Abrupt climate changes of the last deglaciation detected in a Western Mediterranean forest record

Abrupt changes in Western Mediterranean climate during the last deglaciation (20 to 6 cal ka BP) are detected in marine core MD95-2043 (Alboran Sea) through the investigation of high-resolution pollen data and pollen-based climate reconstructions by the modern analogue technique (MAT) for annual precipitation (Pann) and mean temperatures of the coldest and warmest months (MTCO and MTWA). Changes in temperate Mediterranean forest development and composition and MAT reconstructions indicate major climatic shifts with parallel temperature and precipitation changes at the onsets of Heinrich stadial 1 (equivalent to the Oldest Dryas), the Bölling-Allerød (BA), and the Younger Dryas (YD). Multi-centennial-scale oscillations in forest development occurred throughout the BA, YD, and early Holocene. Shifts in vegetation composition and (Pann reconstructions indicate that forest declines occurred during dry, and generally cool, episodes centred at 14.0, 13.3, 12.9, 11.8, 10.7, 10.1, 9.2, 8.3 and 7.4 cal ka BP. The forest record also suggests multiple, low-amplitude Preboreal (PB) climate oscillations, and a marked increase in moisture availability for forest development at the end of the PB at 10.6 cal ka BP. Dry atmospheric conditions in the Western Mediterranean occurred in phase with Lateglacial events of high-latitude cooling including GI-1d (Older Dryas), GI-1b (Intra-Allerød Cold Period) and GS-1 (YD), and during Holocene events associated with high-latitude cooling, meltwater pulses and N. Atlantic ice-rafting. A possible climatic mechanism for the recurrence of dry intervals and an opposed regional precipitation pattern with respect to Western-central Europe relates to the dynamics of the westerlies and the prevalence of atmospheric blocking highs. Comparison of radiocarbon and ice-core ages for well-defined climatic transitions in the forest record suggests possible enhancement of marine reservoir ages in the Alboran Sea by 200 years (surface water age 600 years) during the Lateglacial

Adapting Component-based Systems at Runtime via Policies with Temporal Patterns

International audienceDynamic reconfiguration allows adding or removing components of component-based systems without incurring any system downtime. To satisfy specific requirements, adaptation policies provide the means to dynamically reconfigure the systems in relation to (events in) their environment. This paper extends event-based adaptation policies by integrating temporal requirements into them. The challenge is to reconfigure component-based systems at runtime while considering both their functional and non-functional requirements. We illustrate our theoretical contributions with an example of an autonomous vehicle location system. An implementation using the Fractal component model constitutes a practical contribution. It enables dynamic reconfigurations guided by either enforcement or reflection adaptation policies

Decentralised Evaluation of Temporal Patterns over Component-based Systems at Runtime

Long version of the paper accepted for FACS 2014 - The 11th International Symposium on Formal Aspects of Component SoftwareInternational audienceSelf-adaptation allows systems to modify their structure and/or their behaviour depending on the environment and the system itself. Since reconfigurations must not happen at any but in suitable circumstances, guiding and controlling dynamic reconfigurations at runtime is an important issue. This paper contributes to two essential topics of the self-adaptation---a runtime temporal properties evaluation, and a decentralization of control loopsSelf-adaptation allows systems to modify their structure and/or their behaviour depending on the environment and the system itself. Since reconfigurations must not happen at any but in suitable circumstances, guiding and controlling dynamic reconfigurations at runtime is an important issue. This paper contributes to two essential topics of the self-adaptation - a runtime temporal properties evaluation, and a decentralization of control loops. It extends the work on the adaptation of component-based systems at runtime via policies with temporal patterns by providing a) a specific progressive semantics of temporal patterns and b) a decentralised method which is suitable to deal with temporal patterns of component-based systems at runtime

Runtime Verification of Temporal Patterns for Dynamic Reconfigurations of Components

International audienceDynamic reconfigurations increase the availability and the reliability of component-based systems by allowing their architectures to evolve at runtime. Recently we have proposed a temporal pattern logic, called FTPL, to characterize the correct reconfigurations of component-based systems under some temporal and architectural constraints. As component-based architectures evolve at runtime, there is a need to check these FTPL constraints on the fly, even if only a partial information is expected. Firstly, given a generic component-based model, we review FTPL from a runtime verification point of view. To this end we introduce a new four-valued logic, called RV-FTPL (Runtime Verification for FTPL), characterizing the "potential" (un)satisfiability of the architectural constraints in addition to the basic FTPL semantics. Potential true and potential false values are chosen whenever an observed behaviour has not yet lead to a violation or satisfiability of the property under consideration. Secondly, we present a prototype developed to check at runtime the satisfiability of RV-FTPL formulas when reconfiguring a Fractal component-based system. The feasability of a runtime property enforcement is also shown. It consists in supervising on the fly the reconfiguration execution against desired RV-FTPL properties. The main contributions are illustrated on the example of a HTTP server architecture

Deglacial and Holocene vegetation and climatic changes in the southern Central Mediterranean from a direct land–sea correlation

International audienceDespite a large number of studies, the long-term and millennial to centennial-scale climatic variability in the Mediterranean region during the last deglaciation and the Holocene is still debated, including in the southern Central Mediterranean. In this paper, we present a new marine pollen sequence (core MD04-2797CQ) from the Siculo-Tunisian Strait documenting the regional vegetation and climatic changes in the southern Central Mediterranean during the last deglaciation and the Holocene. The MD04-2797CQ marine pollen sequence shows that semi-desert plants dominated the vegetal cover in the southern Central Mediterranean between 18.2 and 12.3 ka cal BP, indicating prevailing dry conditions during the deglaciation, even during the Greenland Interstadial (GI)-1. Across the transition Greenland Stadial (GS)-1 -Holocene, Asteraceae-Poaceae steppe became dominant till 10.1 ka cal BP. This record underlines with no chronological ambiguity that even though temperatures increased, deficiency in moisture availability persisted into the early Holocene. Temperate trees and shrubs with heath underbrush or maquis expanded between 10.1 and 6.6 ka, corresponding to Sapropel 1 (S1) interval, while Mediterranean plants only developed from 6.6 ka onwards. These changes in vegetal cover show that the regional climate in southern Central Mediterranean was wetter during S1 and became drier during the mid-to late Holocene. Wetter conditions during S1 were likely due to increased winter precipitation while summers remained dry. We suggest, in agreement with published modeling experiments, that the early Holocene increased melting of the Laurentide Ice Sheet in conjunction with weak winter insolation played a major role in the development of winter precipitation maxima in the Mediterranean region in controlling the strength and position of the North Atlantic storm track. Finally, our data provide evidence for centennial-scale vegetation and climatic changes in the southern Central Mediterranean. During the wet early Holocene, alkenone-derived cooling episodes are synchronous with herbaceous composition changes that indicate muted changes in precipitation. In contrast, enhanced aridity episodes, as detected by strong reduction in trees and shrubs, are recorded during the mid-to late Holocene. We show that the impact of the Holocene cooling events on the Mediterranean hydroclimate depend on baseline climate states, i.e. insolation and ice sheet extent, shaping the response of the mid-latitude atmospheric circulation

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation

HuR promotes myogenesis by stabilizing the MyoD, myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis

Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis

Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p