scholarly journals A56 Visualization of recombination in deformed wing virus infecting bees

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Diane Bigot ◽  
Andreas Gogol-Döring ◽  
Peter Koch ◽  
Robert J Paxton
Keyword(s):  
Honey Bees ◽  
Bumble Bees ◽  
Next Generation Sequencing Data ◽  
Sequencing Data ◽  
Wild Bees ◽  
Deformed Wing Virus ◽  
The Impact ◽  
Detection And Quantification

Abstract Honey bees suffer increasing colony mortality worldwide, partially caused by the spread of viral pathogens. Among these pathogens, deformed wing virus (DWV) is one of the major, widespread viruses of honey bees resulting in wing deformities and weakening colonies. DWV can be found in honey bees, bumble bees, and other wild bees as three major genotypes named DWV-A, -B (also named Varroa destructor virus 1), and -C. Various recombinants of DWV-A and -B have been previously found in honey bees, some of which have been suggested to have higher virulence over non-recombinant, parental virus. In most of these cases, recombinants were only shown as consensus sequences from previous assemblies and alignments and may not reflect the biological reality of all variants present within a host bee. It is therefore important to build a method of recombinant detection and quantification within mixed infections in single-host individuals, including both parental and various recombinant genomes, so as to evaluate the relevance of recombinants for viral genome evolution and the impact on hosts. Here, we propose to visualize and quantify these recombinants using next-generation sequencing data to better understand how these genomes evolve within bees. Our method will be performed directly from raw sequence reads from various datasets (including field and lab experiments as well as screening of public databases) in order to obtain an overview of DWV recombination in various in vivo and in vitro conditions. Recombination of viral genomes is a key point for virus evolution. The detection and quantification of recombination will facilitate analysis of the determinants of recombination and help in understanding the routes by which new viral variants emerge. The emergence of new (more virulent) recombinant viruses can result from acquisition of new capabilities, such as escape from host immunity or increased transmission rates. Recombination can also lead to adaptation to new environments and new hosts by a change in cell tropism, allowing cross-species transmission, which may be particularly relevant for bumble bees and wild bees infected by honey bee-derived DWV.

scholarly journals Macrophage proliferation machinery leads to PDAC progression, but susceptibility to innate immunotherapy.

2021 ◽  
Author(s):  
David G DeNardo ◽  
Chong Zuo ◽  
John M. Baer ◽  
Brett L. Knolhoff ◽  
Jad I. Belle ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Genetically Engineered ◽  
Macrophage Phenotype ◽  
Sequencing Data ◽  
In Vitro Systems ◽  
Regulation Of Cell Cycle ◽  
The Impact

Tumor-associated macrophages (TAMs) are involved in many aspects of cancer progression and correlate with poor clinical outcomes in many cancer types, including pancreatic ductal adenocarcinomas (PDACs). Previous studies have shown that TAMs can populate PDAC tumors not only by monocyte recruitment but also by local proliferation. However, the impact local proliferation might have on macrophage phenotype and cancer progression is unknown. Here, we utilized genetically engineered cancer models, single-cell RNA-sequencing data, and in vitro systems to show that proliferation of TAMs was driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. The p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling p21 expression levels in TAMs, we found that p21-driven macrophage immunosuppression in vivo drove tumor progression. Serendipitously, the same p21-driven pathways that drive tumor progression, also drive response to CD40 agonist. These data suggest that stromal or therapy-induced regulation of cell cycle machinery can regulate both macrophage-mediated immune suppression and susceptibility to innate immunotherapy.

scholarly journals The relationship between managed bees and the prevalence of parasites in bumblebees

2014 ◽  
Author(s):  
Peter Graystock ◽  
Dave Goulson ◽  
William O Hughes
Keyword(s):  
Honey Bee ◽  
Honey Bees ◽  
Parasite Prevalence ◽  
Wild Bees ◽  
Deformed Wing Virus ◽  
Nosema Bombi ◽  
Crithidia Bombi ◽  
Parasite Spillover ◽  
The Impact ◽  
The Relationship

Honey bees and, more recently, bumblebees have been domesticated and are now managed commercially primarily for crop pollination, mixing with wild pollinators during foraging on shared flower resources. There is mounting evidence that managed honey bees or commercially produced bumblebees may affect the health of wild pollinators such as bumblebees by increasing competition for resources and the prevalence of parasites in wild bees. Here we screened 764 bumblebees from around five greenhouses that either used commercially produced bumblebees or did not, as well as bumblebees from 10 colonies placed at two sites either close to or far from a honey bee apiary, for the parasites Apicystis bombi, Crithidia bombi, Nosema bombi, N. ceranae, N. apis and deformed wing virus. We found that A. bombi and C. bombi were more prevalent around greenhouses using commercially produced bumblebees, while C. bombi was 18% more prevalent in bumblebees at the site near to the honey bee apiary than those at the site far from the apiary. Whilst these results are from only a limited number of sites, they support previous reports of parasite spillover from commercially produced bumblebees to wild bumblebees, and suggest that the impact of stress from competing with managed bees or the vectoring of parasites by them on parasite prevalence in wild bees needs further investigation. It appears increasingly likely that the use of managed bees comes at a cost of increased parasites in wild bumblebees, which is not only a concern for bumblebee conservation, but which may impact other pollinators as well.

scholarly journals DENA: training an authentic neural network model using Nanopore sequencing data of Arabidopsis transcripts for detection and quantification of N6-methyladenosine on RNA

2021 ◽  
Author(s):  
Xuan Li ◽  
Hang Qin ◽  
Liang Ou ◽  
Jian Gao ◽  
Longxian Chen ◽  
...  
Keyword(s):  
Neural Network ◽  
Rna Sequencing ◽  
Neural Network Model ◽  
Nanopore Sequencing ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Superimposed Signals ◽  
Detection And Quantification

Models developed using Nanopore direct RNA sequencing data from in vitro synthetic RNA with all adenosine replaced by N6-methyladenosine (m6A), are likely distorted due to superimposed signals from saturated m6A residues. Here, we develop a neural network, DENA, for m6A quantification using the sequencing data of in vivo transcripts from Arabidopsis. DENA identifies 90% of miCLIP-detected m6A sites in Arabidopsis, and obtains modification rates in human consistent to those found by SCARLET, demonstrating its robustness across species. We sequence the transcriptome of two additional m6A-deficient Arabidopsis, mtb and fip37-4, using Nanopore and evaluate their single-nucleotide m6A profiles using DENA.

scholarly journals The relationship between managed bees and the prevalence of parasites in bumblebees

2014 ◽  
Author(s):  
Peter Graystock ◽  
Dave Goulson ◽  
William O Hughes
Keyword(s):  
Honey Bee ◽  
Honey Bees ◽  
Parasite Prevalence ◽  
Wild Bees ◽  
Deformed Wing Virus ◽  
Nosema Bombi ◽  
Crithidia Bombi ◽  
Parasite Spillover ◽  
The Impact ◽  
The Relationship

Honey bees and, more recently, bumblebees have been domesticated and are now managed commercially primarily for crop pollination, mixing with wild pollinators during foraging on shared flower resources. There is mounting evidence that managed honey bees or commercially produced bumblebees may affect the health of wild pollinators such as bumblebees by increasing competition for resources and the prevalence of parasites in wild bees. Here we screened 764 bumblebees from around five greenhouses that either used commercially produced bumblebees or did not, as well as bumblebees from 10 colonies placed at two sites either close to or far from a honey bee apiary, for the parasites Apicystis bombi, Crithidia bombi, Nosema bombi, N. ceranae, N. apis and deformed wing virus. We found that A. bombi and C. bombi were more prevalent around greenhouses using commercially produced bumblebees, while C. bombi was 18% more prevalent in bumblebees at the site near to the honey bee apiary than those at the site far from the apiary. Whilst these results are from only a limited number of sites, they support previous reports of parasite spillover from commercially produced bumblebees to wild bumblebees, and suggest that the impact of stress from competing with managed bees or the vectoring of parasites by them on parasite prevalence in wild bees needs further investigation. It appears increasingly likely that the use of managed bees comes at a cost of increased parasites in wild bumblebees, which is not only a concern for bumblebee conservation, but which may impact other pollinators as well.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals GCH1 induces immunosuppression through metabolic reprogramming and IDO1 upregulation in triple-negative breast cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002383
Author(s):  
Jin-Li Wei ◽  
Si-Yu Wu ◽  
Yun-Song Yang ◽  
Yi Xiao ◽  
Xi Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Taxonomy ◽  
Underlying Mechanism ◽  
Metabolic Reprogramming ◽  
Sequencing Data ◽  
Aryl Hydrocarbon

PurposeRegulatory T cells (Tregs) heavily infiltrate triple-negative breast cancer (TNBC), and their accumulation is affected by the metabolic reprogramming in cancer cells. In the present study, we sought to identify cancer cell-intrinsic metabolic modulators correlating with Tregs infiltration in TNBC.Experimental designUsing the RNA-sequencing data from our institute (n=360) and the Molecular Taxonomy of Breast Cancer International Consortium TNBC cohort (n=320), we calculated the abundance of Tregs in each sample and evaluated the correlation between gene expression levels and Tregs infiltration. Then, in vivo and in vitro experiments were performed to verify the correlation and explore the underlying mechanism.ResultsWe revealed that GTP cyclohydrolase 1 (GCH1) expression was positively correlated with Tregs infiltration and high GCH1 expression was associated with reduced overall survival in TNBC. In vivo and in vitro experiments showed that GCH1 increased Tregs infiltration, decreased apoptosis, and elevated the programmed cell death-1 (PD-1)-positive fraction. Metabolomics analysis indicated that GCH1 overexpression reprogrammed tryptophan metabolism, resulting in L-5-hydroxytryptophan (5-HTP) accumulation in the cytoplasm accompanied by kynurenine accumulation and tryptophan reduction in the supernatant. Subsequently, aryl hydrocarbon receptor, activated by 5-HTP, bound to the promoter of indoleamine 2,3-dioxygenase 1 (IDO1) and thus enhanced the transcription of IDO1. Furthermore, the inhibition of GCH1 by 2,4-diamino-6-hydroxypyrimidine (DAHP) decreased IDO1 expression, attenuated tumor growth, and enhanced the tumor response to PD-1 blockade immunotherapy.ConclusionsTumor-cell-intrinsic GCH1 induced immunosuppression through metabolic reprogramming and IDO1 upregulation in TNBC. Inhibition of GCH1 by DAHP serves as a potential immunometabolic strategy in TNBC.

scholarly journals The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhicheng Zheng ◽  
Peiyu Liang ◽  
Baohua Hou ◽  
Xin Lu ◽  
Qianwen Ma ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neurological Diseases ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Sequencing Data ◽  
Migration Ability ◽  
Dpp4 Inhibitor ◽  
Phenotypic Transformation

Abstract Background Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown. Methods Analysis of public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for epilepsy related to DAM conversion. Anti-epileptic effect was assessed by electroencephalogram recordings and immunohistochemistry in a kainic acid (KA)-induced mouse model of epilepsy. The phenotype, morphology and function of microglia were assessed by qPCR, western blotting and microscopic imaging. Results Our results demonstrated that DPP4 participated in DAM conversion and epilepsy. The treatment of sitagliptin (a DPP4 inhibitor) attenuated KA-induced epilepsy and promoted the expression of DAM markers (Itgax and Axl) in both mouse epilepsy model in vivo and microglial inflammatory model in vitro. With sitagliptin treatment, microglial cells did not display an inflammatory activation state (enlarged cell bodies). Furthermore, these microglia exhibited complicated intersections, longer processes and wider coverage of parenchyma. In addition, sitagliptin reduced the activation of NF-κB signaling pathway and inhibited the expression of iNOS, IL-1β, IL-6 and the proinflammatory DAM subset gene CD44. Conclusion The present results highlight that the DPP4 inhibitor sitagliptin can attenuate epilepsy and promote DAM phenotypic transformation. These DAM exhibit unique morphological features, greater migration ability and better surveillance capability. The possible underlying mechanism is that sitagliptin can reduce the activation of NF-κB signaling pathway and suppress the inflammatory response mediated by microglia. Thus, we propose DPP4 may act as an attractive direction for DAM research and a potential therapeutic target for epilepsy.

scholarly journals Transcriptional Profiling of Porcine Blastocysts Produced In Vitro in a Chemically Defined Culture Medium

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1414
Author(s):  
Josep M. Cambra ◽  
Emilio A. Martinez ◽  
Heriberto Rodriguez-Martinez ◽  
Maria A. Gil ◽  
Cristina Cuello
Keyword(s):  
Culture Medium ◽  
Embryo Quality ◽  
Transcriptional Profiling ◽  
Defined Medium ◽  
Platelet Factor ◽  
Defined Media ◽  
Defined Culture ◽  
The Impact

The development of chemically defined media is a growing trend in in vitro embryo production (IVP). Recently, traditional undefined culture medium with bovine serum albumin (BSA) has been successfully replaced by a chemically defined medium using substances with embryotrophic properties such as platelet factor 4 (PF4). Although the use of this medium sustains IVP, the impact of defined media on the embryonic transcriptome has not been fully elucidated. This study analyzed the transcriptome of porcine IVP blastocysts, cultured in defined (PF4 group) and undefined media (BSA group) by microarrays. In vivo-derived blastocysts (IVV group) were used as a standard of maximum embryo quality. The results showed no differentially expressed genes (DEG) between the PF4 and BSA groups. However, a total of 2780 and 2577 DEGs were detected when comparing the PF4 or the BSA group with the IVV group, respectively. Most of these genes were common in both in vitro groups (2132) and present in some enriched pathways, such as cell cycle, lysosome and/or metabolic pathways. These results show that IVP conditions strongly affect embryo transcriptome and that the defined culture medium with PF4 is a guaranteed replacement for traditional culture with BSA.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

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