Thresholds in deep-seabed mining: A primer for their development

The establishment of thresholds is integral to environmental management. This paper introduces the use of thresholds in the context of deep-seabed mining, a nascent industry for which an exploitation regime of regulations, standards and guidelines is still in the process of being developed, and for which the roles and values of thresholds have yet to be finalised. There are several options for integrating thresholds into the International Seabed Authority’s regulatory regime, from being stipulated in regulations to being part of a mining contract, each option having its own advantages and disadvantages. Here we explore the range of ways that thresholds can be derived, set out the challenges in translating ecological and management data into thresholds, highlight factors for acceptance and operationalisation of thresholds in deep-seabed mining, and explain the necessity of refining thresholds as knowledge on impacts to features improves. Some comparable marine industries already use thresholds and these could potentially be used as starting points for the development of thresholds for deep-seabed mining. In order to be acceptable to the wide range of deep-seabed mining stakeholders, thresholds need to strike a balance among levels of harm acceptable by society, levels of environmental precaution justifiable by governments, scientific robustness, and operational practicality

Distinct Transcriptome Expression of the Temporal Cortex of the Primate Microcebus murinus during Brain Aging versus Alzheimer's Disease-Like Pathology

Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, “AD-like” animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and “AD-like” animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and “AD-like” in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in “AD-like” animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the “AD-like” group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in “AD-like” animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in “AD-like” animals. These results open the way to new exploration of physiological and “AD-like” aging in primates

The Variant rs1867277 in FOXE1 Gene Confers Thyroid Cancer Susceptibility through the Recruitment of USF1/USF2 Transcription Factors

In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30–1.70; P = 5.9×10−9). Functional assays of rs1867277 (NM_004473.3:c.−283G>A) within the FOXE1 5′ UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/αCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era

Promoter Complexity and Tissue-Specific Expression of Stress Response Components in Mytilus galloprovincialis, a Sessile Marine Invertebrate Species

The mechanisms of stress tolerance in sessile animals, such as molluscs, can offer fundamental insights into the adaptation of organisms for a wide range of environmental challenges. One of the best studied processes at the molecular level relevant to stress tolerance is the heat shock response in the genus Mytilus. We focus on the upstream region of Mytilus galloprovincialis Hsp90 genes and their structural and functional associations, using comparative genomics and network inference. Sequence comparison of this region provides novel evidence that the transcription of Hsp90 is regulated via a dense region of transcription factor binding sites, also containing a region with similarity to the Gamera family of LINE-like repetitive sequences and a genus-specific element of unknown function. Furthermore, we infer a set of gene networks from tissue-specific expression data, and specifically extract an Hsp class-associated network, with 174 genes and 2,226 associations, exhibiting a complex pattern of expression across multiple tissue types. Our results (i) suggest that the heat shock response in the genus Mytilus is regulated by an unexpectedly complex upstream region, and (ii) provide new directions for the use of the heat shock process as a biosensor system for environmental monitoring

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Respiratory response of the deep-sea amphipod Stephonyx biscayensis indicates bathymetric range limitation by temperature and hydrostatic pressure

Depth zonation of fauna on continental margins is well documented. Whilst increasing hydrostatic pressure with depth has long been considered a factor contributing significantly to this pattern, discussion of the relative significance of decreasing temperature with depth has continued. This study investigates the physiological tolerances of fed and starved specimens of the bathyal lysianassoid amphipod Stephonyx biscayensis at varying temperature to acute pressure exposure by measuring the rate of oxygen consumption. Acclimation to atmospheric pressure is shown to have no significant interaction with temperature and/or pressure effects. Similarly, starvation is shown to have no significant effect on the interaction of temperature and pressure. Subsequently, the effect of pressure on respiration rate is revealed to be dependent on temperature: pressure equivalent to 2000 m depth was tolerated at 1 and 3°C; pressure equivalent to 2500 m depth was tolerated at 5.5°C; at 10°C pressure equivalent to 3000 m depth was tolerated. The variation in tolerance is consistent with the natural distribution range reported for this species. There are clear implications for hypotheses relating to the observed phenomenon of a biodiversity bottleneck between 2000 and 3000 metres, and for the potential for bathymetric range shifts in response to global climate change

The secret to successful deep-sea invasion: does low temperature hold the key?

There is a general consensus that today’s deep-sea biodiversity has largely resulted from recurrent invasions and speciations occurring through homogenous waters during periods of the Phanerozoic eon. Migrations likely continue today, primarily via isothermal water columns, such as those typical of Polar Regions, but the necessary ecological and physiological adaptations behind them are poorly understood. In an evolutionary context, understanding the adaptations, which allow for colonisation to high-pressure environments, may enable us to predict future events. In this investigation, we examine pressure tolerance during development, in the shallow-water neogastropod Buccinum undatum using thermally acclimated egg masses from temperate and sub-polar regions across the species range. Fossil records indicate neogastropods to have a deep-water origin, suggesting shallow-water species may be likely candidates for re-emergence into the deep sea. Our results show population level differences in physiological thresholds, which indicate low temperature acclimation to increase pressure tolerance. These findings imply this species is capable of deep-sea penetration through isothermal water columns prevailing at high latitudes. This study gives new insight into the fundamentals behind past and future colonisation events. Such knowledge is instrumental to understand better how changes in climate envelopes affect the distribution and radiation of species both along latitudinal as well as bathymetric temperature gradients