Acta Physiologica

This review attempts to touch on the history and application of amperometry at PC12 cells for fundamental investigation into the exocytosis process. PC12 cells have been widely used as a model for neural differentiation and as such they have been used to examine the effects of differentiation on exocytotic release and specifically release at varicosities. In addition, dexamethasone‐differentiated cells have been shown to have an increased number of releasable vesicles with increased quantal size, thereby allowing for an even broader range of applications including neuropharmacological and neurotoxicological studies. PC12 cells exhibiting large numbers of events have two distinct pools of vesicles, one about twice the quantal size of the other and each about half the total releasable vesicles. As will be outlined in this review, these cells have served as an extremely useful model of exocytosis in the study of the latency of stimulation‐release coupling, the role of exocytotic proteins in regulation of release, effect of drugs on quantal size, autoreceptors, fusion pore biophysics, environmental factors, health and disease. As PC12 cells have some advantages over other models for neurosecretion, including chromaffin cells, it is more than likely that in the following decade PC12 cells will continue to serve as a model to study exocytosis.

MicroRNAs (miRNAs) have within the past decade emerged as key regulators of metabolic homoeostasis. Major tissues in intermediary metabolism important during development of the metabolic syndrome, such as β‐cells, liver, skeletal and heart muscle as well as adipose tissue, have all been shown to be affected by miRNAs. In the pancreatic β‐cell, a number of miRNAs are important in maintaining the balance between differentiation and proliferation (miR‐200 and miR‐29 families) and insulin exocytosis in the differentiated state is controlled by miR‐7, miR‐375 and miR‐335. MiR‐33a and MiR‐33b play crucial roles in cholesterol and lipid metabolism, whereas miR‐103 and miR‐107 regulates hepatic insulin sensitivity. In muscle tissue, a defined number of miRNAs (miR‐1, miR‐133, miR‐206) control myofibre type switch and induce myogenic differentiation programmes. Similarly, in adipose tissue, a defined number of miRNAs control white to brown adipocyte conversion or differentiation (miR‐365, miR‐133, miR‐455). The discovery of circulating miRNAs in exosomes emphasizes their importance as both endocrine signalling molecules and potentially disease markers. Their dysregulation in metabolic diseases, such as obesity, type 2 diabetes and atherosclerosis stresses their potential as therapeutic targets. This review emphasizes current ideas and controversies within miRNA research in metabolism.

The neuropeptide gonadotropin‐releasing hormone (GnRH) has a central role in the neural control of vertebrate reproduction. This review describes an overview of what is currently known about GnRH in vertebrates in the context of its structural and functional evolution. A large body of evidence has demonstrated the existence of three paralogous genes for GnRH (GnRH1, GnRH2 and GnRH3) in the vertebrate lineage. They are most probably the products of whole‐genome duplications that occurred early in vertebrate evolution. Although GnRH3 has been identified only in teleosts, comparative genomic analyses indicated that GnRH3 has not arisen from a teleost‐specific genome duplication, but has been derived from an earlier genome duplication in an ancestral vertebrate, followed by its loss in the tetrapod lineage. A loss of other paralogous genes has also occurred independently in different vertebrate lineages, leading to species‐specific differences in the organization of the GnRH system. In addition to the GnRH3 gene, the GnRH2 gene has been deleted or silenced in certain mammalian species, while some teleosts seem to have lost the GnRH1 or GnRH3 gene. The duplicated GnRH genes have undergone subfunctionalization during the evolution of vertebrates; GnRH1 has become the major stimulator of gonadotropins and probably other pituitary hormones as well, whereas GnRH2 and GnRH3 would have functioned as neuromodulators, affecting reproductive behaviour. Conversely, in cases where a paralogous gene for GnRH has been lost, one of the remaining paralogues appears to have adopted its role.

Background:  Occupations characterized by a static low load and by repetitive actions show a high prevalence of work‐related musculoskeletal disorders (WMSD) in the neck–shoulder region. Moreover, muscle fatigue and discomfort are reported to play a relevant initiating role in WMSD. Aims: To investigate relationships between altered sensory information, i.e. localized muscle fatigue, discomfort and pain and their associations to changes in motor control patterns.

Materials & Methods:  In total 101 subjects participated. Questionnaires, subjective assessments of perceived exertion and pain intensity as well as surface electromyography (SEMG), mechanomyography (MMG), force and kinematics recordings were performed.

Results:  Multi‐channel SEMG and MMG revealed that the degree of heterogeneity of the trapezius muscle activation increased with fatigue. Further, the spatial organization of trapezius muscle activity changed in a dynamic manner during sustained contraction with acute experimental pain. A graduation of the motor changes in relation to the pain stage (acute, subchronic and chronic) and work experience were also found. The duration of the work task was shorter in presence of acute and chronic pain. Acute pain resulted in decreased activity of the painful muscle while in subchronic and chronic pain, a more static muscle activation was found. Posture and movement changed in the presence of neck–shoulder pain. Larger and smaller sizes of arm and trunk movement variability were respectively found in acute pain and subchronic/chronic pain. The size and structure of kinematics variability decreased also in the region of discomfort. Motor variability was higher in workers with high experience. Moreover, the pattern of activation of the upper trapezius muscle changed when receiving SEMG/MMG biofeedback during computer work.

Discussion:  SEMG and MMG changes underlie functional mechanisms for the maintenance of force during fatiguing contraction and acute pain that may lead to the widespread pain seen in WMSD. A lack of harmonious muscle recruitment/derecruitment may play a role in pain transition. Motor behavior changed in shoulder pain conditions underlining that motor variability may play a role in the WMSD development as corroborated by the changes in kinematics variability seen with discomfort. This prognostic hypothesis was further, supported by the increased motor variability among workers with high experience.

Conclusion:  Quantitative assessments of the functional motor adaptations can be a way to benchmark the pain status and help to indentify signs indicating WMSD development. Motor variability is an important characteristic in ergonomic situations. Future studies will investigate the potential benefit of inducing motor variability in occupational settings.

Although very often exposed to a rapid changing environment, plants are in general unable to evade from unfavourable conditions. Therefore, a fine tuned adaptation of physiology including the water balance appears to be of crucial importance. As a consequence a relatively large number of aquaporin genes are present in plant genomes. So far aquaporins in plants were shown to be involved in root water uptake, reproduction or photosynthesis. Accordingly, plant aquaporin classification as simple water pores has changed corresponding to their molecular function into channels permeable for water, small solutes and/or gases. An adjustment of the respective physiological process could be achieved by regulation mechanisms, which range from post‐translational modification, molecular trafficking to heteromerization of aquaporin isoforms. Here the function of the four plant aquaporin family subclasses with regard to substrate specificity, regulation and physiological relevance is described.

Aim:  This study assessed segmental changes in the mechanical properties of the aorta at low, physiologic and high stresses, in relation with wall composition and morphometry.

Methods:  The aorta of 10 healthy pigs was divided into six thoracic and three abdominal segments. Aortic specimens were mechanically tested to failure, i.e. rupture, using a uniaxial tension device. Elastic modulus–stress curves were obtained for low (part I), physiologic (part II) and high (part III) stresses, and submitted to regression analysis; failure parameters were calculated. Histological evaluation was performed using an image‐processing system, with quantification of morphometric parameters and composition of the entire vessel and its layers, i.e. media and adventitia.

Results:  Significant differences were found in the regression parameters of parts I, II and III, and in failure parameters, suggesting that the proximal segments were stiffer at low stresses, whereas the distal were less extensible, stronger and stiffer at physiologic and high stresses. Image analysis demonstrated significant differences in morphometry and composition among the different layers and segments of the aorta, with higher elastin content proximally and collagen content distally. Good correlations were found between the regression parameters of parts I and II and elastin content, and between the failure and regression parameters of parts II and III and collagen content.

Conclusion:  Segmental changes exist in the structure and mechanical properties of the aorta, depending on the level of aortic pressure. This information is necessary for understanding aortic function at general non‐physiologic stress states.