Tardigrada (also known as "water bears") are hydrophilous microinvertebrates with a bilaterally symmetrical body and four pairs of legs usually terminating with claws. Water bears are quite complex animals and range from 50 to 1200μm in length. Their body is divided into a head segment and four trunk segments, each bearing a pair of legs. They inhabit almost all terrestrial and aquatic environments, from the ocean depths to highest mountains ranges. However, one of their best known and unusual features is their capability for cryptobiosis. In this state tardigrades are able to survive extremely low and high temperatures and atmospheric pressures, complete lack of water, high doses of radiation, high concentrations of toxins and even a cosmic vacuum. The cellular mechanisms enabling cryptobiosis are poorly understood, although it appears the synthesis of certain types of molecules (sugars and proteins) enable the prevention of cellular damage at different levels. The endoplasmic reticulum (ER) is a morphologically and functionally diverse organelle able to integrate multiple extracellular and internal signals and generate adaptive cellular responses. However, the ER morphology and activity in the case of tardigrades has been studied rarely and in the context of oogenesis, functioning of the digestive system, and in the role and function of storage cells. Thus, there are no direct studies on the contribution of the ER in the ability of this organism to cope with environmental stress during cryptobiosis. Nevertheless, it is highly probable that the ER has a crucial role in this uncommon process. Since water bears are easy to handle laboratory animals, they may represent an ideal model organism to uncover the important role of the ER in the cell response to extreme environmental stress conditions.

The twenty-first century began with a certain indifference to the research of satellite DNA (satDNA). Neither genome sequencing projects were able to accurately encompass the study of satDNA nor classic methodologies were able to go further in undertaking a better comprehensive study of the whole set of satDNA sequences of a genome. Nonetheless, knowledge of satDNA has progressively advanced during this century with the advent of new analytical techniques. The enormous advantages that genome-wide approaches have brought to its analysis have now stimulated a renewed interest in the study of satDNA. At this point, we can look back and try to assess more accurately many of the key questions that were left unsolved in the past about this enigmatic and important component of the genome. I review here the understanding gathered on plant satDNAs over the last few decades with an eye on the near future.

Endoplasmic reticulum (ER) stress is a prominent cellular alteration of diseases impacting the nervous system that are associated to the accumulation of misfolded and aggregated protein species during aging. The unfolded protein response (UPR) is the main pathway mediating adaptation to ER stress, but it can also trigger deleterious cascades of inflammation and cell death leading to cell dysfunction and neurodegeneration. Genetic and pharmacological studies in experimental models shed light into molecular pathways possibly contributing to ER stress and the UPR activation in human neuropathies. Most of experimental models are, however, based on the overexpression of mutant proteins causing familial forms of these diseases or the administration of neurotoxins that induce pathology in young animals. Whether the mechanisms uncovered in these models are relevant for the etiology of the vast majority of age-related sporadic forms of neurodegenerative diseases is an open question. Here, we provide a systematic analysis of the current evidence linking ER stress to human pathology and the main mechanisms elucidated in experimental models. Furthermore, we highlight the recent association of metabolic syndrome to increased risk to undergo neurodegeneration, where ER stress arises as a common denominator in the pathogenic crosstalk between peripheral organs and the nervous system.

The unfolded protein response (UPR) is an evolutionarily conserved adaptive regulatory pathway that alleviates protein-folding defects in the endoplasmic reticulum (ER). Physiological demands, environmental perturbations and pathological conditions can cause accumulation of unfolded proteins in the ER and the stress signal is transmitted to the nucleus to turn on a series of genes to respond the challenge. In metazoan, the UPR pathways consisted of IRE1/XBP1, PEK-1 and ATF6, which function in parallel and downstream transcriptional activation triggers the proteostasis networks consisting of molecular chaperones, protein degradation machinery and other stress response pathways ((Labbadia J, Morimoto RI, F1000Prime Rep 6:7, 2014); (Shen X, Ellis RE, Lee K, Annu Rev Biochem 28:893-903, 2014)). The integrated responses act on to resolve the ER stress by increasing protein folding capacity, attenuating ER-loading translation, activating ER-associated proteasomal degradation (ERAD), and regulating IRE1-dependent decay of mRNA (RIDD). Therefore, the effective UPR to internal and external causes is linked to the multiple pathophysiological conditions such as aging, immunity, and neurodegenerative diseases. Recent development in the research of the UPR includes cell-nonautonomous features of the UPR, interplay between the UPR and other stress response pathways, unconventional UPR inducers, and noncanonical UPR independent of the three major branches, originated from multiple cellular and molecular machineries in addition to ER. Caenorhabditis elegans model system has critically contributed to these unprecedented aspects of the ER UPR and broadens the possible therapeutic targets to treat the ER-stress associated human disorders and time-dependent physiological deterioration of aging.

The endoplasmic reticulum (ER) is a biosynthetic organelle in eukaryotic cells. Its capacity to produce proteins, lipids and oligosaccharides responds to physiologic and pathologic demand. The transcriptional and translational unfolded protein response (UPR) programs increase ER size and activity. In contrast, ER-phagy programs in all their flavors select ER subdomains for lysosomal clearance. These programs are activated by nutrient deprivation, accumulation of excess ER (recov-ER-phagy), production of misfolded proteins that cannot be degraded by ER-associated degradation and that are removed from cells by the so-called ER-to-lysosome-associated degradation (ERLAD). Selection of ER subdomains to be cleared from cells relies on ER-phagy receptors, a class of membrane-bound proteins displaying cytosolic domains that engage the cytosolic ubiquitin-like protein LC3. Mechanistically, ER clearance proceeds via macro-ER-phagy, micro-ER-phagy and LC3-regulated vesicular delivery.

Intracellular Ca2+ signaling regulates a plethora of cellular functions. A central role in these processes is reserved for the inositol 1,4,5-trisphosphate receptor (IP3R), a ubiquitously expressed Ca2+-release channel, mainly located in the endoplasmic reticulum (ER). Three IP3R isoforms (IP3R1, IP3R2 and IP3R3) exist, encoded respectively by ITPR1, ITPR2 and ITPR3. The proteins encoded by these genes are each about 2700 amino acids long and assemble into large tetrameric channels, which form the target of many regulatory proteins, including several tumor suppressors and oncogenes. Due to the important role of the IP3Rs in cell function, their dysregulation is linked to multiple pathologies. In this review, we highlight the complex role of the IP3R in cancer, as it participates in most of the so-called "hallmarks of cancer". In particular, the IP3R directly controls cell death and cell survival decisions via regulation of autophagy and apoptosis. Moreover, the IP3R impacts cellular proliferation, migration and invasion. Typical examples of the role of the IP3Rs in these various processes are discussed. The relative levels of the IP3R isoforms expressed and their subcellular localization, e.g. at the ER-mitochondrial interface, is hereby important. Finally, evidence is provided about how the knowledge of the regulation of the IP3R by tumor suppressors and oncogenes can be exploited to develop novel therapeutic approaches to fight cancer.

Calreticulin is well known as an ER-resident protein that serves as the major endoplasmic reticulum (ER) Ca2+ binding protein. This protein has been the major topic of discussion in an international workshop that has been meeting for a quarter of a century. In sharing information about this protein, the field also witnessed remarkable insights into the importance of the ER as an organelle and the role of ER Ca2+ in coordinating ER and cellular functions. Recent technological advances have helped to uncover the contributions of calreticulin in maintaining Ca2+ homeostasis in the ER and to unravel its involvement in a multitude of cellular processes as highlighted in this collection of articles. The continuing revelations of unexpected involvement of calreticulin and Ca2+ in many critical aspects of cellular function promises to further improve insights into the significance of this protein in the promotion of physiology as well as prevention of pathology.

Drug resistance mechanisms in the commensal human pathogen Candida albicans are continually evolving. Over time, Candida species have implemented diverse strategies to vanquish the effects of various classes of drugs, thereby emanating as a serious life threat. Apart from the repertoire of well-established strategies, which predominantly comprise permeability constraints, increased drug efflux or compromised drug import, alteration, overexpression of drug targets, and chromosome duplication, C. albicans has evolved novel regulatory mechanisms of drug resistance. For instance, recent evidences point to newer circuitry involving different mediators of the stress-responsive machinery of oxidative, osmotic, thermal, nitrosative, and nutrient limitation, which contribute to the emergence of drug resistance. Contemporary advances in genome-wide studies of transcription factors, for instance, the Zn2Cys6 transcription factors, TAC1 (transcriptional activator of CDR) in Candida albicans, or YRR1 in yeast have made it feasible to dissect their involvement for the elucidation of unexplored regulatory network of drug resistance. The coordination of implementers of the conventional and nonconventional drug resistance strategies provides robustness to this commensal human pathogen. In this review, we shed light not only on the established strategies of antifungal resistance but also discuss emerging cellular circuitry governing drug resistance of this human pathogen.

Zygosaccharomyces bailii and two closely related species, Z. parabailii and Z. pseudobailii ("Z. bailii species complex", "Z. bailii sensu lato" or simply "Z. bailii (s.l.)"), are frequently implicated in the spoilage of acidified preserved foods and beverages due to their tolerance to very high concentrations of weak acids used as food preservatives. The recent sequencing and annotation of these species' genomes have clarified their genomic organization and phylogenetic relationship, which includes events of interspecies hybridization. Mechanistic insights into their adaptation and tolerance to weak acids (e.g., acetic and lactic acids) are also being revealed. Moreover, the potential of Z. bailii (s.l.) to be used in industrial biotechnological processes as interesting cell factories for the production of organic acids, reduction of the ethanol content, increase of alcoholic beverages aroma complexity, as well as of genetic source for increasing weak acid resistance in yeast, is currently being considered. This chapter includes taxonomical, ecological, physiological, and biochemical aspects of Z. bailii (s.l.). The focus is on the exploitation of physiological genomics approaches that are providing the indispensable holistic knowledge to guide the effective design of strategies to overcome food spoilage or the rational exploitation of these yeasts as promising cell factories.

Cells face genetic and/or environmental changes in order to outlast and proliferate. Characterization of changes after stress at different "omics" levels is crucial to understand the adaptation of yeast to changing conditions. Wine fermentation is a stressful situation which yeast cells have to cope with. Genome-wide analyses extend our cellular physiology knowledge by pointing out the mechanisms that contribute to sense the stress caused by these perturbations (temperature, ethanol, sulfites, nitrogen, etc.) and related signaling pathways. The model organism, Saccharomyces cerevisiae, was studied in response to industrial stresses and changes at different cellular levels (transcriptomic, proteomic, and metabolomics), which were followed statically and/or dynamically in the short and long terms. This chapter focuses on the response of yeast cells to the diverse stress situations that occur during wine fermentations, which induce perturbations, including nutritional changes, ethanol stress, temperature stress, oxidative stress, etc.