The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway

Background: The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized.Results: Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors.Conclusions: Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude

Direct and inverse measurement of thin films magnetostriction

Two techniques of measurements of thin film magnetostriction are compared: direct, when changes of the substrate curvature caused by the film magnetization are controlled, and inverse ("indirect"), when the modification of the magnetic anisotropy induced by the substrate deformation (usually bending) is measured. We demonstrate how both the elastic strength of the substrate and the effective magneto-mechanical coupling between the substrate deformation and magnetic anisotropy of the film depend on different conditions of bending. Equations to be used for magnetostriction value determination in typical cases are given and critical parameters for the corresponding approximations are identified.Comment: 13 pages, 10 figures, 1 table, submitted to JMM

Heterogeneous Timed Machines

International audienceWe present an algebra of discrete timed input/output au- tomata that execute in the context of different clock granularities -- timed machines -- as models of systems that can be dynamically inter- connected at run time in a heterogeneous context. We show how timed machines can be refined to a lower granularity of time and how timed machines with different clock granularities can be composed. We propose techniques for checking whether timed machines are consistent or feasi- ble. Finally, we investigate how consistency and feasibility of composition can be proved at run-time without computing products of automata

Mapping the Semantic Space for the Subjective Experience of Emotional Responses to Odors

Two studies were conducted to examine the nature of the verbal labels that describe emotional effects elicited by odors. In Study 1, a list of terms selected for their relevance to describe affective feelings induced by odors was assessed while participants were exposed to a set of odorant samples. The data were submitted to a series of exploratory factor analyses to 1) reduce the set of variables to a smaller set of summary scales and 2) get a preliminary sense of the differentiation of affective feelings elicited by odors. The goal of Study 2 was to replicate the findings of Study 1 with a larger sample of odorant samples and participants and to validate the preliminary model obtained in Study 1 by using confirmatory factor analysis. Overall, the findings point to a structure of affective responses to odors that differs from the classical taxonomies of emotion such as posited by discrete or bidimensional emotion theories. These findings suggest that the subjective affective experiences or feelings induced by odors are structured around a small group of dimensions that reflect the role of olfaction in well-being, social interaction, danger prevention, arousal or relaxation sensations, and conscious recollection of emotional memorie

Emotional Processing of Odors: Evidence for a Nonlinear Relation between Pleasantness and Familiarity Evaluations

Pleasantness, familiarity, and intensity are 3 interdependent dimensions commonly used to describe the perceived qualities of an odor. In particular, many empirical studies have demonstrated a positive correlation between familiarity and pleasantness. However, on the basis of both theoretical and methodological perspectives, we questioned the validity of such a relation for malodors. We report 2 studies based on subjective judgments of a large sample of odorants (Experiment 1) associated with autonomic recordings (Experiment 2). Multivariate exploratory analysis performed on the data splits the whole odorant set into 2 subsets composed, respectively, of unpleasant and pleasant odorants. Subsequent correlation analyses have shown that the relation between pleasantness and familiarity is specific for the pleasant odors in the 2 experiments. Moreover, autonomic activity was more important in response to malodors than to pleasant odors and was significantly correlated with unpleasantness ratings in the subset of unpleasant odors. These 2 studies argue in favor of a functional dissociation in the relations between both subjective and autonomic responses to odors as a function of pleasantness and indicate that researchers in the olfactory domain should consider the relations between pleasantness and familiarity as more complex than linea

An investment plan for low-emission rice production in the Mekong River Delta region in support of Vietnam's Nationally Determined Contribution to the Paris Agreement

Rice production is integral to agriculture and food security in Vietnam, but it also contributes greenhouse gas emissions. In 2010, paddy rice production emitted 44.61 million tons carbon dioxide equivalents (MtCO2e), 18% of total national GHG emissions. A variety of options to mitigate GHG emissions from paddy rice show promise and will contribute to implementing Vietnam’s Nationally Determined Contribution (NDC) and green growth strategies. One of the most promising options is alternate wetting and drying (AWD), a technique in which fields are allowed to dry out to a certain point before irrigation instances. This paper focuses on the Mekong River Delta region, which produces more than 50% of total rice production and 95% of rice exported from Vietnam. This study employs a literature review, a study of promising GHG mitigation options, and an analysis of cost and benefits of AWD to develop an investment plan for AWD in the Mekong River Delta. In our field survey, we found AWD contributed to increasing farmers’ net incomes primarily by decreasing production costs. The study proposes an investment plan with four outputs and 15 investment activities with a goal of practicing AWD on 900,000 hectares in the Mekong River Delta and mitigating 10.97 M.tCO2e. A co-benefit is additional net income for farmers of 8,540 billion VND (USD 371.36 million) per year compared to conventional rice cultivation. The budget is USD 721.78 million (81.32% for hard infrastructure, 18.19% for MRV operation, research, performance and planning), of which 36.9% is provided by the state, 29.92% from local provinces, 21.77% from international support and 11.42% from the private sector. Mobilization of financial resources from public and private sectors and the integration into government plans and programs are recommended

Similar self-organizing scale-invariant properties characterize early cancer invasion and long range species spread

Occupancy of new habitats through dispersion is a central process in nature. In particular, long range dispersal is involved in the spread of species and epidemics, although it has not been previously related with cancer invasion, a process that involves spread to new tissues. We show that the early spread of cancer cells is similar to the species individuals spread and that both processes are represented by a common spatio-temporal signature, characterized by a particular fractal geometry of the boundaries of patches generated, and a power law-scaled, disrupted patch size distribution. We show that both properties are a direct result of long-distance dispersal, and that they reflect homologous ecological processes of population self-organization. Our results are significant for processes involving long-range dispersal like biological invasions, epidemics and cancer metastasis.Comment: 21 pages, 2 figure

Sulfate production by reactive bromine: Implications for the global sulfur and reactive bromine budgets

Sulfur and reactive bromine (Bry) play important roles in tropospheric chemistry and the global radiation budget. The oxidation of dissolved SO2 (S(IV)) by HOBr increases sulfate aerosol abundance and may also impact the Bry budget, but is generally not included in global climate and chemistry models. In this study, we implement HOBr + S(IV) reactions into the GEOS-Chem global chemical transport model and evaluate the global impacts on both sulfur and Bry budgets. Modeled HOBr mixing ratios on the order of 0.1-1.0 parts per trillion (ppt) lead to HOBr + S(IV) contributing to 8% of global sulfate production and up to 45% over some tropical ocean regions with high HOBr mixing ratios (0.6-0.9 ppt). Inclusion of HOBr + S(IV) in the model leads to a global Bry decrease of 50%, initiated by the decrease in bromide recycling in cloud droplets. Observations of HOBr are necessary to better understand the role of HOBr + S(IV) in tropospheric sulfur and Bry cycles

Fermi detection of delayed GeV emission from the short GRB 081024B

We report on the detailed analysis of the high-energy extended emission from the short Gamma-Ray Burst (GRB) 081024B, detected by the Fermi Gamma-ray Space Telescope. Historically, this represents the first clear detection of temporal extended emission from a short GRB. The light curve observed by the Fermi Gamma-ray Burst Monitor lasts approximately 0.8 seconds whereas the emission in the Fermi Large Area Telescope lasts for about 3 seconds. Evidence of longer lasting high-energy emission associated with long bursts has been already reported by previous experiments. Our observations, together with the earlier reported study of the bright short GRB 090510, indicate similarities in the high-energy emission of short and long GRBs and open the path to new interpretations.Comment: 19 pages, 4 figures, 2 tables. Accepted for publication in Ap

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN