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Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter

Kaposi sarcoma-associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kC

Cell cycle-dependent phosphorylation of C/EBPβ mediates oncogenic cooperativity between C/EBPβ and H-RasV12

CCAAT/enhancer binding protein β (C/EBPβ) is a widely expressed transcription factor whose activity is regulated by oncogenic Ha-Ras V12 signaling. C/EBPβ is essential for the development of mouse skin tumors containing Ras mutations and can cooperate with Ras V12 to transform NIH 3T3 cells. Here we have investigated Ras-induced phosphorylation of C/EBPβ in fibroblasts and report a novel proline

Functions of creatine kinase isoenzymes in spermatozoa

Spermatozoa have a defined function, that is, the fertilization of an egg. To achieve this goal, spermatozoa have to move actively toward the egg and inject the male pronucleus into the egg. Therefore, sperm motility is one of the crucial determinants for male fertility. Surprisingly, however, structure and energy metabolism can differ substantially between spermatozoa from different species. Here

Core-shell Cu-Ag Nanoparticles Produced by Spark Discharge Generation

The synthesis of core@shell nanoparticles has predominantly been carried out by chemical methods or physical deposition of a shell material post-growth onto core particles. By combining immiscible materials that differ in surface energy, we demonstrate the spontaneous atomic rearrangement to monodisperse Cu@Ag core@shell particles directly in the aerosol phase, starting from pure Cu and Ag electro

The dynamics of insulin release from mouse pancreatic islet cells in suspension

The overall dynamics of glucose-induced insulin release was strikingly similar in dispersed cells and intact islets perifused in parallel. Both preparations exhibited a latency of 1-2 min, after which period there was a brisk rise of insulin release followed by a sustained second phase. During the second phase, insulin release from dispersed cells attained a stable plateau rate, whereas the releas

Human PNPLA3-I148M variant increases hepatic retention of polyunsaturated fatty acids

The common patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant I148M predisposes to nonalcoholic liver disease but not its metabolic sequelae. We compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFA) in vivo in humans and in cells harboring different PNPLA3 genotypes. In 148M homozygous individuals, triglycerides (TGs) in very low-

A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity

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

MEN1 tumorigenesis in the pituitary and pancreatic islet requires CDK4 but not Cdk2

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

CDK2 is dispensable for adult hippocampal neurogenesis

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed

p27kip1 (cyclin-dependent kinase inhibitor 1B) controls ovarian development by suppressing follicle endowment and activation and promoting follicle atresia in mice

In humans, the molecular mechanisms underlying ovarian follicle endowment and activation, which are closely related to the control of female reproduction, occurrence of menopause, and related diseases such as premature ovarian failure, are poorly understood. In the current study, we provide several lines of genetic evidence that the cyclin-dependent kinase (Cdk) inhibitor 1B (commonly known as p27

p205, A potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation

p205 is a member of the interferon-inducible p200 family of proteins that regulate cell proliferation. Over-expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. Therefore, we evaluated the effect of p205 on the p53 and Rb-dependent pathways of cell cycle regulation. p205 expression results in elevated levels of p21, and activates the p21 promoter in vitro

Tissue remodelling in pulmonary fibrosis linked to 5-HT2 receptor activation

After an injury, an immediate reparative response is triggered to replace the damaged tissue, however, in fibrosis, cells remain active despite wound resolution causing a steady build-up of fibrotic tissue. In pulmonary fibrosis,there is a constant regeneration and remodelling of lung tissue where the thin architecture of alveoli become thickened, hampering efficient diffusion of oxygen, as seen i