An Emerging Picture of Neoproterozoic Ocean Chemistry: Insights from the Chuar Group, Grand Canyon, USA

Detailed iron, sulfur and carbon chemistry through the > 742 million year old ChuarGroup reveals a marine basin dominated by anoxic and ferrous iron-rich (ferruginous) bottom waters punctuated, late in the basin's development, by an intrusion of sulfide-rich (euxinic) conditions. The observation that anoxia occurred frequently in even the shallowest of Chuar environments (10s of meters or less) suggests that global atmospheric oxygen levels were significantly lower than today. In contrast, the transition from ferruginous to euxinic subsurface water is interpreted to reflect basinal control—specifically, increased export of organic carbon from surface waters. Low fluxes of organic carbon into subsurface water masses should have been insufficient to deplete oxygen via aerobic respiration, resulting in an oxic oxygen minimum zone (OMZ). Where iron was available, larger organic carbon fluxes should have depleted oxygen and facilitated anaerobic respiration using ferric iron as the oxidant, with iron carbonate as the expected mineralogical signature in basinal shale. Even higher organic fluxes would, in turn, have depleted ferric iron and up-regulated anaerobic respiration by sulfate reduction, reflected in high pyrite abundances. Observations from the ChuarGroup are consistent with these hypotheses, and gain further support from pyrite and sulfate sulfur isotope abundances. In general, Chuar data support the hypothesis that ferruginous subsurface waters returned to the oceans, replacing euxinia, well before the Ediacaran emergence of persistently oxygenated conditions, and even predating the Sturtian glaciation. Moreover, our data suggest that the reprise of ferruginous water masses may relate to widespread rifting during the break-up of Rodinia. This environmental transition, in turn, correlates with both microfossil and biomarker evidence for an expanding eukaryotic presence in the oceans, suggesting a physiologically mediated link among tectonics, environmental chemistry and life in the dynamic Neoproterozoic Earth system.Earth and Planetary Science

Biodiversity Conservation in the REDD

Deforestation and forest degradation in the tropics is a major source of global greenhouse gas (GHG) emissions. The tropics also harbour more than half the world's threatened species, raising the possibility that reducing GHG emissions by curtailing tropical deforestation could provide substantial co-benefits for biodiversity conservation. Here we explore the potential for such co-benefits in Indonesia, a leading source of GHG emissions from land cover and land use change, and among the most species-rich countries in the world. We show that focal ecosystems for interventions to reduce emissions from deforestation and forest degradation in Indonesia do not coincide with areas supporting the most species-rich communities or highest concentration of threatened species. We argue that inherent trade-offs among ecosystems in emission reduction potential, opportunity cost of foregone development and biodiversity values will require a regulatory framework to balance emission reduction interventions with biodiversity co-benefit targets. We discuss how such a regulatory framework might function, and caution that pursuing emission reduction strategies without such a framework may undermine, not enhance, long-term prospects for biodiversity conservation in the tropics

Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.

BACKGROUND: Bacille Calmette-Guérin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across the globe generating formulations that may differ in clinical efficacy. Innate immune recognition of live BCG contributes to immunogenicity suggesting that differences in BCG viability may contribute to divergent activity of licensed formulations. METHODS: We compared BCG-Denmark (DEN), -Japan (JPN), -India (IND), -Bulgaria (BUL) and -USA in vitro with respect to a) viability as measured by colony-forming units (CFU), mycobacterial membrane integrity, and RNA content, and b) cytokine/chemokine production in newborn cord and adult peripheral blood. RESULTS: Upon culture, relative growth was BCG-USA > JPN ? DEN > BUL = IND. BCG-IND and -BUL demonstrated >1000-fold lower growth than BCG-JPN in 7H9 medium and >10-fold lower growth in commercial Middlebrook 7H11 medium. BCG-IND demonstrated significantly decreased membrane integrity, lower RNA content, and weaker IFN-? inducing activity in whole blood compared to other BCGs. BCG-induced whole blood cytokines differed significantly by age, vaccine formulation and concentration. BCG-induced cytokine production correlated with CFU, suggesting that mycobacterial viability may contribute to BCG-induced immune responses. CONCLUSIONS: Licensed BCG vaccines differ markedly in their content of viable mycobacteria possibly contributing to formulation-dependent activation of innate and adaptive immunity and distinct protective effects

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Human brain slices for epilepsy research:pitfalls, solutions and future challenges

Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits

Implanted Radio Telemetry in Orangutan Reintroduction and Post-release Monitoring and its Application in Other Ape Species

Designed as a new method to facilitate the reintroduction and post-release monitoring of orangutans and other apes, implanted radio-telemetry (IRT) was developed and first deployed in 2009. Since that time, it has been necessary to collate and review information on its uptake and general efficacy to inform its ongoing development and that of other emerging tracking technologies. We present here technical specifications and the surgical procedure used to implant miniaturized radio transmitters, as well as a formal testing procedure for measuring detectable transmission distances of implanted devices. Feedback from IRT practitioners (veterinarians and field managers) was gathered through questionnaires and is also presented. To date, IRT has been used in at least 250 individual animals (mainly orangutans) from four species of ape in both Asia and Africa. Median surgical and wound healing times were 30 min and 15 days, respectively, with implants needing to be removed on at least 36 separate occasions. Confirmed failures within the first year of operation were 18.1%, while longer distances were reported from positions of higher elevation relative to the focal animal. IRT has been a transformational technology in facilitating the relocation of apes after their release, resulting in much larger amounts of post-release data collection than ever before. It is crucial however, that implant casings are strengthened to prevent the requirement for recapture and removal surgeries, especially for gradually adapting apes. As with all emerging technological solutions, IRT carries with it inherent risk, especially so due to the requirement for subcutaneous implantation. These risks must, however, be balanced with the realities of releasing an animal with no means of relocation, as has historically been, and is still, the case with orangutans and gorillas

Neoproterozoic to Paleozoic long-lived accretionary orogeny in the northern Tarim Craton

The Tarim Craton, located in the center of Asia, was involved in the assembly and breakup of the Rodinia supercontinent during the Neoproterozoic and the subduction-accretion of the Central Asian Orogenic Belt (CAOB) during the Paleozoic. However, its tectonic evolution during these events is controversial, and a link between the Neoproterozoic and Paleozoic tectonic processes is missing. Here we present zircon U-Pb ages, Hf isotopes, and whole-rock geochemical data for the extensive granitoids in the western Kuruktag area, northeastern Tarim Craton. Three distinct periods of granitoid magmatism are evident: circa 830–820 Ma, 660–630 Ma, and 420–400 Ma. The magma sources, melting conditions (pressure, temperature, and water availability), and tectonic settings of various granitoids from each period are determined. Based on our results and the geological, geochronological, geochemical, and isotopic data from adjacent areas, a long-lived accretionary orogenic model is proposed. This model involves an early phase (circa 950–780 Ma) of southward advancing accretion from the Tianshan to northern Tarim and a late phase (circa 780–600 Ma) of northward retreating accretion, followed by back-arc opening and subsequent bidirectional subduction (circa 460–400 Ma) of a composite back-arc basin (i.e., the South Tianshan Ocean). Our model highlights a long-lived accretionary history of the southwestern CAOB, which may have initiated as part of the circum-Rodinia subduction zone and was comparable with events occurring at the southern margin of the Siberian Craton, thus challenging the traditional southward migrating accretionary models for the CAOB

Sensory Perception of Food and Insulin-Like Signals Influence Seizure Susceptibility

Food deprivation is known to affect physiology and behavior. Changes that occur could be the result of the organism's monitoring of internal and external nutrient availability. In C. elegans, male mating is dependent on food availability; food-deprived males mate with lower efficiency compared to their well-fed counterparts, suggesting that the mating circuit is repressed in low-food environments. This behavioral response could be mediated by sensory neurons exposed to the environment or by internal metabolic cues. We demonstrated that food-deprivation negatively regulates sex-muscle excitability through the activity of chemosensory neurons and insulin-like signaling. Specifically, we found that the repressive effects of food deprivation on the mating circuit can be partially blocked by placing males on inedible food, E. coli that can be sensed but not eaten. We determined that the olfactory AWC neurons actively suppress sex-muscle excitability in response to food deprivation. In addition, we demonstrated that loss of insulin-like receptor (DAF-2) signaling in the sex muscles blocks the ability of food deprivation to suppress the mating circuit. During low-food conditions, we propose that increased activity by specific olfactory neurons (AWCs) leads to the release of neuroendocrine signals, including insulin-like ligands. Insulin-like receptor signaling in the sex muscles then reduces cell excitability via activation of downstream molecules, including PLC-γ and CaMKII