scholarly journals Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Ng ◽  
Anissa A. Widjaja ◽  
Sivakumar Viswanathan ◽  
Jinrui Dong ◽  
Sonia P. Chothani ◽  
...  
Keyword(s):  
Bone Development ◽  
Lung Fibroblasts ◽  
Long Bone ◽  
Loss Of Function ◽  
Therapeutic Targeting ◽  
Reduced Body ◽  
Body Weights ◽  
Similarities And Differences ◽  
The Impact

AbstractLoss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and incompletely penetrant craniosynostosis. The impact of LOF in IL11 has not been characterized. We generated IL11 knockout (Il11−/−) mice that are born in expected ratios and have normal hematological profiles. Lung fibroblasts from Il11−/− mice are resistant to pro-fibrotic stimulation with TGFβ1. Following bleomycin-induced lung injury, Il11−/− mice are protected from pulmonary fibrosis and exhibit lesser ERK, STAT3 and NF-kB activation, reduced Il1b, Timp1, Ccl2 and diminished IL6 expression, both at baseline and after injury: placing Il11 activity upstream of IL6 in this model. Il11−/− female mice are infertile. Unlike Il11ra1−/− mice, Il11−/− mice do not have craniosynostosis, have normal long bone mass and reduced body weights. These data further establish the role of IL11 signaling in lung fibrosis while suggesting that bone development abnormalities can be associated with mutation of IL11RA but not IL11, which may have implications for therapeutic targeting of IL11 signaling.

scholarly journals Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

2020 ◽  
Author(s):  
Benjamin Ng ◽  
Anissa A. Widjaja ◽  
Sivakumar Viswanathan ◽  
Jinrui Dong ◽  
Sonia P. Chothani ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Lung Fibroblasts ◽  
Loss Of Function ◽  
Wild Type ◽  
Reduced Body ◽  
Body Weights ◽  
Show Evidence ◽  
Similarities And Differences ◽  
The Impact

AbstractGenetic loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and craniosynostosis. The impact of genetic LOF in IL11 has not been characterized. We generated IL11-knockout (Il11-/-) mice, which are born in normal Mendelian ratios, have normal hematological profiles and are protected from bleomycin-induced lung fibro-inflammation. Noticeably, baseline IL6 levels in the lungs of Il11-/- mice are lower than those of wild-type mice and are not induced by bleomycin damage, placing IL11 upstream of IL6. Lung fibroblasts from Il11-/- mice are resistant to pro-fibrotic stimulation and show evidence of reduced autocrine IL11 activity. Il11-/- female mice are infertile. Unlike Il11ra1-/- mice, Il11-/- mice do not have a craniosynostosis-like phenotype and exhibit mildly reduced body weights. These data highlight similarities and differences between LOF in IL11 or IL11RA while establishing further the role of IL11 signaling in fibrosis and stromal inflammation.

scholarly journals Rac signaling in osteoblastic cells is required for normal bone development but is dispensable for hematopoietic development

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 736-744 ◽  
Author(s):  
Steven W. Lane ◽  
Serena De Vita ◽  
Kylie A. Alexander ◽  
Ruchan Karaman ◽  
Michael D. Milsom ◽  
...  
Keyword(s):  
Bone Growth ◽  
Bone Development ◽  
Long Bone ◽  
Perivascular Niche ◽  
Hematopoietic Stem ◽  
Hsc Niche ◽  
Rac1 Gtpase

Abstract Hematopoietic stem cells (HSCs) interact with osteoblastic, stromal, and vascular components of the BM hematopoietic microenvironment (HM) that are required for the maintenance of long-term self-renewal in vivo. Osteoblasts have been reported to be a critical cell type making up the HSC niche in vivo. Rac1 GTPase has been implicated in adhesion, spreading, and differentiation of osteoblast cell lines and is critical for HSC engraftment and retention. Recent data suggest a differential role of GTPases in endosteal/osteoblastic versus perivascular niche function. However, whether Rac signaling pathways are also necessary in the cell-extrinsic control of HSC function within the HM has not been examined. In the present study, genetic and inducible models of Rac deletion were used to demonstrate that Rac depletion causes impaired proliferation and induction of apoptosis in the OP9 cell line and in primary BM stromal cells. Deletion of Rac proteins caused reduced trabecular and cortical long bone growth in vivo. Surprisingly, HSC function and maintenance of hematopoiesis in vivo was preserved despite these substantial cell-extrinsic changes. These data have implications for therapeutic strategies to target Rac signaling in HSC mobilization and in the treatment of leukemia and provide clarification to our evolving concepts of HSC-HM interactions.

The impact of cultural similarities and differences on performance in strategic partnerships: An integrative perspective

2010 ◽  
Vol 16 (1) ◽  
pp. 127-139 ◽  
Author(s):  
Gavriel Meirovich
Keyword(s):  
Common Ground ◽  
Cultural Distance ◽  
Theoretical Research ◽  
Strategic Partnerships ◽  
National Cultures ◽  
Similarities And Differences ◽  
The Impact ◽  
Positive Effect ◽  
Practical Implications

AbstractThis theoretical research endeavors to find common ground in the ostensibly inconsistent results of studies on the impact of cultural similarities and differences on strategic partnerships. Some findings suggested that partners have to possess similar cultural characteristics in order to achieve success while others showed that cultural distance had a positive effect on efficiency and the competitiveness of partnerships. This paper systematically analyzes the equivocal evidence of influence of both commonalities and differences on partnerships' outcomes, highlighting conditions under which they can be either beneficial or dysfunctional. Several propositions are formulated in regard to the role of qualitative and quantitative differences in both organizational and national cultures. Further, the theoretical and practical implications are also discussed.

The role of Has2 on long bone development

2008 ◽  
Vol 27 ◽  
pp. 22-23
Author(s):  
Peter J. Roughley ◽  
Judy Grover ◽  
Eunice R. Lee ◽  
Yu Yamaguchi
Keyword(s):  
Bone Development ◽  
Long Bone

scholarly journals Protrudin-deficient mice manifest depression-like behavior with abnormalities in activity, attention, and cued fear-conditioning

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Michiko Shirane ◽  
Hirotaka Shoji ◽  
Yutaka Hashimoto ◽  
Hiroyuki Katagiri ◽  
Shizuka Kobayashi ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Neuronal Development ◽  
Physiological Role ◽  
Loss Of Function ◽  
Reduced Body ◽  
Intermediate Phenotypes ◽  
Behavioral Abnormalities ◽  
And Behavior ◽  
Deficient Mice

Abstract Protrudin is a protein that resides in the membrane of the endoplasmic reticulum and is highly expressed in the nervous system. Although mutations in the human protrudin gene (ZFYVE27, also known as SPG33) give rise to hereditary spastic paraplegia (HSP), the physiological role of the encoded protein has been largely unclear. We therefore generated mice deficient in protrudin and subjected them to a battery of behavioral tests designed to examine their intermediate phenotypes. The protrudin-deficient mice were found to have a reduced body size and to manifest pleiotropic behavioral abnormalities, including hyperactivity, depression-like behavior, and deficits in attention and fear-conditioning memory. They exhibited no signs of HSP, however, consistent with the notion that HSP-associated mutations of protrudin may elicit neural degeneration, not as a result of a loss of function, but rather as a result of a gain of toxic function. Overall, our results suggest that protrudin might play an indispensable role in normal neuronal development and behavior.

scholarly journals New Insights into the Role of Histone Changes in Aging

2020 ◽  
Vol 21 (21) ◽  
pp. 8241
Author(s):  
Sun-Ju Yi ◽  
Kyunghwan Kim
Keyword(s):  
Chromatin Remodeling ◽  
Regulatory Networks ◽  
Genome Instability ◽  
Histone Variants ◽  
Cellular Tissue ◽  
Metabolic Dysfunction ◽  
Loss Of Function ◽  
Epigenetic Regulators ◽  
The Impact

Aging is the progressive decline or loss of function at the cellular, tissue, and organismal levels that ultimately leads to death. A number of external and internal factors, including diet, exercise, metabolic dysfunction, genome instability, and epigenetic imbalance, affect the lifespan of an organism. These aging factors regulate transcriptome changes related to the aging process through chromatin remodeling. Many epigenetic regulators, such as histone modification, histone variants, and ATP-dependent chromatin remodeling factors, play roles in chromatin reorganization. The key to understanding the role of gene regulatory networks in aging lies in characterizing the epigenetic regulators responsible for reorganizing and potentiating particular chromatin structures. This review covers epigenetic studies on aging, discusses the impact of epigenetic modifications on gene expression, and provides future directions in this area.

The impact of cultural similarities and differences on performance in strategic partnerships: An integrative perspective

2010 ◽  
Vol 16 (1) ◽  
pp. 127-139 ◽  
Author(s):  
Gavriel Meirovich
Keyword(s):  
Common Ground ◽  
Cultural Distance ◽  
Theoretical Research ◽  
Strategic Partnerships ◽  
National Cultures ◽  
Similarities And Differences ◽  
The Impact ◽  
Positive Effect ◽  
Practical Implications

AbstractThis theoretical research endeavors to find common ground in the ostensibly inconsistent results of studies on the impact of cultural similarities and differences on strategic partnerships. Some findings suggested that partners have to possess similar cultural characteristics in order to achieve success while others showed that cultural distance had a positive effect on efficiency and the competitiveness of partnerships. This paper systematically analyzes the equivocal evidence of influence of both commonalities and differences on partnerships' outcomes, highlighting conditions under which they can be either beneficial or dysfunctional. Several propositions are formulated in regard to the role of qualitative and quantitative differences in both organizational and national cultures. Further, the theoretical and practical implications are also discussed.

scholarly journals Gossip, Reputation, and Sustainable Cooperation

2019 ◽  
pp. 21-46 ◽  
Author(s):  
Francesca Giardini ◽  
Rafael Wittek
Keyword(s):  
Research Agenda ◽  
Analytical Framework ◽  
The Other ◽  
Sociological Research ◽  
Similarities And Differences ◽  
Reputation Effects ◽  
The One ◽  
And Control ◽  
The Impact

Gossip is often invoked as playing a fundamental role for creating, sustaining, or destroying cooperation. The reason seems straightforward: gossip can make or break someone’s reputation. This chapter puts this standard reputational model to closer scrutiny. It argues that there are at least three other models to consider, and it presents an analytical framework to disentangle similarities and differences between these models. Explicating all three roles in the gossip triad, it allows to distinguish (a) individual motives behind gossiping, (b) its reputation effects on the actors, (c) the impact of gossip and reputation on the quality and sustainability of cooperation, and (d) the role of the context. Applying the framework reveals a deep divide between reputation and punishment models propagated by experimental economics and evolutionary psychology, on the one hand, and coalition and control models informed by sociology, on the other hand. The chapter discusses implications for a sociological research agenda.

scholarly journals Heterozygous loss-of-function mutation in Odd-skipped related 1 (Osr1) is associated with vesicoureteric reflux, duplex systems, and hydronephrosis

2017 ◽  
Vol 313 (5) ◽  
pp. F1106-F1115 ◽  
Author(s):  
Marie-Lyne Fillion ◽  
Jasmine El Andalousi ◽  
Fatima Tokhmafshan ◽  
Vasikar Murugapoopathy ◽  
Christine L. Watt ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Vesicoureteric Reflux ◽  
Stem Cell Population ◽  
Nucleotide Polymorphisms ◽  
Loss Of Function ◽  
Ureterovesical Junction ◽  
Synonymous Variant ◽  
Developing Kidney ◽  
The Impact

Odd-skipped related 1 (Osr1) is a transcriptional repressor that plays critical roles in maintaining the mesenchymal stem cell population within the developing kidney. Here, we report that newborn pups with a heterozygous null mutation in Osr1 exhibit a 21% incidence of vesicoureteric reflux and have hydronephrosis and urinary tract duplications. Newborn pups have a short intravesical ureter, resulting in a less competent ureterovesical junction which arises from a delay in urinary tract development. We describe a new domain of Osr1 expression in the ureteral mesenchyme and within the developing bladder in the mouse. OSR1 was sequenced in 186 children with primary vesicoureteric reflux, and 17 have single nucleotide polymorphisms. Fifteen children have a common synonymous variant, rs12329305 , one child has a rare nonsynonymous variant, rs3440471 , and one child has a rare 5′-UTR variant, rs45535040 . The impact of these SNPs is not clear; therefore, the role of OSR1 in human disease remains to be elucidated. Osr1 is a candidate gene implicated in the pathogenesis of vesicoureteric reflux and congenital abnormalities of the kidney and urinary tract in mice.

scholarly journals Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate

2019 ◽  
Vol 20 (23) ◽  
pp. 5840 ◽  
Author(s):  
Haraguchi ◽  
Kitazawa ◽  
Kohara ◽  
Ikedo ◽  
Imai ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Growth Plate ◽  
Bone Development ◽  
Growth Period ◽  
Long Bone ◽  
Endochondral Bone Formation ◽  
Molecular Characteristics ◽  
Growth Plate Chondrocytes ◽  
Wide Range

The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the “growth plate”, is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.

Sign in / Sign up

Export Citation Format

Share Document