Increased Metabolic Rate in X-linked Hypophosphatemic Mice

Hyp mice are a model for human X-linked hypophosphatemia, the most common form of vitamin D-resistant rickets. It has previously been observed that Hyp mice have a greater food consumption per gram body weight than do normal mice. This led to the search for some alteration in metabolism in Hyp mice. We found that oxygen consumption was significantly higher in Hyp mice than in normal C57BL/6J mice and this was accompanied by an increased percentage of cardiac output being delivered to organs of heat production (liver and skeletal muscle), to the skin, and to bone and a decreased percentage to the gastrointestinal tract of Hyp mice. The increased oxygen consumption in Hyp mice was not associated with increased plasma free T4 levels and was not affected by alterations in plasma phosphate produced by a low phosphate diet. The cause of the increased oxygen consumption is not known, and the role that this change and reported changes in distribution of cardiac output may play in the development of X-linked hypophosphatemia is also unknown. Study of the cardiovascular and thermoregulatory systems in Hyp mice should help increase understanding of the underlying mechanisms of this disease

Interpreting two-photon imaging data of lymphocyte motility

Recently, using two-photon imaging it has been found that the movement of B and T cells in lymph nodes can be described by a random walk with persistence of orientation in the range of 2 minutes. We interpret this new class of lymphocyte motility data within a theoretical model. The model considers cell movement to be composed of the movement of subunits of the cell membrane. In this way movement and deformation of the cell are correlated to each other. We find that, indeed, the lymphocyte movement in lymph nodes can best be described as a random walk with persistence of orientation. The assumption of motility induced cell elongation is consistent with the data. Within the framework of our model the two-photon data suggest that T and B cells are in a single velocity state with large stochastic width. The alternative of three different velocity states with frequent changes of their state and small stochastic width is less likely. Two velocity states can be excluded

Cutting edge: back to "one-way" germinal centers

The present status of germinal center (GC) research is revisited using in silico simulations based on recent lymphocyte motility data in mice. The generally adopted view of several rounds of somatic hypermutations and positive selection is analyzed with special emphasis on the spatial organization of the GC reaction. We claim that the development of dark zones is not necessary for successful GC reactions to develop. We find that a recirculation of positively selected centrocytes to the dark zone is rather unlikely. Instead we propose a scenario that combines a multiple-step mutation and selection concept with a "one-way" GC in the sense of cell migration

An analysis of B cell selection mechanisms in germinal centres

Affinity maturation of antibodies during immune responses is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for the antigen. The mechanism underlying B cell selection has not yet been defined. By employing an agent-based model, we show that for physiologically reasonable parameter values affinity maturation can be driven by competition for neither binding sites nor antigen—even in the presence of competing secreted antibodies. Within the tested mechanisms, only clonal competition for T cell help or a refractory time for the interaction of centrocytes with follicular dendritic cells is found to enable affinity maturation while generating the experimentally observed germinal centre characteristics and tolerating large variations in the initial antigen density

Analysis of B cell selection mechanisms in the adaptive immune response

The essential task of a germinal centre reaction is the selection of those B cells that bind the antigen with high affinity. The exact mechanisms of B cell selection is still unknown and rather difficult to be accessed in experiment. With the help of an already established agent-based model for the space-time-dynamics of germinal centre reactions [1,2] we compare the most important hypotheses for what the limiting factor for B cell rescue may be. We discuss competition for antigen sites on follicular dendritic cells, a refractory time for centrocytes after every encounter with follicular dendritic cells, competition for the antigen itself, the role of antigen masking with soluble antibodies, and competition for T cell help. The unexpected result is that neither competition for interaction sites nor competition for antigen nor antigen masking are in agreement with present experimental data on germinal centre reactions. We show that these most popular selection mechanisms do not lead to sufficient affinity maturation and do not respect the observed robustness against changes of initial conditions. However, the best agreement with data was found for the newly hypothesized centrocyte refractory time and for competition for T cell help. Thus the in silico experiments point towards selection mechanisms that are not in the main focus of current germinal centre research. Possible experiments to test these hypotheses are proposed

Electron-hole pairs during the adsorption dynamics of O2 on Pd(100) - Exciting or not?

During the exothermic adsorption of molecules at solid surfaces dissipation of the released energy occurs via the excitation of electronic and phononic degrees of freedom. For metallic substrates the role of the nonadiabatic electronic excitation channel has been controversially discussed, as the absence of a band gap could favour an easy coupling to a manifold of electronhole pairs of arbitrarily low energies. We analyse this situation for the highly exothermic showcase system of molecular oxygen dissociating at Pd(100), using time-dependent perturbation theory applied to first-principles electronic-structure calculations. For a range of different trajectories of impinging O2 molecules we compute largely varying electron-hole pair spectra, which underlines the necessity to consider the high-dimensionality of the surface dynamical process when assessing the total energy loss into this dissipation channel. Despite the high Pd density of states at the Fermi level, the concomitant non-adiabatic energy losses nevertheless never exceed about 5% of the available chemisorption energy. While this supports an electronically adiabatic description of the predominant heat dissipation into the phononic system, we critically discuss the non-adiabatic excitations in the context of the O2 spin transition during the dissociation process.Comment: 20 pages including 7 figures; related publications can be found at http://www.fhi-berlin.mpg.de/th/th.html [added two references, changed V_{fsa} to V_{6D}, modified a few formulations in interpretation of spin asymmetry of eh-spectra, added missing equals sign in Eg.(2.10)

Coupling of non-crossing wave modes in a two-dimensional plasma crystal

We report an experimental observation of coupling of the transverse vertical and longitudinal in-plane dust-lattice wave modes in a two-dimensional complex plasma crystal in the absence of mode crossing. A new large diameter rf plasma chamber was used to suspend the plasma crystal. The observations are confirmed with molecular-dynamics simulations. The coupling manifests itself in traces of the transverse vertical mode appearing in the measured longitudinal spectra and vice versa. We calculate the expected ratio of the trace to the principal mode with a theoretical analysis of the modes in a crystal with finite temperature and find good agreement with the experiment and simulations.Comment: 4 figures, 5 pages, accepted for publication in PRL Nov 201

Depletion of molecular gas by an accretion outburst in a protoplanetary disk

We investigate new and archival 3-5 $\mu$m high resolution ($\sim3$ km s$^{-1}$) spectroscopy of molecular gas in the inner disk of the young solar-mass star EX Lupi, taken during and after the strong accretion outburst of 2008. The data were obtained using the CRIRES spectrometer at the ESO Very Large Telescope in 2008 and 2014. In 2008, emission lines from CO, H$_{2}$O, and OH were detected with broad profiles tracing gas near and within the corotation radius (0.02-0.3 AU). In 2014, the spectra display marked differences. The CO lines, while still detected, are much weaker, and the H$_{2}$O and OH lines have disappeared altogether. At 3 $\mu$m a veiled stellar photospheric spectrum is observed. Our analysis finds that the molecular gas mass in the inner disk has decreased by an order of magnitude since the outburst, matching a similar decrease in the accretion rate onto the star. We discuss these findings in the context of a rapid depletion of material accumulated beyond the disk corotation radius during quiescent periods, as proposed by models of episodic accretion in EXor type young stars.Comment: 6 pages, 4 figures, 1 table, accepted for publication in the Astrophysical Journal Letter