scholarly journals Microtubule aging probed by microfluidics-assisted tubulin washout

2016 ◽  
Vol 27 (22) ◽  
pp. 3563-3573 ◽  
Author(s):  
Christian Duellberg ◽  
Nicholas Ian Cade ◽  
Thomas Surrey

Microtubules switch stochastically between phases of growth and shrinkage. The molecular mechanism responsible for the end of a growth phase, an event called catastrophe, is still not understood. The probability for a catastrophe to occur increases with microtubule age, putting constraints on the possible molecular mechanism of catastrophe induction. Here we used microfluidics-assisted fast tubulin washout experiments to induce microtubule depolymerization in a controlled manner at different times after the start of growth. We found that aging can also be observed in this assay, providing valuable new constraints against which theoretical models of catastrophe induction can be tested. We found that the data can be quantitatively well explained by a simple kinetic threshold model that assumes an age-dependent broadening of the protective cap at the microtubule end as a result of an evolving tapered end structure; this leads to a decrease of the cap density and its stability. This analysis suggests an intuitive picture of the role of morphological changes of the protective cap for the age dependence of microtubule stability.

2010 ◽  
Vol 8 (56) ◽  
pp. 345-368 ◽  
Author(s):  
P. Ciarletta ◽  
L. Foret ◽  
M. Ben Amar

Cutaneous melanoma is disproportionately lethal despite its relatively low incidence and its potential for cure in the early stages. The aim of this study is to foster understanding of the role of microstructure on the occurrence of morphological changes in diseased skin during melanoma evolution. The authors propose a biomechanical analysis of its radial growth phase, investigating the role of intercellular/stromal connections on the initial stages of epidermis invasion. The radial growth phase of a primary melanoma is modelled within the multi-phase theory of mixtures, reproducing the mechanical behaviour of the skin layers and of the epidermal–dermal junction. The theoretical analysis takes into account those cellular processes that have been experimentally observed to disrupt homeostasis in normal epidermis. Numerical simulations demonstrate that the loss of adhesiveness of the melanoma cells both to the basal laminae, caused by deregulation mechanisms of adherent junctions, and to adjacent keratynocytes, consequent to a downregulation of E-cadherin, are the fundamental biomechanical features for promoting tumour initiation. Finally, the authors provide the mathematical proof of a long wavelength instability of the tumour front during the early stages of melanoma invasion. These results open the perspective to correlate the early morphology of a growing melanoma with the biomechanical characteristics of its micro-environment.


Author(s):  
R. W. Tucker ◽  
N. S. More ◽  
S. Jayaraman

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.


2017 ◽  
Vol 38 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Jeffrey H. Kahn ◽  
Daniel W. Cox ◽  
A. Myfanwy Bakker ◽  
Julia I. O’Loughlin ◽  
Agnieszka M. Kotlarczyk

Abstract. The benefits of talking with others about unpleasant emotions have been thoroughly investigated, but individual differences in distress disclosure tendencies have not been adequately integrated within theoretical models of emotion. The purpose of this laboratory research was to determine whether distress disclosure tendencies stem from differences in emotional reactivity or differences in emotion regulation. After completing measures of distress disclosure tendencies, social desirability, and positive and negative affect, 84 participants (74% women) were video recorded while viewing a sadness-inducing film clip. Participants completed post-film measures of affect and were then interviewed about their reactions to the film; these interviews were audio recorded for later coding and computerized text analysis. Distress disclosure tendencies were not predictive of the subjective experience of emotion, but they were positively related to facial expressions of sadness and happiness. Distress disclosure tendencies also predicted judges’ ratings of the verbal disclosure of emotion during the interview, but self-reported disclosure and use of positive and negative emotion words were not associated with distress disclosure tendencies. The authors present implications of this research for integrating individual differences in distress disclosure with models of emotion.


2019 ◽  
Author(s):  
Christopher Michael Kavanagh ◽  
Susilo Wibisono ◽  
Rohan Kapitány ◽  
Whinda Yustisia ◽  
Idhamsyah Eka Putra ◽  
...  

Indonesia is the most populous Islamic country and as such is host to a diverse range of Islamic beliefs and practices. Here we examine how the diversity of beliefs and practices among Indonesian Muslims relates to group bonding and parochialism. In particular, we examine the predictive power of two distinct types of group alignment, group identification and identity fusion, among individuals from three Sunni politico-religious groups - a fundamentalist group (PKS), a moderate group (NU), and a control sample of politically unaffiliated citizens. Fundamentalists were more fused to targets than moderates or citizens, but contrary to fusion theory, we found across all groups, that group identification (not fusion) better predicted parochialism, including willingness to carry out extreme pro-group actions. We discuss how religious beliefs and practice impact parochial attitudes, as well as the implications for theoretical models linking fusion to extreme behaviour.


2020 ◽  
Vol 20 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Sonali Bhakta ◽  
Toshifumi Tsukahara

Editing mutated genes is a potential way for the treatment of genetic diseases. G-to-A mutations are common in mammals and can be treated by adenosine-to-inosine (A-to-I) editing, a type of substitutional RNA editing. The molecular mechanism of A-to-I editing involves the hydrolytic deamination of adenosine to an inosine base; this reaction is mediated by RNA-specific deaminases, adenosine deaminases acting on RNA (ADARs), family protein. Here, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.


2020 ◽  
Vol 66 (1) ◽  
Author(s):  
Yoko Okahisa ◽  
Keisuke Kojiro ◽  
Hatsuki Ashiya ◽  
Takeru Tomita ◽  
Yuzo Furuta ◽  
...  

Abstract Age is an important factor that dictates bamboo’s mechanical properties. In Japan, bamboo plants aged 3–5 years are selected for use as materials because of their robustness and decorative or craft-friendly characteristics. In this study, the age-dependent and radial sectional differences in bamboo’s dynamic viscoelastic properties in relation to lignin structural variation, were evaluated. We used Phyllostachys pubescens samples at the current year and at 1.5, 3.5, 6.5, 9.5, 12.5, and 15.5 years of age. There was a clear age dependence in the peak temperature of tan δ and in the yield of thioacidolysis products derived from β-O-4 lignin structures. The highest peak temperature tan δ value was detected in 3.5-year-old bamboo, which contained the highest amount of the thioacidolysis products. Moreover, tan δ’s peak temperature was always higher on the outer side, and the ratio of S/G thioacidolysis products was always higher on the inner side of bamboo plants of all ages. These results suggest that changes in bamboo’s thermal softening properties from aging are caused by the maturation and degradation of lignin in bamboo.


Author(s):  
Jayarami Reddy Medapati ◽  
Deepthi Rapaka ◽  
Veera Raghavulu Bitra ◽  
Santhosh Kumar Ranajit ◽  
Girija Sankar Guntuku ◽  
...  

Abstract Background The endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. Streptozotocin (STZ) (55 mg/kg, i.p., once) is administered to uninephrectomised rats for induction of experimental diabetes mellitus. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks. Results The progress in diabetic nephropathy is estimated biochemically by measuring serum creatinine (1.28±0.03) (p < 0.005), blood urea nitrogen (67.6± 2.10) (p < 0.001), urinary microprotein (74.62± 3.47) (p < 0.005) and urinary albuminuria (28.31±1.17) (p < 0.0001). Renal inflammation was assessed by estimating serum levels of tumor necrosis factor alpha (75.69±1.51) (p < 0.001) and transforming growth factor beta (8.73±0.31) (p < 0.001). Renal morphological changes were assessed by estimating renal hypertrophy (7.38± 0.26) (p < 0.005) and renal collagen content (10.42± 0.48) (p < 0.001). Conclusions From the above findings, it can be said that diabetes-induced nephropathy may be associated with overexpression of CB1 receptors and blockade of CB1 receptors might be beneficial in ameliorating the diabetes-induced nephropathy. Graphical abstract


2021 ◽  
pp. 112972982110154
Author(s):  
Raffaella Mauro ◽  
Cristina Rocchi ◽  
Francesco Vasuri ◽  
Alessia Pini ◽  
Anna Laura Croci Chiocchini ◽  
...  

Background: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. Materials and methods: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. Results: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0–65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 ( p = 0.001) and with NA ( p = 0.001). Conclusions: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.


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