Igf signaling couples retina growth with body growth by modulating progenitor cell division

ABSTRACT How the body and organs balance their relative growth is of key importance for coordinating size and function. This is of particular relevance in organisms, which continue to grow over their entire life span. We addressed this issue in the neuroretina of medaka fish (Oryzias latipes), a well-studied system with which to address vertebrate organ growth. We reveal that a central growth regulator, Igf1 receptor (Igf1r), is necessary and sufficient for proliferation control in the postembryonic retinal stem cell niche: the ciliary marginal zone (CMZ). Targeted activation of Igf1r signaling in the CMZ uncouples neuroretina growth from body size control, and we demonstrate that Igf1r operates on progenitor cells, stimulating their proliferation. Activation of Igf1r signaling increases retinal size while preserving its structural integrity, revealing a modular organization in which progenitor differentiation and neurogenesis are self-organized and highly regulated. Our findings position Igf signaling as a key module for controlling retinal size and composition, with important evolutionary implications.

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Igf signalling uncouples retina growth from body size by modulating progenitor cell division

10.1101/2020.06.10.144360 ◽

2020 ◽

Author(s):

Clara Becker ◽

Katharina Lust ◽

Joachim Wittbrodt

Keyword(s):

Body Size ◽

Progenitor Cell ◽

Structural Integrity ◽

Size Control ◽

Relative Growth ◽

Cell Niche ◽

Igf1 Receptor ◽

And Function ◽

Necessary And Sufficient ◽

Ciliary Marginal Zone

AbstractBalancing the relative growth of body and organs is of key importance for coordinating size and function. This is of particular relevance in post-embryonically growing organisms, facing this challenge life-long. We addressed this question in the neuroretina of medaka fish (Oryzias latipes), where growth and size regulation are crucial for functional homeostasis of the visual system. We find that a central growth regulator, Igf1 receptor, is necessary and sufficient for proliferation control in the postembryonic retinal stem cell niche, the ciliary marginal zone (CMZ). Targeted activation of Igf1r signalling in the CMZ uncouples neuroretina growth from body size control, increasing layer thickness while preserving the structural integrity of the retina. The retinal expansion is driven exclusively by enhanced proliferation of progenitor cells while stem cells do not respond to Igf1r modulation. Our findings position Igf signalling as key module controlling retinal size and structure with far reaching evolutionary implications.

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An Essential Role for Insulin and IGF1 Receptors in Regulating Sertoli Cell Proliferation, Testis Size, and FSH Action in Mice

Molecular Endocrinology ◽

10.1210/me.2012-1258 ◽

2013 ◽

Vol 27 (5) ◽

pp. 814-827 ◽

Cited By ~ 129

Author(s):

Jean-Luc Pitetti ◽

Pierre Calvel ◽

Céline Zimmermann ◽

Béatrice Conne ◽

Marilena D. Papaioannou ◽

...

Keyword(s):

Signaling Pathway ◽

Essential Role ◽

Testis Size ◽

Sperm Production ◽

Igf System ◽

Igf1 Receptor ◽

Sperm Output ◽

And Function ◽

Igf Signaling

Abstract Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.

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Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques

Protein and Peptide Letters ◽

10.2174/0929866526666191002113525 ◽

2020 ◽

Vol 27 (3) ◽

pp. 201-209

Author(s):

Syed Saqib Ali ◽

Mohammad Khalid Zia ◽

Tooba Siddiqui ◽

Haseeb Ahsan ◽

Fahim Halim Khan

Keyword(s):

Ascorbic Acid ◽

Conformational Changes ◽

Structural Changes ◽

The Body ◽

Titration Calorimetry ◽

Spectroscopic Techniques ◽

Human Beings ◽

Plasma Ascorbic Acid ◽

Dietary Antioxidant ◽

And Function

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood. Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.

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A Guide to Old Spanish

10.1093/oso/9780199687312.001.0001 ◽

2018 ◽

Author(s):

Steven N. Dworkin

Keyword(s):

The Body ◽

Standard Language ◽

Function Words ◽

Sound System ◽

Old Spanish ◽

And Function ◽

Linguistic Structures ◽

Verb Tense ◽

Modern Standard

This book describes the linguistic structures that constitute Medieval or Old Spanish as preserved in texts written prior to the beginning of the sixteenth century. It emphasizes those structures that contrast with the modern standard language. Chapter 1 presents methodological issues raised by the study of a language preserved only in written sources. Chapter 2 examines questions involved in reconstructing the sound system of Old Spanish before discussing relevant phonetic and phonological details. The chapter ends with an overview of Old Spanish spelling practices. Chapter 3 presents in some detail the nominal, verbal, and pronominal morphology of the language, with attention to regional variants. Chapter 4 describes selected syntactic structures, with emphasis on the noun phrase, verb phrase, object pronoun placement, subject-verb-object word order, verb tense, aspect, and mood. Chapter 5 begins with an extensive list of Old Spanish nouns, adjectives, verbs, and function words that have not survived into the modern standard language. It then presents examples of coexisting variants (doublets) and changes of meaning, and finishes with an overview of the creation of neologisms in the medieval language through derivational morphology (prefixation, suffixation, compounding). The book concludes with an anthology composed of three extracts from Spanish prose texts, one each from the thirteenth, fourteenth, and fifteenth centuries. The extracts contain footnotes that highlight relevant morphological, syntactic, and lexical features, with cross references to the relevant sections in the body of the book.

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Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽

10.1186/s13568-019-0890-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Neeraja Punde ◽

Jennifer Kooken ◽

Dagmar Leary ◽

Patricia M. Legler ◽

Evelina Angov

Keyword(s):

Protein Structure ◽

Amino Acid ◽

Codon Usage ◽

Dna Sequences ◽

Structural Integrity ◽

Host Cells ◽

Loss Of Function ◽

Species Specific ◽

And Function ◽

The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

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Clinical Relevance of Elastin in the Structure and Function of Skin

Aesthetic Surgery Journal Open Forum ◽

10.1093/asjof/ojab019 ◽

2021 ◽

Author(s):

Leslie Baumann ◽

Eric F Bernstein ◽

Anthony S Weiss ◽

Damien Bates ◽

Shannon Humphrey ◽

...

Keyword(s):

Wound Healing ◽

Clinical Relevance ◽

Structural Integrity ◽

Elastic Fiber ◽

Subcutaneous Fat ◽

Structure And Function ◽

Fiber Formation ◽

Elastic Fibers ◽

Superficial Dermis ◽

And Function

Abstract Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

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Combined Supplementation of Choline and Docosahexaenoic Acid during Pregnancy Enhances Neurodevelopment of Fetal Hippocampus

Neurology Research International ◽

10.1155/2017/8748706 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Huban Thomas Rajarethnem ◽

Kumar Megur Ramakrishna Bhat ◽

Malsawmzuali Jc ◽

Siva Kumar Gopalkrishnan ◽

Ramesh Babu Mugundhu Gopalram ◽

...

Keyword(s):

Docosahexaenoic Acid ◽

Structural Integrity ◽

Fetal Brain ◽

Normal Pregnancy ◽

Saline Control ◽

Fetal Brain Development ◽

Essential Nutrient ◽

Combined Supplementation ◽

And Function ◽

The Brain

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant (p<0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons (p<0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.

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Does Motor Training of the Nonparetic Side Influences Balance and Function in Chronic Stroke? A Pilot RCT

The Scientific World JOURNAL ◽

10.1155/2014/769726 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Shanta Pandian ◽

Kamal Narayan Arya ◽

Dharmendra Kumar

Keyword(s):

Functional Performance ◽

Berg Balance Scale ◽

Chronic Stroke ◽

The Body ◽

Control Group ◽

Therapy Program ◽

Functional Reach Test ◽

Double Blinded ◽

And Function ◽

Experimental Group

Background. Balance and functional abilities are controlled by both sides of the body. The role of nonparetic side has never been explored for such skills.Objective. The objective of the present study was to examine the effect of a motor therapy program primarily involving the nonparetic side on balance and function in chronic stroke.Method. A randomized controlled, double blinded trial was conducted on 39 poststroke hemiparetic subjects (21, men; mean age, 42 years; mean poststroke duration, 13 months). They were randomly divided into the experimental group(n=20)and control group(n=19). The participants received either motor therapy focusing on the nonparetic side along with the conventional program or conventional program alone for 8 weeks (3 session/week, 60 minutes each). The balance ability was assessed using Berg Balance Scale (BBS) and Functional Reach Test (FRT) while the functional performance was measured by Barthel Index (BI).Result. After intervention, the experimental group exhibited significant(P<0.05)change on BBS (5.65 versus 2.52) and BI (12.75 versus 2.16) scores in comparison to the control group.Conclusion. The motor therapy program incorporating the nonparetic side along with the affected side was found to be effective in enhancing balance and function in stroke.

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Antimicrobial mode of action of secretions from the metapleural gland ofMytmecia gulosa(Australian bull ant)

Canadian Journal of Microbiology ◽

10.1139/m95-018 ◽

1995 ◽

Vol 41 (2) ◽

pp. 136-144 ◽

Cited By ~ 23

Author(s):

J. A. Mackintosh ◽

J. E. Trimble ◽

A. J. Beattie ◽

D. A. Veal ◽

M. K. Jones ◽

...

Keyword(s):

Candida Albicans ◽

Antimicrobial Agents ◽

Structural Integrity ◽

Phospholipid Bilayer ◽

Active Components ◽

Cytoplasmic Matrix ◽

Metapleural Glands ◽

Total Leakage ◽

Membrane Bound ◽

And Function

Secretions from exocrine metapleural glands of Myrmecia gulosa (Australian bull ant) exhibit broad-spectrum antimicrobial activity. Treatment of the yeast Candida albicans with metapleural secretion resulted in the rapid and total leakage of K+ions from cells within 10 min. Ultrastructural analysis of the bacteria Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa, and cells and protoplasts of Candida albicans demonstrated gross damage of the cell membrane and aggregation of the cytoplasmic matrix of treated cells. Degradation of membrane-bound organelles was also observed in Candida albicans. The antimicrobially active components of metapleural secretions were nonpolar and interacted with the phospholipid bilayer, causing damage to the structural integrity of liposomes and the release of carboxyfluorescein. The data suggest that the antimicrobial agents in metapleural secretion act primarily by disrupting the structure and function of the phospholipid bilayer of the cytoplasmic membrane.Key words: ant metapleural secretion, antimicrobial, Candida albicans, cytoplasmic membrane.

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