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Biomedical subjects

Ulrich Mueller

Publications and source records attributed to Ulrich Mueller.

9 recordsLinked to original sources

Geographic variation of genetic and behavioral traits in northern and southern tüngara frogs.

We use a combination of microsatellite marker analysis and mate-choice behavior experiments to assess patterns of reproductive isolation of the túngara frog Physalaemus pustulosus along a 550-km transect of 25 populations in Costa Rica and Panama. Earlier studies using allozymes and mitochondrial DNA defined two genetic groups of túngara frogs, one ranging from Mexico to northern Costa Rica (northern group), the second ranging from Panama to northern South America (southern group). Our more fine-scale survey also shows that the northern and southern túngara frogs are genetically different and geographically separated by a gap in the distribution in central Pacific Costa Rica. Genetic differences among populations are highly correlated with geographic distances. Temporal call parameters differed among populations as well as between genetic groups. Differences in calls were explained better by geographic distance than by genetic distance. Phonotaxis experiments showed that females preferred calls of males from their own populations over calls of males from other populations in about two-thirds to three-fourths of the contrasts tested. In mating experiments, females and males from the same group and females from the north with males from the south produced nests and tadpoles. In contrast, females from the south did not produce nests or tadpoles with males from the north. Thus, northern and southern túngara frogs have diverged both genetically and bioacoustically. There is evidence for some prezygotic isolation due to differences in mate recognition and fertilization success, but such isolation is hardly complete. Our results support the general observation that significant differences in sexual signals are often not correlated with strong genetic differentiation.

Animals↗

Ablation of beta1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation.

Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of beta1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured beta1 integrin-null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. beta1 integrin-null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where beta1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for beta1 integrins in prolactin signaling. This study demonstrates that beta1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways.

Animals↗

Beta1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli.

Integrin-extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of beta1 integrin in the mammary gland, Itgbeta1(flox/flox) mice were crossed with WAPiCre transgenic mice, which led to specific ablation of beta1 integrin in luminal alveolar epithelial cells. In the beta1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell-basement membrane associations. Activity of focal adhesion kinase (FAK) was also decreased in mutant mammary glands. Luminal cell proliferation was strongly inhibited in beta1 integrin mutant glands, which correlated with a specific increase of p21 Cip1 expression. In a p21 Cip1 null background, there was a partial rescue of BrdU incorporation, providing in vivo evidence linking p21 Cip1 to the proliferative defect observed in beta1 integrin mutant glands. A connection between p21 Cip1 and beta1 integrin as well as FAK was also established in primary mammary cells. These results point to the essential role of beta1 integrin signaling in mammary epithelial cell proliferation.

Animals↗

Novel heterocyclic thyromimetics.

Novel heterocycle-fused thyromimetics are presented carrying indoles or indazoles instead of the phenolic group in T3. Potent agonists were identified in both series. SAR trends are examined and found to be mostly consistent with previously published thyromimetics. Moderate THRbeta selectivity (approx. 10-fold) was observed in the indole series using isoform-selective transient THR transfection assays.

Animals↗

Testosterone supplementation in the aging male: which questions have been answered?

PURPOSE: There is no consensus on possible benefits and risks of testosterone supplementation. Here we review various controlled studies of testosterone supplementation in aging males. METHODS: We performed a PubMed search using the terms "testosterone/therapeutic use" with the limits " > 65 years of age", "randomized controlled clinical trials", and "male gender", starting in 1999. RESULTS: Forty-three articles have been published since 1999. Some of these studies also included patients in middle-age or younger. Findings reported in these articles were not entirely consistent. After weighting studies by the number of patients, hints are found that testosterone supplementation increases bone mass, lean body mass, muscle mass and hematopoiesis, and improves sexual functioning and perhaps mood, but does not affect serum lipids, cardiovascular parameters, prostate-specific antigen level, or cognition. Considering studies including only men older than 65 years, and in which testosterone supplements were compared with placebo treatment, slightly different results are obtained. In these patient groups, testosterone does not improve sexual function or mood. CONCLUSION: The overall benefit of testosterone supplementation for the aging male remains unclear. Any supplementation in men with age-normal testosterone levels only on grounds of subjective symptoms is not advisable.

Adult↗

Targeted disruption of beta1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction.

Despite evidence demonstrating the role of beta1-integrin in the regulation of cancer cell proliferation in vitro, the importance of this cell adhesion receptor during the initiation and progression of epithelial tumors in vivo remains unclear. Here we have used the Cre/LoxP1 recombination system to disrupt beta1-integrin function in the mammary epithelium of a transgenic mouse model of human breast cancer. Using this approach, we show that beta1-integrin expression is critical for the initiation of mammary tumorigenesis in vivo, and for maintaining the proliferative capacity of late-stage tumor cells. These observations provide a direct demonstration that beta1-integrin plays a critical role in both the initiation and maintenance of mammary tumor growth in vivo.

Animals↗

Artificial life and Piaget.

Artificial life provides important theoretical and methodological tools for the investigation of Piaget's developmental theory. This new method uses artificial neural networks to simulate living phenomena in a computer. A recent study by Parisi and Schlesinger suggests that artificial life might reinvigorate the Piagetian framework. We contrast artificial life with traditional cognitivist approaches, discuss the role of innateness in development, and examine the relation between physiological and psychological explanations of intelligent behaviour.

Journal Article↗

Conditional disruption of beta 1 integrin in Schwann cells impedes interactions with axons.

In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell-specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. beta 1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and alpha 6 beta 4 integrin. These data suggest that beta 1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.

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