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Biomedical subjects

M Maurer

Publications and source records attributed to M Maurer.

At least 37 records · Page 2Linked to original sources

Nutrients in urine: energetic aspects of removal and recovery.

The analysis of different removal and recovery techniques for nutrients in urine shows that in many cases recovery is energetically more efficient than removal and new-production from natural resources. Considering only the running electricity and fossil energy requirements for the traditional way of wastewater treatment and fertiliser production, the following specific energy requirements can be calculated: 45 MJ kg(-1)N for denitrification in a WWTP, 49 MJ kg(-1)p for P-precipitation in a WWTP, 45 MJ kg(-1)N for N-fertiliser and 29 MJ kg(-1)p for P-fertiliser production. These numbers are higher than the values derived for thermal volume reduction of urine (35 MJ kg(-1)N for eliminating 90% water) or production of struvite (102 MJ kg(-1)N, including 2.2 kg P). Considering only the electricity and fossil energy for the traditional way of wastewater treatment and fertiliser production, the energy value of 1 PE urine is 0.87 MJ PE(-1) d(-1) (fertiliser value: 0.44, wastewater treatment: 0.43 MJ PE(-1) d(-1)). A more detailed life cycle assessment (LCA) of the entire urine collection system, including the required materials and the environmental burden, support the energy analysis. The LCA compares conventional denitrification in a wastewater treatment plant with collecting urine in households, reducing the volume by evaporation and using it as a multi-nutrient fertiliser. The primary energy consumption for recovery and reuse of urine, including the nutrients N, P and K, is calculated with 65 MJ kg(-1)N, compared with 153 MJ kg(-1)N derived for the conventional 'recycling over the atmosphere'.

Chemical Precipitation↗

A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist.

IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-alpha 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2-9) and is physically adjacent to IL-20Ralpha and IFN-gammaR1 on chromosome 6q23.3-24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses.

Amino Acid Sequence↗

p53 Involvement in the control of murine hair follicle regression.

p53 is a transcription factor mediating a variety of biological responses including apoptotic cell death. p53 was recently shown to control apoptosis in the hair follicle induced by ionizing radiation and chemotherapy, but its role in the apoptosis-driven physiological hair follicle regression (catagen) remains to be elucidated. Here, we show that p53 protein is strongly expressed and co-localized with apoptotic markers in the regressing hair follicle compartments during catagen. In contrast to wild-type mice, p53 knockout mice show significant retardation of catagen accompanied by significant decrease in the number of apoptotic cells in the hair matrix. Furthermore, p53 null hair follicles are characterized by alterations in the expression of markers that are encoded by p53 target genes and are implicated in the control of catagen (Bax, Bcl-2, insulin-like growth factor binding protein-3). These data suggest that p53 is involved in the control of apoptosis in the hair follicle during physiological regression and imply that p53 antagonists may be useful for the management of hair growth disorders characterized by premature entry into catagen, such as androgenetic alopecia, alopecia areata, and telogen effluvium.

Animals↗

Mast cells as initiators of immunity and host defense.

Until recently, mast cells have been viewed primarily as harmful because of their key role as effector cells of allergic and potentially lethal anaphylactic reactions. Their contribution to human health appeared instead to be limited to the elimination of parasites. There is, however, growing evidence for additional beneficial functions of mast cells, particularly regarding the initiation of acquired immune reactions. Thus, mast cells can phagocytize diverse particles, take up antigens, and express a number of receptors, particularly MHC class I and II antigens, ICAM-1 and -3, CD43, CD80, CD86 and CD40L which allow them to interact with T and B lymphocytes. They can also secrete numerous cytokines that induce and enhance recruitment and functions of lymphocytes. Finally, there is good evidence that mast cells present e.g. pollen and bacterial antigens, respond to bacterial superantigens, but fail to react to endogenously produced antigens or superantigens. Mast cells can also activate B cells directly to produce IgE, but this activity and the ability to produce IL-4 or IL-13 is restricted primarily to basophil leukocytes and mucosal mast cells. Finally, recent evidence attributes a pivotal role to the cells in natural immunity to bacteria. There is also emerging evidence that mast cells can downmodulate the immune response. While these data require further clarification, the basic ability of mast cells to initiate innate and acquired immune reactions can no longer be questioned.

Antigen Presentation↗

Differential gene expression profile of glucocorticoids, testosterone, and dehydroepiandrosterone in human cells.

Glucocorticoids are the major immunomodulating hormones in the human body. Recently, increasing interest in androgens as immunomodulators has emerged. In particular, Dehydroepiandrosterone (DHEA) has been suggested as beneficial in the treatment of some autoimmune disorders. However, the action and role of testicular and adrenal androgens on human immune cells remains unclear. This is the first study to provide large-scale gene expression data on the action of different steroids (DHEA, glucocorticoids, and testosterone) on human peripheral blood mononuclear cells using the recently developed genomic-scale technology of microarrays. Novel computational tools and techniques such as Principal Component Analysis (PCA) were used for analysis, clustering and visualization. We have demonstrated that each steroid has its distinct gene expression profile, although DHEA and testosterone co-regulated most genes in a similar direction while glucocorticoids frequently regulated the same genes in an opposite direction. Our data suggest an important and a complex regulatory role for androgens on human immune cells that should be considered in androgen replacement or treatment strategies.

Dehydroepiandrosterone↗

Seasonal and spatial variability in Lake Michigan sediment small-subunit rRNA concentrations.

We have used molecular biological methods to study the distribution of microbial small-subunit rRNAs (SSU rRNAs), in relation to chemical profiles, in offshore Lake Michigan sediments. The sampling site is at a depth of 100 m, with temperatures of 2 to 4 degrees C year-round. RNA extracted from sediment was probed with radiolabeled oligonucleotides targeting bacterial, archaeal, and eukaryotic SSU rRNAs, as well as with a universal probe. The coverage of these probes in relation to the present sequence database is discussed. Because ribosome production is growth rate regulated, rRNA concentrations are an indicator of the microbial populations active in situ. Over a 1-year period, changes in sedimentary SSU rRNA concentrations followed seasonal changes in surface water temperature and SSU rRNA concentration. Sedimentary depth profiles of oxygen, reduced manganese and iron, and sulfate changed relatively little from season to season, but the nitrate concentration was approximately fivefold higher in April and June 1997 than at the other times sampling was done. We propose that sediment microbial SSU rRNA concentrations at our sampling site are influenced by seasonal inputs from the water column, particularly the settling of the spring diatom bloom, and that the timing of this input may be modulated by grazers, such that ammonia becomes available to sediment microbes sooner than fresh organic carbon. Nitrate production from ammonia by autotrophic nitrifying bacteria, combined with low activity of heterotrophic denitrifying bacteria in the absence of readily degradable organic carbon, could account for the cooccurrence of high nitrate and low SSU rRNA concentrations.

Animals↗

Moving-bed biological treatment (MBBT) of municipal wastewater: denitrification.

Denitrification in a full-scale installation and a pilot plant for moving-bed biological treatment (MBBT) was subject to detailed investigation. Two different types of carriers were used in conventional activated sludge reactors: foam cubes and plastic tubes (Kaldnes). Both investigated carriers showed the same behavior with regard to denitrification capacity, temperature dependency and maximum COD and nitrate turnover. In contrast to the plastic tubes (Kaldnes), the sponge cubes stored remarkable amounts of substrate. The maximum denitrification rate with acetate as a substrate was 420 gNm-3d-1 at 10 degrees C and 730 gNm-3d-1 at 20 degrees C. An average denitrification rate of 240 gNm-3d-1 (10 degrees C) was achieved with wastewater. A maximum of 37% of the COD in the influent was denitrified with a volumetric loading rate in the anoxic zone of 2.2 kgCODm-3d-1.

Acetates↗

A role for CD21/CD35 and CD19 in responses to acute septic peritonitis: a potential mechanism for mast cell activation.

Although it is now appreciated that mast cell-mediated release of TNF-alpha is critical for resolution of acute septic peritonitis, questions remain as to how mast cells are activated upon peritoneal bacterial infection. Clues to how this may occur have been derived from earlier studies by Prodeus et al. in which complement proteins C3 and C4 were shown to be required for survival following cecal ligation and puncture (CLP), a model for acute septic peritonitis. To evaluate the mechanism for mast cell activation in the CLP model, complement receptor CD21/CD35-deficient mice (Cr2(null)) were examined in the present study. Along with CD19-deficient (CD19(null)) mice, these animals exhibit decreased survival following CLP compared with wild-type littermates. Injection of IgM before CLP does not change survival rates for Cr2(null) mice and only partially improves survival of CD19(null) mice, implicating CD21/CD35 and CD19 in mast cell activation. Interestingly, early TNF-alpha release is also impaired in Cr2(null) and CD19(null) animals, suggesting that these molecules directly affect mast cell activation. Cr2(null) and CD19(null) mice demonstrate an impairment in neutrophil recruitment and a corresponding increase in bacterial load. Examination of peritoneal mast cells by flow cytometry and confocal microscopy reveals the expression and colocalization of CD21/CD35 and CD19. Taken together, these findings suggest that the engagement of complement receptors CD21/CD35 along with CD19 on the mast cell surface by C3 fragments may be necessary for the full expression of mast cell activation in the CLP model.

Acute Disease↗

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Amino Acid Sequence↗

p53 is essential for chemotherapy-induced hair loss.

Anticancer drugs stimulate apoptosis in the hair follicles (HF) and cause hair loss, the most common side effect of chemotherapy. In a mouse model for chemotherapy-induced hair loss, we demonstrate that p53 is essential for this process: in contrast to wild-type mice, p53-deficient mice show neither hair loss nor apoptosis in the HF keratinocytes that maintained active proliferation after cyclophosphamide treatment. HF in p53 mutants are characterized by down-regulation of Fas and insulin-like growth factor-binding protein 3 and by increased expression of Bcl-2. These observations indicate that local pharmacological inhibition of p53 may be useful to prevent chemotherapy-associated hair loss.

Alopecia↗

Molecular cloning, chromosome mapping and characterization of UBQLN3 a testis-specific gene that contains an ubiquitin-like domain.

The sequence of the ubiquitin protein is highly conserved between species and has facilitated the cloning of numerous ubiquitin-like proteins. In the present study, we report the cloning of the cDNA for human ubiquilin 3 (UBQLN3). The deduced amino acid sequence of UBQLN3 contains a UBQ domain (ubiquitin-like) in the amino terminus as well as two highly conserved domains found in several recently cloned ubiquitin-like proteins. One of these domains, termed the NP domain, is a highly conserved 93 amino acid region present in UBQLN3 and several ubiquitin-like proteins. The last conserved domain is the UBA domain (ubiquitin-associated) found in a variety of proteins of the ubiquination pathway. The human UBQLN3 gene was mapped to the 11p15 region of chromosome 11. Northern blot analysis of multiple human and mouse tissues demonstrated UBQLN3 mRNA expression specifically in testis.

Amino Acid Sequence↗

Molecular cloning, chromosome mapping and characterization of a testis-specific cystatin-like cDNA, cystatin T.

The cystatin superfamily of cysteine proteinase inhibitors consists of three major families. In the present study, we report the cloning of the cDNA for mouse cystatin T, which is related to family 2 cystatins. The deduced amino acid sequence of cystatin T contains regions of significant sequence homology including the four highly conserved cysteine residues in exact alignment with all cystatin family 2 members. However, cystatin T lacks some of the conserved motifs believed to be important for inhibition of cysteine proteinase activity. These characteristics are seen in two other recently cloned genes, CRES and Testatin. Thus, cystatin T appears to be the third member of the CRES/Testatin subgroup of family 2 cystatins. The mouse cystatin T gene was mapped on a region of chromosome 2 that contains a cluster of cystatin genes, including cystatin C and CRES. Northern blot analysis demonstrated that expression of mouse cystatin T is highly restricted to the mouse testis. Thus, a shared characteristic of the cystatin family 2 subgroup members is an expression pattern limited primarily to the male reproductive tract.

Animals↗

Cross-correlated relaxation for the measurement of angles between tensorial interactions.

Theory,experimental aspects, and use in structure calculation of cross-correlated relaxation rates measured on zero- and double-quantum coherences in liquid state NMR are presented. The relative size of the interaction depends on the projection angle between the two tensorial interactions. The tensorial interaction can be either a dipolar interaction or a chemical shift anisotropy relaxation mechanism (CSA). Effects of additional sources of relaxation on the cross-correlated relaxation rates are analyzed. Also, an easy-to-use formalism is given to manipulate different cross-correlated relaxation interactions. The application addresses measurement of the backbone angle psi in a protein by measuring dipole((15)N-(1)H)-dipole((13)C(alpha)-(1)H(alpha)) and CSA((15)N)-dipole((13)C(alpha)-(1)H(alpha)) cross-correlated relaxation rates. It is shown that ambiguities due to the 3 cos(2)θ-1 dependence of one cross-correlated relaxation rate can be overcome by measuring additional cross-correlated relaxation rates. The use of cross-correlated relaxation rates is demonstrated in structure calculations.

Anisotropy↗

Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo.

The regression phase of the hair cycle (catagen) is an apoptosis-driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor beta1 (TGF-beta1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta1 null mice and age-matched wild-type littermates, and assessed the effects of TGF-beta1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF-beta1 -/- mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta1-/- mice displayed more Ki-67-positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratinocytes was reduced and the number of TUNEL + cells was increased in the TGF-beta1-treated mice compared to controls. Double visualization of TGF-beta type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF-beta1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TGF-betaRII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).

Animals↗

Phenotypical characterization of c-kit receptor deficient mouse femora using non-destructive high-resolution imaging techniques and biomechanical testing.

OBJECTIVE: Pathological processes in bone can lead to fatal health consequences. Therefore, it is important to study factors that possibly influence the activity of bone cells. The mast cell is a normal component of bone, storing and producing many potent bioactive substances. One of the most important factors to influence mast cell number, function, and phenotype is the c-kit ligand. A defect of the c-kit receptor leads to mast cell deficiency. In literature oversight, evidence for the importance of mast cells in skeletal homeostasis is compiled. METHODS: To investigate the influence of c-kit receptor deficiency on bone mass, geometry, microstructure, and strength, 30 femora of profoundly c-kit receptor deficient mouse mutants and 30 control group animals aged 8-20 weeks were phenotypically characterized using peripheral quantitative computed tomography (pQCT), micro-computed tomography (microCT) and 3-point-bending. RESULTS: The femora of the c-kit receptor and therefore mast cell deficient animals were significantly altered in bone mass and geometry but not in bone density and microstructure. The mutants had a lighter femur with a thinner shape. The lower load bearing capacity of the femora of mast cell deficient mouse mutants is more likely explained by the smaller amount of bone material than due to a change in intrinsic material properties. TECHNICAL CONSIDERATIONS: With the little dimensions of mouse bones, it is of prime importance to have precise methods to phenotypically characterize the bone. The pQCT allows the separate assessment and analysis of trabecular and cortical bone density, as well as a statement about bone geometry. Beyond it, the microCT-technique delivers a 3-D analysis of bone microstructure, which so far was only achieved with 2-D histomorphometry. microCT is an efficient alternative to destructive histological preparations allowing further biomechanical testing of the same specimens to also deliver measures for bone strength.

Animals↗