Systematic Functional Analysis of BicD Serine Phosphorylation and Intragenic Suppression of a Female Sterile Allele of BicD

Protein phosphorylation is involved in posttranslational control of essentially all biological processes. Using mass spectrometry, recent analyses of whole phosphoproteomes led to the identification of numerous new phosphorylation sites. However, the function of most of these sites remained unknown. We chose the Drosophila Bicaudal-D protein to estimate the importance of individual phosphorylation events. Being involved in different cellular processes, BicD is required for oocyte determination, for RNA transport during oogenesis and embryogenesis, and for photoreceptor nuclei migration in the developing eye. The numerous roles of BicD and the available evidence for functional importance of BicD phosphorylation led us to identify eight phosphorylation sites of BicD, and we tested a total of 14 identified and suspected phosphoserine residues for their functional importance in vivo in flies. Surprisingly, all these serines turned out to be dispensable for providing sufficient basal BicD activity for normal growth and development. However, in a genetically sensitized background where the BicD(A40V) protein variant provides only partial activity, serine 103 substitutions are not neutral anymore, but show surprising differences. The S103D substitution completely inactivates the protein, whereas S103A behaves neutral, and the S103F substitution, isolated in a genetic screen, restores BicD(A40V) function. Our results suggest that many BicD phosphorylation events may either be fortuitous or play a modulating function as shown for Ser(103). Remarkably, amongst the Drosophila serines we found phosphorylated, Ser(103) is the only one that is fully conserved in mammalian BicD

Antibodies to the Junctional Adhesion Molecule Cause Disruption of Endothelial Cells and Do Not Prevent Leukocyte Influx into the Meninges after Viral or Bacterial Infection

A hallmark of infectious meningitis is the invasion of leukocytes into the subarachnoid space. In experimental meningitis triggered by tumor necrosis factor—α and interleukin-1β, the interaction of leukocytes with endothelial cells and the subsequent migration of the cells through the vessel wall can be inhibited by an antibody to the junctional adhesion molecule (JAM). In contrast to the cytokine-induced meningitis model, anti-JAM antibodies failed to prevent leukocyte influx into the central nervous system after infection of mice with Listeria monocytogenes or lymphocytic choriomeningitis virus. Furthermore, in bacterial meningitis, anti-JAM IgG antibodies, but not Fab fragments, caused disruption of the endothelium. Likewise complement-dependent antibody-mediated cytotoxicity was observed in cultured brain endothelial cells treated with anti-JAM IgG but not with its Fab fragmen

Ultra-deep optical cooling of coupled nuclear spin-spin and quadrupole reservoirs in a GaAs/(Al,Ga)As quantum well

The physics of interacting nuclear spins in solids is well interpreted within the nuclear spin temperature concept. A common approach to cooling the nuclear spin system is adiabatic demagnetization of the initial, optically created, nuclear spin polarization. Here, the selective cooling of 75As spins by optical pumping followed by adiabatic demagnetization in the rotating frame is realized in a nominally undoped GaAs/(Al,Ga)As quantum well. The lowest nuclear spin temperature achieved is 0.54 μK. The rotation of 6 kG strong Overhauser field at the 75As Larmor frequency of 5.5 MHz is evidenced by the dynamic Hanle effect. Despite the presence of the quadrupole induced nuclear spin splitting, it is shown that the rotating 75As magnetization is uniquely determined by the spin temperature of coupled spin-spin and quadrupole reservoirs. The dependence of heat capacity of these reservoirs on the external magnetic field direction with respect to crystal and structure axes is investigated

Systematic Functional Analysis of Bicaudal-D Serine Phosphorylation and Intragenic Suppression of a Female Sterile Allele of BicD

Protein phosphorylation is involved in posttranslational control of essentially all biological processes. Using mass spectrometry, recent analyses of whole phosphoproteomes led to the identification of numerous new phosphorylation sites. However, the function of most of these sites remained unknown. We chose the Drosophila Bicaudal-D protein to estimate the importance of individual phosphorylation events. Being involved in different cellular processes, BicD is required for oocyte determination, for RNA transport during oogenesis and embryogenesis, and for photoreceptor nuclei migration in the developing eye. The numerous roles of BicD and the available evidence for functional importance of BicD phosphorylation led us to identify eight phosphorylation sites of BicD, and we tested a total of 14 identified and suspected phosphoserine residues for their functional importance in vivo in flies. Surprisingly, all these serines turned out to be dispensable for providing sufficient basal BicD activity for normal growth and development. However, in a genetically sensitized background where the BicDA40V protein variant provides only partial activity, serine 103 substitutions are not neutral anymore, but show surprising differences. The S103D substitution completely inactivates the protein, whereas S103A behaves neutral, and the S103F substitution, isolated in a genetic screen, restores BicDA40V function. Our results suggest that many BicD phosphorylation events may either be fortuitous or play a modulating function as shown for Ser103. Remarkably, amongst the Drosophila serines we found phosphorylated, Ser103 is the only one that is fully conserved in mammalian BicD

Micro-strip sensors based on CVD Diamond

In this article we present the performance of recent chemical vapour deposition (CVD) diamond micro-strip sensors in beam tests. In addition we present the first comparison of a CVD diamond micro-strip sensor before and after proton irradiation

Performance of irradiated CVD diamond micro-strip sensors

CVD diamond detectors are of interest for charged particle detection and tracking due to their high radiation tolerance. In this article we present, for the first time, beam test results from recently manufactured CVD diamond strip detectors and their behavior under low doses of electrons from a $\beta$-source and the performance before and after intense ($>10^{15}/{\rm cm^2}$) proton- and pion-irradiations. We find that low dose irradiations increase the signal-to-noise ratio (pumping of the signal) and slightly deteriorate the spatial resolution. Intense irradiations with protons ($2.2\times 10^{15}~p/{\rm cm^2}$) lowers the signal-to-noise ratio slightly. Intense irradiation with pions ($2.9\times 10^{15}~\pi/{\rm cm^2}$) lowers the signal-to-noise ratio more. The spatial resolution of the diamond sensors improves after irradiations