Combined Effects of Long-Term Sitting and Whole-Body Vibration on Discomfort Onset for Vehicle Occupants

Occupants of automobiles experience discomfort after long drives, irrespective of how well designed a seat might be. Previous studies of discomfort during driving have focused either on the seat shape and materials (“static” properties), long-term discomfort (“fatigue” properties), or dynamics (“vibration” properties). These factors have previously not been considered together. This paper reports three studies with objectives to define and test a model for describing long-term discomfort from vibration. Study 1 was an independent measures laboratory trial using an automobile seat, which lasted 80 minutes; Study 2 was a repeated measures laboratory trial using a rail passenger seat, which lasted 60 minutes; Study 3 was a repeated measures field trial in a people carrier automobile, which involved 70 minutes of travelling. The findings showed that discomfort accrues with time but that more discomfort is experienced when subjects are also exposed to whole-body vibration. Exposure to whole-body vibration accelerates development of discomfort. The relationship between the reported discomfort, the vibration magnitude, and the exposure time can be described using a multifactorial linear model. It is concluded that ignoring parts of the multi-factorial model (i.e., static, dynamic, or temporal factors) will compromise understanding of discomfort in context

Calcium signaling in oomycetes: an evolutionary perspective

Oomycetes are a family of eukaryotic microbes that superficially resemble fungi, but which are phylogenetically distinct from them. These organisms cause major global economic losses to agriculture and fisheries, with representative pathogens being Phytophthora infestans, the cause of late potato blight and Saprolegnia diclina, the instigator of “cotton molds” in fish. As in all eukaryotes, cytoplasmic Ca2+ is a key second messenger in oomycetes, regulating life-cycle transitions, controlling motility and chemotaxis and, in excess, leading to cell-death. Despite this, little is known about the molecular mechanisms regulating cytoplasmic Ca2+ concentrations in these organisms. Consequently, this review analyzed the presence of candidate calcium channels encoded within the nine oomycete genomes that are currently available. This revealed key differences between oomycetes and other eukaryotes, in particular the expansion and loss of different channel families, and the presence of a phylum-specific group of proteins, termed the polycystic kidney disease tandem ryanodine receptor domain (PKDRR) channels

FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels

AbstractThis study compared the relative levels of ryanodine receptor (RyR) isoforms, inositol 1,4,5-trisphosphate receptor (IP3R) isoforms, and calcineurin, plus their association with FKBP12 in brain, skeletal and cardiac tissue. FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. In contrast, FKBP12 was not tightly associated with brain or cardiac microsomes and did not require FK506 for removal from these organelles. Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12–glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP3R isoforms and calcineurin

Combined effects of long-term sitting and whole-body vibration on discomfort onset for vehicle occupants

Occupants of automobiles experience discomfort after long drives, irrespective of how well designed a seat might be. Previous studies of discomfort during driving have focused either on the seat shape and materials (“static” properties), long-term discomfort (“fatigue” properties), or dynamics (“vibration” properties). These factors have previously not been considered together. This paper reports three studies with objectives to define and test a model for describing long-term discomfort from vibration. Study 1 was an independent measures laboratory trial using an automobile seat, which lasted 80 minutes; Study 2 was a repeated measures laboratory trial using a rail passenger seat, which lasted 60 minutes; Study 3 was a repeated measures field trial in a people carrier automobile, which involved 70 minutes of travelling. The findings showed that discomfort accrues with time but that more discomfort is experienced when subjects are also exposed to whole-body vibration. Exposure to whole-body vibration accelerates development of discomfort. The relationship between the reported discomfort, the vibration magnitude, and the exposure time can be described using a multifactorial linear model. It is concluded that ignoring parts of the multi-factorial model (i.e., static, dynamic, or temporal factors) will compromise understanding of discomfort in context

Compliance of the fish outflow tract is altered by thermal acclimation through connective tissue remodelling

From The Royal Society via Jisc Publications RouterHistory: received 2021-06-14, accepted 2021-10-26, collection 2021-11, pub-electronic 2021-11-17Article version: VoRPublication status: PublishedFunder: BBSRCFunder: Leverhulme Trust; Id: http://dx.doi.org/10.13039/501100000275; Grant(s): 240613To protect the gill capillaries from high systolic pulse pressure, the fish heart contains a compliant non-contractile chamber called the bulbus arteriosus which is part of the outflow tract (OFT) which extends from the ventricle to the ventral aorta. Thermal acclimation alters the form and function of the fish atria and ventricle to ensure appropriate cardiac output at different temperatures, but its impact on the OFT is unknown. Here we used ex vivo pressure–volume curves to demonstrate remodelling of passive stiffness in the rainbow trout (Oncorhynchus mykiss) bulbus arteriosus following more than eight weeks of thermal acclimation to 5, 10 and 18°C. We then combined novel, non-biased Fourier transform infrared spectroscopy with classic histological staining to show that changes in compliance were achieved by changes in tissue collagen-to-elastin ratio. In situ gelatin zymography and SDS-PAGE zymography revealed that collagen remodelling was underpinned, at least in part, by changes in activity and abundance of collagen degrading matrix metalloproteinases. Collectively, we provide the first indication of bulbus arteriosus thermal remodelling in a fish and suggest this remodelling ensures optimal blood flow and blood pressure in the OFT during temperature change

Design for Behaviour Change as a Driver for Sustainable Innovation: Challenges and Opportunities for Implementation in the Private and Public Sectors

Over the last decade, design for behaviour change has become increasingly recognised as a strategy for enabling social change. Despite this, we are far from understanding its implementation, especially through the private and public sectors. This study has surveyed private and public sector stakeholders with regard to their current knowledge of, and approach to, design for behaviour change. The aim was to identify the challenges for professional stakeholders in understanding, accessing and implementing design for behaviour change. Underpinned by a literature review of design for behaviour change theories and approaches, an online survey and two focus groups with private and public sector stakeholders were conducted with particular focus on small and medium size enterprises (SMEs). The results identified that there is a significant disconnect between available theoretical knowledge of design for behaviour change and its practical implementation. Reasons for this include a lack of awareness and common language, of evidence based examples, and of evaluation methods and inter-sector collaborations. In response, a set of recommendations has been developed to propose ways forward for the wider understanding and application of design for behaviour change

The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system

Abnormalities in the endosomal-autophagic-lysosomal (EAL) system are an early event in Alzheimer's disease (AD) pathogenesis. However, the mechanisms underlying these abnormalities are unclear. The transient receptor potential channel mucolipin 1(TRPML1, also known as MCOLN1), a vital endosomal-lysosomal Ca2+ channel whose loss of function leads to neurodegeneration, has not been investigated with respect to EAL pathogenesis in late-onset AD (LOAD). Here, we identify pathological hallmarks of TRPML1 dysregulation in LOAD neurons, including increased perinuclear clustering and vacuolation of endolysosomes. We reveal that induced pluripotent stem cell (iPSC)-derived human cortical neurons expressing APOE ε4, the strongest genetic risk factor for LOAD, have significantly diminished TRPML1-induced endolysosomal Ca2+ release. Furthermore, we found that blocking TRPML1 function in primary neurons by depleting the TRPML1 agonist PI(3,5)P2 via PIKfyve inhibition, recreated multiple features of EAL neuropathology evident in LOAD. This included increased endolysosomal Ca2+ content, enlargement and perinuclear clustering of endolysosomes, autophagic vesicle accumulation and early endosomal enlargement. Strikingly, these AD-like neuronal EAL defects were rescued by TRPML1 reactivation using its synthetic agonist ML-SA1. These findings implicate defects in TRPML1 in LOAD EAL pathogenesis and present TRPML1 as a potential therapeutic target