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Yan Liu, Michael J Conboy, Melod Mehdipour, Yutong Liu, Thanhtra P Tran, Aaron Blotnick, Prasanna Rajan, Thalie Cavalcante Santos, Irina M Conboy
No abstract text is available yet for this article.
March 13, 2018: Nature Communications
Livia Garzia, Noriyuki Kijima, A Sorana Morrissy, Pasqualino De Antonellis, Ana Guerreiro-Stucklin, Borja L Holgado, Xiaochong Wu, Xin Wang, Michael Parsons, Kory Zayne, Alex Manno, Claudia Kuzan-Fischer, Carolina Nor, Laura K Donovan, Jessica Liu, Lei Qin, Alexandra Garancher, Kun-Wei Liu, Sheila Mansouri, Betty Luu, Yuan Yao Thompson, Vijay Ramaswamy, John Peacock, Hamza Farooq, Patryk Skowron, David J H Shih, Angela Li, Sherine Ensan, Clinton S Robbins, Myron Cybulsky, Siddhartha Mitra, Yussanne Ma, Richard Moore, Andy Mungall, Yoon-Jae Cho, William A Weiss, Jennifer A Chan, Cynthia E Hawkins, Maura Massimino, Nada Jabado, Michal Zapotocky, David Sumerauer, Eric Bouffet, Peter Dirks, Uri Tabori, Poul H B Sorensen, Priscilla K Brastianos, Kenneth Aldape, Steven J M Jones, Marco A Marra, James R Woodgett, Robert J Wechsler-Reya, Daniel W Fults, Michael D Taylor
While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases...
February 22, 2018: Cell
Yubin Huang, Zhen Xu, Shanshan Xiong, Fangfang Sun, Guangrong Qin, Guanglei Hu, Jingjing Wang, Lei Zhao, Yu-Xiang Liang, Tianzhun Wu, Zhonghua Lu, Mark S Humayun, Kwok-Fai So, Yihang Pan, Ningning Li, Ti-Fei Yuan, Yanxia Rao, Bo Peng
Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis...
February 22, 2018: Nature Neuroscience
Lalit K Beura, Sathi Wijeyesinghe, Emily A Thompson, Marissa G Macchietto, Pamela C Rosato, Mark J Pierson, Jason M Schenkel, Jason S Mitchell, Vaiva Vezys, Brian T Fife, Steven Shen, David Masopust
Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8+ T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes...
February 20, 2018: Immunity
Geraldine Gontier, Manasi Iyer, Jeremy M Shea, Gregor Bieri, Elizabeth G Wheatley, Miguel Ramalho-Santos, Saul A Villeda
Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis...
February 20, 2018: Cell Reports
Jeremie M Lever, Zhengqin Yang, Ravindra Boddu, Oreoluwa O Adedoyin, Lingling Guo, Reny Joseph, Amie M Traylor, Anupam Agarwal, James F George
The immune cellular compartment of the kidney is involved in organ development and homeostasis, as well as in many pathological conditions. Little is known about the mechanisms that drive intrarenal immune responses in the presence of renal tubular and interstitial cell death. However, it is known that tissue-resident leukocytes have the potential to have distinct roles compared with circulating cells. We used a parabiosis model in C57BL/6 CD45 congenic and green fluorescent protein transgenic mice to better understand the dynamics of immune cells in the kidney...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Julia Hoefer, Markus Luger, Christian Dal-Pont, Zoran Culig, Harald Schennach, Stefan Jochberger
Background: High blood levels of the chemokine eotaxin-1 (CCL11) have recently been associated with aging and dementia, as well as impaired memory and learning in humans. Importantly, eotaxin-1 was shown to pass the blood-brain-barrier (BBB) and has been identified as crucial mediator of decreased neurogenesis and cognitive impairment in young mice after being surgically connected to the vessel system of old animals in a parabiosis model. It thus has to be assumed that differences in eotaxin-1 levels between blood donors and recipients might influence cognitive functions also in humans...
2017: Frontiers in Aging Neuroscience
Matthew T Stier, Jian Zhang, Kasia Goleniewska, Jacqueline Y Cephus, Mark Rusznak, Lan Wu, Luc Van Kaer, Baohua Zhou, Dawn C Newcomb, R Stokes Peebles
Group 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and key participants in type 2 immune responses in the context of allergic inflammation and infection. ILC2s develop in the bone marrow from common lymphoid progenitor cells, but little is known about how ILC2s egress from the bone marrow for hematogenous trafficking. In this study, we identified a critical role for IL-33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of ILC2 lineage cells from the bone marrow...
January 2, 2018: Journal of Experimental Medicine
Toshihiro Kawasaki, Akiteru Maeno, Toshihiko Shiroishi, Noriyoshi Sakai
Age-related systemic environments influence neurogenesis and organ regeneration of heterochronic parabiotic partners; however, the difficulty of manipulating small embryos prevents the effects of aged systemic environments on primitive organs at the developmental stage from being analysed. Here, we describe a novel transplantation system to support whole living embryos/larvae as grafts in immunodeficient zebrafish by the intrusion of host blood vessels into the grafts, allowing bodies similar to those of heterochronic parabiosis to be generated by subcutaneous grafting...
November 28, 2017: Scientific Reports
Lucas K Smith, Charles W White, Saul A Villeda
Aging results in impaired neurogenesis in the two neurogenic niches of the adult mammalian brain, the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle. While significant work has characterized intrinsic cellular changes that contribute to this decline, it is increasingly apparent that the systemic environment also represents a critical driver of brain aging. Indeed, emerging studies utilizing the model of heterochronic parabiosis have revealed that immune-related molecular and cellular changes in the aging systemic environment negatively regulate adult neurogenesis...
January 2018: Cell and Tissue Research
Massimo Conese, Annalucia Carbone, Elisa Beccia, Antonella Angiolillo
Transfusion (or drinking) of blood or of its components has been thought as a rejuvenation method since ancient times. Parabiosis, the procedure of joining two animals so that they share each others blood circulation, has revitalized the concept of blood as a putative drug. Since 2005, a number of papers have reported the anti-ageing effect of heterochronic parabiosis, which is joining an aged mouse to a young partner. The hallmark of aging is the decline of regenerative properties in most tissues, partially attributed to impaired function of stem and progenitor cells...
2017: Open Medicine (Warsaw, Poland)
Qi Huang, Yichun Ning, Dong Liu, Ying Zhang, Diangeng Li, Yinping Zhang, Zhong Yin, Bo Fu, Guangyan Cai, Xuefeng Sun, Xiangmei Chen
Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys. The animals were divided into six groups: young (Ycon) and old (Ocon) control groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP) and heterochronic youth (Y-HP) elderly (O-HP) group...
October 13, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Jarrod A Call, Jean Donet, Kyle S Martin, Ashish K Sharma, Xiaobin Chen, Jiuzhi Zhang, Jie Cai, Carolina A Galarreta, Mitsuharu Okutsu, Zhongmin Du, Vitor A Lira, Mei Zhang, Borna Mehrad, Brian H Annex, Alexander L Klibanov, Russell P Bowler, Victor E Laubach, Shayn M Peirce, Zhen Yan
Multiple organ dysfunction syndrome (MODS) is a detrimental clinical complication in critically ill patients with high mortality. Emerging evidence suggests that oxidative stress and endothelial activation (induced expression of adhesion molecules) of vital organ vasculatures are key, early steps in the pathogenesis. We aimed to ascertain the role and mechanism(s) of enhanced extracellular superoxide dismutase (EcSOD) expression in skeletal muscle in protection against MODS induced by endotoxemia. We showed that EcSOD overexpressed in skeletal muscle-specific transgenic mice (TG) redistributes to other peripheral organs through the circulation and enriches at the endothelium of the vasculatures...
December 2017: Free Radical Biology & Medicine
Motohiko Kadoki, Ashwini Patil, Cornelius C Thaiss, Donald J Brooks, Surya Pandey, Deeksha Deep, David Alvarez, Ulrich H von Andrian, Amy J Wagers, Kenta Nakai, Tarjei S Mikkelsen, Magali Soumillon, Nicolas Chevrier
A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. First, analyzing ligand-receptor connectivity across tissues reveals that type I IFNs trigger a whole-body antiviral state, protecting the host within hours after skin vaccination...
October 5, 2017: Cell
Yan Liu, Michael J Conboy, Melod Mehdipour, Yutong Liu, Thanhtra P Tran, Aaron Blotnick, Prasanna Rajan, Thalie Cavalcante Santos, Irina M Conboy
Studies of heterochronic parabiosis demonstrated that with age, the composition of the circulatory milieu changes in ways that broadly inhibit tissue regenerative capacity. In addition, local tissue niches have age-specific influences on their resident stem cells. Here we use bio-orthogonal proteome labeling for detecting in vivo proteins present only in transplanted myoblasts, but not in host tissue, and proteins exclusive to one young mouse and transferred during parabiosis to its old partner. We use a transgenic mouse strain that ubiquitously expresses a modified tRNA methionine synthase, metRS, which preferentially incorporates the methionine surrogate azido-nor-leucine (ANL) into newly generated proteins...
September 21, 2017: Nature Communications
Sara Duhachek-Muggy, Kruttika Bhat, Erina Vlashi, Frank Pajonk
Total-body exposure to radiation causes widespread tissue injury. Damage to the hematopoietic and intestinal stem cell compartments is particularly lethal and mitigators of this damage are critical in providing effective treatment. Parabiosis radiation experiments, in which the vasculatures of two rodents are anastomosed prior to irradiation of one of the animals, have shown that there is a circulating factor that protects mice from radiation-induced intestinal death. Recently reported studies have suggested that growth differentiation factor 11 (GDF11) is responsible for the rejuvenation of stem cells observed in parabiosis experiments involving aging mice...
November 2017: Radiation Research
Alana M Horowitz, Saul A Villeda
Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan...
2017: F1000Research
Mai Nguyen-Chi, Béryl Laplace-Builhé, Jana Travnickova, Patricia Luz-Crawford, Gautier Tejedor, Georges Lutfalla, Karima Kissa, Christian Jorgensen, Farida Djouad
Macrophages are essential for appendage regeneration after amputation in regenerative species. The molecular mechanisms through which macrophages orchestrate blastema formation and regeneration are still unclear. Here, we use the genetically tractable and transparent zebrafish larvae to study the functions of polarized macrophage subsets during caudal fin regeneration. After caudal fin amputation, we show an early and transient accumulation of pro-inflammatory macrophages concomitant with the accumulation of non-inflammatory macrophages which, in contrast to pro-inflammatory macrophages, remain associated to the fin until the end of the regeneration...
August 10, 2017: Cell Death & Disease
John S Davies, Heather L Thompson, Vesna Pulko, Jose Padilla Torres, Janko Nikolich-Žugich
Age-related changes in primary lymphoid organs are well described. Less is known about age-related changes affecting peripheral lymphoid organs, although defects in old peripheral lymph nodes (pLN) were recently described in both steady state and during viral infection. To address whether such pLN defects were intrinsic to old T cells or extrinsic (due to aging microenvironment) we employed heterochronic parabiosis. We found no age-related intrinsic or extrinsic barriers to T cell circulation and seeding of pLN, spleen and bone marrow...
June 3, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Mevyn Nizard, Hélène Roussel, Mariana O Diniz, Soumaya Karaki, Thi Tran, Thibault Voron, Estelle Dransart, Federico Sandoval, Marc Riquet, Bastien Rance, Elie Marcheteau, Elizabeth Fabre, Marion Mandavit, Magali Terme, Charlotte Blanc, Jean-Baptiste Escudie, Laure Gibault, Françoise Le Pimpec Barthes, Clemence Granier, Luis C S Ferreira, Cecile Badoual, Ludger Johannes, Eric Tartour
Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments...
May 24, 2017: Nature Communications
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