Graph complexity analysis identifies an ETV5 tumor-specific network in human and murine low-grade glioma

Conventional differential expression analyses have been successfully employed to identify genes whose levels change across experimental conditions. One limitation of this approach is the inability to discover central regulators that control gene expression networks. In addition, while methods for identifying central nodes in a network are widely implemented, the bioinformatics validation process and the theoretical error estimates that reflect the uncertainty in each step of the analysis are rarely considered. Using the betweenness centrality measure, we identified Etv5 as a potential tissue-level regulator in murine neurofibromatosis type 1 (Nf1) low-grade brain tumors (optic gliomas). As such, the expression of Etv5 and Etv5 target genes were increased in multiple independently-generated mouse optic glioma models relative to non-neoplastic (normal healthy) optic nerves, as well as in the cognate human tumors (pilocytic astrocytoma) relative to normal human brain. Importantly, differential Etv5 and Etv5 network expression was not directly the result of Nf1 gene dysfunction in specific cell types, but rather reflects a property of the tumor as an aggregate tissue. Moreover, this differential Etv5 expression was independently validated at the RNA and protein levels. Taken together, the combined use of network analysis, differential RNA expression findings, and experimental validation highlights the potential of the computational network approach to provide new insights into tumor biology

A numerical study of tropical cross-tropopause transport by convective overshoots during the TROCCINOX golden day

International audienceObservations obtained during the Tropical Convection, Cirrus and Nitrogen Oxides (TROCCINOX) golden day have revealed the presence of ice particles up to 410 K (18.2 km) 2 km above the local tropopause. The case is investigated using a three-dimensional quadruply nested non-hydrostatic simulation and Meteosat Second Generation (MSG) observations. The simulation fairly well reproduces the measurements along the flight track. A reasonable agreement with MSG observations is also achieved: the 10.8-µm brightness temperature (BT) minimum of 187 K is reproduced (a value 6 K colder than the environmental cold-point temperature) as well as the positive BT difference between the 6.2- and 10.8-µm bands, an overshoot signature. The simulation produces several overshooting plumes up to 410 K yielding an upward transport of water vapour of a few tons per second across the tropical tropopause. The estimated mass flux agree with those derived from over tracer budgets indicating that convection transport mass across the tropopause

Regional lightning NOx sources during the TROCCINOX experiment

A lightning NOx (LiNOx) source has been implemented in the deep convection scheme of the Meso-NH mesoscale model following a mass-flux formalism coherent with the transport and scavenging of gases inside the convective scheme. In this approach the vertical transport of NO inside clouds is calculated by the parameterization of deep convective transport, thus eliminating the need for apriori LiNOx profiles. Once produced inside the convective column, NO molecules are redistributed by updrafts and downdrafts and detrained in the environment when the conditions are favorable. The model was applied to three particular flights during the Tropical Convection, Cirrus and Nitrogen Oxides (TROCCINOX) campaign over the tropical area around Bauru on 3-4 March 2004. The convective activity during the three flights was investigated using brightness temperature at 10.7μm observed from GOES-12 satellite. The use of a model-to-satellite approach reveals that the simulation appears rather realistic compared to the observations. The diurnal cycle of the simulated brightness temperature, CAPE, number of IC flashes, NO entrainment flux are in phase, with a succession of three marked peaks at 18:00 UTC (15:00 LT). These simulated peaks precede the observed afternoon one by about three hours. Comparison of the simulated NOx with observations along the flight tracks show that the model reproduces well the observed NOx levels when the LiNOx source is applied. The budget of entrainment, detrainment and LiNOx convective fluxes shows that the majority of the NO detrained back to the environment comes from lightning source inside the convective columns. Entrainment of NO from the environment and vertical transport from the boundary layer were not significant during the episode. The troposphere is impacted by detrainment fluxes of LiNOx from 4 km altitude to 16 km with maximum values around 14 km altitude. Detrainment fluxes vary between 75 kg(N)/s during nighttime to 400 kg(N)/s at the times of maximun convective activity. Extrapolation of the regional LiNOx source would yield a global LiNOx production around 5.7 Tg(N)/year which is within the current estimates but should not hide the overestimation of the number of flash rates by the model

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

Peer reviewe

Importance of the catalytic effect of the substrate in the functionality of lubricant additives: the case of MoDTC

Molybdenum dithiocarbamates (MoDTCs) are lubricant additives very efficient in reducing the friction of steel and they are employed in a number of industrial applications. The functionality of these additives is ruled by the chemical interactions occurring at the buried sliding interface, which are of key importance for the improvement of the lubrication performance. Yet, these tribochemical processes are very difficult to monitor in real time. Ab initio molecular dynamics simulations are the ideal tool to shed light into such a complicated reactivity. In this work we perform ab initio simulations, both in static and tribological conditions, to understand the effect of surface oxidation on the tribochemical reactivity of MoDTC and we find that when the surfaces are covered by oxygen, the first dissociative steps of the additives are significantly hindered. Our preliminary tribological tests on oxidized steel discs support these results. Bare metallic surfaces are necessary for a stable adsorption of the additives, their quick decomposition, and the formation of a durable MoS$_2$ tribolayer. This work demonstrates the importance of the catalytic role of the substrate and confirms the full capability of the computational protocol in the pursuit of materials and compounds more efficient in reducing friction

An integrative approach to discovering cryptic species within the Bemisia tabaci whitefly species complex

Bemisia tabaci is a cryptic whitefly-species complex that includes some of the most damaging pests and plant-virus vectors of a diverse range of food and fibre crops worldwide. We combine experimental evidence of: (i) differences in reproductive compatibility, (ii) hybrid verification using a specific nuclear DNA marker and hybrid fertility confirmation and (iii) high-throughput sequencing-derived mitogenomes, to show that the “Mediterranean” (MED) B. tabaci comprises at least two distinct biological species; the globally invasive MED from the Mediterranean Basin and the “African silver-leafing” (ASL) from sub-Saharan Africa, which has no associated invasion records. We demonstrate that, contrary to its common name, the “ASL” does not induce squash silver-leafing symptoms and show that species delimitation based on the widely applied 3.5% partial mtCOI gene sequence divergence threshold produces discordant results, depending on the mtCOI region selected. Of the 292 published mtCOI sequences from MED/ASL groups, 158 (54%) are low quality and/or potential pseudogenes. We demonstrate fundamental deficiencies in delimiting cryptic B. tabaci species, based solely on partial sequences of a mitochondrial barcoding gene. We advocate an integrative approach to reveal the true species richness within cryptic species complexes, which is integral to the deployment of effective pest and disease management strategies

Does public awareness increase support for invasive species management?:Promising evidence across taxa and landscape types

Management of invasive species often raises substantial conflicts of interest. Since such conflicts can hamper proposed management actions, managers, decision makers and researchers increasingly recognize the need to consider the social dimensions of invasive species management. In this exploratory study, we aimed (1) to explore whether species’ taxonomic position (i.e. animals vs. plants) and type of invaded landscape (i.e. urban vs. nonurban) might influence public perception about the management of invasive species, and (2) to assess the potential of public awareness to increase public support for invasive species management. We reviewed the scientific literature on the conflicts of interest around the management of alien species and administered two-phased questionnaires (before and after providing information on the target species and its management) to members of the public in South Africa and the UK (n = 240). Our review suggests that lack of public support for the management of invasive animals in both urban and non-urban areas derives mainly from moralistic value disagreements, while the management of invasive plants in non-urban areas mostly causes conflicts based on utilitarian value disagreements. Despite these general trends, conflicts are context dependent and can originate from a wide variety of different views. Notably, informing the public about the invasive status and negative impacts of the species targeted for management appeared to increase public support for the management actions. Therefore, our results align with the view that increased public awareness might increase the public support for the management of invasive species, independent of taxonomic position and type of landscape

Genomic changes associated with the evolutionary transition of an insect gut symbiont into a blood-borne pathogen.

The genus Bartonella comprises facultative intracellular bacteria with a unique lifestyle. After transmission by blood-sucking arthropods they colonize the erythrocytes of mammalian hosts causing acute and chronic infectious diseases. Although the pathogen-host interaction is well understood, little is known about the evolutionary origin of the infection strategy manifested by Bartonella species. Here we analyzed six genomes of Bartonella apis, a honey bee gut symbiont that to date represents the closest relative of pathogenic Bartonella species. Comparative genomics revealed that B. apis encodes a large set of vertically inherited genes for amino acid and cofactor biosynthesis and nitrogen metabolism. Most pathogenic bartonellae have lost these ancestral functions, but acquired specific virulence factors and expanded a vertically inherited gene family for harvesting cofactors from the blood. However, the deeply rooted pathogen Bartonella tamiae has retained many of the ancestral genome characteristics reflecting an evolutionary intermediate state toward a host-restricted intraerythrocytic lifestyle. Our findings suggest that the ancestor of the pathogen Bartonella was a gut symbiont of insects and that the adaptation to blood-feeding insects facilitated colonization of the mammalian bloodstream. This study highlights the importance of comparative genomics among pathogens and non-pathogenic relatives to understand disease emergence within an evolutionary-ecological framework