Cubic membranes: a legend beyond the Flatland* of cell membrane organization

Cubic membranes represent highly curved, three-dimensional nanoperiodic structures that correspond to mathematically well defined triply periodic minimal surfaces. Although they have been observed in numerous cell types and under different conditions, particularly in stressed, diseased, or virally infected cells, knowledge about the formation and function of nonlamellar, cubic structures in biological systems is scarce, and research so far is restricted to the descriptive level. We show that the “organized smooth endoplasmic reticulum” (OSER; Snapp, E.L., R.S. Hegde, M. Francolini, F. Lombardo, S. Colombo, E. Pedrazzini, N. Borgese, and J. Lippincott-Schwartz. 2003. J. Cell Biol. 163:257–269), which is formed in response to elevated levels of specific membrane-resident proteins, is actually the two-dimensional representation of two subtypes of cubic membrane morphology. Controlled OSER induction may thus provide, for the first time, a valuable tool to study cubic membrane formation and function at the molecular level

Hábitos de sono e performance académica: estudo comparativo entre Estónia e Portugal

Actualmente, na nossa sociedade, muitas das actividades diárias têm prioridade sobre o sono. A privação do sono em estudantes tem sido documentada em variados países e o problema reside no conflito entre a necessidade física e psicológica, dos estudantes, de dormir e os seus horários. Esta privação do sono é, muitas das vezes, relacionada com a diminuição do humor e do rendimento académico. No intuito de combater estes problemas, alguns estudantes recorrem ao uso de fármacos ou substâncias com vista a melhorar a sua qualidade de vida e o seu rendimento escolar. O objectivo deste estudo é (1) avaliar a qualidade de sono dos estudantes universitários, (2) avaliar a percentagem de estudantes que consomem fármacos ou substâncias para modificar o seu sono e (3) comparar os resultados entre duas escolas de saúde, Escola Superior de Tecnologia da Saúde do Porto, Portugal (ESTSP) e a Tallinn Health Care College, Estónia (THCC)

Structural Evolution, Vein Orientation, and Paragenesis of the Botija Porphyry Cu-Mo-(Au) Deposit, Colón, Panamá

The Botija Cu-Mo-Au porphyry deposit is located in the Cobre Panamá mining district, which contains several deposits with a global measure and indicated and inferred resource of 14.8 MT of Cu. These deposits are associated with the Cerro Petaquilla batholith, which has U/Pb zircon ages of 26-33 Ma (Whattam et al., 2012; Baker et al., 2016). The Botija deposit is an elongate tabular body striking northeast and dipping 20-40° N and measures 2 km (length) x 1 km (width) x 600 m (height) in size. The deposit is hosted in andesite, the equigranular Petaquilla granodiorite, and a younger crowded porphyritic granodiorite with 15-50 vol.% groundmass of quartz and K-feldspar. Phenocrysts include plagioclase, hornblende ± K-feldspar and occasionally 5-15 vol.% rounded quartz eyes. Ore is characterized by Cu-Fe sulfides (chalcopyrite > bornite) that is dominantly disseminated, but also present in magmatic-hydrothermal quartz veins. Systematic vein measurements at Botija demonstrate that copper ores are spatially associated with a quartz vein density >0.5 vol.%; these veins have two modes of structural orientation (azimuth of strike/right-hand dip) of 233/50°NW and 295/45°NE. Most similar early quartz veins are emplaced along near-vertical hydrofractures in numerous porphyry deposits globally. The present dip of these quartz veins suggest that the veins and the Botija deposit have been moderately tilted about 40° south-southeast after mineralization. Typical potassic and sericitic alteration and zonation is present in Botija, however, a late overprint of chlorite and zeolite has obscured much of the original magmatic hydrothermal alteration footprint. Although the Botija deposit exhibits many of the common porphyry copper features, its geometry is atypical with abrupt spatial transitions (<10 m) in alteration and grades (Cu, Mo & Au) whereas most porphyry copper deposits typically exhibit gradual transitions in over hundreds of meters. These sharp breaks in the geology in some cases correspond to observed faults, and together with other faults mapped in field exposures and drill core allow identification of three main fault sets that offset the deposit. A restoration of the Cu and Mo grade shells indicates a multistage post-mineral deformation history with a first stage of ~500 m left-oblique normal offset on the Botija Fault (267/50°N) and Santa Fe fault (268/70°N), normal displacement in excess of 250 m on the NW striking Oeste fault (314/75°NE) and a final stage of normal displacement in excess of 500 m offset on S50°W-striking Strike Central faults (230/65°N). Restoration of these fault offsets brings the ore shells to the appropriate inverted cup shaped geometry typical of porphyry copper deposits. The faults identified at Botija likely accommodated a modest amount (~10-15°) of tilting to the southeast. An additional restoration of the 50°N-dipping quartz veins to vertical restores the ore shells to geometry in line with the classical shape for a porphyry copper deposit. This restoration of quartz veins can be explained by progressive deformation initiated by presently shallowly dipping, southwest striking normal faults (240/35°NW) identified from ZTEM™ geophysics which bound the deposits of Cobre Panamá. This reconstruction suggests the deposits of Cobre Panamá were likely dismembered by normal faulting from two or more original upright and intact porphyry copper deposits, generating the seven segmented and tilted deposits present today. This interpretation of normal displacement of the deposit is in lines with (U-Th)/He age by Farris et al. (2011), which constrain the exhumation of the deposit during a period of localized extension in Panamá between 19.5 – 22.3 Ma shortly after emplacement

Enhanced membrane protein expression by engineering increased intracellular membrane production

Background: Membrane protein research is frequently hampered by the low natural abundance of these proteins in cells and typically relies on recombinant gene expression. Different expression systems, like mammalian cells, insect cells, bacteria and yeast are being used, but very few research efforts have been directed towards specific host cell customization for enhanced expression of membrane proteins. Here we show that by increasing the intracellular membrane production by interfering with a key enzymatic step of lipid synthesis, enhanced expression of membrane proteins in yeast is achieved. Results: We engineered the oleotrophic yeast, Yarrowia lipolytica, by deleting the phosphatidic acid phosphatase, PAH1, which led to massive proliferation of endoplasmic reticulum (ER) membranes. For all eight tested representatives of different integral membrane protein families, we obtained enhanced protein accumulation levels and in some cases enhanced proteolytic integrity in the Delta pah1 strain. We analysed the adenosine A2AR G-protein coupled receptor case in more detail and found that concomitant induction of the unfolded protein response in the Delta pah1 strain enhanced the specific ligand binding activity of the receptor. These data indicate an improved quality control mechanism for membrane proteins accumulating in yeast cells with proliferated ER. Conclusions: We conclude that redirecting the metabolic flux of fatty acids away from triacylglycerol-and sterylester-storage towards membrane phospholipid synthesis by PAH1 gene inactivation, provides a valuable approach to enhance eukaryotic membrane protein production. Complementary to this improvement in membrane protein quantity, UPR co-induction further enhances the quality of the membrane protein in terms of its proper folding and biological activity. Importantly, since these pathways are conserved in all eukaryotes, it will be of interest to investigate similar engineering approaches in other cell types of biotechnological interest, such as insect cells and mammalian cells

Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid particles.

Oxidosqualene cyclase of the yeast encoded by the ERG7 gene converts oxidosqualene to lanosterol, the first cyclic component of sterol biosynthesis. In a previous study (Athenstaedt, K., Zweytick, D., Jandrositz, A, Kohlwein, S. D., and Daum, G. (1999) J. Bacteriol. 181, 6441–6448), Erg7p was identified as a component of yeast lipid particles. Here, we present evidence that Erg7p is almost exclusively associated with this compartment as shown by analysis of enzymatic activity, Western blot analysis, and in vivo localization of Erg7p-GFP. Occurrence of oxidosqualene cyclase in other organelles including the endoplasmic reticulum is negligible. In an erg7 deletion strain or in wild-type cells treated with an inhibitor of oxidosqualene cyclase, the substrate of Erg7p, oxidosqualene, accumulated mostly in lipid particles. Storage in lipid particles of this intermediate produced in excess may provide a possibility to exclude this membrane-perturbing component from other organelles. Thus, our data provide evidence that lipid particles are not only a depot for neutral lipids, but also participate in coordinate sterol metabolism and trafficking and serve as a storage site for compounds that may negatively affect membrane integrity

Adsorption of CO on a Platinum (111) surface - a study within a four-component relativistic density functional approach

We report on results of a theoretical study of the adsorption process of a single carbon oxide molecule on a Platinum (111) surface. A four-component relativistic density functional method was applied to account for a proper description of the strong relativistic effects. A limited number of atoms in the framework of a cluster approach is used to describe the surface. Different adsorption sites are investigated. We found that CO is preferably adsorbed at the top position.Comment: 23 Pages with 4 figure

Generalized pricing formulas for stochastic volatility jump diffusion models applied to the exponential Vasicek model

Path integral techniques for the pricing of financial options are mostly based on models that can be recast in terms of a Fokker-Planck differential equation and that, consequently, neglect jumps and only describe drift and diffusion. We present a method to adapt formulas for both the path-integral propagators and the option prices themselves, so that jump processes are taken into account in conjunction with the usual drift and diffusion terms. In particular, we focus on stochastic volatility models, such as the exponential Vasicek model, and extend the pricing formulas and propagator of this model to incorporate jump diffusion with a given jump size distribution. This model is of importance to include non-Gaussian fluctuations beyond the Black-Scholes model, and moreover yields a lognormal distribution of the volatilities, in agreement with results from superstatistical analysis. The results obtained in the present formalism are checked with Monte Carlo simulations.Comment: 9 pages, 2 figures, 1 tabl

MRI plaque imaging reveals high-risk carotid plaques especially in diabetic patients irrespective of the degree of stenosis

<p>Abstract</p> <p>Background</p> <p>Plaque imaging based on magnetic resonance imaging (MRI) represents a new modality for risk assessment in atherosclerosis. It allows classification of carotid plaques in high-risk and low-risk lesion types (I-VIII). Type 2 diabetes mellitus (DM 2) represents a known risk factor for atherosclerosis, but its specific influence on plaque vulnerability is not fully understood. This study investigates whether MRI-plaque imaging can reveal differences in carotid plaque features of diabetic patients compared to nondiabetics.</p> <p>Methods</p> <p>191 patients with moderate to high-grade carotid artery stenosis were enrolled after written informed consent was obtained. Each patient underwent MRI-plaque imaging using a 1.5-T scanner with phased-array carotid coils. The carotid plaques were classified as lesion types I-VIII according to the MRI-modified AHA criteria. For 36 patients histology data was available.</p> <p>Results</p> <p>Eleven patients were excluded because of insufficient MR-image quality. DM 2 was diagnosed in 51 patients (28.3%). Concordance between histology and MRI-classification was 91.7% (33/36) and showed a Cohen's kappa value of 0.81 with a 95% CI of 0.98-1.15. MRI-defined high-risk lesion types were overrepresented in diabetic patients (n = 29; 56.8%). Multiple logistic regression analysis revealed association between DM 2 and MRI-defined high-risk lesion types (OR 2.59; 95% CI [1.15-5.81]), independent of the degree of stenosis.</p> <p>Conclusion</p> <p>DM 2 seems to represent a predictor for the development of vulnerable carotid plaques irrespective of the degree of stenosis and other risk factors. MRI-plaque imaging represents a new tool for risk stratification of diabetic patients.</p> <p>See Commentary: <url>http://www.biomedcentral.com/1741-7015/8/78/abstract</url></p