Gain-of-function mutations often cluster in specific protein regions, a signal that those mutations provide an adaptive advantage to cancer cells and consequently are positively selected during ...clonal evolution of tumours. We sought to determine the overall extent of this feature in cancer and the possibility to use this feature to identify drivers.
We have developed OncodriveCLUST, a method to identify genes with a significant bias towards mutation clustering within the protein sequence. This method constructs the background model by assessing coding-silent mutations, which are assumed not to be under positive selection and thus may reflect the baseline tendency of somatic mutations to be clustered. OncodriveCLUST analysis of the Catalogue of Somatic Mutations in Cancer retrieved a list of genes enriched by the Cancer Gene Census, prioritizing those with dominant phenotypes but also highlighting some recessive cancer genes, which showed wider but still delimited mutation clusters. Assessment of datasets from The Cancer Genome Atlas demonstrated that OncodriveCLUST selected cancer genes that were nevertheless missed by methods based on frequency and functional impact criteria. This stressed the benefit of combining approaches based on complementary principles to identify driver mutations. We propose OncodriveCLUST as an effective tool for that purpose.
OncodriveCLUST has been implemented as a Python script and is freely available from http://bg.upf.edu/oncodriveclust
nuria.lopez@upf.edu or abel.gonzalez@upf.edu
Supplementary data are available at Bioinformatics online.
Male harvestmen penial armature has a remarkable morphology; however, it is poorly known regarding its functions. We examined the male genitalia of virgin and mated males of the gonyleptid ...Pachyloides thorellii under Scanning Electron Microscope looking for evidence that the penis could remove sperm from the female ovipositor lumen during mating. Micrographs show sperm agglutinations over and within the microsetae fields in six out of the 12 mated males studied. For the mating experiments we used only virgin females, therefore the sperm found in the penis was in all cases their own sperm. This self-sperm removal could be the extraction of sperm excess in cooperation (or not) with the females. This is the first study to show for the Order Opiliones direct evidence that a male penis contains structures that can effectively remove sperm from the female ovipositor. Further behavioral and morphological studies are needed to confirm the conditions of occurrence and participation of each sex in sperm removal processes in this species.
The Juan Fernández islands (Chile) are a volcanic archipelago, 670 km away from the continent. Arachnids still remain understudied in those islands. We report the first two records of Parabalta ...reedii (Butler,
1874
)) (Opiliones, Gonyleptidae) from the Robinson Crusoe Island. One specimen was collected near San Juan Bautista town (in 2011), while a population was documented in 2020, in secondary forests also around town. Since other arachnological expeditions did not report the presence of this species, it is suggested that these findings might correspond to an incipient introduction, possibly associated with imported goods from the continent. Otherwise, it would be hard to explain why such a conspicuous harvestman has not been noticed before. An accurate assessment of the native or introduced nature of these populations will require further mainland and island surveys, as well as molecular studies. We aim to call the attention to a possible new invasive species in the Juan Fernández archipelago. Oceanic islands have a strong conservation value because of their high levels of endemicity and vulnerability to biological invasions. This finding could be considered as a warning call for other potential arthropod introductions.
Four species of Ciboneya Pérez, n. gen. are described from western Cuba: C. nuriae, n. sp. from La Habana and Pinar del Rio Provinces, C. odilere, n. sp., C. parva, n. sp., and C. antraia, n. sp. ...from Pinar del Rio Province. The species share apophyses on the male cheliceral fangs, corresponding pockets or modified areas on the female epigynum, and several details of the male pedipalps. Vertical hairs on the tibiae and metatarsi of the male legs and a retrolateral coxa apophysis on the male palp place the genus close to other Central and South American genera of the New World clade of pholcids, but the exact sister group is obscure. The spiders live in the leaf litter and under rocks in humid forests, or near the floor in caves. The females of C. antraia show a remarkable dimorphism in their genitalia, with rare intermediate forms. The possibly more frequent occurrence of such a dimorphism and the probable bias toward reporting it as two different species are discussed.
Delta ligands regulate Notch signaling in normal intestinal stem cells, while Jagged1 activates Notch in intestinal adenomas carrying active β-catenin. We used the Apc
mouse model, tumor spheroid ...cultures, and patient-derived orthoxenografts to address this divergent ligand-dependent Notch function and its implication in disease. We found that intestinal-specific Jag1 deletion or antibody targeting Jag1 prevents tumor initiation in mice. Addiction to Jag1 is concomitant with the absence of Manic Fringe (MFNG) in adenoma cells, and its ectopic expression reverts Jag1 dependence. In 239 human colorectal cancer patient samples, MFNG imposes a negative correlation between Jag1 and Notch, being high Jag1 in the absence of MFNG predictive of poor prognosis. Jag1 antibody treatment reduces patient-derived tumor orthoxenograft growth without affecting normal intestinal mucosa. Our data provide an explanation to Jag1 dependence in cancer, and reveal that Jag1-Notch1 interference provides therapeutic benefit in a subset of colorectal cancer and FAP syndrome patients.
When the cure kills-CBD limits biodiversity research Prathapan, K Divakaran; Pethiyagoda, Rohan; Bawa, Kamaljit S ...
Science (American Association for the Advancement of Science),
06/2018, Letnik:
360, Številka:
6396
Journal Article
Recenzirano
Odprti dostop
National laws fearing biopiracy squelch taxonomy studies
The Convention on Biological Diversity (CBD) commits its 196 nation parties to conserve biological diversity, use its components sustainably, ...and share fairly and equitably the benefits from the utilization of genetic resources. The last of these objectives was further codified in the Convention's Nagoya Protocol (NP), which came into effect in 2014. Although these aspirations are laudable, the NP and resulting national ambitions on Access and Benefit Sharing (ABS) of genetic resources have generated several national regulatory regimes fraught with unintended consequences (
1
). Anticipated benefits from the commercial use of genetic resources, especially those that might flow to local or indigenous communities because of regulated access to those resources, have largely been exaggerated and not yet realized. Instead, national regulations created in anticipation of commercial benefits, particularly in many countries that are rich in biodiversity, have curtailed biodiversity research by in-country scientists as well as international collaboration (
1
). This weakens the first and foremost objective of the CBD—conservation of biological diversity. We suggest ways that the Conference of the Parties (CoP) of the CBD may proactively engage scientists to create a regulatory environment conducive to advancing biodiversity science.
Some cancer therapies damage DNA and cause mutations in both cancerous and healthy cells. Therapy-induced mutations may underlie some of the long-term and late side effects of treatments, such as ...mental disabilities, organ toxicity and secondary neoplasms. Nevertheless, the burden of mutation contributed by different chemotherapies has not been explored. Here we identify the mutational signatures or footprints of six widely used anticancer therapies across more than 3,500 metastatic tumors originating from different organs. These include previously known and new mutational signatures generated by platinum-based drugs as well as a previously unknown signature of nucleoside metabolic inhibitors. Exploiting these mutational footprints, we estimate the contribution of different treatments to the mutation burden of tumors and their risk of contributing coding and potential driver mutations in the genome. The mutational footprints identified here allow for precise assessment of the mutational risk of different cancer therapies to understand their long-term side effects.
Abstract Phocyx gen. nov. and Phocyx australis sp. nov. have been newly described from New South Wales, Australia. This represents the first record of the family Buemarinoidae in Australia, thereby ...remarkably extending the known distribution of this ancient and relictual group of Opiliones. Our descriptions include images of genital morphology, a critical element in group diagnosis. Additionally, we present a discourse on the conserved external morphology within Triaenonychoidea and underscore the significance of genital morphology in the taxonomy of this superfamily. Very low species diversity and relict taxa surviving in scattered isolated refugia (tropical environments of the Southern Hemisphere and hypogean habitats of the Northern Hemisphere) are a clear signature that extinction probably played a major role in shaping the current distribution ranges of Buemarinoidae. That is also reflected in buemarinoid systematics by the prevalence of monotypic genera, a product of the large-scale extinction process affecting this old harvestman lineage.
The genus Spaeleoleptes was proposed by H. Soares in 1966 to accommodate the first Brazilian troglobitic species of harvestmen, Spaeleoleptes spaeleus H. Soares, 1966. In this work, we redescribe ...this species, including digital images of the type material and drawings of the male genitalia. Since its description, Spaeleoleptes has remained monotypic, and after 56 years, herein is described the second species of the genus, the troglobitic Spaeleoleptes gimli sp. nov. Both species share sexually dimorphic legs I and II with modified regions and swelling on the tibiae and patellae I and II; a penis with robust conductors covering all or part of the capsula interna and a capsula interna with two lateral projections. They are clearly separated by the shape of the modified region of the tibia; by the presence of an apical projection on the apical lamina of the pars distalis in S. spaeleus; and the lateral projections of the capsula interna, which is flattened in S. gimli. Spaeleoleptes gimli greatly increases the distributional range of the genus, as it is now recorded from caves located in two Brazilian phytophysiognomies from the Cerrado of Minas Gerais to the Caatinga of Bahia.
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