcription coupling, or directly as standalone CCAT (Calcium Channel Associated Transcriptional-regulator) peptides encoding distal carboxyl-terminus (DCT) of CaV1, both evidenced in dendritogenesis signaling in neurons. We here discover that DCT peptides opposedly mediate these two sets of transcription signals, all tunable in accordance to C-terminus mediated inhibition (CMI) of Ca2+/CaV1 influx. By electrophysiology, neurite morphology, and FRET 2-hybrid binding analyses, we systematically examined native and derived DCT peptides across CaV1, unveiling that the overall balance between cytosolic inhibition versus nuclear facilitation is spatially and temporally tuned by CMI of each DCT variant. Our findings not only resolve several controversies existing to DCT variants, but also propose a de novo scheme of CaV1-centric gene regulation: two concurrent routes of transcription signals initiated from either membrane CaV1 channels or nuclear CaV1-encoded peptides are subject to autonomous feedback tuning by peptide/channel interactions.

neuroscience↗

bioRxiv2020

SnpReady for Rice (SR4R) Database

The information commons for rice (IC4R) database is a collection of [~]18 million SNPs (single nucleotide polymorphisms) identified by the resequencing of 5,152 rice accessions. Although IC4R offers ultra-high density rice variation map, these raw SNPs are not readily usable for the public. To satisfy different research utilizations of SNPs for population genetics, evolutionary analysis, association studies and genomic breeding in rice, the raw genotypic data of the 18 million SNPs were processed by unified bioinformatics pipelines. The outcomes were used to develop a daughter database of IC4R - SnpReady for Rice (SR4R). The SR4R presents four reference SNP panels, including 2,097,405 hapmapSNPs after data filtration and genotype imputation, 156,502 tagSNPs selected from linkage disequilibrium (LD)-based redundancy removal, 1,180 fixedSNPs selected from genes exhibiting selective sweep signatures, and 38 barcodeSNPs selected from DNA fingerprinting simulation. SR4R thus offers a highly efficient rice variation map that combines reduced SNP redundancy with extensive data describing the genetic diversity of rice populations. In addition, SR4R provides rice researchers with a web-interface that enables them to browse all four SNP panels, use online toolkits, and retrieve the original data and scripts for a variety of population genetics analyses on local computers. The SR4R is freely available to academic users at http://sr4r.ic4r.org/.

bioinformatics↗

bioRxiv2019

Using force data to self-pace an instrumented treadmill and measure self-selected walking speed

BackgroundSelf-selected speed is an important functional index of walking. A self-pacing controller that reliably matches walking speed without additional hardware can be useful for measuring self-selected speed in a treadmill-based laboratory. MethodsWe adapted a previously proposed self-pacing controller for force-instrumented treadmills and validated its use for measuring self-selected speeds. We first evaluated the controllers estimation of subject speed and position from the force-plates by comparing it to those from motion capture data. We then compared five tests of self-selected speed. Ten healthy adults completed a standard 10-meter walk test, a 150-meter walk test, a commonly used manual treadmill speed selection test, a two-minute self-paced treadmill test, and a 150-meter self-paced treadmill test. In each case, subjects were instructed to walk at or select their comfortable speed. We also assessed the time taken for a trial and a survey on comfort and ease of choosing a speed in all the tests. ResultsThe self-pacing algorithm estimated subject speed and position accurately, with root mean square differences compared to motion capture of 0.023 m s-1 and 0.014 m, respectively. Self-selected speeds from both self-paced treadmill tests correlated well with those from the 10-meter walk test (R > 0.93, p < 1 x 10-13). Subjects walked slower on average in the self-paced treadmill tests (1.23 {+/-} 0.27 m s-1) than in the 10-meter walk test (1.32 {+/-} 0.18 m s-1) but the speed differences within subjects were consistent. These correlations and walking speeds are comparable to those from the manual treadmill speed selection test (R = 0.89, p = 3 x 10-11; 1.18 {+/-} 0.24 m s-1). Comfort and ease of speed selection were similar in the self-paced tests and the manual speed selection test, but the self-paced tests required only about a third of the time to complete. Our results demonstrate that these self-paced treadmill tests can be a strong alternative to the commonly used manual treadmill speed selection test. ConclusionsThe self-paced force-instrumented treadmill well adapts to subject walking speed and reliably measures self-selected walking speeds. We provide the self-pacing software to facilitate use by gait researchers and clinicians.

bioengineering↗

bioRxiv2019

Separating overlapping bat calls with a bi-directional long short-term memory network

Acquiring clear and usable audio recordings is critical for acoustic analysis of animal vocalizations. Bioacoustics studies commonly face the problem of overlapping signals, but the issue is often ignored, as there is currently no satisfactory solution. This study presents a bi-directional long short-term memory (BLSTM) network to separate overlapping bat calls and reconstruct waveform audio sounds. The separation quality was evaluated using seven temporal-spectrum parameters. The applicability of this method for bat calls was assessed using six different species. In addition, clustering analysis was conducted with separated echolocation calls from each population. Results showed that all syllables in the overlapping calls were separated with high robustness across species. A comparison between the seven temporal-spectrum parameters showed no significant difference and negligible deviation between the extracted and original calls, indicating high separation quality. Clustering analysis of the separated echolocation calls also produced an accuracy of 93.8%, suggesting the reconstructed waveform sounds could be reliably used. These results suggest the proposed technique is a convenient and automated approach for separating overlapping calls using a BLSTM network. This powerful deep neural network approach has the potential to solve complex problems in bioacoustics. Author summaryIn recent years, the development of recording techniques and devices in animal acoustic experiment and population monitoring has led to a sharp increase in the volume of sound data. However, the collected sound would be overlapped because of the existence of multiple individuals, which laid restrictions on taking full advantage of experiment data. Besides, more convenient and automatic methods are needed to cope with the large datasets in animal acoustics. The echolocation calls and communication calls of bats are variable and often overlapped with each other both in the recordings from field and laboratory, which provides an excellent template for research on animal sound separation. Here, we firstly solved the problem of overlapping calls in bats successfully based on deep neural network. We built a network to separate the overlapping calls of six bat species. All the syllables in overlapping calls were separated and we found no significant difference between the separated syllables with non-overlapping syllables. We also demonstrated an instance of applying our method on species classification. Our study provides a useful and efficient model for sound data processing in acoustic research and the proposed method has the potential to be generalized to other animal species.

ecology↗

bioRxiv2019

Visual impairment, spectacle wear and academic performance among junior high school students in western China

In September 2013, 2248 students from 36 junior high schools in Shaanxi Province underwent assessment of visual acuity (VA), completed a questionnaire about their spectacle use and were administered a standardized mathematics examination. Among 2,248 students (mean age 13.6 years, 52% male), visual impairment was present in 699 (31%, 95% Confidence Interval 29-33%). Spectacle wear was observed in 360 of 966 children needing glasses (37%). Ownership of spectacles among children needing glasses was associated with poorer uncorrected vision in the better-seeing eye (P <0.001) and paternal educational (p=0.001), but not age, sex, boarding at school, both parents having out-migrated for work or maternal education. Spectacle ownership among children with visual impairment was associated with better test performance (P=0.035). Therefore, visual impairment and non-wear of spectacle were common. Wearing spectacles was associated with better academic performance in this cross-sectional analysis, consistent with recent trial results among younger children.

scientific communication and education↗

bioRxiv2019

Comprehensive molecular characterization of PRKCG for glioma diagnosis, prognosis and treatment prediction

Glioma is one of the most common malignant brain tumors and exhibits low resection rate and high recurrence risk. Although a large number of glioma studies powered by high-throughput sequencing technologies have led to massive multi-omics datasets, there lacks of comprehensive integration of glioma datasets for uncovering candidate biomarker genes. In this study, we collected a large-scale assemble of multi-omics multi-cohort datasets from worldwide public resources, involving a total of 16,939 samples across 19 independent studies. Through comprehensive multi-omics molecular profiling across different datasets, we revealed that PRKCG (Protein Kinase C Gamma), a brain-specific gene detectable in cerebrospinal fluid, is closely associated with glioma. Specifically, it presents lower expression and higher methylation in glioma samples compared with normal samples. PRKCG expression/methylation change from high to low is indicative of glioma progression from low-grade to high-grade and high RNA expression is suggestive of good survival. Importantly, PRKCG in combination with MGMT is effective to predict survival outcomes after TMZ chemotherapy in a more precise manner. Collectively, PRKCG bears the great potential for glioma diagnosis, prognosis and therapy, and PRKCG-like genes may represent a set of important genes associated with different molecular mechanisms in glioma tumorigenesis. Accordingly, our study indicates the importance of computational integrative multi-omics data analysis and represents a data-driven scheme toward precision tumor subtyping and accurate personalized healthcare. Author SummaryGlioma is a type of brain tumors that represents one of the most lethal human malignancies with little chance for recovery. Nowadays, more and more studies have adopted high-throughput sequencing technologies to decode the molecular profiles of glioma from different omics levels, accordingly resulting in massive glioma datasets generated from different projects and laboratories throughout the world. Therefore, it has become crucially important on how to make full use of these valuable datasets for computational identification of glioma candidate biomarker genes in aid of precision tumor subtyping and accurate personalized treatment. In this study, we comprehensively integrated glioma datasets from all over the world and performed multi-omics molecular data mining. We revealed that PRKCG, a brain-specific gene abundantly expressed in cerebrospinal fluid, bears the great potential for glioma diagnosis, prognosis and treatment prediction, which has been consistently observed on multiple independent datasets. In the era of big data, our study highlights the significance of computational integrative data mining toward precision medicine in cancer research.

bioinformatics↗

bioRxiv2019

Globins and hemogenic cells in the marine Annelid Platynereis dumerilii shed new light on blood evolution in Bilaterians

BackgroundHow vascular systems and their respiratory pigments evolved is still debated. While many animals present a vascular system, hemoglobin exists as a blood pigment only in a few groups (Vertebrates, Annelids, a few Arthropod and Mollusk species). Hemoglobins are formed of globin sub-units, belonging to multigene families, in various multimeric assemblages. It was so far unclear whether hemoglobin families from different Bilaterian groups had a common origin. ResultsTo unravel globin evolution in Bilaterians, we studied the marine Annelid Platynereis dumerilii, a species with a slow evolving genome. Platynereis exhibits a closed vascular system filled with extracellular hemoglobin. Platynereis genome and transcriptomes reveal a family of 19 globins, nine of which are predicted to be extracellular. Extracellular globins are produced by specialized cells lining the vessels of the segmental appendages of the worm, serving as gills, and thus likely participate in the assembly of the giant hexagonal bilayer hemoglobin of the worm. Extracellular globin mRNAs are absent in smaller juvenile, accumulate considerably in growing and more active worms and peak in swarming adults, as the need for O2 culminates. Next, we conducted a Metazoan-wide phylogenetic analysis of globins using data from complete genomes. We establish that five globin genes (stem globins) were present in the last common ancestor of Bilaterians. Based on these results, we propose a new nomenclature of globins, with five clades. All five ancestral stem-globin clades are retained in some Spiralians, while some clades disappeared early in Deuterostome and Ecdysozoan evolution. All known Bilaterian blood globin families are grouped in a single clade (clade I) together with intracellular globins of Bilaterians devoid of red blood. ConclusionsWe uncover a complex "pre-blood" evolution of globins, with an early gene radiation in ancestral Bilaterians. Circulating hemoglobins in various bilaterian groups evolved convergently, presumably in correlation with animal size and activity. However, all hemoglobins derive from a clade I globin, or cytoglobin, probably involved in intracellular O2 transit and regulation (clade I). The Annelid Platynereis is remarkable in having a large family of extracellular blood globins, while retaining all clades of ancestral Bilaterian globins.

evolutionary biology↗

bioRxiv2019

Saak Transform-Based Machine Learning for Light-Sheet Imaging of Cardiac Trabeculation

Recent advances in light-sheet fluorescence microscopy (LSFM) enable 3-dimensional (3-D) imaging of cardiac architecture and mechanics in toto. However, segmentation of the cardiac trabecular network to quantify cardiac injury remains a challenge. We hereby employed \"subspace approximation with augmented kernels (Saak) transform\" for accurate and efficient quantification of the light-sheet image stacks following chemotherapy-treatment. We established a machine learning framework with augmented kernels based on the Karhunen-Loeve Transform (KLT) to preserve linearity and reversibility of rectification. The Saak transform-based machine learning enhances computational efficiency and obviates iterative optimization of cost function needed for neural networks, minimizing the number of training data sets to three 2-D slices for segmentation in our scenario. The integration of forward and inverse Saak transforms serves as a light-weight module to filter adversarial perturbations and reconstruct estimated images, salvaging robustness of existing classification methods. The accuracy and robustness of the Saak transform are evident following the tests of dice similarity coefficients and various adversary perturbation algorithms, respectively. The addition of edge detection further allows for quantifying the surface area to volume ratio (SVR) of the myocardium in response to chemotherapy-induced cardiac remodeling. The combination of Saak transform, random forest, and edge detection augments segmentation efficiency by 20-fold as compared to manual processing; thus, establishing a robust framework for post light-sheet imaging processing, creating a data-driven machine learning for 3-D quantification of cardiac ultra-structure.

bioengineering↗

bioRxiv2019

Breeding of a high-yield strain for commercial cultivation by crossing Pholiota adiposa and P. limonella

Pholiota adiposa is an edible mushroom with excellent nutritional and medicinal properties. However, fruiting body yields are low, and the commercial cultivation potential of this fungus is limited. In the present study, 279 crossbred strains were obtained by mono-mono crossing of monokaryotic strains derived from P. adiposa HS5 and P. limonella HS4. Ligninolytic enzymes and mycelial growth rate were used as markers to screen the crossbred strains, and 18 were selected for further analysis. Crossbred strain A10B4 displayed the highest yield, i.e., 165.91 {+/-} 12.56 g per bag, which was 31.34 g and 74.48 g more than that of strains HS5 and HS4, respectively. The mycelial colonization time of A10B4 was 25.18 {+/-} 1.33 days, which was 5.64 days shorter than that of HS5. A10B4 was characterized by inter-simple sequence repeat molecular markers and antagonism tests. Differences in PCR products from parental and crossbred strains were observed. Therefore, the newly developed hybrid strain A10B4, named P. adiposa-limonella HS54 and having a high yield and desirable traits, might be suitable for commercial cultivation.

microbiology↗

bioRxiv2019

Cell-of-Origin Analysis of Metastatic Gastric Cancer Uncovers the Origin of Inherent Intratumor Heterogeneity and a Fundamental Prognostic Signature

Intra-tumoral heterogeneity (ITH) is the fundamental property of cancer, however, the origin of ITH remains poorly understood. Here we performed single-cell RNA sequencing of peritoneal carcinomatosis (PC) from 20 patients with advanced gastric adenocarcinoma (GAC), constructed a transcriptome map of 45,048 PC cells, determined the cell-of-origin of each tumor cell, and incisively explored ITH of PC tumor cells at single-cell resolution. The links between cell-of-origin and ITH was illustrated at transcriptomic, genotypic, molecular, and phenotypic levels. This study characterized the origins of PC tumor cells that populate and thrive in the peritoneal cavity, uncovered the diversity in tumor cell-of-origins and defined it as a key determinant of ITH. Furthermore, cell-of-origin-based analysis classified PC into two cellular subtypes that were prognostic independent of clinical variables, and a 12-gene prognostic signature was then derived and validated in multiple large-scale GAC cohorts. The prognostic signature appears fundamental to GAC carcinogenesis/progression and could be practical for patient stratification.

cancer biology↗

bioRxiv2019

Effects of melatonin on germination and amino acid content in different wheat varieties seeds under polyethylene glycol stress

In this research, the effects of melatonin on germination and amino acid content in wheat (Triticum aestivum L.) seeds under polyethylene glycol (PEG-6000) stress were investigated. The results revealed that 10 M melatonin could aggravate the adverse effects of drought stress on germination percentage, germination index, and germination potential of two wheat varieties (JM22 and HG35). However, 300 M melatonin could obviously alleviate the negative effect of water stress on germination and increase radicle length, radicle number and plumule length of germinated seeds. Principal component analysis showed that amino acid content apparently changed in germination and the variation amplitude was different due to melatonin concentrations and wheat varieties. Lys content in wheat seed under 300 M melatonin plus PEG treatment increased compared with that under PEG. Meanwhile, Lys content was significantly and positively correlated with germination percentage, germination index, germination potential, radicle length, and plumule length, respectively. Our results suggested Lys play an important role in the regulation of melatonin on drought resistance of wheat seed during germination. This may be of value for saving water resources in North China Plain.

physiology↗

bioRxiv2019

Decomposing Retrosynthesis into Reactive Center Prediction and Molecule Generation

Chemical retrosynthesis has been a crucial and challenging task in organic chemistry for several decades. In early years, retrosynthesis is accomplished by the disconnection approach which is labor-intensive and requires expert knowledge. Afterward, rule-based methods have dominated in retrosynthesis for years. In this study, we revisit the disconnection approach by leveraging deep learning (DL) to boost its performance and increase the explainability of DL. Concretely, we propose a novel graph-based deep-learning framework, named DeRetro, to predict the set of reactants for a target product by executing the process of disconnection and reactant generation orderly. Experimental results report that DeRetro achieves new state-of-the-art performance in predicting the reactants. In-depth analyses also demonstrate that even without the reaction type as input, DeRetro retains its retrosynthesis performance while other methods show a significant decrease, resulting in a large margin of 19% between DeRetro and previous state-of-the-art rule-based method. These results have established DeRetro as a powerful and useful computational tool in solving the challenging problem of retrosynthetic analysis.

bioengineering↗

bioRxiv2019

Persister Cells Resuscitate via Ribosome Modification by 23S rRNA Pseudouridine Synthase RluD

Upon a wide range of stress conditions (e.g., nutrient, antibiotic, oxidative), a subpopulation of bacterial cells known as persisters survive by halting metabolism. These cells resuscitate rapidly to reconstitute infections once the stress is removed and nutrients are provided. However, how these dormant cells resuscitate is not understood well but involves reactivating ribosomes. By screening 10,000 compounds directly for stimulating Escherichia coli persister cell resuscitation, we identified that 2-{[2-(4-bromophenyl)-2-oxoethyl]thio}-3-ethyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (BPOET) stimulates resuscitation. Critically, by screening 4,267 E. coli proteins, we determined that BPOET activates hibernating ribosomes via 23S rRNA pseudouridine synthase RluD, which increases ribosome activity. Corroborating the increased waking with RluD, production of RluD increased the number of active ribosomes in persister cells. Also, inactivating the small RNA RybB which represses rluD led to faster persister resuscitation. Hence, persister cells resuscitate via activation of RluD.

molecular biology↗

bioRxiv2019

Manipulation of Seedling Traits with Pulsed Light in Closed Controlled Environments

There is substantial interest in growing crops in closed controlled environments, yet the energy requirements are high. Energy is required to produce light, but also to remove the heat generated when producing light. The goal of the current work examines a possible approach to decrease the energy requirement. The effect of pulsed light treatments was examined by monitoring seedling traits during early photomorphogenic development. Daily light integral remained unchanged between treatments, but the frequency of the pulses was varied. Developmental traits (such as inhibition of hypocotyl elongation rate) were most conspicuous during a normal photoperiod, as in twelve hours light, twelve hours darkness. Consistent with historical reports, when treatments were delivered in shorter durations (e.g. 1 hour on/off) photomorphogenic development was hindered, with the same daily light integral. However, at even shorter light intervals (e.g. seconds) seedlings developed as if they were provided full 12 h treatments. Extension of the dark period following a 5 s pulse was tested to determine the effect on seedling traits. The results showed that the dark period could be extended to at least 10 s without affecting seedling development, and extension to 20 s only had slight effects on seedling traits. The mechanism of the phenomenon was examined in Arabidopsis photosensory mutants, with substantial contributions from the phyA and cry1 pathways. The results suggest that pulsed light with extended dark periods can decrease energy input by at least 30% to >50% without affecting visible seedling traits. These pilot experiments in seedlings demonstrate that implementation of short-interval, pulsed-light strategies may lower energy requirements for growing crops in artificially illuminated environments.

plant biology↗

bioRxiv2019

ppGpp Ribosome Dimerization Model for Bacterial Persister Formation and Resuscitation

Stress is ubiquitous for bacteria and converts a subpopulation of cells into a dormant state known as persistence, in which cells are tolerant to antimicrobials. These cells revive rapidly when the stress is removed and are likely the cause of many recurring infections such as those associated with tuberculosis, cystic fibrosis, and Lyme disease. However, how persister cells are formed is not understood well. Here we propose the ppGpp ribosome dimerization persister (PRDP) model in which the alarmone guanosine pentaphosphate/tetraphosphate (henceforth ppGpp) generates persister cells directly by inactivating ribosomes via the ribosome modulation factor (RMF) and the hibernation promoting factor (Hpf). We demonstrate both RMF and HpF increase persistence and reduce single-cell persister resuscitation and that ppGpp has no effect on single-cell persister resuscitation. Hence, a direct connection between ppGpp and persistence is shown.

microbiology↗

bioRxiv2019

iTALK: an R Package to Characterize and Illustrate Intercellular Communication

Crosstalk between tumor cells and other cells within the tumor microenvironment (TME) plays a crucial role in tumor progression, metastases, and therapy resistance. We present iTALK, a computational approach to characterize and illustrate intercellular communication signals in the multicellular tumor ecosystem using single-cell RNA sequencing data. iTALK can in principle be used to dissect the complexity, diversity, and dynamics of cell-cell communication from a wide range of cellular processes.

cancer biology↗

bioRxiv2019

Combined Transcriptomics and Proteomics Forecast Analysis for Potential Genes Regulating the Columbian Plumage Color in Chickens

BackgroundColoration is one of the most recognizable characteristics in chickens, and clarifying the coloration mechanisms will help us understand feather color formation. \"Yufen I\" is an commercial egg-laying chicken breed in China, that was developed by a three-line cross using lines H, N and D. Columbian plumage is a typical feather character of the \"Yufen I\" H line. To elucidate the molecular mechanism underlying pigmentation of Columbian plumage, this study utilizes the technology of high-throughput sequencing to compare the transcriptome and proteome differences in different feather follicular tissue, including the dorsal neck with black and white striped feather follicles (Group A) and the ventral neck with white feather follicles (Group B) in the \"Yufen I\" H line.\n\nResultsIn this study, we identified a total of 21,306 genes and 5203 proteins in chicken feather follicles. Among these, 209 genes and 382 proteins were differentially expressed in two different locations, Group A and Group B, respectively. A total of 8 differentially expressed genes (DEGs) and 9 differentially expressed proteins (DEPs) were found to be involved in the melanogenesis pathway. Besides, a specifically expressed MED23 gene and a differential expressed GNAQ protein were involved in melanin synthesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis mapped 190 DEGs and 322 DEPs, to 175 and 242 pathways, respectively, and there were 166 pathways correlated with both DEGs and DEPs. 49 DEPs/DEGs overlapped and were enriched for 12 pathways. Transcriptomic and proteomic analyses revealed that the following pathways were activated: melanogenesis, cardiomycete adrenergic, calcium and the cGMP-PKG. The expression of DEGs was validated by real-time quantitative polymerase chain reaction (qRT-PCR) that was similar to that of RNA-seq. In addition, we found that MED23, FZD10, WNT7B and WNT11 genes expression peaked at approximately 8 weeks in the \"Yufen I\" H line, which is consistent with the molting cycle. As both the groups showed significant differences in terms of expression of the genes studied, this study opens up avenues for study in the future to assess their exact function in color of plumage.\n\nConclusionThese common DEGs and DEPs were enriched in the melanogenesis pathway. The MED23 and GNAQ were also reported to have a crucial part synthesis of melanin. In addition, this study is the first to reveal variations in gene and protein in the \"Yufen I\" H line during Columbian feather color development, and discover principal genes and proteins that would aid in the functional genomics studies in future. The results of the present study provide a significant conceptual basis for the \"Yufen I\" H line future breeding schemes and provide a basis for research on the mechanisms of feather pigmentation.

molecular biology↗

bioRxiv2018

Rousing Persisters through Ribosome Resuscitation and Rescue

Persistence, the dormant, stress-tolerant state formed primarily through the cessation of protein synthesis after antibiotic and nutrient stress, is arguably one of most vital phenotypes for bacteria since nearly all cells experience nutrient stress. Persisters are also responsible for many recurring infections. However, how persister cells wake to reconstitute infections is not understood well, beyond that the level of ribosomes governs their waking speed in rich medium. Here, using single cell observations, we determined that alanine as the sole carbon source wakes Escherichia coli persister cells and that persister cells do not wake stochastically but wake primarily when presented with a carbon source. By screening all E. coli proteins, we found that the mechanism of persister cell waking is through sensing nutrients by the chemotaxis and flagellum systems and by reducing levels of the secondary messenger cAMP, which leads to ribosome resuscitation and rescue. Hence, persister cells wake using pathways evolved for nutrient sensing.

microbiology↗