Mitochondria form cholesterol-rich contact sites with the nucleus during retrograde response

Cholesterol metabolism is pivotal to cellular homeostasis, hormones production, and membranes composition. Its dysregulation associates with malignant reprogramming and therapy resistance. Cholesterol is trafficked into the mitochondria for steroidogenesis by the transduceome protein complex, which assembles on the outer mitochondrial membrane (OMM). The highly conserved, cholesterol-binding, stress-reactive, 18kDa translocator protein (TSPO), is a key component of this complex. Here, we modulate TSPO to study the process of mitochondrial retrograde signalling with the nucleus, by dissecting the role played by cholesterol and its oxidized forms. Using confocal and ultrastructural imaging, we describe that TSPO enriched mitochondria, remodel around the nucleus, gathering in cholesterol-enriched domains (or contact sites). This communication is controlled by HMG-CoA reductase inhibitors (statins), molecular and pharmacological regulation of TSPO. The described Nucleus-Associated Mitochondria (NAM) seem to be implementing survival signalling in aggressive forms of breast cancer. This work therefore provides the first evidence for a functional and bio-mechanical tethering between mitochondria and nucleus, as being the basis of pro-survival mechanisms, thus establishing a new paradigm in cross-organelle communication via cholesterol re-distribution

Shedding Light on Fish Otolith Biomineralization Using a Bioenergetic Approach

Otoliths are biocalcified bodies connected to the sensory system in the inner ears of fish. Their layered, biorhythm-following formation provides individual records of the age, the individual history and the natural environment of extinct and living fish species. Such data are critical for ecosystem and fisheries monitoring. They however often lack validation and the poor understanding of biomineralization mechanisms has led to striking examples of misinterpretations and subsequent erroneous conclusions in fish ecology and fisheries management. Here we develop and validate a numerical model of otolith biomineralization. Based on a general bioenergetic theory, it disentangles the complex interplay between metabolic and temperature effects on biomineralization. This model resolves controversial issues and explains poorly understood observations of otolith formation. It represents a unique simulation tool to improve otolith interpretation and applications, and, beyond, to address the effects of both climate change and ocean acidification on other biomineralizing organisms such as corals and bivalves

Reading the biomineralized book of life: expanding otolith biogeochemical research and applications for fisheries and ecosystem-based management

Chemical analysis of calcified structures continues to flourish, as analytical and technological advances enable researchers to tap into trace elements and isotopes taken up in otoliths and other archival tissues at ever greater resolution. Increasingly, these tracers are applied to refine age estimation and interpretation, and to chronicle responses to environmental stressors, linking these to ecological, physiological, and life-history processes. Here, we review emerging approaches and innovative research directions in otolith chemistry, as well as in the chemistry of other archival tissues, outlining their value for fisheries and ecosystem-based management, turning the spotlight on areas where such biomarkers can support decision making. We summarise recent milestones and the challenges that lie ahead to using otoliths and archival tissues as biomarkers, grouped into seven, rapidly expanding and application-oriented research areas that apply chemical analysis in a variety of contexts, namely: (1) supporting fish age estimation; (2) evaluating environmental stress, ecophysiology and individual performance; (3) confirming seafood provenance; (4) resolving connectivity and movement pathways; (5) characterising food webs and trophic interactions; (6) reconstructing reproductive life histories; and (7) tracing stock enhancement efforts. Emerging research directions that apply hard part chemistry to combat seafood fraud, quantify past food webs, as well as to reconcile growth, movement, thermal, metabolic, stress and reproductive life-histories provide opportunities to examine how harvesting and global change impact fish health and fisheries productivity. Ultimately, improved appreciation of the many practical benefits of archival tissue chemistry to fisheries and ecosystem-based management will support their increased implementation into routine monitoring.[GRAPHICS]

Psychologie der Kreativität

Ein kleiner Streifzug durch die psychologische Kreativitätsforschung befasst sich mit den Möglichkeiten der Erfassung kreativer Prozesse, ihrer Manifestation, den Determinanten, der Frage nach der Notwendigkeit zu kreativem Denken und schließlich Erkenntnissen darüber, wie kreatives Denken gefördert werden kann

Exposure to viral and bacterial pathogens among Soay sheep (Ovis aries) of the St Kilda archipelago

We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen–host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta

Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo

A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo

ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed