Approaches to identify and characterize microProteins and their potential uses in biotechnology

MicroProteins are small proteins that contain a single protein domain and are related to larger, often multi-domain proteins. At the molecular level, microProteins act by interfering with the formation of higher order protein complexes. In the past years, several microProteins have been identified in plants and animals that strongly influence biological processes. Due to their ability to act as dominant regulators in a targeted manner, microProteins have a high potential for biotechnological use. In this review, we present different ways in which microProteins are generated and we elaborate on techniques used to identify and characterize them. Finally, we give an outlook on possible applications in biotechnology.     

Sequence of the human insulin gene

The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region. A comparison of the human with the rat insulin genes indicates potential regulatory regions in the DNA segment preceding the gene and suggests that the ancestral form of the insulin gene had two intervening sequences.     

Surfing the Third Wave: Experiential Reflections on New Working Practices

Systemic Practice and Action Research - This paper deals with issues and presents changes in practices relating to the new working as realized in the developing e-working world. The paper begins by...     

Mesenchymal stem cells within tumour stroma promote breast cancer metastasis

Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.     

Base excision repair and design of small molecule inhibitors of human DNA polymerase β

Base excision repair (BER) can protect a cell after endogenous or exogenous genotoxic stress, and a deficiency in BER can render a cell hypersensitive to stress-induced apoptotic and necrotic cell death, mutagenesis, and chromosomal rearrangements. However, understanding of the mammalian BER system is not yet complete as it is extraordinarily complex and has many back-up processes that complement a deficiency in any one step. Due of this lack of information, we are unable to make accurate predictions on therapeutic approaches targeting BER. A deeper understanding of BER will eventually allow us to conduct more meaningful clinical interventions. In this review, we will cover historical and recent information on mammalian BER and DNA polymerase β and discuss approaches toward development and use of small molecule inhibitors to manipulate BER. With apologies to others, we will emphasize results obtained in our laboratory and those of our collaborators.     

First Pleistocene jumping mouse ( Zapus , Zapodinae, Rodentia) from Utah

Two of the Little Dell Dam fossil localities produced the 1st Pleistocene records of the jumping mouse Zapus from Utah. We describe these teeth in detail and compare their morphology with both extinct and extant jumping mouse taxa. Although it is not possible to confidently assign these specimens to a particular species, the Little Dell Dam fossils are clearly distinct from the only living jumping mouse ( Zapus princeps ) currently known from Utah. The paracone is attached to the rest of the occlusal surface of the upper 1st and 2nd molars in modern Z. princeps from Utah; the paracone is isolated in the molars from Little Dell Dam. The fossils from Little Dell Dam are the 1st reported records of Pleistocene Zapus west of the Rocky Mountains.