Biology subjects

Cai, R.

Publications and source records attributed to Cai, R..

44 records · Page 3Linked to original sources

bioRxiv2020

Computational analysis suggests putative intermediate animal hosts of the SARS-CoV-2

The recent emerged SARS-CoV-2 may first transmit to intermediate animal host from bats before the spread to humans. The receptor recognition of ACE2 protein by SARS-CoVs or bat-originated coronaviruses is one of the most important determinant factors for the cross-species transmission and human-to-human transmission. To explore the hypothesis of possible intermediate animal host, we employed molecular dynamics simulation and free energy calculation to examine the binding of bat coronavirus with ACE2 proteins of 47 representing animal species collected from public databases. Our results suggest that intermediate animal host may exist for the zoonotic transmission of SARS-CoV-2. Furthermore, we found that tree shrew and ferret may be two putative intermediate hosts for the zoonotic spread of SARS-CoV-2. Collectively, the continuous surveillance of pneumonia in human and suspicious animal hosts are crucial to control the zoonotic transmission events caused by SARS-CoV-2.

bioinformatics↗

bioRxiv2020

Synthetic Agonist of Growth Hormone-Releasing Hormone as Novel Treatment for Heart Failure with Preserved Ejection Fraction

ObjectiveTo test the hypothesis that the activation of the growth hormone-releasing hormone (GHRH) receptor signaling pathway within the myocardium both prevents and reverses heart failure with preserved ejection fraction (HFpEF). BackgroundHFpEF is characterized by impaired myocardial relaxation, fibrosis and ventricular stiffness. Despite the rapidly increasing prevalence of HFpEF, no effective therapies have emerged. Synthetic agonists of the GHRH receptors reduce myocardial fibrosis, hypertrophy and improve performance, independently of the growth-hormone axis. MethodsWe generated a HFpEF-like phenotype with continuous infusion of angiotensin-II (Ang-II) in CD1 mice. Mice were injected with either vehicle or a potent synthetic agonist of the growth hormone-releasing hormone, MR-356. ResultsAng-II treated animals had diastolic dysfunction, ventricular hypertrophy, and normal ejection fraction and isolated cardiomyocytes (ex vivo) exhibited incomplete relaxation, depressed contractile responses and altered myofibrillar protein phosphorylation. Calcium handling mechanisms were disturbed in cardiomyocytes from mice with HFpEF. MR-356 both prevented and reversed the development of the pathological phenotype in vivo and ex vivo. ConclusionThese findings indicate that the GHRH receptor signaling pathway represents a new molecular target to counteract HFpEF-associated cardiomyocyte dysfunction by targeting myofilament phosphorylation. Accordingly, activation of the GHRH receptor with potent synthetic GHRH agonists may provide a novel therapeutic approach to management of the HFpEF syndrome. Condensed abstractHeart failure with preserved ejection fraction (HFpEF) is characterized by a remodeled myocardium conferring ventricular stiffness and diastolic dysfunction. There are no effective therapies. Agonists of growth hormone-releasing hormone (GHRH) receptors have beneficial effects on the heart. We hypothesize that activation of GHRH receptors suppresses this HFpEF phenotype. Treatment with a synthetic agonist of GHRH, prevented the development of the pathological phenotype in a murine model of HFpEF-induced by chronic angiotensin-II infusion. These findings indicate that activation of GHRH receptors represents a novel molecular strategy to counteract HFpEF-associated cardiomyocyte dysfunction and provide a potential approach to management of HFpEF syndrome. HighlightsO_LIA synthetic growth hormone-releasing hormone agonist (GHRH-A) prevents and reverses the pathological remodeling in a mouse model of HFpEF induced by infusion of low dose Ang II. C_LIO_LIGHRH-A improves intracellular calcium handling by reducing the sarcoplasmic reticulum calcium leakage and enhancing phospholamban phosphorylation. C_LIO_LIGHRH-A treatment prevents and reverses diastolic dysfunction by enhancing the rate of sarcomere re-lengthening. C_LIO_LIActivation of the GHRH receptor with the GHRH-A, MR-356, leads to targeting myofibrillar proteins and desensitizing myofilaments in response to calcium. C_LI

cell biology↗

bioRxiv2020

Heimdallarchaeota harness light energy through photosynthesis

Photosynthesis is an ancient process that originated after the origin of life, and has only been found in the Bacterial and Eukaryotic kingdoms, but has never been reported in any member of the domain Archaea. Heimdallarchaeota, a member of Asgard archaea, are supposed as the most probable candidates (to date) for the archaeal protoeukaryote ancestor and might exist in light-exposed habitats during their evolutionary history. Here we describe the discovery that Heimdallarchaeota genomes are enriched for proteins formerly considered specific to photosynthetic apparatus and are suggestive performing oxygenic photosynthesis. Our results provide strong support for hypotheses in which Heimdallarchaeota harvest light by bacteriochlorophyll and/or carotenoid, then transport electron from photosystems to Calvin-Benson-Bassham cycle along with CO2 fixation and ATP biosynthesis, and release oxygen as a waste product. Given the possessing of phototrophic lifestyle together with other anaerobic and aerobic metabolic pathways, Heimdallarchaeota are firmly believed to be photomixotrophic and have a facultative aerobic metabolism. Our results expand our knowledge that archaea have played an important role in the molecular evolution of eukaryotic photosynthesis and raise the significant possibility that Heimdallarchaeota might be ancestor of eukaryotic photosynthetic organisms.

microbiology↗

bioRxiv2020

Metagenomic insights into the metabolism and ecologic functions of the widespread DPANN archaea from deep-sea hydrothermal vents

Due to the particularity of metabolism and the importance of ecological roles, the archaea living in deep-sea hydrothermal system always attract great attention. Included, the DPANN superphylum archaea, which are massive radiation of organisms, distribute widely in hydrothermal environment, but their metabolism and ecology remain largely unknown. In this study, we assembled 20 DPANN genomes comprised in 43 reconstructed genomes from deep-sea hydrothermal sediments, presenting high abundance in the archaea kingdom. Phylogenetic analysis shows 6 phyla comprising Aenigmarchaeota, Diapherotrites, Nanoarchaeota, Pacearchaeota, Woesearchaeota and a new candidate phylum designated DPANN-HV-2 are included in the 20 DPANN archaeal members, indicating their wide diversity in this extreme environment. Metabolic analysis presents their metabolic deficiencies because of their reduced genome size, such as gluconeogenesis, de novo nucleotide and amino acid synthesis. However, they possess alternative and economical strategies to fill this gap. Furthermore, they were detected to have multiple capacities of assimilating carbon dioxide, nitrogen and sulfur compounds, suggesting their potentially important ecologic roles in the hydrothermal system. IMPORTANCEDPANN archaea show high distribution in the hydrothermal system. However, they possess small genome size and some incomplete biological process. Exploring their metabolism is helpful to know how such small lives adapt to this special environment and what ecological roles they play. It was ever rarely noticed and reported. Therefore, in this study, we provide some genomic information about that and find their various abilities and potential ecological roles. Understanding their lifestyles is helpful for further cultivating, exploring deep-sea dark matters and revealing microbial biogeochemical cycles in this extreme environment.

microbiology↗

bioRxiv2019

A 3D High Resolution Generative Deep-learning Network for Fluorescence Microscopy Image

Deep learning technology enables us acquire high resolution image from low resolution image in biological imaging free from sophisticated optical hardware. However, current methods require a huge number of the precisely registered low-resolution (LR) and high-resolution (HR) volume image pairs. This requirement is challengeable for biological volume imaging. Here, we proposed 3D deep learning network based on dual generative adversarial network (dual-GAN) framework for recovering HR volume images from LR volume images. Our network avoids learning the direct mappings from the LR and HR volume image pairs, which need precisely image registration process. And the cycle consistent network makes the predicted HR volume image faithful to its corresponding LR volume image. The proposed method achieves the recovery of 20x/1.0 NA volume images from 5x/0.16 NA volume images collected by light-sheet microscopy. In essence our method is suitable for the other imaging modalities.

neuroscience↗

bioRxiv2019

Cellular and Molecular Probing of Intact Transparent Human Organs

Optical tissue transparency permits cellular and molecular investigation of complex tissues in 3D, a fundamental need in biomedical sciences. Adult human organs are particularly challenging for this approach, owing to the accumulation of dense and sturdy molecules in decades-aged human tissues. Here, we introduce SHANEL method utilizing a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to generate the first intact transparent adult human brain and kidney, and perform 3D histology using antibodies and dyes in centimeters depth. Thereby, we revealed structural details of sclera, iris and suspensory ligament in the human eye, and the vessels and glomeruli in the human kidney. We also applied SHANEL on transgenic pig organs to map complex structures of EGFP expressing beta cells in >10 cm size pancreas. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of intact large mammalian organs.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC=\"FIGDIR/small/643908v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (89K):\norg.highwire.dtl.DTLVardef@14fea50org.highwire.dtl.DTLVardef@1a04274org.highwire.dtl.DTLVardef@6ae1fforg.highwire.dtl.DTLVardef@11b31b0_HPS_FORMAT_FIGEXP M_FIG C_FIG Supplementary Movies of SHANEL are available at http://discotechnologies.org/SHANEL/

cell biology↗

bioRxiv2019

Deep learning reveals cancer metastasis and therapeutic antibody targeting in whole body

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of tumor cells more than 100-fold by applying the vDISCO method to image single cancer cells in intact transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantifications in a model of spontaneous metastasis using human breast cancer cells allowed us to systematically analyze clinically relevant features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in whole mice. DeepMACT can thus considerably improve the discovery of effective therapeutic strategies for metastatic cancer. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/541862v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@ffe1b9org.highwire.dtl.DTLVardef@13c55eborg.highwire.dtl.DTLVardef@2ccb6corg.highwire.dtl.DTLVardef@df55e9_HPS_FORMAT_FIGEXP M_FIG C_FIG Supplementary Movies and deep learning algorithms of DeepMACT are available at http://discotechnologies.org/DeepMACT/

cancer biology↗

bioRxiv2018

Panoptic vDISCO imaging reveals neuronal connectivity, remote trauma effects and meningeal vessels in intact transparent mice

Analysis of entire transparent rodent bodies could provide holistic information on biological systems in health and disease. However, it has been challenging to reliably image and quantify signal from endogenously expressed fluorescent proteins in large cleared mouse bodies due to the low signal contrast. Here, we devised a pressure driven, nanobody based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image subcellular details in transparent mouse bodies through bones and highly autofluorescent tissues, and perform quantifications. We visualized for the first-time whole-body neuronal connectivity of an entire adult mouse and discovered that brain trauma induces degeneration of peripheral axons. We also imaged meningeal lymphatic vessels and immune cells through the intact skull and vertebra in naive animals and trauma models. Thus, our new approach can provide an unbiased holistic view of biological events affecting the nervous system and the rest of the body.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC=\"FIGDIR/small/374785_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (62K):\norg.highwire.dtl.DTLVardef@8fad72org.highwire.dtl.DTLVardef@c41ed5org.highwire.dtl.DTLVardef@1c470eaorg.highwire.dtl.DTLVardef@1d144cb_HPS_FORMAT_FIGEXP M_FIG C_FIG Note: Manuscript videos are available at Supplementary material section of BioRxiv and at the following link http://vdisco.isd-muc.de/

neuroscience↗