Biology subjects

Cao, Q.

Publications and source records attributed to Cao, Q..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

Multi-Omic Analysis of Tyrophagus putrescentiae Reveals Insights into the Allergen Complexity of Storage Mites

BackgroundThe storage mite Tyrophagus putrescentiae is one of the major mites causing allergies in Chinese and Korean populations, but its allergen profile in incomplete when compared with that of house dust mites. Multiple genome-based methods have been introduced into the allergen study of mites and have enabled a better understanding of these medically important organisms. ObjectiveWe sought to reveal a comprehensive allergen profile of Tyrophagus putrescentiae and advance the allergen study of storage mites. MethodsBased on a high-quality assembled and annotated genome, an in silico analysis was performed by searching reference sequences to identify allergens. Immunoassay ELISA assessed the allergenicities of recombinant proteins. MALDI-TOF mass spectrometry identified the IgE-binding proteins. Comparative genomics analysis was employed for the important allergen gene families. ResultsA complete allergen profile of Tyrophagus putrescentiae was revealed, including thirty-seven allergen groups (up to Tyr p 42). Among them, five novel allergens were verified using the sera of allergy patients. Massive allergen homologs were identified as the result of gene duplications in genome evolution. Proteomic identification again revealed a wide range of allergen homologs. In the NPC2 family and GSTs, comparative analysis shed light on the expansion and diversification of the allergen groups. ConclusionUsing multi-omic approaches, the comprehensive allergen profile including massive homologs was disclosed in Tyrophagus putrescentiae, which revealed the allergen complexity of the storage mite and could ultimately facilitate the component-resolved diagnosis.

immunology↗

bioRxiv2022

The porcine cGAS-STING pathway exerts an unusual antiviral function independent of IFN and autophagy

The innate immune DNA sensing cGAS-STING pathway exerts strong antiviral activity through the downstream interferon (IFN) production; however, it has been recently recognized that IFN independent activity of STING also plays an important role in antiviral functions. Nevertheless, the IFN independent antiviral activity of STING is not fully understood. In this study, we showed that porcine STING (pSTING) played a critical role in anti-HSV1 and anti-VSV infections, and IFN defective mutants including pSTING pLxIS sub, S365A and {Delta}CTT all exhibited similar antiviral functions to wild type (WT) pSTING. Further, all these IFN defective pSTING mutants possessed a comparable autophagy activity relative to WT pSTING as expected. From pSTING WT, S365A and {Delta}CTT, the residues responsible for autophagy were mutated, which included L333A/R334A, Y167A/L170A and Y245A/L248A, respectively. Surprisingly, all these autophagy defective pSTING mutants still resisted from the two viral infections, demonstrating the pSTING antiviral function independent of IFN as well as autophagy. On the other hand, all the autophagy defective pSTING mutants triggered cell apoptosis, which was associated with the antiviral functions. Additionally, pSTING lost its antiviral activity in TBK1-/- and IRF3-/- porcine macrophages, indicating the involvement of TBK1 and IRF3 in other STING activity such as apoptosis. Collectively, our results revealed that STING exerts both IFN and autophagy independent antiviral activity, and also suggested that STING triggered cell apoptosis might resist from virus infections.

immunology↗

bioRxiv2022

Regulatory roles of three-dimensional structures of topologically associating domains

1Transcriptional enhancers usually, but not always, regulate genes within the same topologically associating domain (TAD). We hypothesize that this incomplete insulation is due to three-dimensional structures of corresponding chromatin domains in individual cells: Whereas enhancers and genes buried inside the "core" of a domain interact mostly with other regions in the same domain, those on the "surface" can more easily interact with the outside. Here we show that a simple measure, the intra-TAD ratio, can quantify the "coreness" of a region with respect to single-cell domains it belongs. We show that domain surfaces are permissive for high gene expression, and cell type-specific active cis-regulatory elements (CREs), active histone marks, and transcription factor binding sites are enriched on domain surfaces, most strongly in chromatin subcompartments typically considered inactive. These findings suggest a "domain surface CRE" model of gene regulation. We also find that disease-associated non-coding variants are enriched on domain surfaces.

bioinformatics↗

bioRxiv2022

Structural polymorphism of amyloid fibrils in cardiac ATTR amyloidosis revealed by cryo-electron microscopy

The deposition of amyloidogenic transthyretin (ATTR) in ATTR amyloidosis leads to an unexplained variety of clinical phenotypes, including cardiomyopathy. In brain amyloid conditions, there is an apparent association between the clinical phenotype and the amyloid fibril structure. Here, we question this phenotype-structure association in cardiac amyloidoses by determining the cryo-electron microscopy structures of fibrils extracted from the hearts of seven ATTR amyloidosis patients. We found that, in contrast to brain fibrils, cardiac ATTR fibrils display a structural polymorphism that is not genotype-specific, can co-exist within the same individual, and is independent of the cardiac phenotype. This polymorphism challenges the current paradigm of "one disease equals one fibril fold" proposed in tauopathies and synucleinopathies, and questions whether a similar structural heterogeneity occurs in other amyloidoses. One-Sentence SummaryUnlike brain amyloid fibrils, cardiac ATTR fibrils are polymorphic independent of genotype and even within the same patient.

molecular biology↗

bioRxiv2022

Single-cell analysis reveals the range of transcriptional states of circulating human neutrophils

Neutrophils are the most abundant leukocytes in human blood and are essential components of innate immunity. Until recently, neutrophils were considered homogeneous and transcriptionally inactive cells, but both concepts are being challenged. To date, neutrophils have been characterized based on discrete parameters including cell-surface markers, buoyancy, maturation status, or tissue localization. Single-cell RNA sequencing (scRNA-seq) offers an unbiased view of cells along a continuum of transcriptional states. However, the use of scRNA-seq to characterize neutrophils has proven technically difficult, explaining in part the paucity of published single-cell data on neutrophils. We have found that modifications to the data analysis pipeline, rather than to the existing scRNA-seq chemistries, can significantly increase the detection of human neutrophils in scRNA-seq. We have then applied a modified pipeline to the study of human peripheral blood neutrophils. Our findings indicate that circulating human neutrophils are transcriptionally heterogeneous cells, which can be classified into one of four transcriptional clusters that are reproducible among healthy human subjects. We demonstrate that peripheral blood neutrophils shift from relatively immature (Nh0) cells, through a transitional phenotype (Nh1), into one of two endpoints defined by either relative transcriptional inactivity (Nh2) or high expression of type I interferon-inducible genes (Nh3). Transitions among states are characterized by the expression of specific transcription factors. By simultaneously measuring surface proteins and intracellular transcripts at the single-cell level, we show that these transcriptional subsets are independent of the canonical surface proteins that are commonly used to define and characterize human neutrophils. These findings provide a new view of human neutrophil heterogeneity, with potential implications for the characterization of neutrophils in health and disease.

immunology↗

bioRxiv2022

Amyloid fibrils in frontotemporal lobar degeneration with TDP-43 inclusions are composed of TMEM106B, rather than TDP-43

FTLD is the third most common neurodegenerative condition, following only Alzheimers and Parkinsons diseases. FTLD typically presents in 45-64-year-olds with behavioral changes or progressive decline of language skills. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions detected by TDP-43 immunoreactivity. Here, we extracted amyloid fibrils from brains of four patients, representing four out of five FTLD-TDP subclasses and determined their near-atomic resolution structures by cryo-EM. Unexpectedly, all amyloid fibrils examined are composed of a 135-residue C-terminal fragment of TMEM106B, a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP. In addition to TMEM106B fibrils, abundant non-fibrillar aggregated TDP-43 is present, as revealed by immunogold labeling. Our observations confirm that FTLD-TDP is an amyloid-involved disease and suggest that amyloid involvement in FTLD-TDP is of protein TMEM106B, rather than of TDP-43.

molecular biology↗

bioRxiv2022

Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation

In neurodegenerative diseases including Alzheimers and ALS, proteins that bind RNA are found in aggregated forms in autopsied brains. Evidence suggests that RNA aids nucleation of these pathological aggregates; however, the mechanism has not been investigated at the level of atomic structure. Here we present the 3.4 [A] resolution structure of fibrils of full-length recombinant tau protein in the presence of RNA, determined by electron cryo-microscopy (cryoEM). The structure reveals the familiar in-register cross-{beta} amyloid scaffold, but with a small fibril core spanning residues Glu391 to Ala426, a region disordered in the fuzzy coat in all previously studied tau polymorphs. RNA is bound on the fibril surface to the positively charged residues Arg406 and His407 and runs parallel to the fibril axis. The fibrils dissolve when RNAse is added, showing that RNA is necessary for fibril integrity. While this structure cannot exist simultaneously with the tau fibril structures extracted from patients brains, it could conceivably account for the nucleating effects of RNA cofactors followed by remodeling as fibrils mature. Significance statementApplication of cryoEM has greatly expanded our understanding of atomic structures of mature pathological amyloid fibrils, but little is known at the molecular level of the initiation of fibril formation. RNA has been shown to be one cofactor for formation of fibrils of tau protein, and is known also to bind to other proteins, including TDP-43, FUS, and HNRNPA2, which form pathological inclusions. Our cryoEM structure of recombinant tau protein with RNA reveals a 36 residue, C-terminal fibril core bound to RNA which runs parallel to the fibril axis. We speculate that this structure could represent an early step in the formation of tau fibrils.

biophysics↗

bioRxiv2022

Barley stripe mosaic virus γb protein targets thioredoxin h-type 1 to dampen SA-mediated antiviral defenses

Salicylic acid (SA) acts as a signaling molecule to perceive and defend against pathogen infections. Accordingly, pathogens evolve versatile strategies to disrupt the SA-mediated signal transduction. However, it is necessary to further characterize how plant viruses manipulate the SA-dependent defense responses. Here, we show that Barley stripe mosaic virus (BSMV) infection activates SA-mediated defense signaling pathway and upregulates the expression of Nicotiana benthamiana thioredoxin h-type 1 (NbTRXh1). The {gamma}b protein interacts directly with NbTRXh1 in vivo and in vitro. Overexpression of NbTRXh1, but not a reductase-defective mutant, impedes BSMV infection, whereas low NbTRXh1 expression level results in increased viral accumulation. Similar with its orthologues in Arabidopsis, NbTRXh1 also plays an essential role in SA signaling transduction in N. benthamiana. To counteract NbTRXh1-mediated defenses, the BSMV {gamma}b protein targets NbTRXh1 to dampen its reductase activity and thereby impairing downstream SA defense genes expression to optimize viral cell-to-cell movement. We also found that NbTRXh1-mediated resistance defends against Lychnis ringspot virus, Beet black scorch virus, and Beet necrotic yellow vein virus. Taken together, our results reveal a novel role for the multifunctional {gamma}b protein in counteracting plant defense responses, and broadens the broad-spectrum antibiotic role of SA signaling pathway. One sentence summaryBSMV {gamma}b protein impairs NbTRXh1 reductase activity and dampen downstream SA-related genes expression to facilitate viral cell-to-cell movement.

microbiology↗

bioRxiv2022

Sulfane sulfur post-translationally modifies the global regulator AdpA to influence actinorhodin production and morphological differentiation of Streptomyces coelicolor

The transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multi-level regulations at transcriptional, post-transcriptional, and translational levels, yet no post-translational regulation has been reported. Sulfane sulfur, such as organic polysulfide (RSnH, n[≥]2), is common inside microorganisms, but its physiological functions are largely unknown. Herein, we discovered that sulfane sulfur post-translationally modifies AdpA in S. coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces. IMPORTANCEStreptomyces produce myriad of polyketide compounds having (potential) clinical applications. While the database of polyketide gene clusters are quickly expanding, the regulation mechanisms of them are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Herein, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation related genes, to form sulfhydrated AdpA. This modification changes dynamics of AdpA-controlled gene network and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of polyketide gene clusters. Thus, this finding provides a new strategy for mining and activating valuable polyketide gene clusters.

microbiology↗

bioRxiv2021

RPRM negatively regulates ATM levels involving its phosphorylation mediated by CDK4/CDK6

Sensitizing cancer cells to radio- and chemotherapy remains a hot topic in cancer treatment. Here it is identified that Protein Reprimo (RPRM) negatively regulates the levels of ataxia-telangiectasia mutated (ATM) protein kinase, a master regulator of DNA damage response (DDR) in the presence of DNA double-strand breaks (DSBs), resulting in impaired DNA repair efficiency and enhanced cellular sensitivity to genotoxic agents. Mechanistically, although RPRM is primarily located in cytoplasm, it rapidly translocates to nucleus shortly after induced by X-irradiation, interacts with ATM and promotes the nuclear export and proteasomal degradation of ATM. The nuclear translocation of RPRM is associated with its phosphorylation at serine 98, which is mediated by cyclin-dependent kinases 4/6 (CDK4/6). Inhibition of CDK4/6 stabilizes RPRM and promotes its nuclear import, in turn enhances the nuclear export of ATM and the reduction of ATM levels. As a result, RPRM overexpression and its phosphorylation inhibition sensitize cells to genotoxic agents. Moreover, RPRM deficiency significantly increases resistance to radiation-induced damage both in vitro and in vivo. These findings establish a crucial regulatory mechanism in which ATM is negatively modulated by RPRM, suggesting that RPRM may serve as a novel target for both cancer therapy and radiation protection.

cancer biology↗

bioRxiv2021

Different structures and pathologies of alpha-synuclein fibrils derived from preclinical and postmortem patients of Parkinson's disease

-Synuclein (-syn) fibrillar aggregates are the major component of Lewy bodies and Lewy neurites presenting as the pathology hallmark of Parkinsons disease (PD). Studies have shown that -syn is potential to form different conformational fibrils associated with different synucleinopathies, but whether the conformation of -syn fibrils changes in different phases of related diseases is to be explored. Here, we amplified -syn aggregates from the cerebrospinal fluid (CSF) of preclinical (pre-PD) and late-stage postmortem PD (post-PD) patients. Our results show that compared to the CSF of pre-PD, that of post-PD is markedly stronger in seeding in vitro -syn aggregation, and the amplified fibrils are more potent in inducing endogenous -syn aggregation in neurons. Cryo-electron microscopic structures further reveal that the difference between the pre-PD- and post-PD-derived fibrils lies on a minor polymorph which in the pre-PD fibrils is morphologically straight, while in the post-PD fibrils represents a single protofilament assembled by a distinctive conformation of -syn. Our work demonstrates structural and pathological differences between pre-PD and post-PD -syn aggregation and suggests potential alteration of -syn fibrils during the progression of PD clinical phases. Significance StatementIncreasing evidence support different conformational -syn fibrils in patients with different -synucleinopathies, but whether the conformation of -syn fibrils changes in different phases of related diseases is unknown. Here, we show that -syn fibrils amplified from the cerebrospinal fluid (CSF) of the late-stage postmortem PD (post-PD) patient are more potent in inducing endogenous -syn aggregation in neurons than that amplified from the preclinical (pre-PD) patient. Cryo-EM structures further reveal that the post-PD fibrils contain a novel conformation that is distinct from either the pre-PD fibrils or those previously reported. Our work suggests conformational evolution of -syn fibrils along with PD progression.

biophysics↗

bioRxiv2021

African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

African swine fever (ASF) is highly contagious, causes high mortality in domestic and feral swine, and has a significant economic impact on the global swine industry due to the lack of a vaccine or an effective treatment. African swine fever virus (ASFV) encodes more than 150 polypeptides, which may have intricate and delicate interactions with the host for the benefit of the virus to evade the hosts defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that the p17, encoded by D117L gene could suppress porcine cGAS-STING signaling pathway, exhibiting the inhibitions of TBK1 and IRF3 phosphorylations, downstream promoter activities, cellular mRNA transcriptions and ISG56 induction, and antiviral responses. Further, we found that p17 was located in endoplasmic reticulum (ER) and Golgi apparatus, and interacted with STING, perturbing it in the recruitment of TBK1 and IKK{varepsilon}. Additionally, it appeared that the transmembrane domain (amino acids 39-59) of p17 could be required for interacting with STING and inhibiting cGAS-STING pathway. Taken together, p17 could inhibit the cGAS-STING pathway through its interaction with STING and interference with STING in the recruitment of TBK1 and IKK{varepsilon}. ImportanceAfrican swine fever (ASF) is a highly contagious disease in domestic and feral swine, posing significant economic impacts on the global swine industry, and the pathogen ASFV is a large icosahedral DNA virus. The innate immune cGAS-STING DNA sensing pathway plays a critical role in sensing invading ASFV and triggering antiviral responses. However, there is still a lack of information regarding the molecular mechanisms of ASFV evasion of the cGAS-STING pathway. We have analyzed the effects of whole genomic open reading frames (ORFs) of ASFV China 2018/1 on the activation of cGAS-STING pathway, and found that p17 was able to inhibit cGAS-STING mediated type I IFN production by targeting STING, altering its capacity to recruit both TBK1 and IKK{varepsilon}. Findings presented here will expand our knowledge on the molecular mechanisms by which ASFV counteracts the antiviral innate immunity and provide deep insights into ASF pathogenesis.

immunology↗

bioRxiv2021

The African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKε

African swine fever virus (ASFV), a large and complex cytoplasmic double-stranded DNA virus, has developed multiple strategies to evade the antiviral innate immune responses. Cytosolic DNA arising from invading ASFV is mainly detected by the cyclic GMP-AMP synthase (cGAS) and then triggers a series of innate immune responses to prevent virus invasion. However, the immune escape mechanism of ASFV remains to be fully clarified. The pS273R of ASFV is a member of the SUMO-1-specific protease family and is crucial for valid virus replication. In this study, we identified pS273R as a suppressor of cGAS-STING pathway mediated type I interferon (IFN) production by ASFV genomic open reading frame screening. The pS273R was further confirmed as an inhibitor of IFN production as well as its downstream antiviral genes in cGAS-STING pathway. Mechanistically, pS273R greatly decreased the cGAS-STING signaling by targeting IKK{varepsilon} but not TBK1 and pS273R was found to disturb the interaction between IKK{varepsilon} and STING through its interaction with IKK{varepsilon}. Further, mutational analyses revealed that pS273R antagonized the cGAS-STING pathway by enzyme catalytic activity, which may affect the IKK{varepsilon} sumoylation state required for the interaction with STING. In summary, our results revealed for the first time that pS273R acts as an obvious negative regulator of cGAS-STING pathway by targeting IKK{varepsilon} via its enzymatic activity, which shows a new immune evasion mechanism of ASFV. ImportanceAfrican swine fever (ASF) is a devastating disease for domestic pigs and wild boar and the pathogen ASFV is a cytoplasmic double-stranded DNA virus. The innate immune cGAS-STING-IFN signaling pathway exerts a critical role in sensing ASFV infection. However, the functions of half ASFV encoded 150 plus proteins are still unknown and the evasion against the cGAS-STING pathway is not resolved. In our study, via ASFV genomic open reading frame (ORF) screening, we found that 29 ASFV proteins could inhibit cGAS-STING signaling pathway, with pS273R showing the most obvious inhibitory effect. Surprisingly, pS273R was found to antagonize the cGAS-STING signaling by targeting IKK{varepsilon}. Moreover, the pS273R enzyme activity is required for its ability to inhibit the cGAS-STING pathway. Our findings deepen the understanding of the immune evasion mechanism of ASFV, which will provide a support for the development of safe and effective ASFV vaccines.

immunology↗

bioRxiv2021

MiR-384 Regulates Reelin by Inhibiting ADAMTS4 in Neuronal Cell Lines

MicroRNAs (miRNAs) are important regulators of gene expression at the post-transcriptional level. The present study aims to investigate the role of miR-384 in Reelin by regulating ADAMTS4 in neuronal cell lines. Brain tissues from A{beta}1-42 induced mouse model of Alzheimers disease and the control group were collected. RT-PCR, Western blotting and immunohistochemistry were performed to detect the levels of ADAMTS4 and miR-384 in tissues. Luciferase reporter assay, Western blotting and in vitro assay were used to validate that ADAMTS4 was the target gene of miR-384. Neuronal cell line, Neuro-2a, was selected for transfection assay. ADAMTS4 was significantly down-regulated in hippocampi of Alzheimers disease mouse model, and negatively correlated with miR-384. Then, ADAMTS4 was identified as a direct target of miR-384. Over-expressing of miR-384 in Neuro-2a showed that ADAMTS4 and the cleaved Reelin fragments were down regulated, and proliferation of neuronal cell lines (Neuro-2a and SH-SY5Y) were inhibited through DAB-1 pathway. In conclusion, these results revealed that miR-384 may play a regulatory role in Reelin via inhibiting ADAMTS4 in neuronal cell lines.

biochemistry↗

bioRxiv2021

Dynamics of the auditory continuity illusion

Illusions give intriguing insights into perceptual and neural dynamics. In the auditory continuity illusion, two brief tones separated by a silent gap may be heard as one continuous tone if a noise burst with appropriate characteristics fills the gap. This illusion probes the conditions under which listeners link related sounds across time and maintain perceptual continuity in the face of sudden changes in sound mixtures. Conceptual explanations of this illusion have been proposed, but its neural basis is still being investigated. In this work we provide a dynamical systems framework, grounded in principles of neural dynamics, to explain the continuity illusion. We construct an idealized firing rate model of a neural population and analyze the conditions under which firing rate responses persist during the interruption between the two tones. First, we show that sustained inputs and hysteresis dynamics (a mismatch between tone levels needed to activate and inactivate the population) can produce continuous responses. Second, we show that transient inputs and bistable dynamics (coexistence of two stable firing rate levels) can also produce continuous responses. Finally, we combine these input types together to obtain neural dynamics consistent with two requirements for the continuity illusion as articulated in a well-known theory of auditory scene analysis: sustained responses occur if noise provides sufficient evidence that the tone continues and if there is no evidence of discontinuities between the tones and noise. By grounding these notions in a quantitative model that incorporates elements of neural circuits (recurrent excitation, and mutual inhibition, specifically), we identify plausible mechanisms for the continuity illusion. Our findings can help guide future studies of neural correlate of this illusion and inform development of more biophysically-based models of the auditory continuity illusion.

neuroscience↗

bioRxiv2020

Honeybee gut microbiota modulates host behaviors and neurological processes

Honeybee is a highly social insect with a reach behavioral repertoire and is a versatile model for neurobiological research. The honeybee gut microbiota is composed of a limited number of bacterial phylotypes that play an important role in host health. However, it remains unclear whether the microbiota can shape brain profiles and behaviors. Here, we revealed that the gut microbiota is requisite for the olfactory learning and memory ability of honeybees and alters the level of neurotransmitters in the brain. Transcriptomic and proteomic analysis showed distinctive gene expression and protein signatures for gnotobiotic bees associated with different gut bacteria. Specifically, genes related to olfactory functions and labor division are most upregulated. Moreover, differentially spliced genes in the brains of colonized bees largely overlapped with the datasets for human autism. The circulating metabolome profiles identified that different gut species regulated specific module of metabolites in the host hemolymph. Most altered metabolites are involved in the amino acid and glycerophospholipid metabolism pathways for the production of neuroactive compounds. Finally, antibiotic treatment disturbed the gut community and the nursing behavior of worker bees under field conditions. The brain transcripts and gut metabolism was also greatly interfered in treated bees. Collectively, we demonstrate that the gut microbiota regulates honeybee behaviors, brain gene transcription, and the circulating metabolism. Our findings highlight the contributions of honeybee gut microbes in the neurological processes with striking parallels to those found in other animals, thus providing a promising model to understand the host-microbe interactions via the gut-brain axis.

microbiology↗

bioRxiv2020

An Adhesive Based Fabrication Technique for Culture of Lung Airway Epithelial Cells with Applications in Microfluidics and Lung on a Chip

1This work describes a versatile and cost-effective cell culture method for growing adherent cells on a porous membrane using pressure-sensitive double-sided adhesives. This technique allows cell culture using conventional methods and easy transfer to microfluidic chip devices. To support the viability of our system, we evaluate the toxicity effect of four different adhesives on two distinct airway epithelial cell lines and show functional applications for microfluidic cell culture chip fabrication. We showed that cells could be grown and expanded on a "floating" membrane, which can be transferred upon cell confluency to a microfluidic chip for further analysis. The viability of cells and their inflammatory responses to IL-1{beta} stimulation was investigated. Such a technique would be useful to culture cells in a conventional fashion, which is more convenient and faster, and stimulate cells in an advanced model with perfusion when needed.

bioengineering↗

bioRxiv2020

Transcriptome Profiling of different types of human respiratory tract cells infected by SARS-CoV-2 Highlight an unique Role for Inflammatory and Interferon Response

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) at the end of 2019 has caused a large global outbreak and now become a major public health issue. Lack of data underlying how the human host interacts with SARS-CoV-2 virus. In the current study, We performed Venn-analysis, Gene ontology (GO), KEGG pathway analysis and Protein-protein interaction analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during human respiratory tract cells infected with SARS-CoV-2. We selected four studies through a systematic search of the Gene Expression Omnibus (GEO) database or published article about SARS-CoV-2 infection in different types of respiratory tract cells. We found 36 overlapping upregulated genes among different types of cells after viral infection. Further functional enrichment analysis revealed these DEGs are most likely involved in biological processes related to inflammatory response and response to cytokine, cell component related to extracellular space and I-kappaB/NF-kappaB complex, molecular function related to protein binding and cytokine activity. KEGG pathways analysis highlighted altered conical and casual pathways related to TNF, NF-kappa B, Cytokine-cytokine receptor interaction and IL17 signaling pathways during SARS-CoV-2 infection with CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, IL32, CX3CL1, CCL20, IRF1, NFKB2 and NFKB1A up-regulated which may explain the inflammatory cytokine storms associated with severe cases of COVID-19.

immunology↗