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1.
J Cell Mol Med ; 26(5): 1456-1465, 2022 03.
Article in English | MEDLINE | ID: mdl-35181997

ABSTRACT

The extracellular signal-regulated kinase (ERK) pathway is a well-known regulator of vascular smooth muscle cell proliferation, but it also serves as a regulator of caldesmon, which negatively regulates vascular contractility. This study examined whether aortic contractile function requires ERK activation and if this activation is regulated by ageing. Biomechanical experiments revealed that contractile responses to the alpha1-adrenergic agonist phenylephrine are attenuated specifically in aged mice, which is associated with downregulation of ERK phosphorylation. ERK inhibition attenuates phenylephrine-induced contractility, indicating that the contractile tone is at least partially ERK-dependent. To explore the mechanisms of this age-related downregulation of ERK phosphorylation, we transfected microRNAs, miR-34a and miR-137 we have previously shown to increase with ageing and demonstrated that in A7r5 cells, both miRs downregulate the expression of Src and paxillin, known regulators of ERK signalling, as well as ERK phosphorylation. Further studies in aortic tissues transfected with miRs show that miR-34a but not miR-137 has a negative effect on mRNA levels of Src and paxillin. Furthermore, ERK phosphorylation is decreased in aortic tissue treated with the Src inhibitor PP2. Increases in miR-34a and miR-137 with ageing downregulate the expression of Src and paxillin, leading to impaired ERK signalling and aortic contractile dysfunction.


Subject(s)
Extracellular Signal-Regulated MAP Kinases , MicroRNAs , Aging/genetics , Animals , Extracellular Signal-Regulated MAP Kinases/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Paxillin/genetics , Paxillin/metabolism , Phenotype , Phenylephrine/pharmacology , Phosphorylation
2.
Biol Rev Camb Philos Soc ; 97(3): 1179-1192, 2022 06.
Article in English | MEDLINE | ID: mdl-35098647

ABSTRACT

How innovations such as vision, flight and pregnancy evolve is a central question in evolutionary biology. Examination of transitional (intermediate) forms of these traits can help address this question, but these intermediate phenotypes are very rare in extant species. Here we explore the biology and evolution of transitional forms of pregnancy that are midway between the ancestral state of oviparity (egg-laying) and the derived state, viviparity (live birth). Transitional forms of pregnancy occur in only three vertebrates, all of which are lizard species that also display intraspecific variation in reproductive phenotype. In these lizards (Lerista bougainvillii, Saiphos equalis, and Zootoca vivipara), geographic variation of three reproductive forms occurs within a single species: oviparity, viviparity, and a transitional form of pregnancy. This phenomenon offers the valuable prospect of watching 'evolution in action'. In these species, it is possible to conduct comparative research using different reproductive forms that are not confounded by speciation, and are of relatively recent origin. We identify major proximate and ultimate questions that can be addressed in these species, and the genetic and genomic tools that can help us understand how transitional forms of pregnancy are produced, despite predicted fitness costs. We argue that these taxa represent an excellent prospect for understanding the major evolutionary shift between egg-laying and live birth, which is a fundamental innovation in the history of animals.


Subject(s)
Lizards , Viviparity, Nonmammalian , Animals , Biological Evolution , Lizards/genetics , Oviparity/genetics , Reproduction/genetics , Snakes , Viviparity, Nonmammalian/genetics
3.
J Autism Dev Disord ; 52(11): 4843-4860, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34783992

ABSTRACT

If neurotypical people rely on specialized perceptual mechanisms when perceiving biological motion, then one would not expect an association between task performance and IQ. However, if those with ASD recruit higher order cognitive skills when solving biological motion tasks, performance may be predicted by IQ. In a meta-analysis that included 19 articles, we found an association between biological motion perception and IQ among observers with ASD but no significant relationship among typical observers. If the task required emotion perception, then there was an even stronger association with IQ in the ASD group.


Subject(s)
Autism Spectrum Disorder , Motion Perception , Autism Spectrum Disorder/psychology , Humans
4.
Front Cardiovasc Med ; 8: 649489, 2021.
Article in English | MEDLINE | ID: mdl-33748198

ABSTRACT

Reentrant cardiac arrhythmias such as atrial fibrillation (AF) and ventricular fibrillation (VF) are common cardiac arrhythmias that account for substantial morbidity and mortality throughout the world. However, the mechanisms and optimal ablation treatment strategies for such arrhythmias are still unclear. Using 2D optical mapping of a mouse model with AF and VF, we have identified regional heterogeneity of the action potential duration (APD) in the atria and ventricles of the heart as key drivers for the initiation and persistence of reentry. The purpose of this paper is to discuss theoretical patterns of dispersion, demonstrate patterns of dispersion seen in our mouse model and discuss the computational analysis of APD dispersion patterns. These analyses and discussions may lead to better understanding of dispersion patterns in patients with these arrhythmias, as well as help comprehend whether and how reducing dispersion can lead to arrhythmia risk stratification and treatment strategies for arrhythmias.

5.
Nutr Diet ; 76(3): 284-289, 2019 07.
Article in English | MEDLINE | ID: mdl-31050115

ABSTRACT

AIM: Cakes and muffins are commonly consumed discretionary foods that have increased significantly in portion size over the past decades. The present study aimed to (i) investigate serving sizes and energy per serving of cakes and muffins sold in supermarkets and coffee chains, (ii) compare to standard discretionary serves and (iii) propose feasible and appropriate serving size recommendations. METHODS: Serving sizes and energy content of cakes and muffins were collected from four major Australian supermarkets (n = 219) and eight coffee chains (n = 248) between March and April 2017 and classified into eight categories and compared using Mann-Whitney tests. Median energy per serving of cakes and muffins from supermarkets and coffee chains were compared to the Australian Dietary Guidelines standard serve of 600 kJ for discretionary food. RESULTS: The median serving size of cakes and muffins from supermarkets, 58 g (interquartile range, IQR: 47-83) and their energy content, 915 kJ (IQR: 745-1243) were significantly smaller compared with coffee chain equivalents, 148 g (IQR: 115-171, P < 0.001) and 1805 kJ (IQR: 1436-2004, P < 0.001), respectively. The majority of cakes and muffins exceeded the Australian Dietary Guidelines standard serve (78% from supermarkets and 99% from coffee chains). CONCLUSIONS: The larger servings of cakes and muffins sold in coffee chains contain nearly double the energy content of smaller servings sold in supermarkets. We recommend reference serving sizes for industry and food retail are set for this category, in combination with consumer education to guide consumers to select appropriate portion sizes.


Subject(s)
Dietary Carbohydrates , Portion Size/statistics & numerical data , Snacks , Australia , Commerce , Humans , Nutrition Policy , Portion Size/standards
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