The (r)evolution of cancer genetics

The identification of an increasing number of cancer genes is opening up unexpected scenarios in cancer genetics. When analyzed for their systemic properties, these genes show a general fragility towards perturbation. A recent paper published in BMC Biology shows how the founder domains of known cancer genes emerged at two macroevolutionary transitions - the advent of the first cell and the transition to metazoan multicellularity

Evolving gaps: Occupational structure in southern and northern Italy, 1400–1861

During the Risorgimento (1800–61), southern Italy was less industrial than central-northern Italy and initially agricultural provinces in the north saw rapid structural transformation. During the Renaissance (1400–1600), structural transformation in the south led to a near halving of the initial difference in agricultural employment share between the centre-north and the south, but convergence came to a halt with the ‘seventeenth-century crisis’. These trends suggest that regional inequality was evolving rather than persistent

FancyGene: dynamic visualization of gene structures and protein domain architectures on genomic loci

Summary: FancyGene is a fast and user-friendly web-based tool for producing images of one or more genes directly on the corresponding genomic locus. Starting from a variety of input formats, FancyGene rebuilds the basic components of a gene (UTRs, intron, exons). Once the initial representation is obtained, the user can superimpose additional features—such as protein domains and/or a variety of biological markers—in specific positions. FancyGene is extremely flexible allowing the user to change the resulting image dynamically, modifying colors and shapes and adding and/or removing objects. The output images are generated either in portable network graphics (PNG) or portable document format (PDF) formats and can be used for scientific presentations as well as for publications. The PDF format preserves editing capabilities, allowing picture modification using any vector graphics editor

Coordination between leaf and root traits in Mediterranean coastal dune plants

Plant trait-based functional spectra are crucial to assess ecosystem functions and services. Whilst most research has focused on aboveground vegetative traits (leaf economic spectrum, LES), contrasting evidence on any coordination between the LES and root economic spectrum (RES) has been reported. Studying spectra variation along environmental gradients and accounting for species' phylogenetic relatedness may help to elucidate the strength of coordination between above- and belowground trait variation.center dot We focused on leaf and root traits of 39 species sampled in three distinct habitats (front, back and slack) along a shoreline-inland gradient on coastal dunes. We tested, within a phylogenetic comparative framework, for the presence of the LES and RES, for any coordination between these spectra, and explored their relation to variation in ecological strategies along this gradient.center dot In each habitat, three-quarters of trait variation is captured in two-dimensional spectra, with species' phylogenetic relatedness moderately influencing coordination and trade-off between traits. Along the shoreline-inland gradient, aboveground traits support the LES in all habitats. Belowground traits are consistent with the RES in the back-habitat only, where the environmental constraints are weaker, and a coordination between leaf and root traits was also found, supporting the whole-plant spectrum (PES).center dot This study confirms the complexity when seeking any correlation between the LES and RES in ecosystems characterized by multiple environmental pressures, such as those investigated here. Changes in traits adopted to resist environmental constraints are similar among species, independent of their evolutionary relatedness, thus explaining the low phylogenetic contribution in support of our results

The PAM domain, a multi-protein complex-associated module with an all-alpha-helix fold

BACKGROUND: Multimeric protein complexes have a role in many cellular pathways and are highly interconnected with various other proteins. The characterization of their domain composition and organization provides useful information on the specific role of each region of their sequence. RESULTS: We identified a new module, the PAM domain (PCI/PINT associated module), present in single subunits of well characterized multiprotein complexes, like the regulatory lid of the 26S proteasome, the COP-9 signalosome and the Sac3-Thp1 complex. This module is an around 200 residue long domain with a predicted TPR-like all-alpha-helical fold. CONCLUSIONS: The occurrence of the PAM domain in specific subunits of multimeric protein complexes, together with the role of other all-alpha-helical folds in protein-protein interactions, suggest a function for this domain in mediating transient binding to diverse target proteins

Magnonic Charge Pumping via Spin-Orbit Coupling

The interplay between spin, charge, and orbital degrees of freedom has led to the development of spintronic devices like spin-torque oscillators, spin-logic devices, and spin-transfer torque magnetic random-access memories. In this development spin pumping, the process where pure spin-currents are generated from magnetisation precession, has proved to be a powerful method for probing spin physics and magnetisation dynamics. The effect originates from direct conversion of low energy quantised spin-waves in the magnet, known as magnons, into a flow of spins from the precessing magnet to adjacent normal metal leads. The spin-pumping phenomenon represents a convenient way to electrically detect magnetisation dynamics, however, precessing magnets have been limited so far to pump pure spin currents, which require a secondary spin-charge conversion element such as heavy metals with large spin Hall angle or multi-layer layouts to be detectable. Here, we report the experimental observation of charge pumping in which a precessing ferromagnet pumps a charge current, demonstrating direct conversion of magnons into high-frequency currents via the relativistic spin-orbit interaction. The generated electric current, differently from spin currents generated by spin-pumping, can be directly detected without the need of any additional spin to charge conversion mechanism and amplitude and phase information about the relativistic current-driven magnetisation dynamics. The charge-pumping phenomenon is generic and gives a deeper understanding of the recently observed spin-orbit torques, of which it is the reciprocal effect and which currently attract interest for their potential in manipulating magnetic information. Furthermore, charge pumping provides a novel link between magnetism and electricity and may find application in sourcing alternating electric currents.Comment: 3 figure

Pan-cancer detection of driver genes at the single-patient resolution

BACKGROUND: Identifying the complete repertoire of genes that drive cancer in individual patients is crucial for precision oncology. Most established methods identify driver genes that are recurrently altered across patient cohorts. However, mapping these genes back to patients leaves a sizeable fraction with few or no drivers, hindering our understanding of cancer mechanisms and limiting the choice of therapeutic interventions. RESULTS: We present sysSVM2, a machine learning software that integrates cancer genetic alterations with gene systems-level properties to predict drivers in individual patients. Using simulated pan-cancer data, we optimise sysSVM2 for application to any cancer type. We benchmark its performance on real cancer data and validate its applicability to a rare cancer type with few known driver genes. We show that drivers predicted by sysSVM2 have a low false-positive rate, are stable and disrupt well-known cancer-related pathways. CONCLUSIONS: sysSVM2 can be used to identify driver alterations in patients lacking sufficient canonical drivers or belonging to rare cancer types for which assembling a large enough cohort is challenging, furthering the goals of precision oncology. As resources for the community, we provide the code to implement sysSVM2 and the pre-trained models in all TCGA cancer types ( https://github.com/ciccalab/sysSVM2 )

Fire Weather Index application in north-western Italy

International audiencePiedmont region is located in North-Western Italy and is surrounded by the alpine chain and by the Appennines. The region is covered by a wide extension of forests, mainly in its mountain areas (the forests cover 36% of the regional territory). Forested areas are interested by wildfire events. In the period 1997?2005 Piedmont was interested by an average 387 forest fires per year, covering an average 1926 ha of forest per year. Meteorological conditions like long periods without precipitation contribute to create favourable conditions to forest fire development, while the fire propagation is made easier by the foehn winds, frequently interesting the region in winter and spring particularly. The meteorological danger index FWI (Fire Weather Index) was developed by Van Wagner (1987) for the Canadian Forestry Service, providing a complete description of the behaviour of the different forest components in response to the changing weather conditions. We applied the FWI to the Piedmont region on warning areas previously defined for fire management purposes. The meteorological data-set is based on the data of the very-dense non-GTS network of weather stations managed by Arpa Piemonte. The thresholds for the definition of a danger scenarios system were defined comparing historical FWI data with fires occurred on a 5 years period. The implementation of a prognostic FWI prediction system is planned for the early 2008, involving the use of good forecasts of weather parameters at the station locations obtained by the Multimodel SuperEnsemble post-processing technique

T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis

Objectives: Prediction of long term clinical outcome in patients with primary progressive multiple sclerosis (PPMS) using imaging has important clinical implications, but remains challenging. We aimed to determine whether spatial location of T2 and T1 brain lesions predicts clinical progression during a 10-year follow-up in PPMS. Methods: Lesion probability maps of the T2 and T1 brain lesions were generated using the baseline scans of 80 patients with PPMS who were clinically assessed at baseline and then after 1, 2, 5 and 10 years. For each patient, the time (in years) taken before bilateral support was required to walk (time to event (TTE)) was used as a measure of progression rate. The probability of each voxel being ‘lesional’ was correlated with TTE, adjusting for age, gender, disease duration, centre and spinal cord cross sectional area, using a multiple linear regression model. To identify the best, independent predictor of progression, a Cox regression model was used. Results: A significant correlation between a shorter TTE and a higher probability of a voxel being lesional on T2 scans was found in the bilateral corticospinal tract and superior longitudinal fasciculus, and in the right inferior fronto-occipital fasciculus (p<0.05). The best predictor of progression rate was the T2 lesion load measured along the right inferior fronto-occipital fasciculus (p=0.016, hazard ratio 1.00652, 95% CI 1.00121 to 1.01186). Conclusion: Our results suggest that the location of T2 brain lesions in the motor and associative tracts is an important contributor to the progression of disability in PPMS, and is independent of spinal cord involvement