Adaptations to Endosymbiosis in a Cnidarian-Dinoflagellate Association: Differential Gene Expression and Specific Gene Duplications

Trophic endosymbiosis between anthozoans and photosynthetic dinoflagellates forms the key foundation of reef ecosystems. Dysfunction and collapse of symbiosis lead to bleaching (symbiont expulsion), which is responsible for the severe worldwide decline of coral reefs. Molecular signals are central to the stability of this partnership and are therefore closely related to coral health. To decipher inter-partner signaling, we developed genomic resources (cDNA library and microarrays) from the symbiotic sea anemone Anemonia viridis. Here we describe differential expression between symbiotic (also called zooxanthellate anemones) or aposymbiotic (also called bleached) A. viridis specimens, using microarray hybridizations and qPCR experiments. We mapped, for the first time, transcript abundance separately in the epidermal cell layer and the gastrodermal cells that host photosynthetic symbionts. Transcriptomic profiles showed large inter-individual variability, indicating that aposymbiosis could be induced by different pathways. We defined a restricted subset of 39 common genes that are characteristic of the symbiotic or aposymbiotic states. We demonstrated that transcription of many genes belonging to this set is specifically enhanced in the symbiotic cells (gastroderm). A model is proposed where the aposymbiotic and therefore heterotrophic state triggers vesicular trafficking, whereas the symbiotic and therefore autotrophic state favors metabolic exchanges between host and symbiont. Several genetic pathways were investigated in more detail: i) a key vitamin K–dependant process involved in the dinoflagellate-cnidarian recognition; ii) two cnidarian tissue-specific carbonic anhydrases involved in the carbon transfer from the environment to the intracellular symbionts; iii) host collagen synthesis, mostly supported by the symbiotic tissue. Further, we identified specific gene duplications and showed that the cnidarian-specific isoform was also up-regulated both in the symbiotic state and in the gastroderm. Our results thus offer new insight into the inter-partner signaling required for the physiological mechanisms of the symbiosis that is crucial for coral health

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

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

Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM

Emerging organic contaminants in groundwater : a review of sources, fate and occurrence

Emerging organic contaminants (EOCs) detected in groundwater may have adverse effects on human health and aquatic ecosystems. This paper reviews the existing occurrence data in groundwater for a range of EOCs including pharmaceutical, personal care, ‘life-style’ and selected industrial compounds. The main sources and pathways for organic EOCs in groundwater are reviewed, with occurrence data for EOCs in groundwater included from both targeted studies and broad reconnaissance surveys. Nanogram-microgram per litre concentrations are present in groundwater for a large range of EOCs as well as metabolites and transformation products and under certain conditions may pose a threat to freshwater bodies for decades due to relatively long groundwater residence times. In the coming decades, more of these EOCs are likely to have drinking water standards, environmental quality standards and/or groundwater threshold values defined, and therefore a better understanding of the spatial and temporal variation remains a priority

Transsphenoidal surgery in patients with acromegaly: operative strategies for overcoming technically challenging anatomical variations

Object. In addition to difficulties with anesthetic and medical management, transsphenoidal operations in patients with longstanding acromegaly are associated with inherent intraoperative challenges because of anatomical variations that occur frequently in these patients. The object of this study was to review the overall safety profile and anatomical/technical challenges associated with transsphenoidal surgery in patients with acromegaly. Methods. The authors performed a retrospective analysis of 169 patients who underwent endoscopic transsphenoidal operations for growth hormone-secreting adenomas to assess the incidence of surgical complications. A review of frequently occurring anatomical challenges and operative strategies employed during each phase of the operation to address these particular issues was performed. Results. Of 169 cases reviewed, there was no perioperative mortality. Internal carotid artery injury occurred in 1 patient (0.6%) with complex sinus anatomy, who remained neurologically intact following endovascular unilateral carotid artery occlusion. Other complications included: significant postoperative epistaxis (5 patients [3%]), transient diabetes insipidus (5 patients [3%]), delayed symptomatic hyponatremia (4 patients [2%]), CSF leak (2 patients [1%]), and pancreatitis (1 patient [0.6%]). Preoperative considerations in patients with acromegaly should include a cardiopulmonary evaluation and planning regarding intubation and other aspects of the anesthetic technique. During the nasal phase of the transsphenoidal operation, primary challenges include maintaining adequate visualization and hemostasis, which is frequently compromised by redundant, edematous nasal mucosa and bony hypertrophy of the septum and the nasal turbinates. During the sphenoid phase, adequate bony removal, optimization of working space, and correlation of imaging studies to intraoperative anatomy are major priorities. The sellar phase is frequently challenged by increased sellar floor thickness, distinct patterns of tumor extension and bony invasion, and anatomical variations in the caliber and course of the internal carotid artery. Specific operative techniques for addressing each of these intraoperative challenges are discussed. Conclusions. Transsphenoidal surgery in patients with longstanding acromegaly frequently poses greater challenges than operations for other types of sellar lesions, yet these challenges may be safely and effectively overcome with the anticipation of specific issues and implementation of various intraoperative techniques. (DOI: 10.3171/2010.8.FOCUS10156