Protein Unfolding by Peptidylarginine Deiminase SUBSTRATE SPECIFICITY AND STRUCTURAL RELATIONSHIPS OF THE NATURAL SUBSTRATES TRICHOHYALIN AND FILAGGRIN

Peptidylarginine deiminases, which are commonly found in mammalian cells, catalyze the deimination of protein-bound arginine residues to citrullines. However, very little is known about their substrate requirements and the significance or consequences of this postsynthetic modification. We have explored this reaction in vitro with two known substrates filaggrin and trichohyalin. First, the degree and rate of modification of arginines to citrullines directly correlates with the structural order of the substrate. In filaggrin, which has little structural order, the reaction proceeded rapidly to >95% completion. However, in the highly alpha-helical protein trichohyalin, the reaction proceeded slowly to about 25% and could be forced to a maximum of about 65%. Second, the rate and degree of modification depends on the sequence location of the target arginines. Third, we show by gel electrophoresis, circular dichroism, and fluorescence spectroscopy that the reaction interferes with organized protein structure: the net formation of >/=10% citrulline results in protein denaturation. Cyanate modification of the lysines in model alpha-helix-rich proteins to homocitrullines also results in loss of organized structure. These data suggest that the ureido group on the citrulline formed by the peptidylarginine deiminase enzyme modification functions to unfold proteins due to decrease in net charge, loss of potential ionic bonds, and interference with H bonds

Recent development of prebiotic research — statement from an expert workshop

A dietary prebiotic is defined as ‘a substrate that is selectively utilized by host microorganisms conferring a health benefit’. Although this definition evolved concomitantly with the knowledge and technological developments that accrued in the last twenty years, what qualifies as prebiotic continues to be a matter of debate. In this statement, we report the outcome of a workshop where academic experts working in the field of prebiotic research met with scientists from industry. The workshop covered three main topics: (i) evolution of the prebiotic concept/definition; (ii) the gut modeling in vitro technology PolyFermS to study prebiotic effects; and (iii) the potential novel microbiome-modulating effects associated with vitamins. The future of prebiotic research is very promising. Indeed, the technological developments observed in recent years provide scientists with powerful tools to investigate the complex ecosystem of gut microbiota. Combining multiple in vitro approaches with in vivo studies is key to understanding the mechanisms of action of prebiotics consumption and their potential beneficial effects on the host

An Alanine to Proline Mutation in the 1A Rod Domain of the Keratin 10 Chain in Epidermolytic Hyperkeratosis

We report a mutation in a case of epidermolytic hyperkeratosis that results in a proline for alanine substitution in the residue position 12 of the 1A subdomain of the keratin 10 chain (codon 158). The disease phenotype is consistent with the inappropriate substitution of a proline near the beginning of the rod domain, because it is likely to seriously disrupt the structural organization of coiled-coil molecules within keratin intermediate filaments. Mutations/substitutions in this position have not been reported in any keratin disease. Position 12 is an alanine in all intermediate filament chains, and lies in the outer b heptad position of the coiled-coil. In vitro peptide interference assembly assays revealed that substitutions that alter residue size or charge at this position primarily interfere with keratin filament elongation

Compositional and Quantitative Insights Into Bacterial and Archaeal Communities of South Pacific Deep-Sea Sponges (Demospongiae and Hexactinellida)

In the present study, we profiled bacterial and archaeal communities from 13 phylogenetically diverse deep-sea sponge species (Demospongiae and Hexactinellida) from the South Pacific by 16S rRNA-gene amplicon sequencing. Additionally, the associated bacteria and archaea were quantified by real-time qPCR. Our results show that bacterial communities from the deep-sea sponges are mostly host-species specific similar to what has been observed for shallow-water demosponges. The archaeal deep-sea sponge community structures are different from the bacterial community structures in that they are almost completely dominated by a single family, which are the ammonia-oxidizing genera within the Nitrosopumilaceae. Remarkably, the archaeal communities are mostly specific to individual sponges (rather than sponge-species), and this observation applies to both hexactinellids and demosponges. Finally, archaeal 16s gene numbers, as detected by quantitative real-time PCR, were up to three orders of magnitude higher than in shallow-water sponges, highlighting the importance of the archaea for deep-sea sponges in general

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe

Ten new insights in climate science 2022

Non-technical summary We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C. Technical summary We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C. Social media summary Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields

Ten new insights in climate science 2023

Non-technical summary. We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. Technical summary. The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference. Social media summary. We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts