scholarly journals Multi-omics Integrative Analysis of Acute and Relapsing Malaria in a Non-Human Primate Model ofP. vivaxinfection

2019 ◽  
Author(s):  
Yan Tang ◽  
Chester J Joyner ◽  
Regina J Cordy ◽  
Mary R Galinski ◽  
Tracey J Lamb ◽  
...  

SummarySystems-scale analysis of multiple layers of molecular and cellular data has significant potential for providing novel insights into malaria pathology and immunity. We present here a unique longitudinal multi-omics dataset encompassingMacaca mulattablood and bone marrow responses to infection byPlasmodium cynomolgi, a non-human primate (NHP) parasite species used to modelP. vivaxmalaria acute and relapsing infections in humans. We analyzed relationships across multiple biological layers using a mutual information-based machine learning approach to integrate heterogeneous longitudinal datasets and constructed an atlas of multi-omics relatedness networks (MORNs). Using this technique, we were able to detect signatures that defined both acute and relapsing infections. Importantly, relapse infections could be distinguished from both acutely-infected and uninfected NHP, suggesting that the host-parasite interactions during relapses are unique compared to acutePlasmodiuminfections. To our knowledge, this is the first report of large-scale, longitudinal multi-omics analysis of malaria in any system. This dataset, along with the method used to analyze it, provides a unique resource for the malaria research community and demonstrates the power of longitudinal infection study designs, NHP model systems and integrative multi-omics analyses.

2020 ◽  
Author(s):  
Ran Yang ◽  
Alexander Goedel ◽  
Yu Kang ◽  
Chenyang Si ◽  
Chu Chu ◽  
...  

AbstractEssential genes for murine embryonic development can demonstrate a disparate phenotype in human cohorts. By generating a transcriptional atlas containing >30,000 cells from postimplantation non-human primate embryos, we discovered that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 resulted in non-human primate embryos which did not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos displayed a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirmed a similar role of ISL1 in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ran Yang ◽  
Alexander Goedel ◽  
Yu Kang ◽  
Chenyang Si ◽  
Chu Chu ◽  
...  

AbstractEmbryonic development is largely conserved among mammals. However, certain genes show divergent functions. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we uncover that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 results in non-human primate embryos which do not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos display a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirm a similar role of ISL1 in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.


1996 ◽  
Author(s):  
S. C. Koenig ◽  
Craig Reister ◽  
J. Schtaub ◽  
Gary Muniz ◽  
Tim Fergusan

Life Sciences ◽  
2021 ◽  
Vol 276 ◽  
pp. 119374
Author(s):  
Roghayeh Navabi ◽  
Babak Negahdari ◽  
Ensiyeh Hajizadeh-Saffar ◽  
Mostafa Hajinasrollah ◽  
Yaser Jenab ◽  
...  

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 584
Author(s):  
Natalia Nunez ◽  
Louis Réot ◽  
Elisabeth Menu

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Robert W. Cross ◽  
Zachary A. Bornholdt ◽  
Abhishek N. Prasad ◽  
Viktoriya Borisevich ◽  
Krystle N. Agans ◽  
...  

AbstractMonoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.


2017 ◽  
Vol 140 ◽  
pp. 95-105 ◽  
Author(s):  
Géraldine Piorkowski ◽  
Frédéric Jacquot ◽  
Gilles Quérat ◽  
Caroline Carbonnelle ◽  
Delphine Pannetier ◽  
...  

2007 ◽  
Vol &NA; ◽  
pp. S8
Author(s):  
Ponpan Matangkasombut ◽  
Muriel Pichavant ◽  
Takahiro Yasumi ◽  
Carrie Hendricks ◽  
Rosemarie H. DeKruyff ◽  
...  

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