Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.ERDF - Competitive Factors Thematic Operational ProgrammeFCT/PTDC/ QUI/68017/2006FCOMP-01-0124-FEDER-007439SFRH/BD/ 63430/2009National UNESCO Committee - L'Oréal Medals of Honor for Women in Science 200Portuguese National NMR Network - RNRM

Temperature and Magnetic Field Effects on the Transport Controlled Charge State of a Single Quantum Dot

Individual InAs/GaAs quantum dots are studied by micro-photoluminescence. By varying the strength of an applied external magnetic field and/or the temperature, it is demonstrated that the charge state of a single quantum dot can be tuned. This tuning effect is shown to be related to the in-plane electron and hole transport, prior to capture into the quantum dot, since the photo-excited carriers are primarily generated in the barrier

Differential distribution of (Na, K)-ATPase α isoforms in the central nervous system

1. mRNA transcripts for three isoforms of the α subunit of (Na, K)-ATPase have been previously identified in the rat nervous system and designated α 1, α 2 and α 3.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44279/1/10571_2004_Article_BF00769038.pd

O ensino das ciências experimentais no liceu, em Portugal, na I República (1910-1926)

O ensino das ciências experimentais (ECE) em Portugal ficou, como pretendemos demonstrar, fortemente marcado pela instauração da República, que comemorou no ano transacto o seu centenário. A República de 1910 pretendeu reformar toda a mentalidade portuguesa, através do pilar base – a educação – pela qual seria capaz de sacudir a nossa maneira de ser, lançando desta forma o país para um progresso de nível europeu. O estudo a que nos propomos, uma investigação documental no domínio da História da Ciência1, visa aprofundar os conhecimentos existentes sobre esta época e perceber o impacto da reforma do ECE, principalmente nos Liceus, caracterizando as principais figuras, políticas e docentes responsáveis pela sua conceptualização e aplicação. Através desta investigação procuraremos lançar as primeiras bases para descobrir as origens deste pensamento, querendo ainda comparar os fundamentos psicopedagógicos, epistemológicos e sociológicos da época com as principais ideias actualmente presentes no ensino da Ciência. Com este trabalho pretendemos, num primeiro momento, apresentar e divulgar o desenho da investigação e os seus objectivos, na procura de estabelecer parcerias e receber contributos da comunidade académica interessada por esta problemática

Skeletal Muscle-Specific Ablation of γcyto-Actin Does Not Exacerbate the mdx Phenotype

We previously documented a ten-fold increase in γcyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased γcyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased γcyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and γcyto-actin specifically in skeletal muscle (ms-DKO). Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests γcyto-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a γcyto-actin-utrophin interaction

Stretching positions for the coracohumeral ligament: Strain measurement during passive motion using fresh/frozen cadaver shoulders

<p>Abstract</p> <p>Background</p> <p>Contracture of the coracohumeral ligament is reported to restrict external rotation of the shoulder with arm at the side and restrict posterior-inferior shift of the humeral head. The contracture is supposed to restrict range of motion of the glenohumeral joint.</p> <p>Methods</p> <p>To obtain stretching position of the coracohumeral ligament, strain on the ligament was measured at the superficial fibers of the ligament using 9 fresh/frozen cadaver shoulders. By sequential measurement using a strain gauge, the ligament strain was measured from reference length (L0). Shoulder positions were determined using a 3 Space Tracker System. Through a combination of previously reported coracohumeral stretching positions and those observed in preliminary measurement, ligament strain were measured by passive external rotation from 10° internal rotation, by adding each 10° external rotation, to maximal external rotation.</p> <p>Results</p> <p>Stretching positions in which significantly larger strain were obtained compared to the L0 values were 0° elevation in scapula plane with 40°, 50° and maximum external rotation (5.68%, 7.2%, 7.87%), 30° extension with 50°, maximum external rotation (4.20%, 4.79%), and 30° extension + adduction with 30°, 40°, 50° and maximum external rotation (4.09%, 4.67%, 4.78%, 5.05%)(P < 0.05). No positive strain on the coracohumeral ligament was observed for the previously reported stretching positions; ie, 90° abduction with external rotation or flexion with external rotation.</p> <p>Conclusions</p> <p>Significant strain of the coracohumeral ligament will be achieved by passive external rotation at lower shoulder elevations, extension, and extension with adduction.</p

Bioinformatics tools for cancer metabolomics

It is well known that significant metabolic change take place as cells are transformed from normal to malignant. This review focuses on the use of different bioinformatics tools in cancer metabolomics studies. The article begins by describing different metabolomics technologies and data generation techniques. Overview of the data pre-processing techniques is provided and multivariate data analysis techniques are discussed and illustrated with case studies, including principal component analysis, clustering techniques, self-organizing maps, partial least squares, and discriminant function analysis. Also included is a discussion of available software packages

Suppression of superconductivity by non-magnetic disorder in organic superconductor κ\kappa-(BEDT-TTF)2_{2}Cu(NCS)2_{2}

The suppression of superconductivity by nonmagnetic disorder is investigated systematically in the organic superconductor $\kappa$-(BEDT-TTF)$_2$Cu(NCS)$_2$. We introduce a nonmagnetic disorder arising from molecule substitution in part with deuterated BEDT-TTF or BMDT-TTF for BEDT-TTF molecules and molecular defects introduced by X-ray irradiation. A quantitative evaluation of the scattering time $\tau_{\rm dHvA}$ is carried out by de Haas-van Alphen (dHvA) effect measurement. A large reduction in $T_{\rm c}$ with a linear dependence on $1/\tau_{\rm dHvA}$ is found in the small-disorder region below $1/\tau_{\rm dHvA} \simeq$ 1 $\times$ 10$^{12}$ s$^{-1}$ in both the BMDT-TTF molecule-substituted and X-ray-irradiated samples. The observed linear relation between $T_{\rm c}$ and $1/\tau_{\rm dHvA}$ is in agreement with the Abrikosov-Gorkov (AG) formula, at least in the small-disorder region. This observation is reasonably consistent with the unconventional superconductivity proposed thus far for the present organic superconductor. A deviation from the AG formula, however, is observed in the large-disorder region above $1/\tau_{\rm dHvA} \simeq$ 1 $\times$ 10$^{12}$ s$^{-1}$, which reproduces the previous transport study (J. G. Analytis {\it et al.}: Phys. Rev. Lett. {\bf 96} (2006) 177002). We present some interpretations of this deviation from the viewpoints of superconductivity and the inherent difficulties in the evaluation of scattering time.Comment: 11 pages, 6 figure

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules