Characterization of nucleic acids by tandem mass spectrometry - The second decade (2004-2013): From DNA to RNA and modified sequences

Nucleic acids play key roles in the storage and processing of genetic information, as well as in the regulation of cellular processes. Consequently, they represent attractive targets for drugs against gene-related diseases. On the other hand, synthetic oligonucleotide analogues have found application as chemotherapeutic agents targeting cellular DNA and RNA. The development of effective nucleic acid-based chemotherapeutic strategies requires adequate analytical techniques capable of providing detailed information about the nucleotide sequences, the presence of structural modifications, the formation of higher-order structures, as well as the interaction of nucleic acids with other cellular components and chemotherapeutic agents. Due to the impressive technical and methodological developments of the past years, tandem mass spectrometry has evolved to one of the most powerful tools supporting research related to nucleic acids. This review covers the literature of the past decade devoted to the tandem mass spectrometric investigation of nucleic acids, with the main focus on the fundamental mechanistic aspects governing the gas-phase dissociation of DNA, RNA, modified oligonucleotide analogues, and their adducts with metal ions. Additionally, recent findings on the elucidation of nucleic acid higher-order structures by tandem mass spectrometry are reviewed.

Advances in gastropod immunity from the study of the interaction between the snail Biomphalaria glabrata and its parasites: A review of research progress over the last decade

This review summarizes the research progress made over the past decade in the field of gastropod immunity resulting from investigations of the interaction between the snail Biomphalaria glabrata and its trematode parasites. A combination of integrated approaches, including cellular, genetic and comparative molecular and proteomic approaches have revealed novel molecular components involved in mediating Biomphalaria immune responses that provide insights into the nature of host-parasite compatibility and the mechanisms involved in parasite recognition and killing. The current overview emphasizes that the interaction between B. glabrata and its trematode parasites involves a complex molecular crosstalk between numerous antigens, immune receptors, effectors and anti-effector systems that are highly diverse structurally and extremely variable in expression between and within host and parasite populations. Ultimately, integration of these molecular signals will determine the outcome of a specific interaction between a B. glabrata individual and its interacting trematodes. Understanding these complex molecular interactions and identifying key factors that may be targeted to impairment of schistosome development in the snail host is crucial to generating new alternative schistosomiasis control strategies.

Re-viewing history: antiquaries, the graphic arts and Scotland's lost geographies, c.1660-1820

This thesis examines topographical art depicting Scotland’s natural scenery and built environments, architecture, antiquities and signs of modern improvement, made during the period 1660 to 1820. It sets out to demonstrate that topography and topographical art was not exclusively antiquarian in nature, but ranged across various fields of learning and practice. It included the work of artists, geographers, cartographers, travel writers, poets, landscape gardeners, military surveyors, naturalists and historians who were concerned with representing the country’s varied, and often contentious, histories within an increasingly modernising present. The visual images that are considered here were forms of knowledge that found expression in drawings, paintings and engravings, elevations, views and plans. They were made on military surveys and picturesque tours, and were often intended to be included alongside written texts, both published and unpublished, frequently connecting with travels, tours, memoirs, essays and correspondence. It will also be argued that topography was a social practice, involving networks of artists, collectors, publishers and writers, who exchanged information in drawings and letters in a nationwide, and often increasingly commercial enterprise. This thesis will explore some of the strands of such a vast network of picture-making that existed in Scotland, and Britain, between 1660 and 1820, as visual images were circulated, copied, recycled and adapted, and topographical and antiquarian visual culture emerges as a complex, synoptic form of inquiry.

Nanomedicines: are we lost in translation?

International audience

Cuando el miedo invade la ficción. Análisis de Perdidos (Lost, ABC, 2004-2010) y de otros Quality Dramas de la era Post 11S.

521 p.

Biotechnological, nutritional and therapeutic uses of Pleurotus spp. (Oyster mushroom) related with its chemical composition: A review on the past decade findings

The particular characteristics of growth and development of mushrooms in nature result in the accumulation of a variety of secondary metabolites, several of them with biological activities. The genus Pleurotus is a cosmopolitan group of mushrooms with high nutritional value and therapeutic properties, besides a wide array of biotechnological and environmental applications. Scope and approach: The present report aims to provide a critical review on aspects related to chemical compounds isolated from the genus Pleurotus with possible biotechnological, nutritional and therapeutic uses. Investigations on the genus have immensely accelerated during the last ten years, so that only reports published after 2005 have been considered. Key findings and conclusions: The most important Pleurotus species cultivated in large scale are P. ostreatus and P. pulmonarius. However, more than 200 species have already been investigated to various degrees. Both basidiomata and mycelia of Pleurotus are a great renewable and easily accessible source of functional foods/nutraceuticals and pharmaceuticals with antioxidant, antimicrobial, anti-inflammatory, antitumor and immunomodulatory effects. A series of compounds have already been precisely defined including several polysaccharides, phenolics, terpenes and sterols. However, intensification of structure determination is highly desirable and demands considerable efforts. Further studies including clinical trials need to be carried out to ascertain the safety of these compounds as adequate alternatives to conventional drugs. Not less important is to extend the search for novel bioactives to less explored Pleurotus species.

Community School of São Miguel de Machede: A decade of Learning

the Community School of São Miguel de Machede exists since 1998. A model of Community Education has been developed in this decade of existence, which not being confined to the frequent profiles of the most common approaches in Adult Education, has been the result of a process of symbiosis between a practice that normally precedes the conceptualization and a thought which has always expressed the concern of interpreting and enrich that practice. Setting on a model of learning based on the PADéCA – Program of Helping the Development of the Capacity to Learn, proposed by Berbaum (1988), the Community School of São Miguel de Machede has been developing several activities centred on a fundamental concern: to create easy and qualified accesses, in this community (council of Evora), so that the respective members can learn to exercise their principal rights of citizenship, in the territory where they live and in a circumstance of equality of opportunities in relation to the remaining fellow countrymen. Being a project with a decade of life, it is now possible to speak of a history full of stories and learning experiences, which occurred as a result of a rich interaction between the initial thoughts and impulses of the theoretical approaches and a reality full of unexpectedness, mutability and humanity resulting from the complexity that a living community presents, with a history and a present, but not always with clear and positive idea about the respective future.

Oitenta anos de produção e comercialização dos vinhos do Dão

Mestrado em Economia

Design and Applications of a Decade-Spanning Terahertz Frequency Comb Spectrometer: Doppler-limited Rotational Spectroscopy of Methanol and Methanol-OD

This thesis details the design and applications of a terahertz (THz) frequency comb spectrometer. The spectrometer employs two offset locked Ti:Sapphire femtosecond oscillators with repetition rates of approximately 80 MHz, offset locked at 100 Hz to continuously sample a time delay of 12.5 ns at a maximum time delay resolution of 15.6 fs. These oscillators emit continuous pulse trains, allowing the generation of a THz pulse train by the master, or pump, oscillator and the sampling of this THz pulse train by the slave, or probe, oscillator via the electro-optic effect. Collecting a train of 16 consecutive THz pulses and taking the Fourier transform of this pulse train produces a decade-spanning frequency comb, from 0.25 to 2.5 THz, with a comb tooth width of 5 MHz and a comb tooth spacing of ~80 MHz. This frequency comb is suitable for Doppler-limited rotational spectroscopy of small molecules. Here, the data from 68 individual scans at slightly different pump oscillator repetition rates were combined, producing an interleaved THz frequency comb spectrum, with a maximum interval between comb teeth of 1.4 MHz, enabling THz frequency comb spectroscopy.

The accuracy of the THz frequency comb spectrometer was tested, achieving a root mean square error of 92 kHz measuring selected absorption center frequencies of water vapor at 10 mTorr, and a root mean square error of 150 kHz in measurements of a K-stack of acetonitrile. This accuracy is sufficient for fitting of measured transitions to a model Hamiltonian to generate a predicted spectrum for molecules of interest in the fields of astronomy and physical chemistry. As such, the rotational spectra of methanol and methanol-OD were acquired by the spectrometer. Absorptions from 1.3 THz to 2.0 THz were compared to JPL catalog data for methanol and the spectrometer achieved an RMS error of 402 kHz, improving to 303 kHz when excluding low signal-to-noise absorptions. This level of accuracy compares favorably with the ~100 kHz accuracy achieved by JPL frequency multiplier submillimeter spectrometers. Additionally, the relative intensity performance of the THz frequency comb spectrometer is linear across the entire decade-spanning bandwidth, making it the preferred instrument for recovering lineshapes and taking absolute intensity measurements in the THz region. The data acquired by the Terahertz Frequency Comb Spectrometer for methanol-OD is of comparable accuracy to the methanol data and may be used to refine the fit parameters for the predicted spectrum of methanol-OD.