Iron-coproporphyrin III is a natural cofactor in bacterioferritin from the anaerobic bacterium Desulfovibrio desulfuricans

A bacterioferritin was recently isolated from the anaerobic sulphate-reducing bacterium Desulfovibrio desulfuricans ATCC 27774 [Romão et al. (2000) Biochemistry 39, 6841–6849]. Although its properties are in general similar to those of the other bacterioferritins, it contains a haem quite distinct from the haem B, found in bacterioferritins from aerobic organisms. Using visible and NMR spectroscopies, as well as mass spectrometry analysis, the haem is now unambiguously identified as iron-coproporphyrin III, the first example of such a prosthetic group in a biological system. This unexpected finding is discussed in the framework of haem biosynthetic pathways in anaerobes and particularly in sulphate-reducing bacteria.     

Cardiac responses to first ever submergence in double-crested cormorant chicks (Phalacrocorax auritus)

Heart rates were recorded from double-crested cormorant chicks during their first ever and subsequent voluntary head submergences and dives, as well as during longer dives made after the chicks were accustomed to diving. Despite variation between chicks, the cardiac response to first ever and subsequent voluntary submergence (head submergences and dives) was similar to the response observed in adult cormorants. Upon submersion the heart rate fell rapidly when pre-submersion heart rate was high (325–350 beats min⁻¹). The heart rate established within the first second of voluntary submergence was between 230 and 285 beats min⁻¹, well above resting heart rate (143 beats min⁻¹). The same initial cardiac response occurred during longer dives performed after the chicks were accustomed to diving. In these dives the heart rate remained at the level established on submersion, unlike the response observed in shallow diving adult cormorants in which the heart rate declined throughout the dive. The heart rate was also monitored in a separate group of chicks in which the first exposure to water was during whole body forced submergence. Again, the observed response was similar to the adult response, although the cardiac response of chicks to forced submergence was more extreme than to voluntary submergence. Our results do not support the hypothesis that learning (by conditioning or habituation) is involved in the cardiac adjustments to voluntary submergence. It is suggested that the initial cardiac adjustments are reflex in nature and this reflex is fully developed by the first submergence event. Although the nature of this reflex pathway is obscure, cessation of breathing before submersion and the close linkage between breathing and heart rate might provide a plausible mechanism.     

The pineal gland of the gerbil,Meriones unguiculatus

Morphometric analytical procedures were employed to study the pineal gland of the Mongolian gerbil following superior cervical ganglionectomy (SCGX). The purpose of this study was to define the effects of sympathetic denervation on the morphology of the gland at two time periods, 0500 and 1900 h (one hour before lights-on and lights-off, respectively). Fluorescence histochemistry was employed to determine catecholamine and indoleamine content in intact and denervated pineal glands. After SCGX, the pinealocytes decrease in size, concretions are prevented from forming, and the yellow fluorescence in the gland is lost. Following denervation a depression in the volume of most of the pinealocyte organelles, i.e., SER, RER/ribosomes, free cytoplasm, mitochondria and presumptive secretory vesicles, was also observed. However, synaptic ribbons increased in volume in the gerbils that had been killed at 1900 h. It appears that the sympathetic innervation to the pineal gland is a requirement for the presumptive secretory activity of the pinealocytes.     

Phytoremediative Capacity of Plants Enriched with Melatonin

Melatonin is an environmentally friendly-molecule with broad spectrum antioxidant capacity. Melatonin is widely present in the plant kingdom. High levels of melatonin exist in an aquatic plant, the water hyacinth, which is highly tolerant of environmental pollutants. Elevated levels of melatonin probably help plants to protect against environmental stress caused by water and soil pollutants. To investigate the potential relationships between melatonin supplementation and environmental tolerance in plants, pea plants were treated with high levels of copper in the soil. The results show that copper contamination kills pea plants; however, melatonin added to the soil significantly enhanced their tolerance to the copper contamination and, therefore, increased their survival. Based on the theory and these preliminary data, we speculate that melatonin could be used to improve the phytoremediative efficiency of plants against different pollutants. Since melatonin is safe to animals and humans as well as being inexpensive, it may be a feasible and cost-effective approach to clean environmental contaminations.Key Words: phytoremediation, plants, melatonin, antioxidant     

Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science

The presence of melatonin in plants is universal. Evidence has confirmed that a major portion of the melatonin is synthesized by plants themselves even though a homologue of the classic arylalkylamine N-acetyltransferase (AANAT) has not been identified as yet in plants. Thus, the serotonin N-acetylating enzyme in plants may differ greatly from the animal AANAT with regard to sequence and structure. This would imply multiple evolutionary origins of enzymes with these catalytic properties. A primary function of melatonin in plants is to serve as the first line of defence against internal and environmental oxidative stressors. The much higher melatonin levels in plants compared with those found in animals are thought to be a compensatory response by plants which lack means of mobility, unlike animals, as a means of coping with harsh environments. Importantly, remarkably high melatonin concentrations have been measured in popular beverages (coffee, tea, wine, and beer) and crops (corn, rice, wheat, barley, and oats). Billions of people worldwide consume these products daily. The beneficial effects of melatonin on human health derived from the consumption of these products must be considered. Evidence also indicates that melatonin has an ability to increase the production of crops. The mechanisms may involve the roles of melatonin in preservation of chlorophyll, promotion of photosynthesis, and stimulation of root development. Transgenic plants with enhanced melatonin content could probably lead to breakthroughs to increase crop production in agriculture and to improve the general health of humans.     

The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published.     

Comparative study of the activity/rest rhythms in young and old ringdove (Streptopelia risoria): correlation with serum levels of melatonin and serotonin

Aging is characterized by changes in the circadian rhythms of melatonin, serotonin, and sleep/wakefulness, alterations that affect sleep quality. The authors studied the circadian rhythms of serotonin and melatonin in young and old ringdoves (Streptopelia risoria) (2-3 and 10-12 yrs old, respectively), animals that are characterized by being monophasic and active by day, like humans. The aim was to correlate the indole rhythms with the animals' activity/rest periods. The animals were kept under a 12:12 h light/dark cycle, fed ad libitum, and housed in separate cages equipped for activity recording. Activity pulses were recorded with one actometer per animal (two perpendicular infrared transmitters) and were logged every 15 min by a computer program (DAS 16) throughout the experiment. Melatonin was measured by radioimmunoassay and serotonin by ELISA at intervals of 3 h (from 09:00 to 18:00 h) and 1 h (from 21:00 to 06:00 h), respectively. The results showed a reduction in nocturnal vs. diurnal activity of 89% and 61% in the young and old animals, respectively, with 100% considered to be the diurnal activity of each group. The amplitude of a cosine function fit to the melatonin concentrations of the old animals was half that of the young birds. The acrophase and nadir were at 02:00 and 14:00 h in the young and 01:00 and 13:00 h in the old animals, respectively. The amplitude of the corresponding cosine function fit to the serotonin concentrations in the old birds was one-third that of the young animals. The acrophase and nadir were at 15:00 and 03:00 h in the young and 16:00 and 04:00 h in the old animals, respectively. For both melatonin and serotonin, the concentrations in the young animals were significantly higher than in the old at most of the measurement times. There was a clear negative correlation between the circadian rhythms of activity and the serum melatonin levels in both young and old animals. The equivalent correlation for serotonin was positive, and stronger in the case of the young animals. The results suggest a possible relationship between the observed decline in the amplitude of the old animals' melatonin and serotonin rhythms and the lower percentage reduction in their nocturnal relative to diurnal activity pulses compared to the young animals. In conclusion, the circadian rhythms of melatonin and serotonin undergo alterations with age that could be involved in the changes in age-associated sleep.     

Thermodynamics of binding of regulatory ligands to tissue transglutaminase

Amino Acids - The transamidating activity of tissue transglutaminase is regulated by the ligands calcium and GTP, via conformational changes which facilitate or interfere with interaction with the...