scholarly journals Comparison of Gene Expression During Early Phases of Limb Regeneration Between Regeneration-permissive Neotenic and Regeneration-deficient Metamorphic Axolotl

2019 ◽  
Author(s):  
Mustafa Sibai ◽  
Ebru Altuntaş ◽  
Barış Ethem Süzek ◽  
Betül Şahin ◽  
Cüneyd Parlayan ◽  
...  

ABSTRACTThe axolotl (Ambystoma Mexicanum) salamander, an urodele amphibian, has an exceptional regenerative capacity to fully restore an amputated limb throughout the life-long lasting neoteny. By contrast, when axolotls are experimentally induced to metamorphosis, attenuation of the limb’s regenerative competence is noticeable. Here, we sought to discern the proteomic profiles of the early stages of blastema formation of neotenic and metamorphic axolotls after limb amputation by means of LC-MS/MS technology. We quantified a total of 714 proteins having an adjusted p < 0.01 with FC greater or equal to 2 between two conditions. Principal component analysis revealed a conspicuous clustering between neotenic and metamorphic samples at 7 days post-amputation. Different set of proteins was identified as differentially expressed at all of the time points (1, 4, and 7 days post-amputations against day0) for neotenic and metamorphic stages. Although functional enrichment analyses underline the presence of common pathways between regenerative and nonregenerative stages, cell proliferation and its regulation associated pathways, immune system related pathways and muscle tissue and ECM remodeling and degradation pathways were represented at different rate between both stages. To validate the proteomics results and provide evidence for the putative link between immune system activity and regenerative potential, qRT-PCR for selected genes was performed.

1994 ◽  
Vol 72 (5-6) ◽  
pp. 188-194 ◽  
Author(s):  
Patrick Scaps ◽  
François Bernet ◽  
Jean Gautron ◽  
Bénoni Boilly

Amputation of an axolotl limb causes severance of the brachial nerves, followed by their regeneration into a blastema. It is known that these nerves provide a neurotophic factor to blastemal cells. To approach the problem of the response of spinal cord nerve centers to forelimb amputation, we have studied biosynthetic activities in the nerve centers involved in axonal injury during limb regeneration. We report that the acetylcholinesterase (AChE) activity in the spinal cord is elevated 2 days (+ 69%) and 7 days (+ 28%) after limb amputation compared with levels in unamputated control animals, but is not significantly elevated at 3 h or 15 days. The percentages of slow (3.6 S and 6.0 S) and fast (18 S) sedimenting forms of AChE progressively decrease 2 and 7 days after amputation, while those of intermediate sedimenting forms (10.5 S and 14.0 S) increase. Fifteen days after amputation, lower molecular weight forms return to the control level, but the heavy molecular weight form of AChE is absent as at 7 days; consequently intermediate molecular weight forms are in a greater proportion than the other two forms. Choline acetyltransferase activity was measured only 2 days after amputation (when AChE was at its highest level). It increases by about 34% with regard to the controls. Adrenaline is higher than controls 2 days after amputation, while noradrenaline is not significantly modified. The metabolic changes observed in the spinal cord during limb regeneration probably are the result of a general reaction to the stress of amputation (transection of brachial nerves) and regeneration of nerve fibers, since similar metabolic activities were observed after a simple denervation of the two unamputated forelimbs.Key words: acetylcholinesterase, choline acetyltransferase, catecholamines, regeneration, axolotl.


1988 ◽  
Vol 66 (9) ◽  
pp. 2065-2070 ◽  
Author(s):  
Steven R. Scadding

Vitamin A is known to cause proximodistal duplication of parts of the limb during limb regeneration in amphibians. The objective of this study was to investigate the nature and location of the cellular changes induced by vitamin A when it causes this duplication in the axolotl Ambystoma mexicanum. When axolotls were treated with retinol palmitate by immersion for 14 days before limb amputation, proximodistal duplications were still observed in subsequent regenerates of limbs amputated after vitamin A treatment was discontinued. This observation suggests that some characteristic of the cells is changed by vitamin A and that exogenous vitamin A need not be present while the limb is regenerating. When a limb that was induced to undergo proximodistal duplication by vitamin A was reamputated 49 days later through the original mid radius–ulna amputation plane, it regenerated a limb of normal structure. A regeneration blastema transplanted from a vitamin A treated axolotl to an untreated axolotl regenerated on the host limb stump, producing a limb with proximodistal duplication; this indicates that the blastema cells underwent some change by the early to mid cone stage, which was expressed later when the blastema redifferentiated into a new limb. Conversely, when an untreated blastema was transplanted onto a vitamin A treated axolotl from which the forelimb blastema had been removed, proximodistal duplications developed. This result is interpreted to mean that the stump cells, although morphologically of the radius–ulna level, were proximalized by the prior vitamin A treatment and still displayed proximal positional values, leading to intercalation of missing proximodistal structures. These results are consistent with the hypothesis that vitamin A brings about a temporary change in the positional information of the limb stump and blastema cells, and that when the vitamin A treatment is discontinued, there is a gradual return to normal positional values over a period of several weeks.


1981 ◽  
Vol 59 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Steven R. Scadding

This paper reports a histological analysis of limb regeneration capacity in 20 species of amphibians. These data, along with a survey of other species reported in the literature, are used as a basis for the following generalizations. (1) Limb regeneration in the amphibians is not an all-or-none process, but regenerative capacity covers a continuum from normal regeneration to total absence of regenerative ability. (2) In adult anurans, regenerative outgrowth is common in discoglossids and pipids, occurs frequently in hylids, rarely in ranids, and has never been reported in bufonids. In the anurans, there is no correlation between size and regenerative capacity. (3) In the urodeles, limb regeneration capacity is correlated with size. Urodele species with a mean snout–vent length over 100 mm regenerate heteromorphically or not at all. Those under 75 mm regenerate consistently normally. Those species of intermediate size give variable responses to limb amputation, and may regenerate normally, heteromorphically, or not at all. Hypotheses that might explain differences in regenerative ability are discussed.


Author(s):  
Seyed M Matloobi ◽  
Mohammad Riahi

Reducing the cost of unscheduled shutdowns and enhancing the reliability of production systems is an important goal for various industries; this could be achieved by condition monitoring and artificial intelligence. Cavitation is a common undesired phenomenon in centrifugal pumps, which causes damage and its detection in the preliminary stage is very important. In this paper, cavitation is identified by use of vibration and current signal and artificial immune network that is modeled on the base of the human immune system. For this purpose, first data collection were done by a laboratory setup in health and five stages damage condition; then various features in time, frequency, and time–frequency were extracted from vibration and current signals in addition to pressure and flow rate; next feature selection and dimensions reduction were done by artificial immune method to use for classification; finally, they were used by artificial immune network and some other methods to identify the system condition and classification. The results of this study showed that this method is more accurate in the detection of cavitation in the initial stage compared to methods such as non-linear supportive vector machine, multi-layer artificial neural network, K-means and fuzzy C-means with the same data. Also, selected features with artificial immune system were better than principal component analysis results.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hadeel R. Bakhsh ◽  
Nilüfer Kablan ◽  
Walaa Alammar ◽  
Yaşar Tatar ◽  
Giorgio Ferriero

Abstract Background The Client Satisfaction with Devices (CSD) module of the Orthotics and Prosthetics Users’ Survey is an extensively used questionnaire that measures patients’ satisfaction with orthosis and prosthesis. However, the validated version for Arabic speakers (CSD-Ar) is only applicable for orthosis users. Objectives The aim of this study was to evaluate the psychometric proprieties of the CSD-Ar for prosthetics users. Methods The study used a convenience sample of prosthesis users from Saudi Arabia and Turkey (N = 183), who completed the CSD-Ar. The collected data were analysed using Rasch analysis to evaluate item fit, reliability indices, item difficulty, local item dependency, and differential item functioning (DIF) using WINSTEPS version 4.6.1. Results Based on the analysis, the four-response Likert-scale was acceptable, as shown by the category functioning test, All eight items did achieve a fit to the Rasch Model [(infit) and (outfit) mean-square 0.75 to 1.3]. Person separation reliability was 0.76, and item separation reliability was 0.94. A principal component analysis (PCA) showed satisfactory unidimensionality and no local item dependency. The DIF analysis showed no notable dependency among items on participant characteristics in terms of age, gender, duration of use, country, and level of amputation. Conclusion This study contributes to the confidence of using CSD-Ar to evaluate users’ satisfaction with different prostheses, affirming the need for further refinement of the quality of the outcome measure.


1987 ◽  
Vol 65 (8) ◽  
pp. 739-749 ◽  
Author(s):  
Roy A. Tassava ◽  
David J. Goldhamer ◽  
Bruce L. Tomlinson

Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium.


1999 ◽  
Vol 77 (11) ◽  
pp. 1835-1837 ◽  
Author(s):  
Steven R Scadding

While the effects of exogenous retinoids on amphibian limb regeneration have been studied extensively, the role of endogenous retinoids is not clear. Hence, I wished to investigate the role of endogenous retinoic acid during axolotl limb regeneration. Citral is a known inhibitor of retinoic acid synthesis. Thus, I treated regenerating limbs of the larval axolotl Ambystoma mexicanum with citral. The result of this inhibition of retinoic acid synthesis was that limb regeneration became extremely irregular and hypomorphic, with serious pattern defects, or was inhibited altogether. I conclude that endogenous retinoic acid plays an important role in pattern formation during limb regeneration.


1998 ◽  
Vol 76 (9) ◽  
pp. 1795-1796 ◽  
Author(s):  
Steven R Scadding ◽  
Andrew Burns

The purpose of this investigation was to determine whether there were any asymmetries in the vascularization of the limb-regeneration blastema in the axolotl, Ambystoma mexicanum, that might be related to pattern formation, and to determine if retinoic acid could modify the vascular patterns of the blastema. We used acrylic casts of the vascular system of the limbs to assess the pattern of vascularization. We observed a very regular symmetrical arrangement of capillaries in the limb-regeneration blastema that did not appear to be modified by doses of retinoic acid sufficient to modify the limb pattern.


2020 ◽  
Author(s):  
aida santaolalla ◽  
Sam Sollie ◽  
Ali Rislan ◽  
Debra H. Josephs ◽  
Niklas Hammar ◽  
...  

Abstract Background: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions.Methods: From the AMORIS cohort, 5,513 individuals were identified with baseline measurements of serum humoral immune (immunoglobulin G, A & M (IgG, IgA, IgM)) and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.Results: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.Conclusions: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.


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