Emerging Themes for the Role of Antibodies in Tuberculosis.

The best way to debunk a scientific dogma is to throw irrefutable evidence at it. This is especially true if the dogma in question has been nurtured over many decades, as is the case with the apparent redundancy of antibodies (Abs) against intracellular pathogens. Although not fully compelling yet, that 'hard core' evidence is nevertheless now slowly beginning to emerge. This is true for several clinically relevant infections but none more so than Mycobacterium tuberculosis, the archetype intracellular pathogen that poses a great health challenge to the mankind. Here, prompted by a spate of recent high-profile reports on the effects of Abs in various experimental models of tuberculosis, we step back and take a critical look at the progress that has been made in the last 5 years and highlight some of the strengths and shortcomings of the presented evidence. We conclude that the tide of the opinion has begun to turn in favour of Abs but we also caution against overinterpreting the currently available limited evidence. For, until definitive evidence that can withstand even the most rigorous of experimental tests is produced, the dogma may yet survive. Or indeed, we may find that the truth is hidden somewhere in between the dogma and the unfulfilled scientific prophecy

Cooperative Carbon Dioxide Adsorption in Alcoholamine- and Alkoxyalkylamine-Functionalized Metal-Organic Frameworks.

A series of structurally diverse alcoholamine- and alkoxyalkylamine-functionalized variants of the metal-organic framework Mg2 (dobpdc) are shown to adsorb CO2 selectively via cooperative chain-forming mechanisms. Solid-state NMR spectra and optimized structures obtained from van der Waals-corrected density functional theory calculations indicate that the adsorption profiles can be attributed to the formation of carbamic acid or ammonium carbamate chains that are stabilized by hydrogen bonding interactions within the framework pores. These findings significantly expand the scope of chemical functionalities that can be utilized to design cooperative CO2 adsorbents, providing further means of optimizing these powerful materials for energy-efficient CO2 separations

Molecular Characterization of Two Monoclonal Antibodies against the Same Epitope on B-Cell Receptor Associated Protein 31

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Signal peptide peptidases and gamma-secretase: Cousins of the same protease family?

Signal peptide peptidase (SPIP) is an unusual aspartyl protease, which mediates clearance of signal peptides by proteolysis within the endoplasmic reticulum (ER). Like presenilins, which provide the proteolytically active subunit of the,gamma-secretase complex, SPP contains a conserved GxGD motif in its C-terminal domain which is critical for its activity. While SPIP is known to be an aspartyl protease of the GxGD type, several presenilin homologues/SPP-like proteins (PSHs/ SPPL) of unknown function have been identified by database searches. In contrast to SPP and SPPL3, which are both restricted to the endoplasmic reticulum, SPPL2b is targeted through the secretory pathway to endosomes/lysosomes. As suggested by the differential subcellular localization of SPPL2b and SPPL3 distinct phenotypes were found upon antisense gripNA-mediated knockdown in zebrafish. spp and sppl3 knockdowns in zebrafish result in cell death within the central nervous system, whereas reduction of sppl2b expression causes erythrocyte accumulation in an enlarged caudal vein. Moreover, expression of D/A mutants of the putative C-terminal active sites of spp, sppl2, and spp13 produced phenocopies of the respective knockdown phenotypes. These data suggest that all investigated PSHs/SPPLs are members of the novel family of GxGD aspartyl proteases. More recently, it was shown that SPPL2b utilizes multiple intramembrane cleavages to liberate the TNF(x intracellular domain into the cytosol and to release the C-terminal counterpart into the lumen. These findings suggest common principles of intramembrane proteolysis by GxGD type aspartyl proteases. In this article,we will review the similarities of SPPs and gamma-secretase based on recent findings by us and others

30 inch Roll-Based Production of High-Quality Graphene Films for Flexible Transparent Electrodes

We report that 30-inch scale multiple roll-to-roll transfer and wet chemical doping considerably enhance the electrical properties of the graphene films grown on roll-type Cu substrates by chemical vapor deposition. The resulting graphene films shows a sheet resistance as low as ~30 Ohm/sq at ~90 % transparency which is superior to commercial transparent electrodes such as indium tin oxides (ITO). The monolayer of graphene shows sheet resistances as low as ~125 Ohm/sq with 97.4% optical transmittance and half-integer quantum Hall effect, indicating the high-quality of these graphene films. As a practical application, we also fabricated a touch screen panel device based on the graphene transparent electrodes, showing extraordinary mechanical and electrical performances

Effects of electron-electron interactions on the electronic Raman scattering of graphite in high magnetic fields

We report the observation of strongly temperature-dependent, asymmetric spectral lines in electronic Raman scattering spectra of graphite in a high magnetic field up to 45 T applied along the c-axis. The magnetic field quantizes the in-plane motion, while the out-of-plane motion remains free, effectively reducing the system dimension from three to one. Optically created electron-hole pairs interact with, or shake up, the one-dimensional Fermi sea in the lowest Landau subbands. Based on the Tomonaga-Luttinger liquid theory, we show that interaction effects modify the van Hove singularity to the form $(\omega-\Delta)^{2\alpha-1/2}$ at zero temperature. At finite temperature, we predict a thermal broadening factor that increases linearly with the temperature. Our model reproduces the observed temperature-dependent line-shape, determining $\alpha$ to be $\sim$0.05 at 40 T

Magnetophonon resonance in graphite: High-field Raman measurements and electron-phonon coupling contributions

We perform Raman scattering experiments on natural graphite in magnetic fields up to 45 T, observing a series of peaks due to interband electronic excitations over a much broader magnetic field range than previously reported. We also explore electron-phonon coupling in graphite via magnetophonon resonances

Measurement of filling-factor-dependent magnetophonon resonances in graphene using Raman spectroscopy.

We perform polarization-resolved Raman spectroscopy on graphene in magnetic fields up to 45 T. This reveals a filling-factor-dependent, multicomponent anticrossing structure of the Raman G peak, resulting from magnetophonon resonances between magnetoexcitons and E(2g) phonons. This is explained with a model of Raman scattering taking into account the effects of spatially inhomogeneous carrier densities and strain. Random fluctuations of strain-induced pseudomagnetic fields lead to increased scattering intensity inside the anticrossing gap, consistent with the experiments

Evaluating an in-home multicomponent cognitive behavioural programme to manage concerns about falls and associated activity avoidance in frail community-dwelling older people: Design of a randomised control trial [NCT01358032]

<p>Abstract</p> <p>Background</p> <p>Concerns about falls are frequently reported by older people. These concerns can have serious consequences such as an increased risk of falls and the subsequent avoidance of activities. Previous studies have shown the effectiveness of a multicomponent group programme to reduce concerns about falls. However, owing to health problems older people may not be able to attend a group programme. Therefore, we adapted the group approach to an individual in-home programme.</p> <p>Methods/Design</p> <p>A two-group randomised controlled trial has been developed to evaluate the in-home multicomponent cognitive behavioural programme to manage concerns about falls and associated activity avoidance in frail older people living in the community. Persons were eligible for study if they were 70 years of age or over, perceived their general health as fair or poor, had at least some concerns about falls and associated avoidance of activity. After screening for eligibility in a random sample of older people, eligible persons received a baseline assessment and were subsequently allocated to the intervention or control group. Persons assigned to the intervention group were invited to participate in the programme, while those assigned to the control group received care as usual. The programme consists of seven sessions, comprising three home visits and four telephone contacts. The sessions are aimed at instilling adaptive and realistic views about falls, as well as increasing activity and safe behaviour. An effect evaluation, a process evaluation and an economic evaluation are conducted. Follow-up measurements for the effect evaluation are carried out 5 and 12 months after the baseline measurement. The primary outcomes of the effect evaluation are concerns about falls and avoidance of activity as a result of these concerns. Other outcomes are disability and falls. The process evaluation measures: the population characteristics reached; protocol adherence by facilitators; protocol adherence by participants (engagement in exposure and homework); opinions about the programme of participants and facilitators; perceived benefits and achievements; and experienced barriers. The economic evaluation examines the impact on health-care utilisation, as well as related costs.</p> <p>Discussion</p> <p>A total number of 389 participants is included in the study. Final results are expected in 2012.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01358032">NCT01358032</a></p