Reduced high affinity 5 -dihydrotestosterone receptor capacity in the ventral prostate of the aging rat

Cytoplasmic extracts of ventral prostates obtained from young (50–90 day old) rats 24 hours post orchidectomy contained high affinity binding activity for 5α-dihydrotestosterone which migrated with a sedimentation coefficient of 10–11S on linear sucrose gradients. By contrast, when cytoplasmic extracts were prepared from ventral prostates of aging rats (10–14 months old), 80 percent of the animals evidenced a complete absence of 10–11S binding activity. A single extract prepared from the ventral prostates of the remaining aging animals in the 10–14 month age category had a level of 10–11S binding activity that was about 20 to 25 percent of the value routinely obtained for identical preparations from young animals. Cytoplasmic extracts prepared from the ventral prostate of animals older than 14 months were always found to be devoid of 10–11S binding activity.     

Effect of pyridoxine deficiency on nucleic acid metabolism in the rat

1. The nucleic acid metabolism in the pyridoxine-deficient rat has been investigated through studies on the incorporation of radioactivity from various isotopically labelled compounds into liver and spleen DNA and RNA. 2. In pyridoxine deficiency, the incorporation of radioactivity from sodium [¹⁴C]formate was apparently increased. The magnitude of this effect on incorporation into liver RNA and DNA and spleen RNA was approximately the same. The incorporation into spleen DNA was enhanced to a much greater degree. Administration of pyridoxine 24hr. before the rats were killed reversed the changes in incorporation of radioactivity from [¹⁴C]formate. 3. In pyridoxine deficiency, the incorporation of radioactivity from dl-[3-¹⁴C]serine, [8-¹⁴C]adenine, [Me-³H]thymidine and [2-¹⁴C]deoxyuridine was decreased. The incorporation of radioactivity from l-[Me-¹⁴C]methionine was not affected. No noteworthy differences in the effect of pyridoxine deficiency on the incorporation of radioactivity from dl-[3-¹⁴C]serine into DNA and RNA were observed, whereas the effect of the deficiency on the incorporation of radioactivity from [8-¹⁴C]adenine into spleen DNA was somewhat greater than that into spleen RNA. Administration of pyridoxine 24hr. before the rats were killed reversed the changes in incorporation of radioactivity from [3-¹⁴C]serine and [8-¹⁴C]adenine. 4. The adverse effects of pyridoxine deficiency on the biosynthesis of nucleic acids and cell multiplication are discussed in relation to the role of pyridoxal phosphate in the production of C₁ units via the serine-hydroxymethylase reaction.     

Mutational analysis of the receptor-activating region of human parathyroid hormone.

The first 4 residues of parathyroid hormone (PTH) are highly conserved in evolution and are important for biological activity. We randomly mutated codons 1-4 of human PTH (hPTH) with degenerate oligonucleotides and, after expression in COS cells, screened the mutants for receptor binding and cAMP-stimulating activity using ROS 17/2.8 cells. This survey identified Glu4 and Val2 as important determinants of receptor binding and activation, respectively. Positions 1 and 3 were more tolerant of substitutions indicating that these sites are less vital to hormone function. Activities of synthetic hPTH(1-34) analogs further demonstrated the importance of positions 2 and 4. The binding affinity of [Ala4,Tyr34] hPTH(1-34)NH2 was 100-fold reduced relative to [Tyr34]hPTH(1-34)NH2 (Kd values = 653 +/- 270 and 4 +/- 1 nM, respectively), and [Arg2, Tyr34]hPTH(1-34)NH2 was a weak partial agonist which bound well to the ROS cell receptor (Kd = 31 +/- 10 nM). The Arg2 analog was nearly as potent as PTH(3-34) as an in vitro PTH antagonist in osteoblast derived cells. However, unlike PTH(3-34), [Arg2]PTH was a full agonist in opossum kidney (OK) cells. These observations suggest that the activation domains of the OK and ROS cell PTH receptors are different. Thus, amino-terminal PTH analogs may be useful as probes for distinguishing properties of PTH receptors.     

Different Scenarios for Inter-Protein Electron Tunneling: The Effect of Water-Mediated Pathways

Recent theoretical developments now allow for reliable calculation oftunneling matrix elements in unimolecular biological electron transferreactions that have been tested experimentally. Most biological ETprocesses, however, are bimolecular, or involve large-scale proteindomain motions. In this paper, initial advances in this direction bystudying the inter-protein electron transfer between cytochrome c ₂andthe photosynthetic reaction center. Utilizing an approach that integratesmolecular dynamics and the Pathways method, we have observed that theensemble dominant tunneling pathways in this reaction go though thetyrosine 162 or are water mediated.     

An interpretation of Cretaceous and tertiary biota in polar regions

Rich fossil floras and vertebrate faunas lived within the Arctic and Atarctic Circles during the Cretaceous and Paleogene. These occurrences seem explicable by the nature of the thermal environments in polar regions and by the physiological responses of plants and animals allied to those that lived there. There seems no need to invoke a lower tilt to the Earth's axis to provide greater warmth and light in polar regions to account for these fossil records.