Defective regulation of the cytosolic Ca2+ activity in parathyroid cells from patients with hyperparathyroidism

The parathyroid hormone (PTH) release and cytosolic Ca²⁺ activity were determined in normal bovine parathyroid cells and parathyroid cells obtained from patients with hyperparathyroidism (HPT). There was a sigmoid relation between the cytosolic Ca²⁺ activity and the extracellular calcium concentration between 0.5 and 6.0 mmol/l. The PTH release was inhibited in parallel with the rise in the cytosolic Ca²⁺ activity. Both the hormone release and the cytosolic Ca²⁺ activity were lower in cells from human adenomas and hyperplastic glands~ and in comparison with the bovine preparations these ceils had higher set points for the cytosolic Ca²⁺ activity and PTH release. There was a close correlation between the individual set points for the cytosolic Ca²⁺ activity and PTH release in a material containing both normal and pathological cells. The results indicate that the abnormal PTH release characteristic of HPT is due to a defective regulation of the cytosolic Ca²⁺ activity.     

Genetic Variation and Atherosclerosis

A family history of atherosclerosis is independently associated with an increased incidence of cardiovascular events. The genetic factors underlying the importance of inheritance in atherosclerosis are starting to be understood. Genetic variation, such as mutations or common polymorphisms has been shown to be involved in modulation of a range of risk factors, such as plasma lipoprotein levels, inflammation and vascular calcification. This review presents examples of present studies of the role of genetic polymorphism in atherosclerosis.     

E,E,E-1-(4-Arylamino-4-oxo-2-butenoyl)-3,5-bis(arylidene)-4-piperidones: a topographical study of some novel potent cytotoxins

A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 microM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice.     

QCM-D sensitivity to protein adsorption reversibility

Using a quartz crystal microbalance with dissipative monitoring (QCM-D) we have determined the adsorption reversibility and viscoelastic properties of ribonuclease A adsorbed to hydrophobic self-assembled monolayers. Consistent with previous work with proteins unfolding on hydrophobic surfaces, high protein solution concentrations, reduced adsorption times, and low ammonium sulfate concentrations lead to increased adsorption reversibility. Measured rigidity of the protein layers normalized for adsorbed protein amounts, a quantity we term specific dissipation, correlated with adsorption reversibility of ribonuclease A. These results suggest that specific dissipation may be correlated with changes in structure of adsorbed proteins.     

Altered White Matter Architecture in BDNF Met Carriers

Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin''s activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects'' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture.     

Through the Eyes of Children: Perceptions of Environmental Change in Tropical Forests

This study seeks to understand children''s perceptions of their present and future environments in the highly biodiverse and rapidly changing landscapes of Kalimantan, Indonesian Borneo. We analyzed drawings by children (target age 10–15 years) from 22 villages, which show how children perceive the present conditions of forests and wildlife surrounding their villages and how they expect conditions to change over the next 15 years. Analyses of picture elements and their relationships to current landscape variables indicate that children have a sophisticated understanding of their environment and how different environmental factors interact, either positively or negatively. Children appear to have landscape-dependent environmental perceptions, showing awareness of past environmental conditions and many aspects of recent trends, and translating these into predictions for future environmental conditions. The further removed their present landscape is from the originally forested one, the more environmental change they expect in the future, particularly declines in forest cover, rivers, animal diversity and increases in temperature and natural disasters. This suggests that loss of past perceptions and associated “shifting environmental baselines” do not feature strongly among children on Borneo, at least not for the perceptions we investigated here. Our findings that children have negative expectations of their future environmental conditions have important political implications. More than other generations, children have a stake in ensuring that future environmental conditions support their long-term well-being. Understanding what drives environmental views among children, and how they consider trade-offs between economic development and social and environmental change, should inform optimal policies on land use. Our study illuminates part of the complex interplay between perceptions of land cover and land use change. Capturing the views of children through artistic expressions provides a potentially powerful tool to influence public and political opinions, as well as a valuable approach for developing localized education and nature conservation programs.     

Lipids,lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.

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