Nme Gene Family Evolutionary History Reveals Pre-Metazoan Origins and High Conservation between Humans and the Sea Anemone, Nematostella vectensis

There was an error in affiliation 1 for authors Thomas Desvignes and Julien Bobe. Affiliation 1 should be: INRA, UR1037 SCRIBE, Campus de Beaulieu, F-35000 Rennes, FranceBackground: The Nme gene family is involved in multiple physiological and pathological processes such as cellular differentiation, development, metastatic dissemination, and cilia functions. Despite the known importance of Nme genes and their use as clinical markers of tumor aggressiveness, the associated cellular mechanisms remain poorly understood. Over the last 20 years, several non-vertebrate model species have been used to investigate Nme functions. However, the evolutionary history of the family remains poorly understood outside the vertebrate lineage. The aim of the study was thus to elucidate the evolutionary history of the Nme gene family in Metazoans. [br/]Methodology/Principal Findings: Using a total of 21 eukaryote species including 14 metazoans, the evolutionary history of Nme genes was reconstructed in the metazoan lineage. We demonstrated that the complexity of the Nme gene family, initially thought to be restricted to chordates, was also shared by the metazoan ancestor. We also provide evidence suggesting that the complexity of the family is mainly a eukaryotic innovation, with the exception of Nme8 that is likely to be a choanoflagellate/metazoan innovation. Highly conserved gene structure, genomic linkage, and protein domains were identified among metazoans, some features being also conserved in eukaryotes. When considering the entire Nme family, the starlet sea anemone is the studied metazoan species exhibiting the most conserved gene and protein sequence features with humans. In addition, we were able to show that most of the proteins known to interact with human NME proteins were also found in starlet sea anemone. [br/]Conclusion/Significance: Together, our observations further support the association of Nme genes with key cellular functions that have been conserved throughout metazoan evolution. Future investigations of evolutionarily conserved Nme gene functions using the starlet sea anemone could shed new light on a wide variety of key developmental and cellular processes

Nme protein family evolutionary history, a vertebrate perspective

Background: The Nme family, previously known as Nm23 or NDPK, is involved in various molecular processes including tumor metastasis and some members of the family, but not all, exhibit a Nucleoside Diphosphate Kinase (NDPK) activity. Ten genes are known in humans, in which some members have been extensively studied. In non-mammalian species, the Nme protein family has received, in contrast, far less attention. The picture of the vertebrate Nme family remains thus incomplete and orthology relationships with mammalian counterparts were only partially characterized. The present study therefore aimed at characterizing the Nme gene repertoire in vertebrates with special interest for teleosts, and providing a comprehensive overview of the Nme gene family evolutionary history in vertebrates. Results: In the present study, we present the evolutionary history of the Nme family in vertebrates and characterize the gene family repertoire for the first time in several non-mammalian species. Our observations show that vertebrate Nme genes can be separated in two evolutionary distinct groups. Nme1, Nme2, Nme3, and Nme4 belong to Group I while vertebrate Nme5, Nme6, Nme7, Nme8, and Nme9 belong to Group II. The position of Nme10 is in contrast more debatable due to its very specific evolutionary history. The present study clearly indicates that Nme5, Nme6, Nme7, and Nme8 originate from duplication events that occurred before the chordate radiation. In contrast, Nme genes of the Group I have a very different evolutionary history as our results suggest that they all arise from a common gene present in the chordate ancestor. In addition, expression patterns of all zebrafish nme transcripts were studied in a broad range of tissues by quantitative PCR and discussed in the light of the function of their mammalian counterparts. Conclusion: This work offers an evolutionary framework that will pave the way for future studies on vertebrate Nme proteins and provides a unified vertebrate Nme nomenclature that is consistent with the nomenclature in use in mammals. Based on protein structure and expression data, we also provide new insight into molecular functions of Nme proteins among vertebrates and raise intriguing questions on the roles of Nme proteins in gonads

Adaptation of Proteins to the Cold in Antarctic Fish: A Role for Methionine?

The evolution of antifreeze glycoproteins has enabled notothenioid fish to flourish in the freezing waters of the Southern Ocean. Whereas successful at the biodiversity level to life in the cold, paradoxically at the cellular level these stenothermal animals have problems producing, folding, and degrading proteins at their ambient temperatures of -1.86 °C. In this first multi-species transcriptome comparison of the amino acid composition of notothenioid proteins with temperate teleost proteins, we show that, unlike psychrophilic bacteria, Antarctic fish provide little evidence for the mass alteration of protein amino acid composition to enhance protein folding and reduce protein denaturation in the cold. The exception was the significant overrepresentation of positions where leucine in temperate fish proteins was replaced by methionine in the notothenioid orthologues. We hypothesize that these extra methionines have been preferentially assimilated into the genome to act as redox sensors in the highly oxygenated waters of the Southern Ocean. This redox hypothesis is supported by analyses of notothenioids showing enrichment of genes associated with responses to environmental stress, particularly reactive oxygen species. So overall, although notothenioid fish show cold-associated problems with protein homeostasis, they may have modified only a selected number of biochemical pathways to work efficiently below 0 °C. Even a slight warming of the Southern Ocean might disrupt the critical functions of this handful of key pathways with considerable impacts for the functioning of this ecosystem in the future

The Time is Right for an Antarctic Biorepository Network

Antarctica is a central driver of the Earth’s climate and health. The Southern Ocean surrounding Antarctica serves as a major sink for anthropogenic CO2 and heat (1), and the loss of Antarctic ice sheets contributes significantly to sea level rise and will continue to do so as the loss of ice sheets accelerates, with sufficient water stores to raise sea levels by 58 m (2). Antarctica\u27s marine environment is home to a number of iconic species, and the terrestrial realm harbors a remarkable oasis for life, much of which has yet to be discovered (3). Distinctive oceanographic features of the Southern Ocean—including the Antarctic Circumpolar Current, the Antarctic Polar Front, and exceptional depths surrounding the continent—coupled with chronically cold temperatures have fostered the evolution of a vast number of uniquely coldadapted species, many of which are found nowhere else on the Earth (4). The Antarctic marine biota, for example, displays the highest level of species endemism on the Earth (5). However, warming, ocean acidification, pollution, and commercial exploitation threaten the integrity of Antarctic ecosystems (6). Understanding changes in the biota and its capacities for adaptation is imperative for establishing effective policies for mitigating the impacts of climate change and sustaining the Antarctic ecosystems that are vital to global health

Tests of gravitational symmetries with pulsar binary J1713+0747

Symmetries play a fundamental role in modern theories of gravity. The strong equivalence principle (SEP) constitutes a collection of gravitational symmetries which are all implemented by general relativity. Alternative theories, however, are generally expected to violate some aspects of SEP. We test three aspects of SEP using observed change rates in the orbital period and eccentricity of binary pulsar J1713+0747: (1) the gravitational constant's constancy as part of locational invariance of gravitation; (2) the universality of free fall (UFF) for strongly self-gravitating bodies; (3) the post-Newtonian parameter \\hat{α }_3 in gravitational Lorentz invariance. Based on the pulsar timing result of the combined data set from the North American Nanohertz Gravitational Observatory and the European Pulsar Timing Array, we find \\dot{G}/G = (-0.1 ± 0.9) × 10^{-12} yr^{-1}, which is weaker than Solar system limits, but applies for strongly self-gravitating objects. Furthermore, we obtain an improved test for a UFF violation by a strongly self-gravitating mass falling in the gravitational field of our Galaxy, with a limit of |Δ| < 0.002 (95 per cent C.L.). Finally, we derive an improved limit on the self-acceleration of a gravitationally bound rotating body, to a preferred reference frame in the Universe, with -3× 10^{-20} \\lt \\hat{α }_3 \\lt 4× 10^{-20} (95 per cent C.L.). These results are based on direct UFF and \\hat{α }_3 tests using pulsar binaries, and they overcome various limitations of previous tests of this kind

Retinal oxygen supply shaped the functional evolution of the vertebrate eye

Article explores the hypothesis that oxygen diffusion limited the evolution of retinal morphology by reconstructing the evolution of retinal thickness and the various mechanisms for retinal oxygen supply, including capillarization and acid-induced haemoglobin oxygen unloading

Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis

Genetically modified mice have advanced our understanding of valve development and disease. Yet, human pathophysiological valvulogenesis remains poorly understood. Here we report that, by combining single cell sequencing and in vivo approaches, a population of human pre-valvular endocardial cells (HPVCs) can be derived from pluripotent stem cells. HPVCs express gene patterns conforming to the E9.0 mouse atrio-ventricular canal (AVC) endocardium signature. HPVCs treated with BMP2, cultured on mouse AVC cushions, or transplanted into the AVC of embryonic mouse hearts, undergo endothelial-to-mesenchymal transition and express markers of valve interstitial cells of different valvular layers, demonstrating cell specificity. Extending this model to patient-specific induced pluripotent stem cells recapitulates features of mitral valve prolapse and identified dysregulation of the SHH pathway. Concurrently increased ECM secretion can be rescued by SHH inhibition, thus providing a putative therapeutic target. In summary, we report a human cell model of valvulogenesis that faithfully recapitulates valve disease in a dish.We thank the Leducq Fondation for supporting Tui Neri, and funding this research under the framework of the MITRAL network and for generously awarding us for the equipment of our cell imaging facility in the frame of their program “Equipement de Recherche et Plateformes Technologiques” (ERPT to M.P.), the Genopole at Evry and the Fondation de la recherche Medicale (grant DEQ20100318280) for supporting the laboratory of Michel Puceat. Part of this work in South Carolina University was conducted in a facility constructed with support from the National Institutes of Health, Grant Number C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. Other funding sources: National Heart Lung and Blood Institute: RO1-HL33756 (R.R.M.), COBRE P20RR016434–07 (R.R.M., R.A. N.), P20RR016434–09S1 (R.R.M. and R.A.N.); American Heart Association: 11SDG5270006 (R.A.N.); National Science Foundation: EPS-0902795 (R.R.M. and R.A. N.); American Heart Association: 10SDG2630130 (A.C.Z.), NIH: P01HD032573 (A.C. Z.), NIH: U54 HL108460 (A.C.Z), NCATS: UL1TR000100 (A.C.Z.); EH was supported by a fellowship of the Ministere de la recherche et de l’éducation in France.TM-M was supported by a fellowship from the Fondation Foulon Delalande and the Leducq Foundation. P.v.V. was sponsored by a UC San Diego Cardiovascular Scholarship Award and a Postdoctoral Fellowship from the California Institute for Regenerative Medicine (CIRM) Interdisciplinary Stem Cell Training Program II. S.M.E. was funded by a grant from the National Heart, Lung, and Blood Institute (HL-117649). A.T. is supported by the National Heart, Lung, and Blood Institute (R01-HL134664).S

A parasite outbreak in notothenioid fish in an Antarctic fjord

20 pages, 4 figures, supplemental information https://doi.org/10.1016/j.isci.2022.104588.-- Data and code availability: • All data have been deposited at NCBI GenBank: OL630144 and OL630145, NCBI SRA BioProject: PRJNA789574, at MorphoSource Project: 000405843, and at USAP-DC Project: p0010221, and are publicly available as of the date of publication. Biological materials have been deposited at the Zoological Museum of the University of Copenhagen. Additional accession numbers and DOIs are listed in the key resources. • This paper does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon requestClimate changes can promote disease outbreaks, but their nature and potential impacts in remote areas have received little attention. In a hot spot of biodiversity on the West Antarctic Peninsula, which faces among the fastest changing climates on Earth, we captured specimens of two notothenioid fish species affected by large skin tumors at an incidence never before observed in the Southern Ocean. Molecular and histopathological analyses revealed that X-cell parasitic alveolates, members of a genus we call Notoxcellia, are the etiological agent of these tumors. Parasite-specific molecular probes showed that xenomas remained within the skin but largely outgrew host cells in the dermis. We further observed that tumors induced neovascularization in underlying tissue and detrimentally affected host growth and condition. Although many knowledge gaps persist about X-cell disease, including its mode of transmission and life cycle, these findings reveal potentially active biotic threats to vulnerable Antarctic ecosystemsThis work was funded by the National Science Foundation grants OPP-1947040 (JHP and ArV), PLR-1444167 (HWD), and OPP-1543383 (JHP, TD, and HWD)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

First M87 Event Horizon Telescope Results. VII. Polarization of the Ring

In 2017 April, the Event Horizon Telescope (EHT) observed the near-horizon region around the supermassive black hole at the core of the M87 galaxy. These 1.3 mm wavelength observations revealed a compact asymmetric ring-like source morphology. This structure originates from synchrotron emission produced by relativistic plasma located in the immediate vicinity of the black hole. Here we present the corresponding linear-polarimetric EHT images of the center of M87. We find that only a part of the ring is significantly polarized. The resolved fractional linear polarization has a maximum located in the southwest part of the ring, where it rises to the level of ∼15%. The polarization position angles are arranged in a nearly azimuthal pattern. We perform quantitative measurements of relevant polarimetric properties of the compact emission and find evidence for the temporal evolution of the polarized source structure over one week of EHT observations. The details of the polarimetric data reduction and calibration methodology are provided. We carry out the data analysis using multiple independent imaging and modeling techniques, each of which is validated against a suite of synthetic data sets. The gross polarimetric structure and its apparent evolution with time are insensitive to the method used to reconstruct the image. These polarimetric images carry information about the structure of the magnetic fields responsible for the synchrotron emission. Their physical interpretation is discussed in an accompanying publication. </p