Pan-cancer analysis reveals recurrent BCAR4 gene fusions across solid tumors

UNLABELLED: Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation. IMPLICATIONS: BCAR4 gene fusions represent an underappreciated class of gene fusions that may have biological and clinical implications across solid tumors

Recombinant proteins in plants.

Edição do Congress of the Brazilian Biotechnology Society, Florianópolis, 2013

Integrated Weed Management in Coffee for Sustainable Agriculture—A Practical Brazilian Approach

Brazil is the largest coffee exporter in the world market and ranks second among coffee-consuming countries. The use of technology has been largely responsible for the great development of Brazilian agriculture in recent years. Then, the efficiency of integrated weed management has made the country more competitive in coffee farming. Therefore, integrated weed management (IWM) practices are the foundation for sustainable weed management in coffee fields. Weed competition cause losses in crop production. In weed control, besides chemical control, there are other methods that are efficient, economical, and beneficial to the coffee plant and to the environment that can be used on any property, such as preventive and cultural managements; and mechanical, biological, and physical controls. The combination of weed control methods has proven to be a sustainable practice in coffee production. In integrated management, the inherent advantages of each control method must be combined. Lastly, IWM provides an efficient control action with lower costs, better environmental conservation, and higher crop productivity. Thus, this chapter discusses the main practices of sustainable weed management in coffee, addressing issues such as competition, benefits, main weeds, and IWM systems

Optimal Regulation in the Presence of Reputation Concerns

In all markets, firms go through a process of creative destruction: entry, random growth and exit. In many of these markets there are also regulations that restrict entry, possibly distorting this process. We study the public interest rationale for entry taxes in a general equilibrium model with free entry and exit of firms in which firm dynamics are driven by reputation concerns. In our model firms can produce high-quality output by making a costly but efficient initial unobservable investment. If buyers never learn about this investment, an extreme “lemons problem” develops, no firm invests, and the market shuts down. Learning introduces reputation incentives such that a fraction of entrants do invest. We show that, if the market operates with spot prices, entry taxes always enhance the role of reputation to induce investment, improving welfare despite the impact of these taxes on equilibrium prices and total productio

Characterization of rubberized cement bound aggregate mixtures using indirect tensile testing and fractal analysis

The main focus of this paper is to investigate the tensile properties of virgin and rubberized cement bound granular mixtures. This was conducted using indirect tensile testing with lateral displacement measurements, nondestructive resonant frequency testing, X-ray CT and quantitative assessment for cracking pattern using fractal analysis. The investigated properties were density, compacity, indirect tensile strength (ITS), indirect tensile static modulus, toughness, dynamic modulus of elasticity, dynamic modulus of rigidity, dynamic poison’s ratio, fractal dimension and fracture energy. To keep the same aggregate packing, the natural aggregate was replaced by waste tyres’ crumb rubber of similar gradation. Four volumetric replacement percentages (0%, 15%, 30% and 45%) of the 6 mm fraction size were utilized. This adjustment was observed to affect the material density not only due to the lower specific gravity, but because it also affects the compactibility of the mixture negatively due to the damping action of the rubber particles. In addition, strength was also affected detrimentally. However, material toughness was improved and stiffness was mitigated. The latter findings were supported by quantitative assessment of the cracking pattern which revealed more tortuosity and a higher fractal dimension as a result of rubber content increasing. A failure mechanism for this type of mixture was suggested and support by examining the internal structure of failed samples using X-ray CT. Overall, construction of cement-stabilized aggregate base with a small percentage of added crumb rubber may ensure a more sustainable and environmental-friendly pavement material and, at the same time, improve the properties of stabilized layers. However, behaviour of these mixtures under cyclic loading and evaluation of their durability should be assessed to fully validate their use

Phase 1 Trial of Malaria Transmission Blocking Vaccine Candidates Pfs25 and Pvs25 Formulated with Montanide ISA 51

Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion.The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5 microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity.It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.ClinicalTrials.gov NCT00295581

Phenotyping patients with ischaemic heart disease at risk of developing heart failure: an analysis of the HOMAGE trial

Aims: We aim to characterize the clinical and proteomic profiles of patients at risk of developing heart failure (HF), with and without coronary artery disease (CAD) or prior myocardial infarction (MI). Methods and results: HOMAGE evaluated the effect of spironolactone on plasma and serum markers of fibrosis over 9 months of follow-up in participants with (or at risk of having) CAD, and raised natriuretic peptides. In this post hoc analysis, patients were classified as (i) neither CAD nor MI; (ii) CAD; or (iii) MI. Proteomic between-group differences were evaluated through logistic regression and narrowed using backward stepwise selection and bootstrapping. Among the 527 participants, 28% had neither CAD or MI, 31% had CAD, and 41% had prior MI. Compared with people with neither CAD nor MI, those with CAD had higher baseline plasma concentrations of matrix metalloproteinase-7 (MMP-7), galectin-4 (GAL4), plasminogen activator inhibitor 1 (PAI-1), and lower plasma peptidoglycan recognition protein 1 (PGLYRP1), whilst those with a history of MI had higher plasma MMP-7, neurotrophin-3 (NT3), pulmonary surfactant-associated protein D (PSPD), and lower plasma tumour necrosis factor-related activation-induced cytokine (TRANCE). Proteomic signatures were similar for patients with CAD or prior MI. Treatment with spironolactone was associated with an increase of MMP7, NT3, and PGLYRP1 at 9 months. Conclusions: In patients at risk of developing HF, those with CAD or MI had a different proteomic profile regarding inflammatory, immunological, and collagen catabolic processes

Synthesis and Characterization of Hybrid Materials Consisting of n-octadecyltriethoxysilane by Using n-Hexadecylamine as Surfactant and Q0 and T0 Cross-Linkers

Novel hybrid xerogel materials were synthesized by a sol-gel procedure. n-octadecyltriethoxysilane was co-condensed with and without different cross-linkers using Q0 and T0 mono-functionalized organosilanes in the presence of n-hexadecylamine with different hydroxyl silica functional groups at the surface. These polymer networks have shown new properties, for example, a high degree of cross-linking and hydrolysis. Two different synthesis steps were carried out: simple self-assembly followed by sol-gel transition and precipitation of homogenous sols. Due to the lack of solubility of these materials, the compositions of the new materials were determined by infrared spectroscopy, 13C and 29Si CP/MAS NMR spectroscopy and scanning electron microscopy