The regulation of matrix metalloproteinases and their inhibitors

The matrix metalloproteinases (MMP) are a family of 23 enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. Control over MMP and/or tissue inhibitor of metalloproteinases (TIMP) activity in vivo occurs at different levels and involves factors such as regulation of gene expression, activation of zymogens and inhibition of active enzymes by specific inhibitors. Whilst these enzymes and inhibitors have clear roles in physiological tissue turnover and homeostasis, if control of their expression or activity is lost, they contribute to a number of pathologies including e.g. cancer, arthritis and cardiovascular disease. The expression of many MMPs and TIMPs is regulated at the level of transcription by a variety of growth factors, cytokines and chemokines, though post-transcriptional pathways may contribute to this regulation in specific cases. The contribution of epigenetic modifications has also been uncovered in recent years. The promoter regions of many of these genes have been, at least partly, characterised including the role of identified single nucleotide polymorphisms. This article aims to review current knowledge across these gene families and use a bioinformatic approach to fill the gaps where no functional data are available

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

Defining the functional role of NaV1.7 in human nociception

Loss-of-function mutations in NaV1.7 cause congenital insensitivity to pain (CIP); this voltage-gated sodium channel is therefore a key target for analgesic drug development. Utilizing a multi-modal approach, we investigated how NaV1.7 mutations lead to human pain insensitivity. Skin biopsy and microneurography revealed an absence of C-fiber nociceptors in CIP patients, reflected in a reduced cortical response to capsaicin on fMRI. Epitope tagging of endogenous NaV1.7 revealed the channel to be localized at the soma membrane, axon, axon terminals, and the nodes of Ranvier of induced pluripotent stem cell (iPSC) nociceptors. CIP patient-derived iPSC nociceptors exhibited an inability to properly respond to depolarizing stimuli, demonstrating that NaV1.7 is a key regulator of excitability. Using this iPSC nociceptor platform, we found that some NaV1.7 blockers undergoing clinical trials lack specificity. CIP, therefore, arises due to a profound loss of functional nociceptors, which is more pronounced than that reported in rodent models, or likely achievable following acute pharmacological blockade

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

A multidisciplinary approach for generating globally consistent data on mesophotic, deep-pelagic, and bathyal biological communities

Approaches to measuring marine biological parameters remain almost as diverse as the researchers who measure them. However, understanding the patterns of diversity in ocean life over different temporal and geographic scales requires consistent data and information on the potential environmental drivers. As a group of marine scientists from different disciplines, we suggest a formalized, consistent framework of 20 biological, chemical, physical, and socioeconomic parameters that we consider the most important for describing environmental and biological variability. We call our proposed framework the General Ocean Survey and Sampling Iterative Protocol (GOSSIP). We hope that this framework will establish a consistent approach to data collection, enabling further collaboration between marine scientists from different disciplines to advance knowledge of the ocean (deep-sea and mesophotic coral ecosystems)

An atlas of seabed biodiversity for Aotearoa New Zealand

\ua9 2023 Copernicus GmbH. All rights reserved. The waters of Aotearoa New Zealand span over 4.2ĝ€\uafmillionĝ€\uafkm2 of the South Pacific Ocean and harbour a rich diversity of seafloor-Associated taxa. Due to the immensity and remoteness of the area, there are significant gaps in the availability of data that can be used to quantify and map the distribution of seafloor and demersal biodiversity, limiting effective management. In this study, we describe the development and accessibility of an online atlas of seabed biodiversity that aims to fill these gaps. Species distribution models were developed for 579 taxa across four taxonomic groups: demersal fish, reef fish, subtidal invertebrates and macroalgae. Spatial layers for taxa distribution based on habitat suitability were statistically validated and then, as a further check, evaluated by taxonomic experts to provide measures of confidence to guide the future use of these layers. Spatially explicit uncertainty (SD) layers were also developed for each taxon distribution. We generated layer-specific metadata, including statistical and expert evaluation scores, which were uploaded alongside the accompanying spatial layers to the open access database Zenodo. This database provides the most comprehensive source of information on the distribution of seafloor taxa for Aotearoa New Zealand and is thus a valuable resource for managers, researchers and the public that will guide the management and conservation of seafloor communities. The atlas of seabed biodiversity for Aotearoa New Zealand is freely accessible via the open-Access database Zenodo under 10.5281/zenodo.7083642 (Stephenson et al., 2022)

Science Priorities for Seamounts: Research Links to Conservation and Management

Seamounts shape the topography of all ocean basins and can be hotspots of biological activity in the deep sea. The Census of Marine Life on Seamounts (CenSeam) was a field program that examined seamounts as part of the global Census of Marine Life (CoML) initiative from 2005 to 2010. CenSeam progressed seamount science by collating historical data, collecting new data, undertaking regional and global analyses of seamount biodiversity, mapping species and habitat distributions, challenging established paradigms of seamount ecology, developing new hypotheses, and documenting the impacts of human activities on seamounts. However, because of the large number of seamounts globally, much about the structure, function and connectivity of seamount ecosystems remains unexplored and unknown. Continual, and potentially increasing, threats to seamount resources from fishing and seabed mining are creating a pressing demand for research to inform conservation and management strategies. To meet this need, intensive science effort in the following areas will be needed: 1) Improved physical and biological data; of particular importance is information on seamount location, physical characteristics (e.g. habitat heterogeneity and complexity), more complete and intensive biodiversity inventories, and increased understanding of seamount connectivity and faunal dispersal; 2) New human impact data; these shall encompass better studies on the effects of human activities on seamount ecosystems, as well as monitoring long-term changes in seamount assemblages following impacts (e.g. recovery); 3) Global data repositories; there is a pressing need for more comprehensive fisheries catch and effort data, especially on the high seas, and compilation or maintenance of geological and biodiversity databases that underpin regional and global analyses; 4) Application of support tools in a data-poor environment; conservation and management will have to increasingly rely on predictive modelling techniques, critical evaluation of environmental surrogates as faunal “proxies”, and ecological risk assessment

Expressions 1980

Expressions contains selected work from the 1980 Creative Writing Contest winners and honorable mentions, Campus Chronicle Photography Contest entrants, and the Commercial Art students at Des Moines Area Community College. Design, typography and layout was done by Journalism students.https://openspace.dmacc.edu/expressions/1002/thumbnail.jp

Novel Cytochrome P450, cyp6a17, Is Required for Temperature Preference Behavior in Drosophila

Perception of temperature is an important brain function for organisms to survive. Evidence suggests that temperature preference behavior (TPB) in Drosophila melanogaster, one of poikilothermal animals, is regulated by cAMP-dependent protein kinase (PKA) signaling in mushroom bodies of the brain. However, downstream targets for the PKA signaling in this behavior have not been identified. From a genome-wide search for the genes regulated by PKA activity in the mushroom bodies, we identified the cyp6a17 Cytochrome P450 gene as a new target for PKA. Our detailed analysis of mutants by genetic, molecular and behavioral assays shows that cyp6a17 is essential for temperature preference behavior. cyp6a17 expression is enriched in the mushroom bodies of the adult brain. Tissue-specific knockdown and rescue experiments demonstrate that cyp6a17 is required in the mushroom bodies for normal temperature preference behavior. This is the first study, to our knowledge, to show PKA-dependent expression of a cytochrome P450 gene in the mushroom bodies and its role as a key factor for temperature preference behavior. Taken together, this study reveals a new PKA-Cytochrome P450 pathway that regulates the temperature preference behavior

Distribution, Population Biology, and Trophic Ecology of the Deepwater Demersal Fish Halosauropsis macrochir (Pisces: Halosauridae) on the Mid-Atlantic Ridge

Halosauropsis macrochir ranked amongst the most abundant and widespread demersal fishes on the mid-Atlantic Ridge of the North Atlantic (Iceland-Azores) with greatest abundance at 1700–3500 m. All sizes, ranging from 10–76 cm total length, occurred in the area without any apparent spatial pattern or depth trend. Using otolith sections displaying growth increments assumed to represent annuli, the age range recorded was 2–36 years, but most individuals were <20 years. Length and weight at age data were used to fit growth models. No differences between sexes in length and weight at age were observed. The majority of samples had a surplus of males. Diet analysis showed that H. macrochir feeds on Crustacea, Teleostei, Polychaeta, and Cephalopoda, but few prey could be identified to lower taxonomical levels. The mid-Atlantic Ridge constitutes a major portion of the North Atlantic living space of the abyssal halosaur where it completes its full life cycle, primarily as an actively foraging euryophagous micronekton/epibenthos and infauna feeder, becoming a partial piscivore with increasing size