The Impact of TGF-ß, GM-CSF and Antibody Response for Diagnosis as well as Etiopathology of Lyme Disease

In this study the pathogenesis of lyme disease was investigated in vivo by means of the wild-type mouse strains C3H/HeN and FVB/N as well as transgenic mouse strains, which are tissue specific modulated in their TGF-ß or GM-CSF (granulocyte-monocyte colony stimulating factor) activity and sensitivity. The mice were infected intradermally with B. burgdorferi. Progression of lyme disease was monitored using a number of diagnostic tests (recultivation of borrelia from tissue, ELISA, Western blot, histologic analysis). The study confirms the mouse strain FVB/N WT (wild type) to be susceptible to B. burgdorferi infections and that this represents a suitable in vivo model for investigations concerning the progression of a B. burgdorferi infection. We further demonstrate transgenic modification of TGF-ß or GM-CSF activity, and sensitivity in T cells and epithelium respectively, do not affect the pathogenesis of lyme disease. Our data show a positive linear correlation between antibody response and the severity of arthritic processes due to B. burgdorferi infection. Determination of the increase in antibody titer in sera of infected organisms therefore might be a useful tool to predict the progression of inflammatory processes in the course of lyme disease

μ-Bromido-dibromido-μ-hydroxido-bis­[(4S)-2-halo-6-(4-isopropyl-4,5-dihydro­oxazol-2-yl)pyridine]dicopper(II) (halo: Cl/Br = 3:1)

The crystal structure of the title complex, [Cu2Br3(OH)(C11H13Br0.5Cl1.5N2O)2], consists of two (2-halo-6-oxazolin­yl)pyridine·CuBr units bridged by a Br atom and a hydroxide group. The CuII atoms are five-coordinate with an (N,N)BrCu(Br)(OH) distorted tetra­gonal–pyramidal core, and relatively short contacts to the bridging atoms (Cu—μ-OH and Cu—μ-Br). There are two symmetry-independent half-mol­ecules in the asymmetric unit, which differ only in the arrangement of the isopropyl group. The mol­ecules are located on a twofold rotation axes

Susceptibility to collagen-induced arthritis is modulated by TGFβ responsiveness of T cells

The objective of our study was to determine the regulatory effects that endogenous transforming growth factor β (TGFβ) exerts on T cells in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in transgenic mice expressing a dominant negative TGFβ type II receptor in T cells under the control of the human CD2 promoter. Clinical and histological arthritis scores were determined and experiments on disease induction and the healing phase of disease were performed. The proliferation and cytokine production of draining lymph node cells in vitro were analyzed. Transgenic mice were more susceptible to induction of CIA. The overall incidence was higher in transgenic mice than in wild-type mice (57% vs 35%, P < 0.05). Affected transgenic animals displayed a significantly higher clinical (4.5 ± 0.6 vs 1.67 ± 0.19, P = 0.001) and histological arthritis score (8.01 ± 0.9 vs 4.06 ± 1.1, P < 0.05). Draining lymph node cells of transgenic mice secreted more tumor necrosis factor α and IFNγ and proliferated more vigorously in response to collagen type II and upon CD3/CD28 costimulation in vitro. Therefore, the regulation of T cells by endogenous TGFβ is important for the maintenance of joint integrity after arthritis induction. Defects in TGFβ-signalling as a susceptibility factor for rheumatoid arthritis may warrant further investigation

Transgenic Mice for a Tamoxifen-Induced, Conditional Expression of the Cre Recombinase in Osteoclasts

Background: Studies on osteoclasts, the bone resorbing cells, have remained limited due to the lack of transgenic mice allowing the conditional knockout of genes in osteoclasts at any time during development or adulthood. Methodology/Principal Finding: We report here on the generation of transgenic mice which specifically express a tamoxifen-inducible Cre recombinase in osteoclasts. These mice, generated on C57BL/6 and FVB background, express a fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of cathepsin K (CtsK), a gene highly expressed in osteoclasts. We tested the cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ positive adult mice and E17.5 embryos show that Cre activity is restricted largely to bone tissue. In vitro, primary osteoclasts derived from the bone marrow of CtsKCreERT2+/2LacZ+/2 adult mice show a Cre-dependent b-galactosidase activity after tamoxifen stimulation

The Vinculin-ΔIn20/21 Mouse: Characteristics of a Constitutive, Actin-Binding Deficient Splice Variant of Vinculin

BACKGROUND: The cytoskeletal adaptor protein vinculin plays a fundamental role in cell contact regulation and affects central aspects of cell motility, which are essential to both embryonal development and tissue homeostasis. Functional regulation of this evolutionarily conserved and ubiquitously expressed protein is dominated by a high-affinity, autoinhibitory head-to-tail interaction that spatially restricts ligand interactions to cell adhesion sites and, furthermore, limits the residency time of vinculin at these sites. To date, no mutants of the vinculin protein have been characterized in animal models. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigate vinculin-DeltaEx20, a splice variant of the protein lacking the 68 amino acids encoded by exon 20 of the vinculin gene VCL. Vinculin-DeltaEx20 was found to be expressed alongside with wild type protein in a knock-in mouse model with a deletion of introns 20 and 21 (VCL-DeltaIn20/21 allele) and shows defective head-to-tail interaction. Homozygous VCL-DeltaIn20/21 embryos die around embryonal day E12.5 showing cranial neural tube defects and exencephaly. In mouse embryonic fibroblasts and upon ectopic expression, vinculin-DeltaEx20 reveals characteristics of constitutive head binding activity. Interestingly, the impact of vinculin-DeltaEx20 on cell contact induction and stabilization, a hallmark of the vinculin head domain, is only moderate, thus allowing invasion and motility of cells in three-dimensional collagen matrices. Lacking both F-actin interaction sites of the tail, the vinculin-DeltaEx20 variant unveils vinculin's dynamic binding to cell adhesions independent of a cytoskeletal association, and thus differs from head-to-tail binding deficient mutants such as vinculin-T12, in which activated F-actin binding locks the protein variant to cell contact sites. CONCLUSIONS/SIGNIFICANCE: Vinculin-DeltaEx20 is an active variant supporting adhesion site stabilization without an enhanced mechanical coupling. Its presence in a transgenic animal reveals the potential of splice variants in the vinculin gene to alter vinculin function in vivo. Correct control of vinculin is necessary for embryonic development

Tevatron constraints on models of the Higgs boson with exotic spin and parity using decays to bottom-antibottom quark pairs.

Combined constraints from the CDF and D0 Collaborations on models of the Higgs boson with exotic spin J and parity P are presented and compared with results obtained assuming the standard model value JP=0+. Both collaborations analyzed approximately 10  fb−1 of proton-antiproton collisions with a center-of-mass energy of 1.96 TeV collected at the Fermilab Tevatron. Two models predicting exotic Higgs bosons with JP=0− and JP=2+ are tested. The kinematic properties of exotic Higgs boson production in association with a vector boson differ from those predicted for the standard model Higgs boson. Upper limits at the 95% credibility level on the production rates of the exotic Higgs bosons, expressed as fractions of the standard model Higgs boson production rate, are set at 0.36 for both the JP=0− hypothesis and the JP=2+ hypothesis. If the production rate times the branching ratio to a bottom-antibottom pair is the same as that predicted for the standard model Higgs boson, then the exotic bosons are excluded with significances of 5.0 standard deviations and 4.9 standard deviations for the JP=0− and JP=2+ hypotheses, respectively

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

10 Action

Entwicklung eines Kommunikationskonzeptes für den Solar Decathlon Europe 2012, um das Bewusstsein der Öffentlichkeit für die Ziele der EU-Energiepolitik zu schärfen