Glucose Transporter Oligomeric Structure Determines the Mechanism of Glucose Transport: A Dissertation

The relationship between human erythrocyte glucose transporter (GLUT1) oligomeric structure and function was studied. GLUT1 was purified from human erythrocytes in the absence (GLUT1-DTT) or the presence (GLUT1+DTT) of dithiothreitol. Chemical cross-linking studies of lipid bilayer-resident purified GLUT1 and hydrodynamic studies of cholate-solubilized GLUT1 support the view that GLUT1-DTT is a homotetramer and GLUT1+DTT is a homodimer. Parallel studies on human erythrocyte, and studies employing conformation-specific antibodies (anti-GLUT1-DTT antibodies, ∂-IgGs), indicate that erythrocyte-resident GLUT1 resembles GLUT1-DTT (a homotetramer). While the D-glucose binding capacities of GLUT1-DTT and GLUT1+DTT are indistinguishable, GLUT1-DTT presents at least two population of binding sites to D-glucose whereas GLUT1+DTT presents only one population of sugar binding sites. The cytochalasin B (CCB) binding capacity of GLUT1-DTT (0.4 sites/monomer) is one half of that of GLUT1+DTT. GLUT1-DTT and GLUT1+DTT contain 2 and 6 free sulfhydryls per monomer respectively. The subunits (monomers) of tetrameric and dimeric GLUT1 are not linked by disulfide bridges. Erythrocyte resident GLUT1 presents at least two binding sites to D-glucose and binds CCB with a molar stoichiometry of 0.55 sites per GLUT1 monomer. Following treatment with high pH plus dithiothreitol, the sugar binding capacity of erythrocyte membrane resident transporter is unaltered but the transporter now presents only one population of binding sites to D-glucose, binds CCB with molar stoichiometry of 1.3 sites per GLUT1 monomer and displays significantly reduced affinity for ∂-IgGs. These findings demonstrate that erythrocyte resident glucose transporter is GLUT1-DTT (a GLUT1 tetramer) and that GLUT1 oligomeric structure determines GLUT1 functional properties. A model which rationalizes these findings is proposed

Quantum Monte Carlo Study of an Interaction-Driven Band Insulator to Metal Transition

We study the transitions from band insulator to metal to Mott insulator in the ionic Hubbard model on a two dimensional square lattice using determinant Quantum Monte Carlo. Evaluation of the temperature dependence of the conductivity demonstrates that the metallic region extends for a finite range of interaction values. The Mott phase at strong coupling is accompanied by antiferromagnetic (AF) order. Inclusion of these intersite correlations changes the phase diagram qualitatively compared to dynamical mean field theory.Comment: 4 pages, 6 figure

Patents and Antitrust: Application to Adjacent Markets

We examine the intersection of patents and antitrust where a patent holder uses the monopoly power it possesses in the market for a patented product to exclude competitors in an adjacent market and attempt to monopolize or monopolize the adjacent market. The present scheme for awarding patents cannot judge when the issuance of a patent will lead to the appropriate balance between innovation and economic efficiency. Where a patent holder’s invention uses an interface with adjacent products, the patent holder may be tempted to extend its patent monopoly into adjacent markets that depend upon the interface with the patented invention. Economic theory suggests that it is inappropriate to immunize a patent holder from antitrust liability when it attempts to extend its patent monopoly into adjacent markets because it could decrease consumer surplus. Courts have expressed their reluctance to scrutinize a patent holder’s innovations and design changes because of the potential benefits of the innovations and their reluctance to second-guess the marketplace. However, applying traditional antitrust principles, courts have found that monopolists could be liable for unlawfully extending their monopoly positions into adjacent markets in the areas of computer peripherals and software applications; aftermarkets for replacement parts, service and maintenance of durable goods; design changes to medical devices; and changes in drug formulas. While the patent laws provide a spur to innovation by granting limited monopoly rights, the antitrust laws curb the excessive reach of these monopoly rights by acting as a check on excessive expansion of the scope of the patent grant. Courts are the only participants in the legal process that have the competence to ensure that patents do not cause economic stagnation and harm by permitting a patent holder to extend its monopoly into an adjacent market. Consequently, courts should be willing to apply antitrust principles to cases involving the monopolization of interfaces through design changes

DNA barcode-based delineation of putative species : efficient start for taxonomic workflows

The analysis of DNA barcode sequences with varying techniques for cluster recognition provides an efficient approach for recognizing putative species (operational taxonomic units, OTUs). This approach accelerates and improves taxonomic workflows by exposing cryptic species and decreasing the risk of synonymy. This study tested the congruence of OTUs resulting from the application of three analytical methods (ABGD, BIN, GMYC) to sequence data for Australian hypertrophine moths. OTUs supported by all three approaches were viewed as robust, but 20% of the OTUs were only recognized by one or two of the methods. These OTUs were examined for three criteria to clarify their status. Monophyly and diagnostic nucleotides were both uninformative, but information on ranges was useful as sympatric sister OTUs were viewed as distinct, while allopatric OTUs were merged. This approach revealed 124 OTUs of Hypertrophinae, a more than twofold increase from the currently recognized 51 species. Because this analytical protocol is both fast and repeatable, it provides a valuable tool for establishing a basic understanding of species boundaries that can be validated with subsequent studies.Peer reviewe

On the relevance of large scale pulsed-laser deposition: Evidence of structural heterogeneities in ZnO thin films

Pulsed-laser deposition is known as a well-suited method for growing thin films of oxide compounds presenting a wide range of functional properties. A limitation of this method for industrial process is the very anisotropic expansion dynamics of the plasma plume, which induces difficulties to grow on large scale films with homogeneous thickness and composition. The specific aspect of the crystalline or orientation uniformity has not been investigated, despite its important role on oxide films properties. In this work, the crystalline parameters and the texture of zinc oxide films are studied as a function of position with respect to the central axis of the plasma plume. We demonstrate the existence of large non-uniformities in the films. The stoichiometry, the lattice parameter, and the distribution of crystallites orientations drastically depend on the position with respect to the plume axis, i.e., on the oblique incidence of the ablated species. The origin of these non-uniformities, in particular, the unexpected tilted orientation of the ZnO c-axis may be attributed to the combined effects of the oblique incidence and of the ratio between oxygen and zinc fluxes reaching the surface of the growing film

Protein Translocons Multifunctional Mediators of Protein Translocation across Membranes

AbstractProtein translocation systems consist of complex molecular machines whose activities are not limited to unidirectional protein targeting. Protein translocons and their associated receptor systems can be viewed as dynamic modular units whose interactions, and therefore functions, are regulated in response to specific signals. This flexibility allows translocons to interact with multiple signal receptor systems to manage the targeting of topologically distinct classes of proteins, to mediate targeting to different suborganellar compartments, and to respond to stress and developmental cues. Furthermore, the activities of translocons are tightly coordinated with downstream events, thereby providing a direct link between targeting and protein maturation

Organized sport participation is associated with higher levels of overall health-related physical activity in children (CHAMPS Study-DK)

Introduction Many children fail to meet international guideline recommendations for health-related activity (≥60 minutes/day of moderate-to-vigorous physical activity [MVPA]), and intervention studies to date have reported negligible effects. Objective Explore the associations of organized leisure-time sport participation with overall physical activity levels and health-related physical activity guideline concordance. Methods This prospective cohort study was nested in the Childhood Health, Activity, and Motor Performance School Study Denmark. Study participants were a representative sample of 1124 primary school students. Organized leisure-time sport participation was reported via text messaging and physical activity was objectively measured over seven days with accelerometry. Associations between sport participation and physical activity level were explored with multilevel mixed-effects regression models and reported with beta coefficients (b) and adjusted odds ratios (aOR). Results Participants were 53% female, with mean(SD) age = 8.4(1.4) years. Boys were more active than girls (p<0.001), and physical activity levels and guideline concordance decreased with age (p<0.001). Soccer participation at any frequency was associated with greater overall MVPA (b[95% CI] = 0.66[0.20,1.13] to 2.44[1.44,3.44]). Depending on participation frequency, this equates to 5–20 minutes more MVPA on the average day and 3 to 15 fold increased odds of achieving recommended levels of health-related physical activity (aOR[95%CI] = 3.04[1.49,6.19] to 14.49[1.97,106.56]). Similar associations were identified among children playing handball at least twice per week. Relationships with other sports (gymnastics, basketball, volleyball) were inconsistent. Conclusions Many children, particularly girls and those in higher grade levels do not adhere to health-related physical activity recommendations. Organized leisure-time sport participation may be a viable strategy to increase overall health-related physical activity levels and international guideline concordance in children

Local ocean response to a multiphase westerly wind burst: 1. Dynamic response

The dynamic response to a westerly wind burst which occurred during the Coupled Ocean Atmosphere Response Experiment in the warm pool of the equatorial Pacific Ocean is described using velocity, hydrography, and microstructure measurements. Turbulent fluxes distributed momentum input from the wind over a near‐surface layer of variable thickness. Coriolis and pressure gradient terms combined to induce a wavelike response whose frequency was close to the local inertial frequency. Wind stress variations on near‐inertial timescales interfered both constructively and destructively with the wave response, exerting considerable influence on the observed currents

Changes in copepod distributions associated with increased turbulence from wind stress

Vertical profiles of turbulent kinetic energy dissipation rate (ε), current velocity, temperature, salinity, chlorophyll fluorescence, and copepods were sampled for 4 d at an anchor station on the southern flank of Georges Bank when the water column was stratified in early June 1995. Copepodite stages of Temora spp., Oithona spp., Pseudocalanus spp., and Calanus finmarchicus, and all of their naupliar stages except for Temora spp., were found deeper in the water column when turbulent dissipation rates in the surface mixed layer increased in response to increasing wind stress. Taxa that initially occurred at the bottom of the surface mixed layer at 10 to 15 m depth ( ε ¾ 10-8 W kg-1) before the wind event were located in the pycnocline at 20 to 25 m depth when dissipation rates at 10 m increased up to 10-6 W kg-1. Dissipation rates in the pycnocline were similar to those experienced at shallower depths before the wind event. After passage of the wind event and with relaxation of dissipation rates in the surface layer, all stages returned to prior depths above the pycnocline. Temora spp. nauplii did not change depth during this period. Our results indicate that turbulence from a moderate wind event can influence the vertical distribution of copepods in the surface mixed layer. Changes in the vertical distribution of copepods can impact trophic interactions, and movements related to turbulence would affect the application of turbulence theory to encounter and feeding rates