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  • Author: Jan Mollenhauer x
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Summary

Electronic laboratory notebooks (ELNs) are more accessible and reliable than their paper based alternatives and thus find widespread adoption. While a large number of commercial products is available, small- to mid-sized laboratories can often not afford the costs or are concerned about the longevity of the providers. Turning towards free alternatives, however, raises questions about data protection, which are not sufficiently addressed by available solutions. To serve as legal documents, ELNs must prevent scientific fraud through technical means such as digital signatures. It would also be advantageous if an ELN was integrated with a laboratory information management system to allow for a comprehensive documentation of experimental work including the location of samples that were used in a particular experiment. Here, we present OpenLabNotes, which adds state-of-the-art ELN capabilities to OpenLabFramework, a powerful and flexible laboratory information management system. In contrast to comparable solutions, it allows to protect the intellectual property of its users by offering data protection with digital signatures. OpenLabNotes effectively closes the gap between research documentation and sample management, thus making Open- LabFramework more attractive for laboratories that seek to increase productivity through electronic data management.

Abstract

Salivary agglutinin (SAG), lung glycoprotein-340 (gp-340) and Deleted in Malignant Brain Tumours 1 (DMBT1) are three names for identical proteins encoded by the dmbt1 gene. DMBT1/SAG/gp-340 belongs to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins, a superfamily of secreted or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. On the one hand, DMBT1 may represent an innate defence factor acting as a pattern recognition molecule. It interacts with a broad range of pathogens, including cariogenic streptococci and Helicobacter pylori, influenza viruses and HIV, but also with mucosal defence proteins, such as IgA, surfactant proteins and MUC5B. Stimulation of alveolar macrophage migration, suppression of neutrophil oxidative burst and activation of the complement cascade point further to an important role in the regulation of inflammatory responses. On the other hand, DMBT1 has been demonstrated to play a role in epithelial and stem cell differentiation. Inactivation of the gene coding for this protein may lead to disturbed differentiation, possibly resulting in tumour formation. These data strongly point to a role for DMBT1 as a molecule linking innate immune processes with regenerative processes.

Abstract

At epithelial barriers molecular pattern recognition mechanisms act as minesweepers against harmful environmental factors and thereby play a crucial role in the defense against invading bacterial and viral pathogens. However, it became evident that some of the proteins participating in these host defense processes may simultaneously function as regulators of tissue regeneration when in the extracellular matrix, thus coupling defense functions with regulation of stem cells. Although molecular pattern recognition has complex physiological roles and we just begin to understand its various functions, the simplicity of the underlying principles for recognition of specific classes of molecules may generate novel starting points for nanomedical approaches in drug delivery across epithelial barriers. The present article aims to provide an introduction into the biological context, processes, proteins, and general mechanisms of molecular pattern recognition in humans and, by using selected examples, to identify potential areas in nanomedicine for the exploitation of these mechanisms.

Abstract

Radioisotope therapy of cancer is on the rise applying mainly β-emitting radionuclides. However, due to exposure of healthy tissues, the maximum achievable radiation dose with these is limited. Auger-electron emitters (AEs) represent a promising alternative because of their mode of decay within a short nanometer range. The challenge is that their therapeutic efficacy relies on a close vicinity to DNA. To overcome this and to minimize toxicity, the construction of smart nanomedical devices is required, which ascertain tumor cell targeting with succeeding cellular uptake and nuclear translocation. In this review we describe the potential of AEs with focus on their delivery down to the DNA level and their cellular effects. Reported efforts comprise different tumor-targeting strategies, including the use of antibodies or peptides with nuclear localizing sequences. Recently, attention has shifted to various nanoparticle formats for overcoming delivery problems. To this end, these approaches have mostly been tested in cell lines in vitro applying AEs more suited for imaging than therapy. This defines a demand for nanomedical formulations with documented in vivo activity, using AEs selected for their therapeutic potential to come closer to real clinical settings.

Abstract

The identification of so-called cancer stem cells (CSCs) has sustainably changed our views on cancer by adding hierarchical principles, where tumor cells emerge from a founder population similar to steady-state regenerative processes in normal tissues. The rare founder population of CSCs is thought to be responsible for the recurrence of treatment-resistant tumors and metastatic spread and thus has been declared as the number one target for the next generation of anti-cancer drugs. Here, we will review the state of the art in research on breast cancer stem cells (BCSCs), for which a huge amount of data has accumulated in the past few years. Initial studies have suggested that the CD44+/CD24- profile and epithelial-to-mesenchymal transition (EMT) are associated with BCSCs, which has resulted in the recent identification of first compounds with BCSC-eliminating properties. In this early phase, however, it remains mostly unclear, to which extent these new compounds may exert toxicity to normal stem cells, since a substantial part targets molecular pathways critical for normal stem cell function. Moreover, these new drugs often require combination with conventional chemotherapeutics potentially posing new challenges to nanomedicine in circumventing toxicity and enabling targeted delivery. Most recent data further suggests that normal breast cancer cells might be able to re-create BCSCs and that additional, yet undiscovered kinds of BCSCs may exist. This points to future escape mechanisms. As a consequence, another broad future field of nanomedicine might be finding new drugs via systematic screening approaches. Collectively, this area provides ample possibilities for both traditional and novel nanomedical approaches.