Resuscitation-promoting factors possess a lysozyme-like domain

The novel bacterial cytokine family – resuscitation-promoting factors (Rpfs) – share a conserved domain of uncharacterized function. Predicting the structure of this domain suggests that Rpfs possess a lysozyme-like domain. The model highlights the good conservation of residues involved in catalysis and substrate binding. A lysozyme-like function makes sense for this domain in the light of experimental characterization of the biological function of Rpfs

Local infrastructure in Australian tourist destinations: modelling tourism demand and estimating casts of water provisions and operation

With so many tourist activities in Australia, consideration must be given to the impact of the tourist on the environments in which they are located. Sustainable practices and in particular those associated with water use and wastewater production are important in planning for current tourist activity and future growth of visitors in urban and rural areas. The objectives of this research include an investigation and review of the options available to provide, operate and fund water and wastewater infrastructure to meet growing tourism needs in a sustainable manner. This has led to the development of a modelling framework for facilitating a range of analysis related to water use at Australian tourism destinations. The adopted modelling methodology includes procedures for estimating base year and forecasted tourist population at the tourist destination, water and wastewater demands associated with the visitor population, infrastructure required to satisfy water demands at the tourism region and the cost of such infrastructure provisions. This is achieved by incorporating tourist and residential population estimation for a base year and for a series of forecast future years. Population estimations are based on current and available survey data including regional tourism surveys, international and national visitor surveys and Australian census data. Water and wastewater requirements for these combined populations at the tourist destination are calculated with inclusions for irrigation based on CROPWAT software outputs. The corresponding costs of water provision and wastewater collection can then be summarised, based on the preceding estimations. To allow for application to all Australian tourism localities, the modelling process is adapted to suit data that is readily available or easily collected and involves principles that can be readily applied by the user. This methodology outlines some urban water use and wastewater production statistics across Australian capital cities, useful in later calculations. Case study applications of the model are developed for the Australian tourist destinations of Daylesford in Victoria and Byron Bay in New South Wales. Analysis includes full calculations for the water and wastewater needs and associated costs for the forecast year of 2031. Some key findings from the analysis are that for the year 2031, the costs associated with Daylesford’s residential and tourist population demand will be $32,289,650 for the total water demand and$11,128,000 for wastewater treatment. For the town of Byron Bay in 2031, these costs will be $53,601,500 for the total water demand and$18,644,000 for wastewater treatment. Major benefits of this research include better knowledge and understanding of tourist demands, and the need for water and wastewater infrastructure and analytical tools, enabling councils and other authorities to quantify present and future tourist demands, infrastructure requirements to meet demand, and the associated costs of infrastructure provision and operation

Post-translational Protein Deimination in Cod (Gadus morhua L.) Ontogeny: Novel Roles in Tissue Remodelling and Mucosal Immune Defences?

Peptidylarginine deiminases (PADs) are calcium dependent enzymes with physiological and pathophysiological roles conserved throughout phylogeny. PADs promote post-translational deimination of protein arginine to citrulline, altering the structure and function of target proteins. Deiminated proteins were detected in the early developmental stages of cod from 11 days post fertilisation to 70 days post hatching. Deiminated proteins were present in mucosal surfaces and in liver, pancreas, spleen, gut, muscle, brain and eye during early cod larval development. Deiminated protein targets identified in skin mucosa included nuclear histones; cytoskeletal proteins such as tubulin and beta-actin; metabolic and immune related proteins such as galectin, mannan-binding lectin, toll-like receptor, kininogen, Beta2-microglobulin, aldehyde dehydrogenase, bloodthirsty and preproapolipoprotein A-I. Deiminated histone H3, a marker for anti-pathogenic neutrophil extracellular traps, was particularly elevated in mucosal tissues in immunostimulated cod larvae. PAD-mediated protein deimination may facilitate protein moonlighting, allowing the same protein to exhibit a range of biological functions, in tissue remodelling and mucosal immune defences in teleost ontogeny

Pentraxins CRP-I and CRP-II are post-translationally deiminated and differ in tissue specificity in cod (Gadus morhua L.) ontogeny

Pentraxins are fluid phase pattern recognition molecules that form an important part of the innate immune defence and are conserved between fish and human. In Atlantic cod (Gadus morhua L.), two pentraxin-like proteins have been described, CRP-I and CRP-II. Here we show for the first time that these two CRP forms are post-translationally deiminated (an irreversible conversion of arginine to citrulline) and differ with respect to tissue specific localisation in cod ontogeny from 3 to 84 days post hatching. While both forms are expressed in liver, albeit at temporally differing levels, CRP-I shows a strong association with nervous tissue while CRP-II is strongly associated to mucosal tissues of gut and skin. This indicates differing roles for the two pentraxin types in immune responses and tissue remodelling, also elucidating novel roles for CRP-I in the nervous system. The presence of deimination positive bands for cod CRPs varied somewhat between mucus and serum, possibly facilitating CRP protein moonlighting, allowing the same protein to exhibit a range of biological functions and thus meeting different functional requirements in different tissues. The presented findings may further current understanding of the diverse roles of pentraxins in teleost immune defences and tissue remodelling, as well as in various human pathologies, including autoimmune diseases, amyloidosis and cancer

Modulation of outer bank erosion by slump blocks: Disentangling the protective and destructive role of failed material on the three-dimensional flow structure

The three-dimensional flow field near the banks of alluvial channels is the primary factor controlling rates of bank erosion. Although submerged slump blocks and associated large-scale bank roughness elements have both previously been proposed to divert flow away from the bank, direct observations of the interaction between eroded bank material and the 3-D flow field are lacking. Here we use observations from multibeam echo sounding, terrestrial laser scanning, and acoustic Doppler current profiling to quantify, for the first time, the influence of submerged slump blocks on the near-bank flow field. In contrast to previous research emphasizing their influence on flow diversion away from the bank, we show that slump blocks may also deflect flow onto the bank, thereby increasing local shear stresses and rates of erosion. We use our measurements to propose a conceptual model for how submerged slump blocks interact with the flow field to modulate bank erosion.UK Natural Environment Research Council (NERC

Peptidylarginine deiminase and deiminated proteins are detected throughout early halibut ontogeny - Complement components C3 and C4 are post-translationally deiminated in halibut (Hippoglossus hippoglossus L.)

Post-translational protein deimination is mediated by peptidylarginine deiminases (PADs), which are calcium dependent enzymes conserved throughout phylogeny with physiological and pathophysiological roles. Protein deimination occurs via the conversion of protein arginine into citrulline, leading to structural and functional changes in target proteins. In a continuous series of early halibut development from 37 to 1050° d, PAD, total deiminated proteins and deiminated histone H3 showed variation in temporal and spatial detection in various organs including yolksac, muscle, skin, liver, brain, eye, spinal cord, chondrocytes, heart, intestines, kidney and pancreas throughout early ontogeny. For the first time in any species, deimination of complement components C3 and C4 is shown in halibut serum, indicating a novel mechanism of complement regulation in immune responses and homeostasis. Proteomic analysis of deiminated target proteins in halibut serum further identified complement components C5, C7, C8 C9 and C1 inhibitor, as well as various other immunogenic, metabolic, cytoskeletal and nuclear proteins. Post-translational deimination may facilitate protein moonlighting, an evolutionary conserved phenomenon, allowing one polypeptide chain to carry out various functions to meet functional requirements for diverse roles in immune defences and tissue remodelling

Peptidylarginine Deiminases Post-Translationally Deiminate Prohibitin and Modulate Extracellular Vesicle Release and MicroRNAs in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most aggressive form of adult primary malignant brain tumour with poor prognosis. Extracellular vesicles (EVs) are a key-mediator through which GBM cells promote a pro-oncogenic microenvironment. Peptidylarginine deiminases (PADs), which catalyze the post-translational protein deimination of target proteins, are implicated in cancer, including via EV modulation. Pan-PAD inhibitor Cl-amidine affected EV release from GBM cells, and EV related microRNA cargo, with reduced pro-oncogenic microRNA21 and increased anti-oncogenic microRNA126, also in combinatory treatment with the chemotherapeutic agent temozolomide (TMZ). The GBM cell lines under study, LN18 and LN229, differed in PAD2, PAD3 and PAD4 isozyme expression. Various cytoskeletal, nuclear and mitochondrial proteins were identified to be deiminated in GBM, including prohibitin (PHB), a key protein in mitochondrial integrity and also involved in chemo-resistance. Post-translational deimination of PHB, and PHB protein levels, were reduced after 1 h treatment with pan-PAD inhibitor Cl-amidine in GBM cells. Histone H3 deimination was also reduced following Cl-amidine treatment. Multifaceted roles for PADs on EV-mediated pathways, as well as deimination of mitochondrial, nuclear and invadopodia related proteins, highlight PADs as novel targets for modulating GBM tumour communication

Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment

Outer membrane and membrane vesicles (OMV/MV) are released from bacteria and participate in cell communication, biofilm formation and host-pathogen interactions. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that catalyze post-translational deimination/citrullination of proteins, causing structural and functional changes in target proteins. PADs also play major roles in the regulation of eukaryotic extracellular vesicle release. Here we show phylogenetically conserved pathways of PAD-mediated OMV/MV release in bacteria and describe deiminated/citrullinated proteins in E. coli and their derived OMV/MVs. Furthermore, we show that PAD inhibitors can be used to effectively reduce OMV/MV release, both in Gram-negative and Gram-positive bacteria. Importantly, this resulted in enhanced antibiotic sensitivity of both E. coli and S. aureus to a range of antibiotics tested. Our findings reveal novel strategies for applying pharmacological OMV/MV-inhibition to reduce antibiotic resistance

Tuning gaps and phases of a two-subband system in a quantizing magnetic field

In this work we study the properties of a two-subband quasi-two-dimensional electron system in a strong magnetic field when the electron filling factor is equal to four. When the cyclotron energy is close to the intersubband splitting the system can be mapped onto a four-level electron system with an effective filling factor of two. The ground state is either a ferromagnetic state or a spin-singlet state, depending on the values of the inter-level splitting and Zeeman energy. The boundaries between these phases are strongly influenced by the inter-electron interaction. A significant exchange-mediated enhancement of the excitation gap results in the suppression of the electron-phonon interaction. The rate of absorption of non-equilibrium phonons is calculated as a function of Zeeman energy and inter-subband splitting. The phonon absorption rate has two peaks as a function of intersubband splitting and has a step-like structure as a function of Zeeman energy

When work keeps us apart: a thematic analysis of the experience of business travellers

Whilst business travel is deemed important for organizational success and economic outcomes, little is known about the actual process of business travelling from the perspective of individuals who undertake such travel on a regular basis. Thus the current qualitative study examined how business travellers (three women and eight men) attempt to find a balance between work and family, by focusing on how time together and time apart are experienced. The results can be interpreted and framed within work/family border theory in that business travellers’ borders are less defined and less permeable, thus requiring them to border-cross more frequently. This necessitates a process of negotiation with key border-keepers (their spouse/partner). Business travellers also undertake compensatory behaviours to make up for their time away from family. In order to find a work/family balance they go through a process of adapting, negotiating and tailoring their lives around their work commitments to alleviate work-life conflict