Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks
ISSN: 0013-7227

hal-01187409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187409
DOI : 10.1210/EN.2015-1350
PUBMED : 26241067

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Cyanobacteria are ubiquitous microorganisms considered as important contributors to the formation of Earth's atmosphere and nitrogen fixation. However, they are also frequently associated with toxic blooms. Indeed, the wide range of hepatotoxins, neurotoxins and dermatotoxins synthesized by these bacteria is a growing environmental and public health concern. This paper provides a state of the art on the occurrence and management of harmful cyanobacterial blooms in surface and drinking water, including economic impacts and research needs. Cyanobacterial blooms usually occur according to a combination of environmental factors e.g., nutrient concentration, water temperature, light intensity, salinity, water movement, stagnation and residence time, as well as several other variables. These environmental variables, in turn, have promoted the evolution and biosynthesis of strain-specific, gene-controlled metabolites (cyanotoxins) that are often harmful to aquatic and terrestrial life, including humans. Cyanotoxins are primarily produced intracellularly during the exponential growth phase. Release of toxins into water can occur during cell death or senescence but can also be due to evolutionary-derived or environmentally-mediated circumstances such as allelopathy or relatively sudden nutrient limitation. Consequently, when cyanobacterial blooms occur in drinking water resources, treatment has to remove both cyanobacteria (avoiding cell lysis and subsequent toxin release) and aqueous cyanotoxins previously released. Cells are usually removed with limited lysis by physical processes such as clarification or membrane filtration. However, aqueous toxins are usually removed by both physical retention, through adsorption on activated carbon or reverse osmosis, and chemical oxidation, through ozonation or chlorination. While the efficient oxidation of the more common cyanotoxins (microcystin, cylindrospermopsin, anatoxin and saxitoxin) has been extensively reported, the chemical and toxicological characterization of their by-products requires further investigation. In addition, future research should also investigate the removal of poorly considered cyanotoxins (β-methylamino-alanine, lyngbyatoxin or aplysiatoxin) as well as the economic impact of blooms.
Environment International

hal-00875835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00875835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00875835/document
DOI : 10.1016/j.envint.2013.06.013
PUBMED : 23892224