242 research outputs found
Recombinant Antibody Fusion Proteins for Depletion of Autoreactive B Lymphocytes
For most autoimmune diseases known, treatment options are very limited. In fact, there is not a single autoimmune indication where a disease-specific treatment regimen has been described. It was the aim of this work to investigate novel strategies for specific depletion of autoreactive B cells as the root cause of many autoimmune diseases.
Taken together, this work shows that single-chain fusion proteins can be engineered to target B cells specific for the autoantigen MOG for depletion via immune-effector mechanisms. This was achieved by coupling the MOG extracellular domain to a C-terminally attached effector domain consisting of either an Fc part of human IgG1 or a single-chain variable domain (scFv) directed against CD3e. These proteins induced the efficient depletion of MOG-specific B cells in vitro, ex vivo and in vivo, and thus represent a novel approach for recombinant proteins targeting autoreactive B cells in antibody-mediated autoimmunity. Due to the exacerbating potential of the autoantigen fragment, their use as a therapeutic option in autoimmune conditions requires further development.For most autoimmune diseases known, treatment options are very limited. In fact, there is not a single autoimmune indication where a disease-specific treatment regimen has been described. It was the aim of this work to investigate novel strategies for specific depletion of autoreactive B cells as the root cause of many autoimmune diseases.
Taken together, this work shows that single-chain fusion proteins can be engineered to target B cells specific for the autoantigen MOG for depletion via immune-effector mechanisms. This was achieved by coupling the MOG extracellular domain to a C-terminally attached effector domain consisting of either an Fc part of human IgG1 or a single-chain variable domain (scFv) directed against CD3e. These proteins induced the efficient depletion of MOG-specific B cells in vitro, ex vivo and in vivo, and thus represent a novel approach for recombinant proteins targeting autoreactive B cells in antibody-mediated autoimmunity. Due to the exacerbating potential of the autoantigen fragment, their use as a therapeutic option in autoimmune conditions requires further development
Performance, digestive disorders and the intestinal microbiota in weaning rabbits are affected by a herbal feed additive
[EN] A herbal feed additive (Digestarom(R), containing a mixture of onion, garlic, caraway, fennel, gentian, melissa, peppermint, anise, oak bark and clove) was fed to rabbit does and kits to study its impact on performance, post-weaning digestive disorders and intestinal microbiota. Two groups of 9 doe rabbits and their offspring, after weaning, were fed a standard diet without or with the addition of 300 mg Digestarom(R)/kg diet. Forty kits from each group were weaned at 28 d of age weighing 0.614±0.005 kg. They were caged in groups of four rabbits (10 cages/treatment) and fed the same diet as their mothers for 13 d. Weight gain and feed intake of the kits fed Digestarom(R) was 18 and 14% higher, respectively, than those fed control diet (P<0.001), with no differences in the feed conversion. Rabbits were killed 13 d after weaning and 10 healthy animals from the Digestarom(R) group and 10 healthy and 10 diseased animals from the control group were dissected. Healthy rabbits fed control diet and those fed Digestarom(R) showed closer intestinal digesta dry matter, pH and volatile fatty acid (VFA) profi les, compared to diseased animals. VFA concentration in the small intestine was higher (P=0.030) in the diseased animals of the control group compared with the healthy and Digestarom(R) fed rabbits. However, no differences were observed in VFA concentration in stomach or caecum contents. The fermentation profi le of diseased animals was characterised by a higher proportion of propionic, i- and n-valeric acids in the caecal contents (P<0.001), and an increased i-butyric acid concentration in the stomach and caecum contents (P=0.014), whereas n-butyric acid was reduced (P<0.033) compared with the healthy or Digestarom(R) fed rabbits. Denaturing gradient gel electrophoresis indicated a higher caecal bacterial diversity in the control rabbits compared with kits fed Digestarom(R) (P=0.008). The reduced evenness factor (P<0.010) also indicated that the bacterial composition included more dominant species in the Digestarom(R) group. Under our experimental conditions, the tested herbal feed additive Digestarom(R) had protective effects in rabbit kits after weaning, making it an interesting alternative for establishing nutritional strategies.Krieg, R.; Vahjen, W.; Awad, W.; Sysel, M.; Kroeger, S.; Zocher, E.; Hulan, H.... (2009). Performance, digestive disorders and the intestinal microbiota in weaning rabbits are affected by a herbal feed additive. World Rabbit Science. 17(2):87-95. doi:10.4995/wrs.2009.662879517
De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis
Adult neurogenesis enables the life-long addition of functional neurons to the hippocampus and is regulated by both cell-intrinsic molecular programs and behavioral activity. De novo DNA methylation is crucial for embryonic brain development, but its role during adult hippocampal neurogenesis has remained unknown. Here, we show that de novo DNA methylation is critical for maturation and functional integration of adult-born neurons in the mouse hippocampus. Bisulfite sequencing revealed that de novo DNA methyltransferases target neuronal enhancers and gene bodies during adult hippocampal neural stem cell differentiation, to establish neuronal methylomes and facilitate transcriptional up-regulation of neuronal genes. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells did not affect proliferation or fate specification, but specifically impaired dendritic outgrowth and synaptogenesis of newborn neurons, thereby hampering their functional maturation. Consequently, abolishing de novo DNA methylation modulated activation patterns in the hippocampal circuitry and caused specific deficits in hippocampus-dependent learning and memory. Our results demonstrate that proper establishment of neuronal methylomes during adult neurogenesis is fundamental for hippocampal function
Parity Breaking in Nematic Tactoids
We theoretically investigate under what conditions the director field in a
spindle-shaped nematic droplet or tactoid obtains a twisted, parity-broken
structure. By minimizing the sum of the bulk elastic and surface energies, we
show that a twisted director field is stable if the twist and bend elastic
constants are small enough compared to the splay elastic constant, but only if
the droplet volume is larger than some minimum value. We furthermore show that
the transition from an untwisted to a twisted director-field structure is a
sharp function of the various control parameters. We predict that suspensions
of rigid, rod-like particles cannot support droplets with a parity broken
structure, whereas they could possibly occur in those of semi-flexible,
worm-like particles.Comment: 20 pages, 9 figures, submitted to Journal of Physics: Condensed
Matte
Spin-Rotation Symmetry Breaking in the Superconducting State of CuxBi2Se3
Spontaneous symmetry breaking is an important concept for understanding
physics ranging from the elementary particles to states of matter. For example,
the superconducting state breaks global gauge symmetry, and unconventional
superconductors can break additional symmetries. In particular, spin rotational
symmetry is expected to be broken in spin-triplet superconductors. However,
experimental evidence for such symmetry breaking has not been conclusively
obtained so far in any candidate compounds. Here, by 77Se nuclear magnetic
resonance measurements, we show that spin rotation symmetry is spontaneously
broken in the hexagonal plane of the electron-doped topological insulator
Cu0.3Bi2Se3 below the superconducting transition temperature Tc=3.4 K. Our
results not only establish spin-triplet superconductivity in this compound, but
may also serve to lay a foundation for the research of topological
superconductivity
Facilities for macromolecular crystallography at the Helmholtz Zentrum Berlin
Three macromolecular crystallography MX beamlines at the Helmholtz Zentrum Berlin HZB are available for the regional, national and international structural biology user community. The state of the art synchrotron beamlines for MX BL14.1, BL14.2 and BL14.3 are located within the low section of the BESSY II electron storage ring. All beamlines are fed from a superconducting 7 T wavelength shifter insertion device. BL14.1 and BL14.2 are energy tunable in the range 5 16 keV, while BL14.3 is a fixed energy side station operated at 13.8 keV. All three beamlines are equipped with CCD detectors. BL14.1 and BL14.2 are in regular user operation providing about 200 beam days per year and about 600 user shifts to approximately 50 research groups across Europe. BL14.3 has initially been used as a test facility and was brought into regular user mode operation during the year 2010. BL14.1 has recently been upgraded with a microdiffractometer including a mini k goniometer and an automated sample changer. Additional user facilities include office space adjacent to the beamlines, a sample preparation laboratory, a biology laboratory safety level 1 and high end computing resources. In this article the instrumentation of the beamlines is described, and a summary of the experimental possibilities of the beamlines and the provided ancillary equipment for the user community is give
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