Mechanisms of neisserial serum resistance

Pathogenic Neisseria use a variety of mechanisms to survive the bactericidal action of the complement system. Serum resistance is a crucial virulence factor for the development of severe meningococcal disease, meningococcal meningitis and disseminated gonococcal infection. Furthermore, local inflammation at the site of gonococcal infection exposes the bacteria to moderate concentrations of complement factors. We review current concepts of neisserial serum resistance with emphasis on porins and polysaccharides exposed on the neisserial surface and their interaction with components of normal human serum.     

Biochemical and cytogenetic studies on the Nucleolus Organizing Regions (NOR) of Man

Summary The hybridization kinetics of DNA with labeled (18s+28s)rRNA from HeLa cells was determined in patients with trisomy 21, healthy probands with normal karyotype and in carriers of a t(DqGq) centric fusion. The results are in, accordance with the saturation values obtained earlier for these probands:Three patients with trisomy 21 showed an increased saturation level. In 2 of these patients the excess of rDNA exceeded the expected value considerably.Three of the investigated translocation carriers t(14q21q) showed significantly reduced saturation values, while results of a fourth proband with a dicentric chromosome t(15q21q) were found to be within the range of normal probands.The heterogeneous results were correlated with the cytogenetic characteristics of the acrocentric chromosomes. It is expected that these differences could be explained on the basis of family analysis.

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Zusammenfassung Hybridisierungskinetiken der DNA mit markierter (18s+28s)rRNA aus HeLa-Zellen wurden ermittelt bei Patienten mit Trisomie 21, gesunden Probanden mit normalem Karyotyp und Trägern einer zentrischen Fusion t(DqGq). Die Ergebnisse bestätigen die bereits früher ermittelten Sättigungswerte von Hybridisierungen bei diesen Probanden:3 Patienten mit Trisomie 21 zeigten erhöhte Sättigungsniveaus. Bei 2 dieser Patienten übersteigt der Überschuß an rDNA den Erwartungswert erheblich.3 der untersuchten Translokationsträger t(14q21q) hatten signifikant erniedrigte Sättigungswerte, während die vierte Probandin mit dem dizentrischen Chromosom t(15q21q) im Normbereich lag.Die unterschiedlichen Befunde werden mit den cytogenetischen Eigenschaften der akrozentrischen Chromosomen in Zusammenhang gebracht. Es wird erwartet, daß diese Unterschiede sich durch Familienuntersuchungen aufklären lassen.

     

Can Newts Cope with the Heat? Disparate Thermoregulatory Strategies of Two Sympatric Species in Water

Many ectotherms effectively reduce their exposure to low or high environmental temperatures using behavioral thermoregulation. In terrestrial ectotherms, thermoregulatory strategies range from accurate thermoregulation to thermoconformity according to the costs and limits of thermoregulation, while in aquatic taxa the quantification of behavioral thermoregulation have received limited attention. We examined thermoregulation in two sympatric newt species, Ichthyosaura alpestris and Lissotriton vulgaris, exposed to elevated water temperatures under semi-natural conditions. According to a recent theory, we predicted that species for which elevated water temperatures pose a lower thermal quality habitat, would thermoregulate more effectively than species in thermally benign conditions. In the laboratory thermal gradient, L. vulgaris maintained higher body temperatures than I. alpestris. Semi-natural thermal conditions provided better thermal quality of habitat for L. vulgaris than for I. alpestris. Thermoregulatory indices indicated that I. alpestris actively thermoregulated its body temperature, whereas L. vulgaris remained passive to the thermal heterogeneity of aquatic environment. In the face of elevated water temperatures, sympatric newt species employed disparate thermoregulatory strategies according to the species-specific quality of the thermal habitat. Both strategies reduced newt exposure to suboptimal water temperatures with the same accuracy but with or without the costs of thermoregulation. The quantification of behavioral thermoregulation proves to be an important conceptual and methodological tool for thermal ecology studies not only in terrestrial but also in aquatic ectotherms.     

A comparative study on steroid sulfatase and arylsulfatase C in fibroblast clones from 45,X/47,XXX and 69,XXY

Summary Steroid sulfatase (STS) and arylsulfatase C (ARSC) were studied in fibroblast clones from a 45,X/47,XXX mosaic and from a 69,XXY triploidy with one or two active X chromosomes. The comparison of the 47,XXX with 45,X clones showed an incomplete gene dosage effect (1.8 for STS and 2.0 for ARSC). This was not the case for the triploid clones with different X-inactivation patterns. These results confirm previous reports on the non-inactivation of the STS gene, and establish X linkage and non-inactivation for the ARSC gene as well.     

Probing binding mechanism of interleukin-6 and olokizumab: in silico design of potential lead antibodies for autoimmune and inflammatory diseases

Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen–antibody (Ag???Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag???Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.     

Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype

Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. In contrast to other members of the PDGF family of growth factors, which have been extensively investigated using different knockout approaches in mice, PDGF-D has until now not been characterized by gene inactivation in mice. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model (Pdgfd^-/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. Inactivation of the Pdgfd gene resulted in a mild phenotype in C57BL/6 mice, and the offspring was viable, fertile and generally in good health. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. The expression was predominantly arterial, often localizing to vascular bifurcations. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd^-/- mice. Furthermore, Pdgfd^-/- mice also had a slightly elevated blood pressure. In summary, the vascular expression pattern together with morphological changes in NG2-expressing cells, and the increase in blood pressure, support a function for PDGF-D in regulating systemic arterial blood pressure, and suggests a role in maintaining vascular homeostasis.