Biology subjects

Liu, L.

Publications and source records attributed to Liu, L..

At least 469 records · Page 26Linked to original sources

bioRxiv2023

Phase-encoded fMRI tracks down brainstorms of natural language processing with sub-second precision

The human language system interacts with cognitive and sensorimotor regions during natural language processing. However, where, when, and how these processes occur remain unclear. Existing noninvasive subtraction-based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed phase-encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging (fMRI) data, as well as overcoming scanner noise and head-motion challenges during overt language tasks. We captured neural information flows as coherent waves traveling over the cortical surface during listening, reciting, and oral cross-language interpreting. The timing, location, direction, and surge of traveling waves, visualized as brainstorms on brain weather maps, reveal the functional and effective connectivity of the brain in action. These maps uncover the functional neuroanatomy of language perception and production and motivate the construction of finer-grained models of human information processing.

neuroscience↗

bioRxiv2023

Colonization and Dissemination of Klebsiella pneumoniae is Dependent on Dietary Carbohydrates

Dysbiosis of the gut microbiota is increasingly appreciated as both a consequence and precipitant of human disease. The outgrowth of the bacterial family Enterobacteriaceae is a common feature of dysbiosis, including the human pathogen Klebsiella pneumoniae. Dietary interventions have proven efficacious in the resolution of dysbiosis, though the specific dietary components involved remain poorly defined. Based on a previous human diet study, we hypothesized that dietary nutrients serve as a key resource for the growth of bacteria found in dysbiosis. Through human sample testing, and ex-vivo, and in vivo modeling, we find that nitrogen is not a limiting resource for the growth of Enterobacteriaceae in the gut, contrary to previous studies. Instead, we identify dietary simple carbohydrates as critical in colonization of K. pneumoniae. We additionally find that dietary fiber is necessary for colonization resistance against K. pneumoniae, mediated by recovery of the commensal microbiota, and protecting the host against dissemination from the gut microbiota during colitis. Targeted dietary therapies based on these findings may offer a therapeutic strategy in susceptible patients with dysbiosis.

microbiology↗

bioRxiv2023

Seasonal Variation in Bacterial Community Structures of Mangrove Sediments

Climate change globally and sea level rise affect the mangrove ecosystem. The high diversity and temporal heterogeneity of the mangrove ecosystem will lead to a high diversity of sediment bacterial community structure and function. However, seasonal variations and potential assembly mechanisms of sediment bacterial communities in mangrove ecosystems remain to be discovered. We collected rhizosphere sediments and bulk sediments from Kandelia obovata and Aegiceras corniculatum at three locations covering Dongzhai Harbour in spring, summer, autumn, and winter, and sequenced 16S rRNAs. The results indicated that the alpha and beta diversity of bacterial communities in mangrove sediments differed significantly between seasons, and the bacterial communities in rhizosphere sediments had smaller seasonal changes and were more stable than those in bulk sediment bacterial communities. The seasonal changes in carbon, nitrogen content, and pH were the main influencing factors. The stochastic process dominated the assembly of bacterial communities in mangrove sediments. The assembly of bacterial communities varies between seasons. We found that the proportion of dispersal limitation was significantly negatively correlated with the carbon and nitrogen content in the sediment. Compared with bulk components, the dispersal limitation of bacterial communities in rhizosphere sediments accounted for a lower proportion of community construction, which might be caused by higher carbon and nitrogen content conditions in rhizosphere sediments. We found that beta diversity based on Bray-Curtis distance was significantly positively correlated with dispersal limitation, which explained why the beta diversity of bacterial communities in rhizosphere sediments was significantly lower than that of bulk components. This study increases the understanding of the responses of mangrove bacterial communities to seasonal change and may be beneficial for the protection of mangrove ecosystems in the face of climate change.

ecology↗

bioRxiv2023

Molecular mechanisms underlying the formation of larval green color and camouflage patterns in swallowtail butterfly, Papilio memnon

Insects have various strategies like mimicry or camouflage to avoid predation. Swallowtail butterfly larvae switch from a black and white pattern mimicking bird droppings to a green camouflage pattern in the fifth (final) instar. This larval pattern switch is regulated during the juvenile hormone (JH)-sensitive period, when JH titer declines rapidly, and clawless (cll), abdominal-A (abd-A), and Abdominal-B (Abd-B) function during this period. However, the molecular mechanism behind the background green color, a crucial aspect of the camouflage pattern, remains poorly understood. Here, we used Papilio memnon, which switches to the camouflage pattern in the fifth instar but is greenish from the third instar, to investigate the mechanism of camouflage pattern formation, particularly the larval green coloration. Through RNA sequencing, we found that BBPs forming a gene cluster are upregulated in the green regions of P. memnon larvae during the fourth instar, whereas P. xuthus larvae, which have not yet turned green, showed minimal BBPs expression. When BBP1 and BBP2, which were particularly highly expressed, were knocked down by RNAi, there was a phenotypic change in green to yellow in both fourth and fifth instar larvae. Expression analysis and knockdown experiments were conducted also for JHBP, which had been previously reported, and confirmed that it is involved in the synthesis of yellow pigment. Furthermore, knockdown of Ubx resulted in no phenotypic change in fourth instar larvae, but in fifth instar larvae, the eyespots pattern characteristic of the camouflage pattern almost entirely disappeared, suggesting that Ubx is also functional only during JH-sensitive period. Our results indicate that the switch from mimetic to camouflage patterns resulted from the function of cll, abd-A, Abd-B, and Ubx prepatterning genes during the JH-sensitive period. And the increased expression of BBPs and JHBPs, independent of the JH-sensitive period, contributed to the development of green coloration.

molecular biology↗

bioRxiv2023

Nutritional composition and metabolic analysis of the newly hatched Anguilla japonica from embryo to preleptocephali obtained from artificial reproduction

The starter diet for Japanese eel (Anguilla japonica) has always been a difficult problem for the realization of total artificial reproduction. Therefore, this research analyzed the nutritional composition of artificially fertilized eggs, and transcriptome of samples from early hatchlings of fry to better understand nutrients requirements. The composition of crude lipid and crude protein in fertilized eggs was 7.24%{+/-}0.32% and 10.56%{+/-}0.41%, respectively. Seven kinds of essential amino acids (EAA) were detected but took a comparable lower content (3.19%) than other marine fish eggs. We randomly assembled 265.74 million clean reads and identified 1751 differentially expressed genes (DEGs) (P < 0.01) from pre-leptocephalus larvae. A total of 23 KEGG pathways related to the digestive and metabolic system were detected. Genes related to the secretion pathway of saliva, pancreatic juice and other digestive juices were significantly changed. The genes of carbohydrate metabolism, glycerolipid metabolism and glycerophospholipid metabolism were up-regulated significantly with the growth of the larvae (day 0 to 12). This study will facilitate future studies on the nutrition of eel larvae and other biological traits to reproductive research.

zoology↗

bioRxiv2023

It All Rolls Downstream: Upstream Control of Physical Activity Regulation

Physical activity is regulated by a variety of genetic molecules. However, the pathways through which those molecules work to regulate activity is largely unknown. The purpose of this study was to gather the known genetic molecules that are associated with activity regulation and define overall upstream regulator pathways through which these molecules work. We conducted a systematic review to gather all available published datasets related to physical activity regulation, standardized the data for genomic location and species, and used this data, in an unbiased manner to create a dataset that was used: (1) to physically map and visualize all identified molecules to homologous chromosome locations and (2) as the dataset for which an Upstream Regulator Analysis (URA) was conducted using Qiagen Ingenuity Pathway Analysis (IPA) software. Our search resulted in 469 genetic molecules (e.g. genomic variant, transcript, protein, micro-RNA) that were split into brain (n=366) and muscle (n=345) sub-groups, which was our attempt to separate differences in central vs peripheral pathways. The brain and muscle data sets had several potential upstream regulators, the top-rated being {beta}-estradiol as a regulator for 19.5% and 21% of the brain and muscle datasets respectively. To our knowledge, {beta}-estradiols identification as a potential regulator, is the first evidence to link the well-known effects of sex hormones on physical activity with genetic regulation of physical activity. There were a variety of potential upstream regulators for the molecules collected in this review, but interestingly, three of the top five for both brain and muscle are nuclear receptor binding ligands; estradiol (estrogen receptor), dexamethasone (glucocorticoid receptor), and tretinoin (retinoic acid receptor), indicating a potential role of nuclear receptors in the regulation of physical activity. Selective nuclear receptor modulation may be an area of interest in future mechanistic studies of the genetic regulation of physical activity.

genetics↗

bioRxiv2023

Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia

Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodelling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodelling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodelling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/539799v4_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@14fa4bcorg.highwire.dtl.DTLVardef@1c86bbborg.highwire.dtl.DTLVardef@118edfcorg.highwire.dtl.DTLVardef@1b06916_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection

SARS-CoV-2-induced impaired antiviral and excessive inflammatory responses cause fatal pneumonia. However, the key pattern recognition receptors that elicit effective antiviral and lethal inflammatory responses in-vivo are not well defined. CoVs possess single-stranded RNA (ssRNA) genome that is abundantly produced during infection and stimulates both antiviral interferon (IFN) and inflammatory cytokine/ chemokine responses. Therefore, in this study, using wild-type control and TLR7 deficient BALB/c mice infected with a mouse-adapted SARS-COV-2 (MA-CoV-2), we evaluated the role of TLR7 signaling in MA-CoV-2-induced antiviral and inflammatory responses and disease outcome. We show that TLR7-deficient mice are more susceptible to MA-CoV-2 infection as compared to infected control mice. Further evaluation of MA-CoV-2 infected lungs showed significantly reduced mRNA levels of antiviral type I (IFN/{beta}) and type III (IFN{lambda}) IFNs, IFN stimulated genes (ISGs, ISG15 and CXCL10), and several pro-inflammatory cytokines/chemokines in TLR7 deficient compared to control mice. Reduced lung IFN/ISG levels and increased morbidity/mortality in TLR7 deficient mice correlated with high lung viral titer. Detailed examination of total cells from MA-CoV-2 infected lungs showed high neutrophil count in TLR7 deficient mice compared to control mice. Additionally, blocking TLR7 activity post-MA-CoV-2 infection using a specific inhibitor also enhanced disease severity. In summary, our results conclusively establish that TLR7 signaling is protective during SARS-CoV-2 infection, and despite robust inflammatory response, TLR7-mediated IFN/ISG responses likely protect the host from lethal disease. Given similar outcomes in control and TLR7 deficient humans and mice, these results show that MA-CoV-2 infected mice serve as excellent model to study COVID-19.

immunology↗

bioRxiv2023

Regulatory mechanisms in multiple vascular diseases locus LRP1 involve repression by SNAIL and extracellular matrix remodeling

BackgroundGenome-wide association studies (GWAS) implicate common genetic variations in the low-density lipoprotein receptor-related protein 1 locus (LRP1) in risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. MethodsFine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells (iPSC) were genome-edited using CRISPR-Cas9 to delete or modify candidate enhancer regions, and generate LRP1 knockout cell lines (KO). Cells were differentiated into smooth muscle cells (SMCs) through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA-sequencing and mass spectrometry. ResultsMulti-trait co-localization analyses pointed at rs11172113 as the most likely causal variant in LRP1 for fibromuscular dysplasia, migraine, pulse pressure and pulmonary function trait. We found rs11172113-T allele to associate with higher LRP1 expression. Genomic deletion in iPSC-derived SMCs supported rs11172113 to locate in an enhancer region regulating LRP1 expression. We found transcription factors MECP2 and SNAIL to repress LRP1 expression through an allele-specific mechanism, involving SNAIL interaction with disease risk allele. LRP1 KO decreased iPSC-derived SMCs proliferation and migration. Differentially expressed genes were enriched for collagen-containing extracellular matrix, connective tissue and lung development. LRP1 KO showed potentiated canonical TGF-{beta} signaling through enhanced phosphorylation of SMAD2/3. Analyses of protein content of decellularized extracts indicated partial extracellular matrix (ECM) remodeling involving enhanced secretion of CYR61, a known LRP1 ligand involved in vascular integrity and TIMP3, implicated in extracellular matrix maintenance and also known to interact with LRP1. ConclusionsOur findings support allele specific LRP1 gene repression by the endothelial-to-mesenchymal transition regulator SNAIL. We propose decreased LRP1 expression in SMCs to remodel the ECM enhanced by TGF- {beta} as a potential mechanism of this pleiotropic locus for vascular diseases. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/539992v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@11926a8org.highwire.dtl.DTLVardef@390a37org.highwire.dtl.DTLVardef@cdad4dorg.highwire.dtl.DTLVardef@12cbf92_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2023

TLR priming licenses NAIP inflammasome activation by immunoevasive ligands

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family, CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages, and not thought to be regulated by inflammatory signals. Here, we demonstrate that Toll-like receptor (TLR) stimulation upregulates NLRC4 transcription and protein expression in murine macrophages, which licenses NAIP detection of evasive ligands. TLR-induced NLRC4 upregulation and NAIP detection of evasive ligands required p38 MAPK signaling. In contrast, TLR priming in human macrophages did not upregulate NLRC4 expression, and human macrophages remained unable to detect NAIP-evasive ligands even following priming. Critically, ectopic expression of either murine or human NLRC4 was sufficient to induce pyroptosis in response to immunoevasive NAIP ligands, indicating that increased levels of NLRC4 enable the NAIP/NLRC4 inflammasome to detect these normally evasive ligands. Altogether, our data reveal that TLR priming tunes the threshold for NAIP/NLRC4 inflammasome activation and enables inflammasome responses against immunoevasive or suboptimal NAIP ligands. Significance StatementCytosolic receptors in the neuronal apoptosis inhibitor protein (NAIP) family detect bacterial flagellin and components of the type III secretion system (T3SS). NAIP binding to its cognate ligand engages the adaptor molecule NLRC4 to form NAIP/NLRC4 inflammasomes culminating in inflammatory cell death. However, some bacterial pathogens evade NAIP/NLRC4 inflammasome detection, thus bypassing a crucial barrier of the immune system. Here, we find that, in murine macrophages, TLR-dependent p38 MAPK signaling increases NLRC4 expression, thereby lowering the threshold for NAIP/NLRC4 inflammasome activation in response to immunoevasive NAIP ligands. Human macrophages were unable to undergo priming-induced upregulation of NLRC4 and could not detect immunoevasive NAIP ligands. These findings provide a new insight into species-specific regulation of the NAIP/NLRC4 inflammasome.

molecular biology↗

bioRxiv2023

Stomatal closure in maize is mediated by subsidiary cells and the PAN2 receptor

Stomata are epidermal pores that facilitate plant gas exchange. Grasses have fast stomatal movements, likely due to their dumbbell-shaped guard cells and lateral subsidiary cells. Subsidiary cells reciprocally exchange water and ions with guard cells. However, the relative contribution of subsidiary cells during stomatal closure is unresolved. We compared stomatal gas exchange and stomatal aperture dynamics in wild type and pan1, pan2, and pan1;pan2 Zea mays (L.) (maize) mutants, which have varying percentages of aberrantly formed subsidiary cells. Stomata with 1 or 2 defective subsidiary cells cannot close properly, indicating that subsidiary cells are essential for stomatal function. Even though the percentage of aberrant stomata is similar in pan1 and pan2, pan2 showed a more severe defect in stomatal closure. In pan1, only stomata with abnormal subsidiary cells fail to close normally. In pan2, all stomata have stomatal closure defects, indicating that PAN2 has an additional role in stomatal closure. Maize Pan2 is orthologous to Arabidopsis GHR1, which is also required for stomatal closure. PAN2 acts downstream of Ca2+ in maize to promote stomatal closure. This is in contrast to GHR1, which acts upstream of Ca2+, and suggests the pathways could be differently wired.

plant biology↗

bioRxiv2023

DeepCORE: An interpretable multi-view deep neural network model to detect co-operative regulatory elements

Gene transcription is an essential process involved in all aspects of cellular functions with significant impact on biological traits and diseases. This process is tightly regulated by multiple elements that co-operate to jointly modulate the transcription levels of target genes. To decipher the complicated regulatory network, we present a novel multi-view attention-based deep neural network that models the relationship between genetic, epigenetic, and transcriptional patterns and identifies co-operative regulatory elements (COREs). We applied this new method, named DeepCORE, to predict transcriptomes in 25 different cell lines, which outperformed the state-of-the-art algorithms. Furthermore, DeepCORE translates the attention values embedded in the neural network into interpretable information, including locations of putative regulatory elements and their correlations, which collectively implies COREs. These COREs are significantly enriched with known promoters and enhancers. Novel regulatory elements discovered by DeepCORE showed epigenetic signatures consistent with the status of histone modification marks.

bioinformatics↗

bioRxiv2023

A mouse-specific model to detect genes under selection in tumors

Mouse is a widely used model organism in cancer research. However, no computational methods exist to identify cancer driver genes in mice due to a lack of labeled training data. To address this knowledge gap, we adapted the GUST (genes under selection in tumors) model, originally trained on human exomes, to mouse exomes using transfer learning. The resulting tool, called GUST-mouse, can estimate long-term and short-term evolutionary selection in mouse tumors, and distinguish between oncogenes, tumor suppressor genes, and passenger genes using high throughput sequencing data. We applied GUST-mouse to analyze 65 exomes of mouse primary breast cancer models, leading to the discovery of 24 driver genes. The GUST-mouse method is available as an open-source R package on github (https://github.com/liliulab/gust.mouse).

bioinformatics↗

bioRxiv2023

The anti-cancer compound JTE-607 reveals hidden sequence specificity of the mRNA 3' processing machinery

JTE-607 is a small molecule compound with anti-inflammation and anti-cancer activities. Upon entering the cell, it is hydrolyzed to Compound 2, which directly binds to and inhibits CPSF73, the endonuclease for the cleavage step in pre-mRNA 3' processing. Although CPSF73 is universally required for mRNA 3' end formation, we have unexpectedly found that Compound 2- mediated inhibition of pre-mRNA 3' processing is sequence-specific and that the sequences flanking the cleavage site (CS) are a major determinant for drug sensitivity. By using massively parallel in vitro assays, we have measured the Compound 2 sensitivities of over 260,000 sequence variants and identified key sequence features that determine drug sensitivity. A machine learning model trained on these data can predict the impact of JTE-607 on poly(A) site (PAS) selection and transcription termination genome-wide. We propose a biochemical model in which CPSF73 and other mRNA 3' processing factors bind to RNA of the CS region in a sequence-specific manner and the affinity of such interaction determines the Compound 2 sensitivity of a PAS. As the Compound 2-resistant CS sequences, characterized by U/A-rich motifs, are prevalent in PASs from yeast to human, the CS region sequence may have more fundamental functions beyond determining drug resistance. Together, our study not only characterized the mechanism of action of a compound with clinical implications, but also revealed a previously unknown and evolutionarily conserved sequence-specificity of the mRNA 3' processing machinery.

molecular biology↗

bioRxiv2023

Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking

SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.

microbiology↗

bioRxiv2023

Establishment and Evaluation of Rat Models of Cervical Spondylopathy with Yin Deficiency Syndrome

ObjectiveCervical spondylosis (CS) with Yin deficiency syndrome is an important classification of traditional Chinese medicine (TCM) symptoms of CS. However, there is no animal model for studying this TCM syndrome. This study aimes to establish and evaluate rat models of cervical spondylopathy with Yin deficiency syndrome. MethodThirty-six Sprague-Dawley male rats were randomly divided into the blank control (control), CS and CS with Yin deficiency syndrome (YCS) groups (n = 12 rats/group). CS was induced using cervical static-dynamic imbalance to mimic disk degeneration (except in the control group). After 30 days of the CS rat model, rats in the YCS group were subjected to sustained sleep deprivation for 168h. After different induction times, the rats in each group were observed for behavior and weight. Pain behavior was assessed by a withdrawal response to von Frey filament application, and heart rate and blood pressure were measured using a rat noninvasive sphygmomanometer. Intervertebral disc pathology sections were observed using hematoxylin and eosin staining and an electron microscope. Western blotting was used to evaluate the protein level of collagen-II, Bcl-2, Bax and Bcl-2/Bax expression in the cervical intervertebral disc. Determination of related laboratory serum indexes, cyclic adenosine monophosphate, and cyclic guanosine phosphate were conducted using enzyme-linked immunosorbent assay. ResultsThe laboratory indexes in the YCS group were significantly different from those in the control and CS groups (P < 0.05), and indicators of 72-, 120-, and 178-h sleep deprivation showed varying degrees of difference from those of the CS group. ConclusionAfter establishing a model of CS, continuous sleep deprivation for 72 h was used to create a rat model of CS with Yin deficiency syndrome. The established rat models of CS with Yin deficiency syndrome met the clinical and Chinese medicine characteristics, and thus, they can be expected to become an ideal model for studying CS with Yin deficiency syndrome in the future.

zoology↗

bioRxiv2023

Insight into the genetic diversity, resistance, and virulence of Listeria from the marine environment: reveal the risk of hypervirulent isolates

Listeria monocytogenes is a major human foodborne pathogen and a ubiquitous environmental saprophyte. In this study, we investigated the prevalence and characteristics of Listeria spp. from beach sand in the coastal environment. Three different Listeria spp., Listeria monocytogenes (n=16), Listeria fleishmanii (n=7), and Listeria aquatica (n=3) were isolated from 769 beach sand samples and demonstrated diverse biofilm forming capacity. The L. monocytogenes isolates belonged to four distinct sequence types (ST87, ST121, ST35, and ST85) and contained the majority of virulence genes, some isolates were hypervirulent clones or had close phylogenetic relatedness with clinical cases. The ST87 isolates showed higher ability of biofilm formation in seawater than other STs strains. As a reservoir of microbes from marine environments and human/animal excrement, coastal sand would play an important role in the spread of L. monocytogenes and is an environmental risk for human listeriosis.

microbiology↗

bioRxiv2023

Probing Altered Receptor Specificities of Antigenically Drifting Human H3N2 Viruses by Chemoenzymatic Synthesis, NMR and Modeling

Prototypic receptors for human influenza viruses are cell surface N-glycans carrying 2,6-linked sialosides. Under immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that appear to recognize 2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) moieties. Here, molecular recognition features of such drifted hemagglutinins (HAs) are examined by chemoenzymatic synthesis of complex N-glycans having 13C-labeled monosaccharides at strategic positions. The labeled glycans were employed in 2D STD-1H and 13C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computational and mutagenesis studies demonstrate that mutations distal to the receptor binding domain of recent HAs have created an extended binding site that can directly interact with the extended LacNAc chain. A fluorine containing sialyl-LacNAc derivative is used as NMR probe to derive relative binding affinities and confirmed the contribution of the extended LacNAc chain for binding.

biochemistry↗