‘Green podiatry’ - reducing our carbon footprints. Lessons from a sustainability panel

Background The eyes of the world will be on COP26 as it meets in Glasgow in November, 2021. Our planet is displaying weather extremes due to climate change which cannot be ignored, and which are deleterious for people’s health. Ironically, healthcare contributes to climate change, contributing approximately 5% of carbon emissions globally. Climate change due to global warming is ‘the biggest global health threat of the 21st century’. Main body The Australian Podiatry Association conference held a sustainability panel, hearing perspectives of industry and science, medicine and sport, fashion, and retail. Content unified a broad planet and human health message, which is highly relevant for podiatrists. Key themes included waste as a resource, exercise as evidence-based intervention, responsibility and circular economy recycling principles for end-of-life product (footwear) purchases, and wider ethical considerations of footwear and clothing. The Anthropocene origin of climate change requires humanity to collaborate and to live more sustainably. Innovation is essential for better energy modes, cleaner air, human health and earth care. Green Podiatry joins the concerted activity of medical and health groups within Australia. The UK’s NHS is an exemplar in this area, having already reduced healthcare emissions by 35%, and aiming for net zero by 2045, and perhaps sooner. Conclusion People are increasingly concerned about climate change, and COP26 is an important and imminent meeting for human and planet health. This commentary on Green Podiatry directs us all to lighten our carbon footprint. A final, and forthcoming commentary will outline practical ways of positively incorporating climate change communication into the clinical setting.

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here we show that the C. elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.

Virally Encoded Connectivity Transgenic Overlay RNA sequencing (VECTORseq) defines projection neurons involved in sensorimotor integration

Behavior arises from concerted activity throughout the brain. Consequently, a major focus of modern neuroscience is defining the physiology and behavioral roles of projection neurons linking different brain areas. Single-cell RNA sequencing has facilitated these efforts by revealing molecular determinants of cellular physiology and markers that enable genetically targeted perturbations such as optogenetics, but existing methods for sequencing of defined projection populations are low-throughput, painstaking, and costly. We developed a straightforward, multiplexed approach, Virally Encoded Connectivity Transgenic Overlay RNA sequencing (VECTORseq). VECTORseq repurposes commercial retrogradely infecting viruses typically used to express functional transgenes, e.g., recombinases and fluorescent proteins, by treating viral transgene mRNA as barcodes within single-cell datasets. VECTORseq is compatible with different viral families, resolves multiple populations with different projection targets in one sequencing run, and identifies cortical and subcortical excitatory and inhibitory projection populations. Our study provides a roadmap for high-throughput identification of neuronal subtypes based on connectivity.

Dynamic Regulation of Peroxisomes and Mitochondria during Fungal Development

Peroxisomes and mitochondria are organelles that perform major functions in the cell and whose activity is very closely associated. In fungi, the function of these organelles is critical for many developmental processes. Recent studies have disclosed that, additionally, fungal development comprises a dynamic regulation of the activity of these organelles, which involves a developmental regulation of organelle assembly, as well as a dynamic modulation of the abundance, distribution, and morphology of these organelles. Furthermore, for many of these processes, the dynamics of peroxisomes and mitochondria are governed by common factors. Notably, intense research has revealed that the process that drives the division of mitochondria and peroxisomes contributes to several developmental processes—including the formation of asexual spores, the differentiation of infective structures by pathogenic fungi, and sexual development—and that these processes rely on selective removal of these organelles via autophagy. Furthermore, evidence has been obtained suggesting a coordinated regulation of organelle assembly and dynamics during development and supporting the existence of regulatory systems controlling fungal development in response to mitochondrial activity. Gathered information underscores an important role for mitochondrial and peroxisome dynamics in fungal development and suggests that this process involves the concerted activity of these organelles.

Genome-scale Co-occurrence and Co-transcription Networks Reveal Key Microbial Taxa in Mangrove Sediments

BackgroundMangroves are highly productive ecosystems, with one of the highest microbial diversities among all ecosystems. The concerted activity of microbial community in mangrove sediment mediates element cycling, but the underpinning mechanism of microbial synergy remains unknown. ResultsHere, we reconstructed 671 strain-resolved metagenome-assembled genomes (MAGs) from three mangrove and two mudflat sediments in Mai Po Nature Reserve. We then inferred the genome-scale co-occurrence and co-transcription networks based on metabolic capacity and transcriptional activity of the carbon, nitrogen, and sulfur cycles. We observed that the centrality was significantly higher in co-transcription networks than in co-occurrence networks, indicating that MAGs had stronger interrelationships when transcriptionally active. Further, we classified 57 microbes with low relative abundance (0.01–0.79%) as keystone taxa, which play key roles in the maintenance of co-transcription network structure, and participate in carbon transformations, denitrification, and sulfate reduction processes. One of the keystone taxa is a newly proposed deltaproteobacterial order, Candidatus Mangrovidesulfobacterales, capable of dissimilatory sulfate reduction and an anaerobic mixotrophic lifestyle. These findings highlight the ecological importance of rare species. ConclusionsCollectively, this first screening of the potential keystone taxa in mangrove ecosystem based on genome-scale transcriptomic analysis revealed unique microbial functional assemblages, shedding light on microbial synergism in this ecosystem.

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

SUMMARYNeuromodulators promote adaptive behaviors in response to either environmental or internal physiological changes. These responses are often complex and may involve concerted activity changes across circuits that are not physically connected. It is not well understood how neuromodulatory systems act across circuits to elicit complex behavioral responses. Here we show that the C. elegans NLP-12 neuropeptide system shapes responses to food availability by selectively modulating the activity of head and body wall motor neurons. NLP-12 modulation of the head and body wall motor circuits is generated through conditional involvement of alternate GPCR targets. The CKR-1 GPCR is highly expressed in the head motor circuit, and functions to enhance head bending and increase trajectory reorientations during local food searching, primarily through stimulatory actions on SMD head motor neurons. In contrast, NLP-12 activation of CKR-1 and CKR-2 GPCRs regulates body bending under basal conditions, primarily through actions on body wall motor neurons. Thus, locomotor responses to changing environmental conditions emerge from conditional NLP-12 stimulation of head or body wall motor neuron targets.

Disruption of membrane cholesterol organization impairs the concerted activity of PIEZO1 channel clusters

ABSTRACTThe human mechanosensitive ion channel PIEZO1 is gated by membrane tension and regulates essential biological processes such as vascular development and erythrocyte volume homeostasis. Currently, little is known about PIEZO1 plasma membrane localization and organization. Using a PIEZO1-GFP fusion protein, we investigated whether cholesterol enrichment or depletion by methyl-β-Cyclodextrin (MBCD) and disruption of membrane cholesterol organization by dynasore affects PIEZO1-GFP’s response to mechanical force. Electrophysiological recordings in the cell-attached configuration revealed that MBCD caused a rightward shift in the PIEZO1-GFP pressure-response curve, increased channel latency in response to mechanical stimuli and markedly slowed channel inactivation. The same effects were seen in native PIEZO1 in N2A cells. STORM super-resolution imaging revealed that, at the nano-scale, PIEZO1-GFP channels in the membrane associate as clusters sensitive to membrane manipulation. Both cluster distribution and diffusion rates were affected by treatment with MBCD (5 mM). Supplementation of poly-unsaturated fatty acids appeared to sensitize the PIEZO1-GFP response to applied pressure. Together, our results indicate that PIEZO1 function is directly dependent on the membrane mechanical properties and lateral organization of membrane cholesterol domains which coordinates the concerted activity of PIEZO1 channels.SUMMARYThe essential mammalian mechanosensitive channel PIEZO1 organizes in the plasma membrane into nanometric clusters which depend on the integrity of cholesterol domains to rapidly detect applied force and especially inactivate syncronously, the most commonly altered feature of PIEZO1 in pathology.