University of Basel

About: University of Basel is a education organization based out in Basel, Basel-Stadt, Switzerland. It is known for research contribution in the topics: Population & Gene. The organization has 25084 authors who have published 52975 publications receiving 2388002 citations. The organization is also known as: Universität Basel & Basel University.

Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis

Abstract: A critical question in tuberculosis control is why some strains of Mycobacterium tuberculosis are preferentially associated with multiple drug resistances. We demonstrate that M. tuberculosis strains from Lineage 2 (East Asian lineage and Beijing sublineage) acquire drug resistances in vitro more rapidly than M. tuberculosis strains from Lineage 4 (Euro-American lineage) and that this higher rate can be attributed to a higher mutation rate. Moreover, the in vitro mutation rate correlates well with the bacterial mutation rate in humans as determined by whole genome sequencing of clinical isolates. Finally, using a stochastic mathematical model, we demonstrate that the observed differences in mutation rate predict a substantially higher probability that patients infected with a drug susceptible Lineage 2 strain will harbor multidrug resistant bacteria at the time of diagnosis. These data suggest that interventions to prevent the emergence of drug resistant tuberculosis should target bacterial as well as treatment-related risk factors.

Indoor time-microenvironment-activity patterns in seven regions of Europe

Abstract: Personal exposure to environmental substances is largely determined by time-microenvironment-activity patterns while moving across locations or microenvironments. Therefore, time-microenvironment-activity data are particularly useful in modeling exposure. We investigated determinants of workday time-microenvironment-activity patterns of the adult urban population in seven European cities. The EXPOLIS study assessed workday time-microenvironment-activity patterns among a total of 1427 subjects (age 19-60 years) in Helsinki (Finland), Athens (Greece), Basel (Switzerland), Grenoble (France), Milan (Italy), Prague (Czech Republic), and Oxford (UK). Subjects completed time-microenvironment-activity diaries during two working days. We present time spent indoors--at home, at work, and elsewhere, and time exposed to tobacco smoke indoors for all cities. The contribution of sociodemographic factors has been assessed using regression models. More than 90% of the variance in indoor time-microenvironment-activity patterns originated from differences between and within subjects rather than between cities. The most common factors that were associated with indoor time-microenvironment-activity patterns, with similar contributions in all cities, were the specific work status, employment status, whether the participants were living alone, and whether the participants had children at home. Gender and season were associated with indoor time-microenvironment-activity patterns as well but the effects were rather heterogeneous across the seven cities. Exposure to second-hand tobacco smoke differed substantially across these cities. The heterogeneity of these factors across cities may reflect city-specific characteristics but selection biases in the sampled local populations may also explain part of the findings. Determinants of time-microenvironment-activity patterns need to be taken into account in exposure assessment, epidemiological analyses, exposure simulations, as well as in the development of preventive strategies that focus on time-microenvironment-activity patterns that ultimately determine exposures.

Atomic force microscopy-based mechanobiology

Abstract: Mechanobiology emerges at the crossroads of medicine, biology, biophysics and engineering and describes how the responses of proteins, cells, tissues and organs to mechanical cues contribute to development, differentiation, physiology and disease. The grand challenge in mechanobiology is to quantify how biological systems sense, transduce, respond and apply mechanical signals. Over the past three decades, atomic force microscopy (AFM) has emerged as a key platform enabling the simultaneous morphological and mechanical characterization of living biological systems. In this Review, we survey the basic principles, advantages and limitations of the most common AFM modalities used to map the dynamic mechanical properties of complex biological samples to their morphology. We discuss how mechanical properties can be directly linked to function, which has remained a poorly addressed issue. We outline the potential of combining AFM with complementary techniques, including optical microscopy and spectroscopy of mechanosensitive fluorescent constructs, super-resolution microscopy, the patch clamp technique and the use of microstructured and fluidic devices to characterize the 3D distribution of mechanical responses within biological systems and to track their morphology and functional state. Mechanobiology describes how biological systems respond to mechanical stimuli. This Review surveys basic principles, advantages and limitations of applying and combining atomic force microscopy-based modalities with complementary techniques to characterize the morphology, mechanical properties and functional response of complex biological systems to mechanical cues.

Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity.

Abstract: Activation of the Fas cell surface molecule, either by specific antibody or by its as yet unidentified ligand, has been shown to induce apoptosis. Because apoptosis is also evoked in target cells by cytolytic T cells, we investigated whether the Fas pathway is involved in CD4+ T cell-mediated cytotoxicity. Analysis of Fas expression in APC, such as the B lymphoma A20.2J and MHC class II-transfected fibroblasts RT2.3, revealed a correlation between the degree of expression and sensitivity to cytotoxic attack, high level of Fas expression in A20.2J being associated with efficient lysis. To examine whether increased Fas expression in RT2.3 would render these cells more susceptible to CD4+ CTL lysis, they were transfected with a Fas gene expression vector. Indeed, Fas- but not mock-transfected RT2.3 proved to be more sensitive to lysis by either Ag specifically or nonspecifically activated CD4+ CTL. Similarly, MHC class II-negative, Fas-transfected L1210 leukemia cells were lysed with nonspecifically activated CD4+ CTL. The importance of the Fas engagement in CD4+ CTL-mediated cytotoxicity is further substantiated by the failure of both cloned and normal CD4+ CTL to lyse B cell blasts from Ipr mice. These mice are known to have a defect in functional Fas expression. Although the bulk of CD4+ T cell-mediated lysis appears to be Fas induced, the fact that the effector phase of A20.2J lysis is only partially Ca2+ independent indicates that other pathways also contribute to target cell death.

Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies.

Abstract: Tissue microarray (TMA) technology allows a massive acceleration of studies correlating molecular in situ findings with clinico-pathological information. In this technique, cylindrical tissue samples are taken from up to 1000 different archival tissue blocks and subsequently placed into one empty ‘recipient’ paraffin block. Sections from TMA blocks can be used for all different types of in situ tissue analyses including immunohistochemistry and in situ hybridization. Multiple studies have demonstrated that findings obtained on TMAs are highly representative of their donor tissues, despite the small size of the individual specimens (diameter 0.6 mm). It is anticipated that TMAs will soon become a widely used tool for all types of tissue-based research. The availability of TMAs containing highly characterized tissues will enable every researcher to perform studies involving thousands of tumours rapidly. Therefore, TMAs will lead to a significant acceleration of the transition of basic research findings into clinical applications. Copyright © 2001 John Wiley & Sons, Ltd.