RET Rearrangements in Lung Adenocarcinoma and Radiation

Background:RET rearrangement, a hallmark of radiation-induced thyroid cancer, has been reported to occur in 1% of lung adenocarcinoma patients. Patients with this rearrangement tend to be younger and never smokers, raising a possibility of other causes, such as radiation. We hypothesized that RET chromosomal rearrangement may represent a genetic mechanism of radiation-induced lung cancer.Methods:Two hundred forty-five consecutive primary lung adenocarcinomas without history of radiation and 38 lung adenocarcinoma patients with a history of therapeutic radiation for breast carcinoma or mediastinal Hodkgin lymphoma were tested for RET rearrangement by fluorescence in situ hybridization. Human lung adenocarcinoma cells (201T) were subjected to γ radiation and tested for RET gene fusions by reverse transcriptase-polymerase chain reaction and Southern blot hybridization.Results:We identified one case with RET rearrangement in the group without history of radiation (1 of 240; 0.4%) and two cases in the group with history of radiation (2 of 37; 5.4%; P=0.0436). Both these patients were women, who were former smokers with a history of breast carcinoma treated with surgery and radiation. Furthermore, we found that RET fusions could be directly induced in 201T human lung cells by exposure to 1 Gy of γ radiation. All fusions identified were between RET and KIF5B genes, and no RET fusions to CCDC6 or NCOA4 genes, characteristic for thyroid cancer, were identified in the irradiated lung cells.Conclusion:RET fusions may represent a genetic mechanism of radiation-induced lung adenocarcinoma

Ecological patterns and conservation opportunities with carbon credits in Brazil nut groves: a study-case in the Southeast Amazon.

BACKGROUND: Brazil Nuts (BN) tree is a species of high importance in Amazon region. Their continuous use by traditional communities is often related to disturbances that lead to larger degraded areas where this species is commonly found ("BN groves"). Here we aimed to explore the ecological patterns of BN groves vegetation and its relationship with BN trees and evaluate their potential as a source of carbon credits. We sampled 15 circular plots, with Brazilian Nut trees as the center (focal trees) and collected morphometric data from the focal trees. Additionally, we evaluated fruit production for a period of 5 years to obtain annual measurements, which were used as a proxy of the anthropic impact associated with the collection process. Through analysis of the data, we: i) examined the effects of BN trees on the adjacent vegetation; ii) quantified the potential amount of carbon credits in the adjacent vegetation and in the focal trees by converting carbon stock to equivalent CO2. RESULTS: The adjacent vegetation structure was influenced by the size of BN trees (focal trees). No important effects of BN trees on the adjacent vegetation floristic composition and functional attributes were found. Additionally, we found that Brazilian Nut groves possess a significant potential for carbon credits that could be leveraged in the future carbon credit market. CONCLUSION: The study highlights the potential for carbon credit generation in Brazil nut groves in the Southeast Amazon as a means of supporting conservation and restoration efforts in these environments

PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma

Background: Recent genomic evidence suggests frequent phosphatidylinositide 3-kinase (PI3K) pathway activation in human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Mutations/amplification of the gene encoding p110α catalytic subunit of phosphoinositide 3-kinase (PIK3CA), loss of phosphatase and tensin homolog (PTEN) and HRAS mutations are known to activate PI3K pathway. Methods and results: PIK3CA mutations were identified by Sanger sequencing in 23 of 75 (31%) HPV-positive oropharyngeal carcinomas, including exon 9 (p.E545K [n = 10] and p.E542K [n = 5]) or exon 20 (p.H1047Y, n = 2) mutations. Five rare and one novel (p.R537Q) PIK3CA mutations were identified. HRAS mutation (p.Q61L) was detected in 1 of 62 tested cases. PIK3CA amplification by fluorescence in situ hybridization (FISH) was identified in 4 cases (4/21, 20%), while PTEN loss was seen in 7 (7/21, 33%) cases (chromosome 10 monosomy [n = 4], homozygous deletion [n = 3]). Conclusions: Overall, genetic alterations that likely lead to PI3K pathway activation were identified in 34 of 75 cases (45%) and did not correlate with disease specific survival. These findings offer a molecular rationale for therapeutic targeting of PI3K pathway in patients with HPV-positive oropharyngeal carcinoma. © 2013 Chiosea et al.; licensee BioMed Central Ltd

THE INFLUENCE OF HIV-1 SUBTYPES C, CRF31_BC AND B ON DISEASE PROGRESSION AND INITIAL VIROLOGIC RESPONSE TO HAART IN A SOUTHERN BRAZILIAN COHORT

Background: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. Methods: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. Conclusion: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response

HIV-1 Diversity in the Envelope Glycoproteins: Implications for Viral Entry Inhibition

Entry of HIV-1 into a host cell is a multi-step process, with the viral envelope gp120 and gp41 acting sequentially to mediate the viral attachment, CD4 binding, coreceptor binding, and fusion of the viral and host membranes. The emerging class of antiretroviral agents, collectively known as entry inhibitors, interfere in some of these steps. However, viral diversity has implications for possible differential responses to entry inhibitors, since envelope is the most variable of all HIV genes. Different HIV genetic forms carry in their genomes genetic signatures and polymorphisms that could alter the structure of viral proteins which are targeted by drugs, thus impairing antiretroviral binding and efficacy. This review will examine current research that describes subtype differences in envelope at the genetic level and the effects of mutations on the efficacy of current entry inhibitors

Robot Companion, an intelligent interactive robot coworker for the Industry 5.0

International audienceTo overcome the limitations of the so-called Industry 4.0 focusing on mass production and full automation, a novel paradigm was recently introduced, namely Industry 5.0, which aims at an increased collaboration between humans and machines, and particularly robots, instead of replacing the former with the latter. This challenge requires novel interactive intelligent robots able to perform complex tasks easily and efficiently and to collaborate on the fly with humans whenever required, be it for training or working. In this work, the Robot Companion, a novel demonstrator of this paradigm, is introduced. It combines robotics, Artificial Intelligence, software engineering and embedded systems technologies, and targets industrial assembly tasks. First tests show that this robot can efficiently assemble a representative gear system autonomously or in collaboration with human operators

An intelligent robotics modular architecture for easy adaptation to novel tasks and applications

International audienceIndustrial robots significantly contributed to the increase of quality and productivity in the industry. Still, their deployment and use remain complex and expensive, limiting their main market to mass production in large factories. This article introduces an intelligent robotics framework intended to solve this issue. It relies on a four-layer modular architecture associating a components-agnostic orchestrator coordinating software modules accessed through a standard middleware, and different hardware running the required functions. This architecture is implemented for performing various tasks in autonomy or in collaboration with a human operator, the different components being turned on and adapted on-demand according to the use-case requirements. We illustrate the proposed concept on four robotic sequences: the assembly of a representative gear unit with one arm, the same application with two robots, the Robothon® Grand Challenge and the insertion of deformable objects in a rail