Switching the Magnetic Vortex Core in a Single Nanoparticle

Imaging and manipulating the spin structure of nano- and mesoscale magnetic systems is a challenging topic in magnetism, yielding a wide range of spin phenomena such as skyrmions, hedgehog-like spin structures, or vortices. A key example has been provided by the vortex spin texture, which can be addressed in four independent states of magnetization, enabling the development of multibit magnetic storage media. Most of the works devoted to the study of the magnetization reversal mechanisms of the magnetic vortices have been focused on micrometer-size magnetic platelets. Here we report the experimental observation of the vortex state formation and annihilation in individual 25 nm molecular-based magnetic nanoparticles measured by low-temperature variable-field magnetic force microscopy. Interestingly, in these nanoparticles the switching of the vortex core can be induced with very small values of the applied static magnetic field

Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity.

DNA double-strand breaks (DSBs) are perhaps the most toxic of all DNA lesions, with defects in the DNA-damage response to DSBs being associated with various human diseases. Although it is known that DSB repair pathways are tightly regulated by ubiquitylation, we do not yet have a comprehensive understanding of how deubiquitylating enzymes (DUBs) function in DSB responses. Here, by carrying out a multidimensional screening strategy for human DUBs, we identify several with hitherto unknown links to DSB repair, the G2/M DNA-damage checkpoint and genome-integrity maintenance. Phylogenetic analyses reveal functional clustering within certain DUB subgroups, suggesting evolutionally conserved functions and/or related modes of action. Furthermore, we establish that the DUB UCHL5 regulates DSB resection and repair by homologous recombination through protecting its interactor, NFRKB, from degradation. Collectively, our findings extend the list of DUBs promoting the maintenance of genome integrity, and highlight their potential as therapeutic targets for cancer.This is the author's accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ncb302

CtIP tetramer assembly is required for DNA-end resection and repair.

Mammalian CtIP protein has major roles in DNA double-strand break (DSB) repair. Although it is well established that CtIP promotes DNA-end resection in preparation for homology-dependent DSB repair, the molecular basis for this function has remained unknown. Here we show by biophysical and X-ray crystallographic analyses that the N-terminal domain of human CtIP exists as a stable homotetramer. Tetramerization results from interlocking interactions between the N-terminal extensions of CtIP's coiled-coil region, which lead to a 'dimer-of-dimers' architecture. Through interrogation of the CtIP structure, we identify a point mutation that abolishes tetramerization of the N-terminal domain while preserving dimerization in vitro. Notably, we establish that this mutation abrogates CtIP oligomer assembly in cells, thus leading to strong defects in DNA-end resection and gene conversion. These findings indicate that the CtIP tetramer architecture described here is essential for effective DSB repair by homologous recombination.We thank M. Kilkenny for help with the collection of X-ray diffraction data, A. Sharff and P. Keller for help with X-ray data processing and J.D. Maman for assistance with SEC-MALS. This work was supported by a Wellcome Trust Senior Research Fellowship award in basic biomedical sciences (L.P.), an Isaac Newton Trust research grant (L.P. and O.R.D.) and a Cambridge Overseas Trust PhD studentship (M.D.S.). Research in the laboratory of S.P.J. is funded by Cancer Research UK (CRUK; programme grant C6/A11224), the European Research Council and the European Community Seventh Framework Programme (grant agreement no. HEALTH-F2-2010-259893 (DDResponse)). Core funding is provided by Cancer Research UK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the University of Cambridge, supplemented by CRUK. J.V.F. is funded by Cancer Research UK programme grant C6/A11224 and the Ataxia Telangiectasia Society. R.B. and J.C. are funded by Cancer Research UK programme grant C6/A11224. Y.G. and M.D. are funded by the European Research Council grant DDREAM.This is the accepted manuscript of a paper published in Nature Structural & Molecular Biology, 22, 150–157 (2015) doi: 10.1038/nsmb.293

Imagining Mexico in 1910: Visions of the Patria in the Centennial Celebration in Mexico City

Mexico’s 1910 Centenario reflected a popular trend in Western Europe and its former colonies to use centenaries of important historical events to promote political programmes and philosophies through the construction of historical memory. Centennial organisers in Mexico linked Miguel Hidalgo y Costilla and Jose´ Maria Morelos to President Porfirio Dı´az in words and symbols, and associated state formation and civic culture with Liberal leaders and policies, such as public education, material progress and secularism. The planners also promoted Morelos as a mestizo icon and symbol for national identity and integration, while they simultaneously celebrated Mexico’s pre-Columbian cultures and criticised contemporary natives as impediments to progress. The Centennial’s audience included hundreds of thousands of Mexicans as well as foreigners from around the globe, who came away with different impressions based on their cultural perspectives, political philosophies and material interests. Following the overthrow of Dı´az in 1911, Mexico’s revolutionary governments continued to use Independence Day celebrations to promote their programmes, including some whose origins lay in the Porfiriato. As we approach the bicentenary of Latin American independence, competing visions of patrias will likely surface and provide insights into the construction of historical memory and contemporary political discourse

The Implementation, Deployment and Evaluation of a Mobile Personal Learning Environment

[EN] The application of ICT to learning, the Web 2.0 trends and the widespread use of technologies such as mobile devices make it necessary to provide new solutions to satisfy the needs of learners. Such solutions should treat the students as the centre of the learning process. The students should be able to decide which tools they will use to learn, and the learning institution must consider the behaviour of students in such personal learning activities independently of the location where learning activities are carried out. In addition, learners can choose the type of devices they will use with special attention to mobile technologies. The work described in this paper proposes a service-based approach to defining mobile personal learning environments that facilitates communication with institutional learning platforms. Such an approach is implemented as a proof-of-concept and evaluated via a pilot study to demonstrate that such types of mobile learning platforms are feasible and can increase students’motivation to help them learn

Small-molecule-induced DNA damage identifies alternative DNA structures in human genes.

Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. A chromatin immunoprecipitation sequencing analysis of the DNA damage marker γH2AX provided the genome-wide distribution of pyridostatin-induced sites of damage and revealed that pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto-oncogene SRC. We observed that pyridostatin reduced SRC protein abundance and SRC-dependent cellular motility in human breast cancer cells, validating SRC as a target of this drug. Our unbiased approach to define genomic sites of action for a drug establishes a framework for discovering functional DNA-drug interactions

Identification of glucose transporters in Aspergillus nidulans

o characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose.The authors would like to thank the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Protected Users: A Moodle Plugin To Improve Confidentiality and Privacy Support through User Aliases

[EN]The privacy policies, terms, and conditions of use in any Learning Management System (LMS) are one-way contracts. The institution imposes clauses that the student can accept or decline. Students, once they accept conditions, should be able to exercise the rights granted by the General Data Protection Regulation (GDPR). However, students cannot object to data processing and public profiling because it would be conceived as an impediment to teachers to execute their work with normality. Nonetheless, regarding GDPR and consulted legal advisors, a student could claim identity anonymization in the LMS, if adequate personal justifications are provided. Per contra, the current LMSs do not have any functionality that enables identity anonymization. This is a big problem that generates undesired situations which urgently requires a definitive solution. In this work, we surveyed students and teachers to validate the feasibility and acceptance of using aliases to anonymize their identity in LMSs as a sustainable solution to the problem. Considering the positive results, we developed a user-friendly plugin for Moodle that enables students' identity anonymization by the use of aliases. This plugin, presented in this work and named Protected users, is publicly available online at GitHub and published under GNU General Public License