Search results

The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the exi

Recent studies suggest that physiological and tumorigenic proliferation of mammalian cells is controlled by multiple cyclin-dependent kinases (CDKs) largely in tissue-specific manners. We and others previously demonstrated that adult mice deficient for the Cyclin D partner CDK4 (Cdk4-/- mice) exhibit hypoplasia in the pituitary and pancreatic islet due to primary postnatal defects in proliferation

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive soft tissue tumor. A subset of UPS is characterized by a CITED2–PRDM10 or a MED12–PRDM10 gene fusion. Preliminary data suggest that these so-called PRDM10-rearranged tumors (PRT) are clinically more indolent than classical high-grade UPS, and hence important to recognize. Here, we assessed the spectrum of accompanying mutations and

CONTEXT: Both bone mineral density (BMD) and fracture risk have a strong genetic component. Estrogen receptor alpha (ESR1) is a candidate gene for osteoporosis, but previous studies of ESR1 polymorphisms in this field were hampered by small sample size, lack of standardization, and inconclusive results.OBJECTIVE: To generate large-scale evidence on whether 3 common ESR1 polymorphisms (intron 1 pol

Peak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms o

Background: Type 2 diabetes (T2D) is a complex disease characterised by chronic hyperglycaemia. The effects of elevated glucose on global gene expression in combination with DNA methylation patterns have not yet been studied in human pancreatic islets. Our aim was to study the impact of 48 h exposure to high (19 mM) versus control (5.6 mM) glucose levels on glucose-stimulated insulin secretion, ge

The cystatin C gene (CST3) encodes a low-molecular-weight cysteine proteinase inhibitor belonging to family II of the cystatin super family and is mutated in cases of hereditary cystatin C amyloid angiopathy (HCCAA). CST3, which along with other family II cystatin genes is a member of the cystatin gene family, has been assigned to chromosome 20. To investigate the genomic organization on chromosom

The alkaliphilic bacterium, Bacillus halodurans S7, produces an alkaline active xylanase (EC 3.2.1.8), which differs from many other xylanases in being operationally stable under alkaline conditions as well as at elevated temperature. Compared to non-alkaline active xylanases, this enzyme has a high percent composition of acidic amino acids which results in high ratio of negatively to positively c

Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation terminat

In this article the organization and functional details of the extracellular matrix, with particular focus on cartilage, are described. All tissues contain a set of molecules that are arranged to contribute structural elements. Examples are fibril-forming collagens forming major fibrillar networks in most tissues. The assembly process is regulated by a number of proteins (thrombospondins, LRR-prot

P>1. Ants show complex interactions with plants, both facultative and mutualistic, ranging from grazers through seed predators and dispersers to herders of some herbivores and guards against others. But ants are rarely pollinators, and their visits to flowers may be detrimental to plant fitness. 2. Plants therefore have various strategies to control ant distributions, and restrict them to foliage

We investigated the mechanism of lysosome-mediated cell death using purified recombinant pro-apoptotic proteins, and cell-free extracts from the human neuronal progenitor cell line NT2, Potential effectors were either isolated lysosomes or purified lysosomal proteases. Purified lysosomal cathepsins B, H, K, L, S, and X or an extract of mouse lysosomes did not directly activate either recombinant c

The ADAM ( a disintegrin and metalloprotease) family consists of multidomain cell-surface proteins that have a major impact on cell behavior. These transmembrane-anchored proteins are synthesized as proforms that have ( from the N terminus): a prodomain; a metalloprotease, disintegrin-like-, cysteine-rich, epidermal growth factor-like, and transmembrane domain; and a cytoplasmic tail. The 90-kDa m

In our inbred strain of cotton rats (Sigmodon hispidus) 50% of the females develop spontaneous ECL cell-derived tumors in the acid-producing part of the stomach due to hypergastrinemia secondary to gastric hypoacidity. Although the mechanism behind the hypoacidity is unknown, the female cotton rat is an excellent model for studying ECL cell-related tumorigenesis. In this study we wanted to explore