CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

A fast and cost-effective approach to develop and map EST-SSR markers: oak as a case study

Background: Expressed Sequence Tags (ESTs) are a source of simple sequence repeats (SSRs) that can be used to develop molecular markers for genetic studies. The availability of ESTs for Quercus robur and Quercus petraea provided a unique opportunity to develop microsatellite markers to accelerate research aimed at studying adaptation of these long-lived species to their environment. As a first step toward the construction of a SSR-based linkage map of oak for quantitative trait locus (QTL) mapping, we describe the mining and survey of EST-SSRs as well as a fast and cost-effective approach (bin mapping) to assign these markers to an approximate map position. We also compared the level of polymorphism between genomic and EST-derived SSRs and address the transferability of EST-SSRs in Castanea sativa (chestnut). Results: A catalogue of 103,000 Sanger ESTs was assembled into 28,024 unigenes from which 18.6% presented one or more SSR motifs. More than 42% of these SSRs corresponded to trinucleotides. Primer pairs were designed for 748 putative unigenes. Overall 37.7% (283) were found to amplify a single polymorphic locus in a reference fullsib pedigree of Quercus robur. The usefulness of these loci for establishing a genetic map was assessed using a bin mapping approach. Bin maps were constructed for the male and female parental tree for which framework linkage maps based on AFLP markers were available. The bin set consisting of 14 highly informative offspring selected based on the number and position of crossover sites. The female and male maps comprised 44 and 37 bins, with an average bin length of 16.5 cM and 20.99 cM, respectively. A total of 256 EST-SSRs were assigned to bins and their map position was further validated by linkage mapping. EST-SSRs were found to be less polymorphic than genomic SSRs, but their transferability rate to chestnut, a phylogenetically related species to oak, was higher. Conclusion: We have generated a bin map for oak comprising 256 EST-SSRs. This resource constitutes a first step toward the establishment of a gene-based map for this genus that will facilitate the dissection of QTLs affecting complex traits of ecological importance

Design of a Customized Neck Orthosis for FDM Manufacturing with a New Sustainable Bio-composite

The interest in developing customized external orthopaedic devices, thanks to the advent of Additive Manufacturing (AM), has grown in recent years. Greater attention was focused on upper limb casts, while applications to other body’s parts, such as the neck, were less investigated. In this paper the computer aided design (CAD) modelling, assessment and 3D printing with fused deposition modelling (FDM) of a customized neck orthosis are reported. The modelling, based on anatomic data of a volunteer subject, was aimed to obtain a lightweight, ventilated, hygienic and comfortable orthosis compared to the produced medical devices generally used for neck injuries. CAD models with different geometrical patterns, introduced for lightening and improving breathability, were considered, specifically, a honeycomb pattern and an elliptical holes pattern. These models were structurally assessed by means of finite elements analysis (FEA). Furthermore, an innovative composite material was considered for 3D printing. The material, Hemp Bio-Plastic® (HBP), composed by polylactic acid (PLA) and hemp shives, offers different advantages including lightweight, improved superficial finish and antibacterial properties. The results obtained in terms of design methodology and manufacturing by 3D printing of a prototype have shown the feasibility to develop customized cervical orthoses, with potentially improved performance with respect to cervical collars available on the market also thanks to the use of the innovative composite material