scholarly journals Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages

2020 ◽  
Vol 5 (48) ◽  
pp. eabc4466 ◽  
Author(s):  
C. C. Bain ◽  
D. A. Gibson ◽  
N. J. Steers ◽  
K. Boufea ◽  
P. A. Louwe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Metastatic Cancer ◽  
Immune Surveillance ◽  
Peritoneal Macrophages ◽  
The Body ◽  
Sexually Dimorphic ◽  
Differential Rate ◽  
Mapping Techniques ◽  
And Function ◽  
The Impact

Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis, and metastatic cancer; thus, understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover, and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single-cell RNA sequencing revealed marked dimorphisms in gene expression between male and female peritoneal macrophages that was, in part, explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2−/− mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow, whereas others are reliant on local microenvironment signals. We demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious diseases.

scholarly journals Origin and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages

2019 ◽  
Author(s):  
Calum C. Bain ◽  
Douglas A. Gibson ◽  
Nicholas Steers ◽  
Katarina Boufea ◽  
Pieter A. Louwe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Metastatic Cancer ◽  
Immune Surveillance ◽  
Peritoneal Macrophages ◽  
The Body ◽  
Sexually Dimorphic ◽  
Differential Rate ◽  
Mapping Techniques ◽  
And Function ◽  
The Impact

AbstractMacrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the aetiology of pathologies including peritonitis, endometriosis and metastatic cancer thus understanding the factors that govern their behaviour is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single cell RNAseq revealed striking dimorphisms in gene expression between male and female peritoneal macrophages that was in part explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2−/− mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow while others are reliant on local microenvironment signals. Importantly, we demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious disease.

Biology of bone marrow-derived endothelial cell precursors

2007 ◽  
Vol 292 (1) ◽  
pp. H1-H18 ◽  
Author(s):  
Gina C. Schatteman ◽  
Martine Dunnwald ◽  
Chunhua Jiao
Keyword(s):  
Bone Marrow ◽  
Endothelial Cell ◽  
Marrow Cell ◽  
Tumor Type ◽  
Physiological Relevance ◽  
Bone Marrow Derived Cells ◽  
And Function ◽  
Endothelial Nitric Oxide ◽  
The Impact ◽  
Endothelial Precursors

Over the past decade, the old idea that the bone marrow contains endothelial cell precursors has become an area of renewed interest. While some still believe that there are no endothelial precursors in the blood, even among those who do, there is no consensus as to what they are or what they do. In this review, we describe the problems in identifying endothelial cells and conclude that expression of endothelial nitric oxide synthase may be the most reliable antigenic indicator of the phenotype. The evidence for two different classes of endothelial precursors is also presented. We suggest that, though there is no single endothelial cell precursor, we may be able to use these phenotypic variations to our advantage in better understanding their biology. We also discuss how a variety of genetic, epigenetic, and methodological differences can account for the seemingly contradictory findings on the physiological relevance of bone marrow-derived precursors in normal vascular maintenance and in response to injury. Data on the impact of tumor type and location on the contribution of bone marrow-derived cells to the tumor vasculature are also presented. These data provide hope that we may ultimately be able to predict those tumors in which bone marrow-derived cells will have a significant contribution and design therapies accordingly. Finally, factors that regulate bone marrow cell recruitment to and function in the endothelium are beginning to be identified, and several of these, including stromal derived factor 1, monocyte chemoattractant factor-1, and vascular endothelial growth factor are discussed.

scholarly journals Sexual dimorphism in a top predator ( Notophthalmus viridescens ) drives aquatic prey community assembly

2018 ◽  
Vol 285 (1890) ◽  
pp. 20181717 ◽  
Author(s):  
Denon Start ◽  
Stephen De Lisle
Keyword(s):  
Sexual Dimorphism ◽  
Sex Ratio ◽  
Intraspecific Variation ◽  
Structure And Function ◽  
Sexually Dimorphic ◽  
Ecological Communities ◽  
Top Predator ◽  
Aquatic Mesocosms ◽  
And Function ◽  
The Impact

Intraspecific variation can have important consequences for the structure and function of ecological communities, and serves to link community ecology to evolutionary processes. Differences between the sexes are an overwhelmingly common form of intraspecific variation, but its community-level consequences have never been experimentally investigated. Here, we manipulate the sex ratio of a sexually dimorphic predacious newt in aquatic mesocosms, then track their impact on prey communities. Female and male newts preferentially forage in the benthic and pelagic zones, respectively, causing corresponding reductions in prey abundances in those habitats. Sex ratio differences also explained a large proportion (33%) of differences in the composition of entire pond communities. Ultimately, we demonstrate the impact of known patterns of sexual dimorphism in a predator on its prey, uncovering overlooked links between evolutionary adaptation and the structure of contemporary communities. Given the extreme prevalence of sexual dimorphism, we argue that the independent evolution of the sexes will often have important consequences for ecological communities.

scholarly journals Regulatory Roles of Bone in Neurodegenerative Diseases

2020 ◽  
Vol 12 ◽  
Author(s):  
Zhengran Yu ◽  
Zemin Ling ◽  
Lin Lu ◽  
Jin Zhao ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
The Elderly ◽  
Lymphoid Organ ◽  
The Body ◽  
Hematopoietic Stem ◽  
Brain Functions ◽  
And Function ◽  
The Impact ◽  
The Brain

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

Characterization of Extramedullary Acute Myeloid Leukemia – Results of the AML96 Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2154-2154
Author(s):  
Friedrich Stölzel ◽  
Christoph Röllig ◽  
Michael Kramer ◽  
Brigitte Mohr ◽  
Uta Oelschlägel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
The Body ◽  
Hematopoietic Stem ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
The Impact ◽  
Acute Myeloid

Abstract Abstract 2154 Background: Myeloid Sarcoma (MS) is defined as an extramedullary mass composed of myeloid blasts occurring at an anatomical site other than the bone marrow. Furthermore, the term extramedullary manifestation (EM) is applied if it accompanies overt acute myeloid leukemia (AML) and represents non-effacing tissue infiltration. EM is reported to correspond often to the skin but can affect almost every site of the body. The prognosis of MS or EM has been discussed controversially in the past. EM at diagnosis of AML is generally thought to be a rare event. However, data defining the prevalence of EM at diagnosis of AML and its prognostic value are missing. The aim of this analysis was to provide data for estimating the prevalence of EM at diagnosis of AML and to determine its relevance by including clinical and laboratory data from patients being treated in the prospective AML96 trial of the Study Alliance Leukemia (SAL) study group. Patients and Methods: A total of 326 patients with AML (age 17 – 83 years) and EM were treated within the AML96 trial with a median follow up of 8.8 years (95% CI, 8.4 to 9.3 years). All patients received double induction chemotherapy. Consolidation therapy contained high-dose cytosine arabinoside and for patients ≤ 60 years of age the option of autologous or allogeneic hematopoietic stem cell transplantation (HSCT). Logistic regression analyses were used to identify prognostic variables for CR rates. The method of Kaplan-Meier was used to estimate OS and EFS. Confidence interval (CI) estimation for the survival curves was based on the cumulative hazard function using the Greenwood's formula for the SE estimation. Survival distributions were compared using the log rank test. Results: 17% of the AML patients entered into the AML96 trial were diagnosed with EM. In 313 of the 326 patients (96%) EM was evident at diagnosis. The majority of patients with EM were diagnosed with de novo AML (84%, n=273), whereas gingival infiltration (51%, n=166) displayed the main EM of AML with CNS involvement being less common (4%, n=14). The majority of patients had a cytogenetic intermediate risk profile (71%, n=221) with a total of 172 patients (56%) harboring a normal karyotype. Patients with EM had a statistically significant lower median CD34-positivity of bone marrow blasts, higher percentage of FAB subtypes M4 and M5, higher WBC counts and LDH at diagnosis and higher percentage of NPM1 mutations compared to those patients without EM (all p<.001). When comparing achievement of CR between patients with EM to patients without EM, no statistical difference between these two groups was observed. Analysis according to the NPM1/FLT3-ITD mutation status revealed highest 5-year-OS (37%, 95% CI: .24 - .508) and 5-year-EFS (36%, 95% CI: .224 - .448) in the NPM1-mut/FLT3-wt group and lowest 5-year-OS (12%, 95% CI: 0 - .261) and 5-year-EFS (4%, 95% CI: 0 - .124) in the NPM1-wt/FLT3-ITD group, p=.007 and p=.001, respectively. Of the 49 relapsed patients with EM who had a NPM1-mutation at diagnosis 48 deceased despite of intensified relapse therapies. Conclusions: This analysis represents the largest study so far investigating the impact of EM AML. Patients with EM AML have distinct differences from AML patients without EM regarding their clinical and molecular characteristics at diagnosis. However these differences do not translate into differences in response to induction chemotherapy. Compared to patients without EM, survival analysis revealed differences according to the NPM1/FLT3-ITD mutation status which is also described for patients without EM AML. However, the prognosis for patients with EM who harbor a mutated NPM1 the prognosis at relapse seems to be dismal. Disclosures: No relevant conflicts of interest to declare.

The Impact of Maternal Preeclampsia and Hyperglycemia on the Cardiovascular Health of the Offspring: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Zahra Hoodbhoy ◽  
Nuruddin Mohammed ◽  
Karim Rizwan Nathani ◽  
Saima Sattar ◽  
Devyani Chowdhury ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Composition ◽  
Birth Weight ◽  
Vascular Function ◽  
Cardiovascular Health ◽  
Meta Analysis ◽  
The Body ◽  
Cochrane Library ◽  
And Function ◽  
The Impact

Objectives The objective of this review was to assess the impact of maternal preeclampsia or hyperglycemia on the body composition and cardiovascular health in the offspring. Study Design We conducted a systematic review utilizing PubMed, EBSCO, CINAHLPlus, Cochrane Library, and Web of Science to include all studies assessing the impact of preeclampsia/eclampsia and/or gestational/pregestational diabetes mellitus on the health of the offspring (children <10 years of age). The health measures included anthropometry, cardiac dimensions and function, and vascular function. We performed a meta-analysis using Review Manager software and computed net risk ratio (RR) with 95% confidence interval (CI) for dichotomous data and mean difference (MD) with 95% CI for continuous data. Results There were 6,376 studies in total, of which 45 were included in the review and 40 in the meta-analysis. The results demonstrated higher birth weight (MD: 0.12 kg; 95% CI: 0.06–0.18) and systolic and diastolic blood pressure (BP; MD: 5.98 mmHg; 95% CI: 5.64–6.32 and MD: 3.27 mmHg; 95% CI: 0.65–5.89, respectively) in the offspring of mothers with gestational diabetes compared to controls. In contrast, the offspring of mothers with preeclampsia had lower birth weight (MD: −0.41 kg; 95% CI: −0.7 to −0.11); however, they had increased systolic (MD: 2.2 mmHg; 95% CI: 1.28–3.12) and diastolic BP (MD: 1.41 mmHg; 95% CI: 0.3–2.52) compared to controls. There is lack of data to conduct a meta-analysis of cardiac morphology, functional, and vascular imaging parameters. Conclusion These findings suggest that the in-utero milieu can have a permanent impact on the body composition and vascular health of the offspring. Future work warrants multicenter prospective studies to understand the mechanism and the actual effect of exposure to maternal hyperglycemia and high BP on the cardiovascular health of the offspring and long-term outcomes. Key Points

scholarly journals Iodothyronine deiodinase structure and function: from ascidians to humans

2012 ◽  
Vol 215 (2) ◽  
pp. 189-206 ◽  
Author(s):  
Veerle M Darras ◽  
Stijn L J Van Herck
Keyword(s):  
Developmental Stages ◽  
The Body ◽  
Thyroid Status ◽  
Iodothyronine Deiodinase ◽  
Relative Contribution ◽  
Iodothyronine Deiodinases ◽  
Different Types ◽  
And Function ◽  
The Impact

Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3′-triiodothyronine (T3) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyronine deiodinases (D1, D2 and D3) have been identified in vertebrates from fish to mammals. They share several common characteristics, including a selenocysteine residue in their catalytic centre, but show also some type-specific differences. These specific characteristics seem very well conserved for D2 and D3, while D1 shows more evolutionary diversity related to itsKm, 6-n-propyl-2-thiouracil sensitivity and dependence on dithiothreitol as a cofactorin vitro. The three deiodinase types have an impact on systemic T3levels and they all contribute directly or indirectly to intracellular T3availability in different tissues. The relative contribution of each of them, however, varies amongst species, developmental stages and tissues. This is especially true for amphibians, where the impact of D1 may be minimal. D2 and D3 expression and activity respond to thyroid status in an opposite and conserved way, while the response of D1 is variable, especially in fish. Recently, a number of deiodinases have been cloned from lower chordates. Both urochordates and cephalochordates possess selenodeiodinases, although they cannot be classified in one of the three vertebrate types. In addition, the cephalochordate amphioxus also expresses a non-selenodeiodinase. Finally, deiodinase-like sequences have been identified in the genome of non-deuterostome organisms, suggesting that deiodination of externally derived THs may even be functionally relevant in a wide variety of invertebrates.

scholarly journals The impact of aging on memory T cell phenotype and function in the human bone marrow

2011 ◽  
Vol 91 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Dietmar Herndler-Brandstetter ◽  
Katja Landgraf ◽  
Alexandar Tzankov ◽  
Brigitte Jenewein ◽  
Regina Brunauer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Phenotype ◽  
Memory T Cell ◽  
And Function ◽  
The Impact

scholarly journals Development and Physiological Functions of the Lymphatic System - Insights from Genetic Studies of Lymphedema

2021 ◽  
Author(s):  
Silvia Martin-Almedina ◽  
Peter Mortimer ◽  
Pia Ostergaard
Keyword(s):  
Lymphatic System ◽  
Imaging Techniques ◽  
The Body ◽  
Genetic Studies ◽  
Disease Mechanisms ◽  
Primary Lymphedema ◽  
And Function ◽  
The Impact

Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focusses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic gene dysfunction can affect immune function so leading to infection; it can influence cancer development and spread; and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological function of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.

scholarly journals The mouse bone metabolome is sexually dimorphic and is associated with whole bone strength

2021 ◽  
Author(s):  
Hope D Welhaven ◽  
Ghazal Vahidi ◽  
Seth T Walk ◽  
Brian Bothner ◽  
Chelsea M Heveran ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cortical Bone ◽  
Bone Tissue ◽  
Material Properties ◽  
High Strength ◽  
Metabolic Profiles ◽  
Sexually Dimorphic ◽  
Female Mice ◽  
Show Evidence ◽  
The Impact

The material properties of bone tissue depend on the activity of remodeling bone cells, but the impact of bone cell metabolism on bone tissue is uncertain. To date, the metabolome of bone has not been evaluated for cortical bone, bone marrow, or whole bone including both tissue types. Furthermore, it is of particular interest whether the cortical bone metabolome reflects the sexual dimorphism observed in cortical bone material properties. We hypothesized that the metabolome of cortical bone differs from that of bone marrow, and that the cortical bone metabolome is sexually dimorphic. We first evaluated the metabolic profiles of isolated cortical bone, bone marrow, and whole bone for 20-week female C57Bl/6 mice (n = 10). We then compared metabolic profiles for isolated cortical bone from a separate group of 20-week female and male C57Bl6/mice (n = 10 / sex). Femurs from the same mice were evaluated for flexural material properties. Strength groupings (high strength males, high strength females, low strength males) were utilized to inform comparisons in the isolated humerus cortical bone metabolome. The metabolome of isolated cortical bone, bone marrow, and whole bone are distinct. The isolated cortical bone metabolome is also distinct between males and females. The female mice show evidence of lipid metabolism, whereas male mice show evidence of amino acid metabolism. Finally, 12 metabolic pathways were differentially regulated between bones that differed in strength. High-strength bones from both male and female mice included metabolites associated with tryptophan and purine metabolism. Taken together, these data demonstrate the power of metabolomics to provide insight into the effects of metabolism on bone physiology. These data add to an intricate picture of bone as an organ that is sexually dimorphic both in material and metabolomic profiles.

Sign in / Sign up

Export Citation Format

Share Document