Showing papers by "University of Tübingen published in 2002"

Ecosystem Decay of Amazonian Forest Fragments: a 22-Year Investigation

Abstract: We synthesized key findings from the Biological Dynamics of Forest Fragments Project, the world's largest and longest-running experimental study of habitat fragmentation. Although initially designed to assess the influence of fragment area on Amazonian biotas, the project has yielded insights that go far beyond the orig- inal scope of the study. Results suggest that edge effects play a key role in fragment dynamics, that the matrix has a major influence on fragment connectivity and functioning, and that many Amazonian species avoid even small ( � 100-m-wide) clearings. The effects of fragmentation are highly eclectic, altering species richness and abundances, species invasions, forest dynamics, the trophic structure of communities, and a variety of ecological and ecosystem processes. Moreover, forest fragmentation appears to interact synergistically with ecological changes such as hunting, fires, and logging, collectively posing an even greater threat to the rainforest biota. Descomposicion del Ecosistema en Fragmentos de Bosque Amazonico, Una Investigacion de 22 Anos Resumen: Sintetizamos resultados clave del proyecto sobre Dinamicas Biologicas de Fragmentos de bosque, el estudio experimental sobre fragmentacion del habitat mas largo y de mayor trayectoria del mundo. A pesar de que inicialmente el proyecto se diseno para evaluar la influencia del area de fragmentos en biotas del Amazo- nas, ha proporcionado un entendimiento que va mas alla del proposito original del estudio. Los resultados sugieren que los efectos de borde juegan un papel clave en las dinamicas de los fragmentos, que la matriz tiene una influencia mayor sobre la conectividad y el funcionamiento del fragmento y que muchas de las especies del Amazonas evitan areas taladas pequenas (de hasta � 100 m de ancho). Los efectos de la fragmentacion son al- tamente eclecticos, alterando la riqueza y abundancia de especies, las invasiones de especies, las dinamicas del bosque, la estructura trofica comunitaria y una variedad de procesos ecologicos y del ecosistema. Mas aun, la fragmentacion del bosque aparentemente interactua sinergisticamente con cambios ecologicos como lo son la caza, los incendios y la tala, representando colectivamente una gran amenaza sobre la biota del bosque lluvioso.

Vector-Valued Laplace Transforms and Cauchy Problems

Abstract: Linear differential equations in Banach spaces are systematically treated with the help of Laplace transforms. The central tool is an “integrated version” of Widder’s theorem (characterizing Laplace transforms of bounded functions). It holds in any Banach space (whereas the vector-valued version of Widder’s theorem itself holds if and only if the Banach space has the Radon-Nikodým property). The Hille-Yosida theorem and other generation theorems are immediate consequences. The method presented here can be applied to operators whose domains are not dense.

Allergy, Parasites, and the Hygiene Hypothesis

Abstract: The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.

Lateral relocation of auxin efflux regulator PIN3 mediates tropism in Arabidopsis

Abstract: Long-standing models propose that plant growth responses to light or gravity are mediated by asymmetric distribution of the phytohormone auxin. Physiological studies implicated a specific transport system that relocates auxin laterally, thereby effecting differential growth; however, neither the molecular components of this system nor the cellular mechanism of auxin redistribution on light or gravity perception have been identified. Here, we show that auxin accumulates asymmetrically during differential growth in an efflux-dependent manner. Mutations in the Arabidopsis gene PIN3, a regulator of auxin efflux, alter differential growth. PIN3 is expressed in gravity-sensing tissues, with PIN3 protein accumulating predominantly at the lateral cell surface. PIN3 localizes to the plasma membrane and to vesicles that cycle in an actin-dependent manner. In the root columella, PIN3 is positioned symmetrically at the plasma membrane but rapidly relocalizes laterally on gravity stimulation. Our data indicate that PIN3 is a component of the lateral auxin transport system regulating tropic growth. In addition, actin-dependent relocalization of PIN3 in response to gravity provides a mechanism for redirecting auxin flux to trigger asymmetric growth.

Staphylococcus and biofilms.

Abstract: Summary The genetic and molecular basis of biofilm formation in staphylococci is multifaceted. The ability to form a biofilm affords at least two properties: the adherence of cells to a surface and accumulation to form multilayered cell clusters. A trademark is the production of the slime substance PIA, a polysaccharide composed of β-1,6-linked N-acetylglucosamines with partly deacetylated residues, in which the cells are embedded and protected against the host’s immune defence and antibiotic treatment. Mutations in the corresponding biosynthesis genes (ica operon) lead to a pleiotropic phenotype; the cells are biofilm and haemagglutination negative, less virulent and less adhesive on hydrophilic surfaces. ica expression is modulated by various environmental conditions, appears to be controlled by SigB and can be turned on and off by insertion sequence (IS) elements. A number of biofilm-negative mutants have been isolated in which polysaccharide intercellular adhesin (PIA) production appears to be unaffected. Two of the characterized mutants are affected in the major autolysin (atlE) and in D-alanine esterification of teichoic acids (dltA). Proteins have been identified that are also involved in biofilm formation, such as the accumulation-associated protein (AAP), the clumping factor A (ClfA), the staphylococcal surface protein (SSP1) and the biofilm-associated protein (Bap). Concepts for the prevention of obstinate polymer-associated infections include the search for new anti-infectives active in biofilms and new biocompatible materials that complicate biofilm formation and the development of vaccines.

Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients

Abstract: Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.

Finite elements in computational electromagnetism

Abstract: This article discusses finite element Galerkin schemes for a number of linear model problems in electromagnetism. The finite element schemes are introduced as discrete differential forms, matching the coordinate-independent statement of Maxwell's equations in the calculus of differential forms. The asymptotic convergence of discrete solutions is investigated theoretically. As discrete differential forms represent a genuine generalization of conventional Lagrangian finite elements, the analysis is based upon a judicious adaptation of established techniques in the theory of finite elements. Risks and difficulties haunting finite element schemes that do not fit the framework of discrete differential forms are highlighted.

Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo.

Abstract: Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo

Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.

Abstract: Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene approach, we identified mutations in TRPM6 (also known as CHAK2), encoding TRPM6, in autosomal-recessive hypomagnesemia with secondary hypocalcemia (HSH, OMIM 602014), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family and is highly similar to TRPM7 (also known as TRP-PLIK), a bifunctional protein that combines calcium- and magnesium-permeable cation channel properties with protein kinase activity. TRPM6 is expressed in intestinal epithelia and kidney tubules. These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease.

Intracytoplasmic Sperm Injection May Increase the Risk of Imprinting Defects

Abstract: In germ cells and the early embryo, the mammalian genome undergoes widespread epigenetic reprogramming. Animal studies suggest that this process is vulnerable to external factors. We report two children who were conceived by intracytoplasmic sperm injection (ICSI) and who developed Angelman syndrome. Molecular studies, including DNA methylation and microsatellite and quantitative Southern blot analysis, revealed a sporadic imprinting defect in both patients. We discuss the possibility that ICSI may interfere with the establishment of the maternal imprint in the oocyte or pre-embryo.

Cutting Edge: Down-Regulation of MICA on Human Tumors by Proteolytic Shedding

Abstract: The immunoreceptor NKG2D stimulates tumor immunity through activation of CD8 T cells and NK cells. Its ligand MICA has been shown to be broadly expressed on human tumors of epithelial origin. MICA expression correlates with an enrichment of Vδ1 T cells in tumor tissue. We report that human tumor cells spontaneously release a soluble form of MICA encompassing the three extracellular domains, which is present at high levels in sera of patients with gastrointestinal malignancies, but not in healthy donors. Release of MICA from tumor cells is blocked by inhibition of metalloproteinases, concomitantly causing accumulation of MICA on the cell surface. Shedding of MICA by tumor cells may modulate NKG2D-mediated tumor immune surveillance. In addition, determination of soluble MICA levels may be implemented as an immunological diagnostic marker in patients with epithelial malignancies.

HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration

Abstract: Erythropoietin (Epo) is upregulated by hypoxia and provides protection against apoptosis of erythroid progenitors in bone marrow and brain neurons. Here we show in the adult mouse retina that acute hypoxia dose-dependently stimulates expression of Epo, fibroblast growth factor 2 and vascular endothelial growth factor via hypoxia-inducible factor-1alpha (HIF-1alpha) stabilization. Hypoxic preconditioning protects retinal morphology and function against light-induced apoptosis by interfering with caspase-1 activation, a downstream event in the intracellular death cascade. In contrast, induction of activator protein-1, an early event in the light-stressed retina, is not affected by hypoxia. The Epo receptor required for Epo signaling localizes to photoreceptor cells. The protective effect of hypoxic preconditioning is mimicked by systemically applied Epo that crosses the blood retina barrier and prevents apoptosis even when given therapeutically after light insult. Application of Epo may, through the inhibition of apoptosis, be beneficial for the treatment of different forms of retinal disease.

The Arabidopsis BODENLOS gene encodes an auxin response protein inhibiting MONOPTEROS-mediated embryo patterning

Abstract: Developmental responses to the plant hormone auxin are thought to be mediated by interacting pairs from two protein families: short-lived inhibitory IAA proteins and ARF transcription factors binding to auxin-response elements. monopteros mutants lacking activating ARF5 and the auxin-insensitive mutant bodenlos fail to initiate the root meristem during early embryogenesis. Here we show that the bodenlos phenotype results from an amino-acid exchange in the conserved degradation domain of IAA12. BODENLOS and MONOPTEROS interact in the yeast two-hybrid assay and the two genes are coexpressed in early embryogenesis, suggesting that BODENLOS inhibits MONOPTEROS action in root meristem initiation.

Potentiation of serum response factor activity by a family of myocardin-related transcription factors.

Abstract: Myocardin is a SAP (SAF-A/B, Acinus, PIAS) domain transcription factor that associates with serum response factor (SRF) to potently enhance SRF-dependent transcription. Here we describe two myocardin-related transcription factors (MRTFs), A and B, that also interact with SRF and stimulate its transcriptional activity. Whereas myocardin is expressed specifically in cardiac and smooth muscle cells, MRTF-A and -B are expressed in numerous embryonic and adult tissues. In SRF-deficient embryonic stem cells, myocardin and MRTFs are unable to activate SRF-dependent reporter genes, confirming their dependence on SRF. Myocardin and MRTFs comprise a previously uncharacterized family of SRF cofactors with the potential to modulate SRF target genes in a wide range of tissues.

Role of nitric oxide in wound repair

Abstract: After injury, wound healing is essential for recovery of the integrity of the body. It is a complex, sequential cascade of events. Nitric oxide (NO) is a small radical, formed from the amino acid L-arginine by three distinct isoforms of nitric oxide synthase. The inducible isoform (iNOS) is synthesized in the early phase of wound healing by inflammatory cells, mainly macrophages. However many cells participate in NO synthesis during the proliferative phase after wounding. NO released through iNOS regulates collagen formation, cell proliferation and wound contraction in distinct ways in animal models of wound healing. Although iNOS gene deletion delays, and arginine and NO administration improve healing, the exact mechanisms of action of NO on wound healing parameters are still unknown. The current review summarizes what is known about the role of NO in wound healing and points out path for further research.

TRIPTYCHON and CAPRICE mediate lateral inhibition during trichome and root hair patterning in Arabidopsis

Abstract: Trichome patterning in Arabidopsis is a model for the generation of a spacing pattern from initially equivalent cells. We show that the TRIPTYCHON gene that functions in lateral inhibition encodes a single-repeat MYB-related transcription factor that lacks a recognizable activation domain. It has high sequence similarity to the root hair patterning gene CAPRICE. Both genes are expressed in trichomes and act together during lateral inhibition. We further show that TRIPTYCHON and CAPRICE act redundantly in the position-dependent cell fate determination in the root epidermis. Thus, the same lateral inhibition mechanism seems to be involved in both de novo patterning and position-dependent cell determination. We propose a model explaining trichome and root hair patterning by a common mechanism.

Sirolimus-Eluting Stents for the Treatment of Obstructive Superficial Femoral Artery Disease Six-Month Results

Abstract: Background— Stent implantation for obstructive femoropopliteal artery disease has been associated with poor long-term outcomes. This study evaluated the effectiveness of shape memory alloy recoverable technology (SMART) nitinol self-expanding stents coated with a polymer impregnated with sirolimus (rapamycin) versus uncoated SMART stents in superficial femoral artery obstructions. Methods and Results— Thirty-six patients were recruited for this double-blind, randomized, prospective trial. All patients had chronic limb ischemia and femoral artery occlusions (57%) or stenoses (average lesion length, 85±57 mm). Patients were eligible for randomization after successful guidewire passage across the lesion. Eighteen patients received sirolimus-eluting SMART stents and 18 patients received uncoated SMART stents. The primary end point of the study was the in-stent mean percent diameter stenosis, as measured by quantitative angiography at 6 months. The in-stent mean percent diameter stenosis was 22.6% in the sirolimus-eluting stent group versus 30.9% in the uncoated stent group ( P =0.294). The in-stent mean lumen diameter was significantly larger in the sirolimus-eluting stent group (4.95 mm versus 4.31 mm in the uncoated stent group; P =0.047). No serious adverse events (death or prolonged hospitalization) were reported. Conclusions— The use of sirolimus-eluting SMART stents for superficial femoral artery occlusion is feasible, with a trend toward reducing late loss compared with uncoated stents. The coated stent also proved to be safe and was not associated with any serious adverse events.

The subcortical anatomy of human spatial neglect: putamen, caudate nucleus and pulvinar.

Abstract: Various studies have documented that right hemispheric lesions restricted to the basal ganglia or to the thalamus may evoke spatial neglect. However, for methodological reasons, the exact anatomical correlate of spatial neglect within these two subcortical structures still remained uncertain. The present study identified these locations by comparing the anatomy of subcortical lesions to the basal ganglia or thalamus between neglect and control patients. Analysis revealed that the putamen, the pulvinar and, to a smaller degree, the caudate nucleus are the subcortical structures typically associated with spatial neglect in humans. All these structures have direct anatomical connections to the superior temporal gyrus (STG), which recently has been identified as the neural correlate of spatial neglect in the human cortex. Therefore, it is assumed that the right putamen, caudate nucleus, pulvinar and STG form a coherent corticosubcortical anatomical network in the genesis of spatial neglect in humans.