Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

On the relationship between the reversed hazard rate and elasticity

Despite hazard and reversed hazard rates sharing a number of similar aspects, reversed hazard functions are far less frequently used. Understanding their meaning is not a simple task. The aim of this paper is to expand the usefulness of the reversed hazard function by relating it to other well-known concepts broadly used in economics: (linear or cumulative) rates of increase and elasticity. This will make it possible (i) to improve our understanding of the consequences of using a particular distribution and, in certain cases, (ii) to introduce our hypotheses and knowledge about the random process in a more meaningful and intuitive way, thus providing a means to achieving distributions that would otherwise be hardly imaginable or justifiable

Stability in Ecosystem Functioning across a Climatic Threshold and Contrasting Forest Regimes

Classical ecological theory predicts that changes in the availability of essential resources such as nitrogen should lead to changes in plant community composition due to differences in species-specific nutrient requirements. What remains unknown, however, is the extent to which climate change will alter the relationship between plant communities and the nitrogen cycle. During intervals of climate change, do changes in nitrogen cycling lead to vegetation change or do changes in community composition alter the nitrogen dynamics? We used long-term ecological data to determine the role of nitrogen availability in changes of forest species composition under a rapidly changing climate during the early Holocene (16k to 8k cal. yrs. BP). A statistical computational analysis of ecological data spanning 8,000 years showed that secondary succession from a coniferous to deciduous forest occurred independently of changes in the nitrogen cycle. As oak replaced pine under a warming climate, nitrogen cycling rates increased. Interestingly, the mechanism by which the species interacted with nitrogen remained stable across this threshold change in climate and in the dominant tree species. This suggests that changes in tree population density over successional time scales are not driven by nitrogen availability. Thus, current models of forest succession that incorporate the effects of available nitrogen may be over-estimating tree population responses to changes in this resource, which may result in biased predictions of future forest dynamics under climate warming

Canadian Arctic sea ice reconstructed from bromine in the Greenland NEEM ice core

Reconstructing the past variability of Arctic sea ice provides an essential context for recent multi-year sea ice decline, although few quantitative reconstructions cover the Holocene period prior to the earliest historical records 1,200 years ago. Photochemical recycling of bromine is observed over first-year, or seasonal, sea ice in so-called "bromine explosions" and we employ a 1-D chemistry transport model to quantify processes of bromine enrichment over first-year sea ice and depositional transport over multi-year sea ice and land ice. We report bromine enrichment in the Northwest Greenland Eemian NEEM ice core since the end of the Eemian interglacial 120,000 years ago, finding the maximum extension of first-year sea ice occurred approximately 9,000 years ago during the Holocene climate optimum, when Greenland temperatures were 2 to 3 degrees C above present values. First-year sea ice extent was lowest during the glacial stadials suggesting complete coverage of the Arctic Ocean by multi-year sea ice. These findings demonstrate a clear relationship between temperature and first-year sea ice extent in the Arctic and suggest multi-year sea ice will continue to decline as polar amplification drives Arctic temperatures beyond the 2 degrees C global average warming target of the recent COP21 Paris climate agreement

Millennial changes in North American wildfire and soil activity over the last glacial cycle

Climate changes in the North Atlantic region during the last glacial cycle were dominated by the slow waxing and waning of the North American ice sheet as well as by intermittent Dansgaard-­‐Oeschger (DO) events. However prior to the last deglaciation, little is known about the response of North American vegetation to such rapid climate changes and especially about the response of biomass burning, an important factor for regional changes in radiative forcing. Here we use continuous, high-­‐resolution ammonium (NH4+) records derived from the NGRIP and GRIP ice cores to document both North American NH4+ background emissions from soils and wildfire frequency over the last 110,000 yr. Soil emissions increased on orbital timescales with warmer climate, related to the northward expansion of vegetation due to reduced ice-­‐covered areas. During Marine Isotope Stage (MIS) 3 DO warm events, a higher fire recurrence rate is recorded, while NH4+ soil emissions rose only slowly during longer interstadial warm periods, in line with slow ice sheet shrinkage and delayed ecosystem changes. Our results indicate that sudden warming events had little impact on NH4+ soil emissions and NH4+ aerosol transport to Greenland during the glacial but triggered a significant increase in the frequency of fire occurrence.This paper has greatly benefitted from the Sir Nicholas Shackleton fellowship, Clare Hall, University of Cambridge, U.K., awarded to HF in 2014. The Division for Climate and Environmental Physics, Physics Institute, University of Bern acknowledges the long-­‐term financial support of ice core research by the Swiss National Science Foundation (SNSF) and the Oeschger Centre for Climate Change Research. EW is supported by a Royal Society professorship. NGRIP is directed and organized by the Department of Geophysics at the Niels Bohr Institute for Astronomy, Physics and Geophysics, University of Copenhagen. It is supported by funding agencies in Denmark (SNF), Belgium (FNRS-­‐CFB), France (IPEV and INSU/CNRS), Germany (AWI), Iceland (RannIs), Japan (MEXT), Sweden (SPRS), Switzerland (SNSF) and the USA (NSF, Office of Polar Programs).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo249

A spill over effect of entrepreneurial orientation on technological innovativeness:an outlook of universities and research based spin offs

partially_open5siBy shifting towards Romer’s (Am Econ Rev 94:1002–1037, 1986) economy and so the spread of knowledge economy, universities started to adopt a collaborative approach with their entrepreneurial ecosystem. They turn out to be risk taker, autonomous, proactive, competitive, and innovative. In a nutshell, they are entrepreneurial oriented with the aim to generate new innovative ventures, known as research-based spin offs. Doubly, this has induced an improvement of technology transfer and the degree of entrepreneurship in the current knowledge economy. However there still is a paucity of studies on the spill over effect of entrepreneurial orientated universities and research-based spin off on technology transfer need to be more explored. Therefore, the article investigates the link between entrepreneurial orientation and such spill overs by offering an outlook of two universities and two research-based spin offs in the United Kingdom. The scope is to provide a deep view of technological innovativeness in a research context, entrepreneurial oriented. Our research suggests that entrepreneurial attitude has become an imperative to succeed in the context where British institutions currently operate. Entrepreneurship brings the necessary technological innovation to the university and its students, which results in better positioning of the university at national and international levels, with the subsequent impact on their ability to attract not only new students and academics but also funding to conduct their research.openScuotto, Veronica; Del Giudice, Manlio; Garcia-Perez, Alexeis; Orlando, Beatrice; Ciampi, FrancescoScuotto, Veronica; Del Giudice, Manlio; Garcia-Perez, Alexeis; Orlando, Beatrice; Ciampi, Francesc

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation

Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene.

The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.NEEM is directed and organized by the Center of Ice and Climate at the Niels Bohr Institute and US NSF, Office of Polar Programs. It is supported by funding agencies and institutions in Belgium (FNRS-CFB and FWO), Canada (NRCan/GSC), China (CAS), Denmark (FIST), France (IPEV, CNRS/INSU, CEA and ANR), Germany (AWI), Iceland (RannIs), Japan (NIPR), Korea (KOPRI), The Netherlands (NWO/ALW), Sweden (VR), Switzerland (SNF), United Kingdom (NERC), and the USA (US NSF, Office of Polar Programs). Long-term support of ice core research at the University of Bern by SNF is gratefully acknowledged

Land-bridge calibration of molecular clocks and the post-glacial colonization of Scandinavia by the Eurasian field vole microtus agrestis

Phylogeography interprets molecular genetic variation in a spatial and temporal context. Molecular clocks are frequently used to calibrate phylogeographic analyses, however there is mounting evidence that molecular rates decay over the relevant timescales. It is therefore essential that an appropriate rate is determined, consistent with the temporal scale of the specific analysis. This can be achieved by using temporally spaced data such as ancient DNA or by relating the divergence of lineages directly to contemporaneous external events of known time. Here we calibrate a Eurasian field vole (Microtus agrestis) mitochondrial genealogy from the well-established series of post-glacial geophysical changes that led to the formation of the Baltic Sea and the separation of the Scandinavian peninsula from the central European mainland. The field vole exhibits the common phylogeographic pattern of Scandinavian colonization from both the north and the south, however the southernmost of the two relevant lineages appears to have originated in situ on the Scandinavian peninsula, or possibly in the adjacent island of Zealand, around the close of the Younger Dryas. The mitochondrial substitution rate and the timescale for the genealogy are closely consistent with those obtained with a previous calibration, based on the separation of the British Isles from mainland Europe. However the result here is arguably more certain, given the level of confidence that can be placed in one of the central assumptions of the calibration, that field voles could not survive the last glaciation of the southern part of the Scandinavian peninsula. Furthermore, the similarity between the molecular clock rate estimated here and those obtained by sampling heterochronous (ancient) DNA (including that of a congeneric species) suggest that there is little disparity between the measured genetic divergence and the population divergence that is implicit in our land-bridge calibration