Small substrate, big surprise: fold, function and phylogeny of dihydroxyacetone kinases

Abstract.: Dihydroxyacetone (Dha) kinases are a family of sequence-conserved enzymes which utilize either ATP (in animals, plants and eubacteria) or phosphoenolpyruvate (PEP, in eubacteria) as their source of high-energy phosphate. The kinases consist of two domains/subunits: DhaK, which binds Dha covalently in hemiaminal linkage to the Nε2 of a histidine, and DhaL, an eight-helix barrel that contains the nucleotide-binding site. The PEP-dependent kinases comprise a third subunit, DhaM, which rephosphorylates in situ the firmly bound ADP cofactor. DhaM serves as the shuttle for the transfer of phosphate from the bacterial PEP: carbohydrate phosphotransferase system (PTS) to the Dha kinase. The DhaL and DhaK subunits of the PEP-dependent Escherichia coli kinase act as coactivator and corepressor of DhaR, a transcription factor from the AAA+ family of enhancerbinding proteins. In Gram-positive bacteria genes for homologs of DhaK and DhaL occur in operons for putative transcription factors of the TetR and DeoR families. Proteins with the Dha kinase fold can be classified into three families according to phylogeny and function: Dha kinases, DhaK and DhaL homologs (paralogs) associated with putative transcription regulators of the TetR and DeoR families, and proteins with a circularly permuted domain order that belong to the DegV famil

Cure of Chronic Viral Infection and Virus-Induced Type 1 Diabetes by Neutralizing Antibodies

The use of neutralizing antibodies is one of the most successful methods to interfere with receptor–ligand interactions in vivo. In particular blockade of soluble inflammatory mediators or their corresponding cellular receptors was proven an effective way to regulate inflammation and/or prevent its negative consequences. However, one problem that comes along with an effective neutralization of inflammatory mediators is the general systemic immunomodulatory effect. It is, therefore, important to design a treatment regimen in a way to strike at the right place and at the right time in order to achieve maximal effects with minimal duration of immunosuppression or hyperactivation. In this review, we reflect on two examples of how short time administration of such neutralizing antibodies can block two distinct inflammatory consequences of viral infection. First, we review recent findings that blockade of IL-10/IL-10R interaction can resolve chronic viral infection and second, we reflect on how neutralization of the chemokine CXCL10 can abrogate virus-induced type 1 diabetes

Pulsed positive discharges in air at moderate pressures near a dielectric rod

We study pulsed positive discharges in air in a cylindrically symmetric setup with an electrode needle close (about 1 mm) above the top of a dielectric cylindrical rod of 4 mm in diameter mounted at its bottom on a grounded plate electrode. We present ICCD (intensified charge-coupled device) pictures and evaluations of experiments as well as simulations with a fluid discharge model; the simulations use cylindrical symmetry. In the experiments, there is an initial inception cloud phase, where the cylindrical symmetry is maintained, and later a streamer phase, where it is broken spontaneously. At 75-150 mbar, discharges with cylindrical symmetry are not attracted to the dielectric rod, but move away from it. The dielectric rod plays the sole role of an obstacle that shades (in the context of photoionization) a cone-shaped part of the inception cloud; the cone size is determined by the geometry of the setup. The material properties of the dielectric rod, such as its dielectric permittivity and the efficiency of the photon induced secondary electron emission do not have a noticeable effect. This is due to the abundance of photoionization in air, which supplies a positive discharge with free electrons and allows it to propagate along the electric field lines. Using some simple field calculations, w

Magnetic Field Saturation in the Riga Dynamo Experiment

After the dynamo experiment in November 1999 had shown magnetic field self-excitation in a spiraling liquid metal flow, in a second series of experiments emphasis was placed on the magnetic field saturation regime as the next principal step in the dynamo process. The dependence of the strength of the magnetic field on the rotation rate is studied. Various features of the saturated magnetic field are outlined and possible saturation mechanisms are discussed.Comment: 4 pages, 8 figure

Temperature Dependence of the Flux Line Lattice Transition into Square Symmetry in Superconducting LuNi2_2B2_2C

We have investigated the temperature dependence of the H || c flux line lattice structural phase transition from square to hexagonal symmetry, in the tetragonal superconductor LuNi_2B_2C (T_c = 16.6 K). At temperatures below 10 K the transition onset field, H_2(T), is only weakly temperature dependent. Above 10 K, H_2(T) rises sharply, bending away from the upper critical field. This contradicts theoretical predictions of H_2(T) merging with the upper critical field, and suggests that just below the H_c2(T)-curve the flux line lattice might be hexagonal.Comment: 4 pages, 3 figure

Can trans-generational experiments be used to enhance species resilience to ocean warming and acidification?

Human-assisted, trans-generational exposure to ocean warming and acidification has been proposed as a conservation and/or restoration tool to produce resilient offspring. To improve our understanding of the need for and the efficacy of this approach, we characterized life-history and physiological responses in offspring of the marine polychaete Ophryotrocha labronica exposed to predicted ocean warming (OW: + 3 degrees C), ocean acidification (OA: pH -0.5) and their combination (OWA: + 3 degrees C, pH -0.5), following the exposure of their parents to either control conditions (within-generational exposure) or the same conditions (trans-generational exposure). Trans-generational exposure to OW fully alleviated the negative effects of within-generational exposure to OW on fecundity and egg volume and was accompanied by increased metabolic activity. While within-generational exposure to OA reduced juvenile growth rates and egg volume, trans-generational exposure alleviated the former but could not restore the latter. Surprisingly, exposure to OWA had no negative impacts within-or trans-generationally. Our results highlight the potential for trans-generational laboratory experiments in producing offspring that are resilient to OW and OA. However, trans-generational exposure does not always appear to improve traits and therefore may not be a universally useful tool for all species in the face of global change

Combining the bulk transfer formulation and surface renewal analysis for estimating the sensible heat flux without involving the parameter KB-1

The single‐source bulk transfer formulation (based on the Monin‐Obukhov Similarity Theory, MOST) has been used to estimate the sensible heat flux, H, in the framework of remote sensing over homogeneous surfaces (HMOST). The latter involves the canopy parameter, , which is difficult to parameterize. Over short and dense grass at a site influenced by regional advection of sensible heat flux, HMOST with  = 2 (i.e., the value recommended) correlated strongly with the H measured using the Eddy Covariance, EC, method, HEC. However, it overestimated HEC by 50% under stable conditions for samples showing a local air temperature gradient larger than the measurement error, 0.4 km−1. Combining MOST and Surface Renewal analysis, three methods of estimating H that avoid dependency have been derived. These new expressions explain the variability of H versus , where is the friction velocity, is the radiometric surface temperature, and is the air temperature at height, z. At two measurement heights, the three methods performed excellently. One of the methods developed required the same readily/commonly available inputs as HMOST due to the fact that the ratio between and the ramp amplitude was found fairly constant under stable and unstable cases. Over homogeneous canopies, at a site influenced by regional advection of sensible heat flux, the methods proposed are an alternative to the traditional bulk transfer method because they are reliable, exempt of calibration against the EC method, and are comparable or identical in cost of application. It is suggested that the methodology may be useful over bare soil and sparse vegetation.This research was funded by CERESS project AGL2011–30498 (Ministerio de Economía y Competitividad of Spain, cofunded FEDER), CGL2012–37416‐C04‐01 (Ministerio de Ciencia y Innovación of Spain), and CEI Iberus, 2014 (Proyecto financiado por el Ministerio de Educación en el marco del Programa Campus de Excelencia Internacional of Spain)

Functional performance of mobile versus fixed bearing total knee prostheses: a randomised controlled trial

PURPOSE: The primary goal of this study was to assess the difference in active flexion between patients with a mobile versus a fixed bearing, cruciate retaining, and total knee arthroplasty. The study was designed as a randomised controlled multi-centre trial. METHODS: Participants were assigned to interventions by using block-stratified, random allocation. Outcome parameters were active flexion, passive flexion, and Knee Society Score (KSS). Outcome parameters were assessed preoperatively and at 3, 6, and 12 months postoperatively by an independent nurse. RESULTS: Ninety-two patients from one centre were included, 46 in each group. Active flexion was comparable for the two groups, 99.9° for the mobile bearing group and 101° for the fixed bearing group with a baseline controlled difference of 1.0 (95% CI −3.9 to 5.8, n.s.). The Clinical KSS was comparable between the two bearing groups (Mobile 90.0 vs. fixed 92.4, n.s.). The functional KSS showed a difference that was attributable to the stair climbing subscore, which showed a difference in favour of the fixed bearing design between preoperative and 3 months (7.3 point difference; 95% CI 2.3–12.5; P = 0.005) as well as 12 months (4.8 point difference; 95% CI 0.1–9.6; P = 0.045). CONCLUSIONS: There were no short-term differences in active flexion between fixed bearing and mobile bearing total knee arthroplasty. LEVEL OF EVIDENCE: I