Lineage Contribution of PDGFRα-Expressing Cells in the Developing Mouse Eye

PDGFRα signaling is critically important in ocular development. Previous data on PDGFRα lacks an expression map with high spatial and temporal resolution and lineage information. In this study, we aim to present a detailed PDGFRα expression and lineage map from early embryogenesis to adulthood. PDGFRα-CreER; mT/mG reporter mice were analyzed. mEGFP-positive cells contributed to multiple ocular lineages in a spatiotemporally regulated manner. A dynamic PDGFRα expression was identified in corneal stromal cells, lens epithelial cells, lens fiber cells, and retinal astrocytes during the entire period of eye development, while PDGFRα expression in retinal astrocytes from E17.5 onwards and in Müller glial cells was identified within two weeks after birth. By revealing detailed characterization of gene expression and function, we present a comprehensive map of PDGFRα-expressing cells in the eye for a better understanding of PDGFRα signaling’s role during eye development.

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Characterization of mesenchymal stem or stromal cells: tissue sources, heterogeneity, and function

Transfusion ◽

10.1111/trf.13561 ◽

2016 ◽

Vol 56 (4) ◽

pp. 2S-5S ◽

Cited By ~ 3

Author(s):

Richard Schäfer ◽

Karen Bieback

Keyword(s):

Stromal Cells ◽

And Function

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Distinct Phosphoisoforms of the XenopusMcm4 Protein Regulate the Function of the Mcm Complex

Molecular and Cellular Biology ◽

10.1128/mcb.20.10.3667-3676.2000 ◽

2000 ◽

Vol 20 (10) ◽

pp. 3667-3676 ◽

Cited By ~ 28

Author(s):

Inna Pereverzeva ◽

Elizabeth Whitmire ◽

Bettina Khan ◽

Martine Coué

Keyword(s):

Cell Cycle ◽

Cyclin B ◽

Detailed Characterization ◽

Cyclin Dependent Kinases ◽

Origins Of Replication ◽

Mcm Complex ◽

Initiation Of Dna Replication ◽

And Function ◽

Mitotic Phosphorylation

ABSTRACT Initiation of DNA replication in eukaryotes requires the assembly of prereplication complexes (pre-Rcs) at the origins of replication. The assembly and function of the pre-Rcs appear to be controlled by phosphorylation events. In this study we report the detailed characterization of the cell cycle phosphorylation of one component of the Xenopus pre-Rcs, the Mcm protein complex. We show that individual Mcm subunits are differentially phosphorylated during the cell cycle. During mitosis, the Mcm4 subunit is hyperphosphorylated, while the other subunits are not actively phosphorylated. The mitotic phosphorylation of Mcm4 requires Cdc2-cyclin B and other unknown kinases. Following exit from mitosis, the Mcm4 subunit of the cytosolic interphase complex undergoes dephosphorylation, and the Mcm2, Mcm3, or Mcm6 subunits are then actively phosphorylated by kinase(s) other than cyclin-dependent kinases (Cdks) or Cdc7. The association of the Mcm complex with the pre-Rcs correlates with the formation of a transient interphase complex. This complex contains an intermediately phosphorylated Mcm4 subunit and is produced by partial dephosphorylation of the mitotic hyperphosphorylated Mcm4 protein. Complete dephosphorylation of the Mcm4 subunit inactivates the Mcm complex and prevents its binding to the chromatin. Once the Mcm complex is assembled on the chromatin the Mcm4 and the Mcm2 proteins are the only subunits phosphorylated during the activation of the pre-Rcs. These chromatin-associated phosphorylations require nuclear transport and are independent of Cdk2-cyclin E. These results suggest that the changes in Mcm4 phosphorylation regulate pre-Rc assembly and the function of the pre-Rcs on the chromatin.

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Excitation-contraction coupling and its relation to synaptic dysfunction in Drosophila

10.1101/2020.07.09.196261 ◽

2020 ◽

Author(s):

Kiel G. Ormerod ◽

Anthony E. Scibelli ◽

J. Troy Littleton

Keyword(s):

Muscle Performance ◽

Synaptic Dysfunction ◽

Muscle Contractility ◽

Detailed Characterization ◽

Synaptic Development ◽

Excitation Contraction Coupling ◽

Contraction Coupling ◽

And Function ◽

Identification And Characterization

AbstractThe Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic deficits alter neuromuscular transduction and muscle contractility that ultimately dictate behavioural output. Here we develop a system for detailed characterization of excitation-contraction coupling at Drosophila larval NMJs and demonstrate how specific synaptic and neuronal manipulations disrupt muscle contractility. Muscle contraction force increases with motoneuron stimulation frequency and duration, showing considerable plasticity between 5-40 Hz, while saturating above 50 Hz. Temperature is negatively correlated with muscle performance and enhanced at lower temperatures. A screen for modulators of muscle contractility led to the identification and characterization of the molecular and cellular pathway by which a specific FMRFa peptide, TPAEDFMRFa, increases muscle performance. These findings indicate Drosophila NMJs provide a robust system to relate synaptic dysfunction to alterations in excitation-contraction coupling.

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Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

Stem Cell Reports ◽

10.1016/j.stemcr.2017.04.019 ◽

2017 ◽

Vol 8 (6) ◽

pp. 1573-1586 ◽

Cited By ~ 34

Author(s):

Rafael Diaz de la Guardia ◽

Belen Lopez-Millan ◽

Jessie R. Lavoie ◽

Clara Bueno ◽

Julio Castaño ◽

...

Keyword(s):

Treatment Outcomes ◽

Stromal Cells ◽

Large Cohort ◽

Detailed Characterization

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Multi-transcription factor reporter mice delineate early precursors to the ILC and LTi lineages

Journal of Experimental Medicine ◽

10.1084/jem.20200487 ◽

2020 ◽

Vol 218 (2) ◽

Author(s):

Darshan N. Kasal ◽

Albert Bendelac

Keyword(s):

Transcription Factor ◽

Fetal Liver ◽

Chromatin Accessibility ◽

Dynamic Changes ◽

Reporter Mice ◽

The Common ◽

And Function ◽

Adult Bone ◽

Lymphoid Tissue Inducer

Transcription factor (TF) reporter mice have proved integral to the characterization of murine innate lymphoid cell (ILC) development and function. Here, we implemented a CRISPR/Cas9-generated combinatorial reporter approach for the simultaneous resolution of several key TFs throughout ILC development in both the fetal liver and adult bone marrow. We demonstrate that the Tcf7-expressing early innate lymphoid precursor (EILP) and the common helper ILC precursor (CHILP) both contain a heterogeneous mixture of specified ILC and lymphoid tissue inducer (LTi) precursors with restricted lineage potential rather than a shared precursor. Moreover, the earliest specified precursor to the LTi lineage was identified upstream of these populations, before Tcf7 expression. These findings match dynamic changes in chromatin accessibility associated with the expression of key TFs (i.e., GATA3 and RORγ(t)), highlighting the distinct origins of ILC and LTi lineages at the epigenetic and functional levels, and provide a revised map for ILC development.

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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Parasite defense mechanisms in bees: behavior, immunity, antimicrobials, and symbionts

Emerging Topics in Life Sciences ◽

10.1042/etls20190069 ◽

2019 ◽

Vol 4 (1) ◽

pp. 59-76 ◽

Cited By ~ 2

Author(s):

Alison E. Fowler ◽

Rebecca E. Irwin ◽

Lynn S. Adler

Keyword(s):

Defense Mechanisms ◽

Poor Quality ◽

Future Research ◽

Immune Priming ◽

Social Bees ◽

Bee Health ◽

Landscape Scales ◽

And Function ◽

Solitary Species

Parasites are linked to the decline of some bee populations; thus, understanding defense mechanisms has important implications for bee health. Recent advances have improved our understanding of factors mediating bee health ranging from molecular to landscape scales, but often as disparate literatures. Here, we bring together these fields and summarize our current understanding of bee defense mechanisms including immunity, immunization, and transgenerational immune priming in social and solitary species. Additionally, the characterization of microbial diversity and function in some bee taxa has shed light on the importance of microbes for bee health, but we lack information that links microbial communities to parasite infection in most bee species. Studies are beginning to identify how bee defense mechanisms are affected by stressors such as poor-quality diets and pesticides, but further research on this topic is needed. We discuss how integrating research on host traits, microbial partners, and nutrition, as well as improving our knowledge base on wild and semi-social bees, will help inform future research, conservation efforts, and management.

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Inhibition of TMEM16A impedes embryo implantation and decidualization in mice

Reproduction ◽

10.1530/rep-18-0197 ◽

2018 ◽

Cited By ~ 2

Author(s):

Qianrong Qi ◽

Yifan Yang ◽

Kailin Wu ◽

Qingzhen Xie

Keyword(s):

Progesterone Receptor ◽

Stromal Cells ◽

Embryo Implantation ◽

Mouse Uterus ◽

Endometrial Stromal Cells ◽

Uterine Endometrium ◽

Molecule Inhibitor ◽

Pathway Inhibition ◽

And Function ◽

Reproductive Processes

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization, and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is up-regulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.

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Intramolecular Proton Transfer in the Isomerization of Hydroxyacetone: A Detailed Characterization Based on Reaction Force Analysis and the Bond Fragility Spectrum

10.26434/chemrxiv.12049062 ◽

2020 ◽

Author(s):

Wallace Derricotte ◽

Huiet Joseph

Keyword(s):

Chemical Potential ◽

Reaction Force ◽

Intramolecular Proton Transfer ◽

Intermediate Energy ◽

Force Analysis ◽

Activation Energy Barrier ◽

Detailed Characterization ◽

Proton Transfers ◽

Reaction Force Constant

The mechanism of isomerization of hydroxyacetone to 2-hydroxypropanal is studied within the framework of reaction force analysis at the M06-2X/6-311++G(d,p) level of theory. Three unique pathways are considered: (i) a step-wise mechanism that proceeds through formation of the Z-isomer of their shared enediol intermediate, (ii) a step-wise mechanism that forms the E-isomer of the enediol, and (iii) a concerted pathway that bypasses the enediol intermediate. Energy calculations show that the concerted pathway has the lowest activation energy barrier at 45.7 kcal mol<sup>-1</sup>. The reaction force, chemical potential, and reaction electronic flux are calculated for each reaction to characterize electronic changes throughout the mechanism. The reaction force constant is calculated in order to investigate the synchronous/asynchronous nature of the concerted intramolecular proton transfers involved. Additional characterization of synchronicity is provided by calculating the bond fragility spectrum for each mechanism.

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Gaunilo Parodies Anselm

History of Philosophy and Logical Analysis ◽

10.30965/26664275-01701004 ◽

2014 ◽

Vol 17 (1) ◽

pp. 45-71

Author(s):

Geo Siegwart

Keyword(s):

Detailed Comparison ◽

The Third ◽

Common Structure ◽

Logical Reconstruction ◽

Points Of View ◽

And Function

The main objective is an interpretation of the island parody, in particular a logical reconstruction of the parodying argument that stays close to the text. The parodied reasoning is identified as the proof in the second chapter of the Proslogion, more specifically, this proof as it is represented by Gaunilo in the first chapter of his Liber pro insipiente. The second task is a detailed comparison between parodied and parodying argument as well as an account of their common structure. The third objective is a tentative characterization of the nature and function of parodies of arguments. It seems that parodying does not add new pertinent points of view to the usual criticism of an argument.

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