Measuring relative acetylcholine receptor agonist binding by selective proton nuclear magnetic resonance relaxation experiments.

A method is presented that uses selective proton Nuclear Magnetic Resonance (NMR) relaxation measurements of nicotine in the presence of the acetylcholine receptor to obtain relative binding constants for acetylcholine, carbamylcholine, and muscarine. For receptors from Torpedo californica the results show that (a) the binding constants are in the order acetylcholine greater than nicotine greater than carbamylcholine greater than muscarine; (b) selective NMR measurements provide a rapid and direct method for monitoring both the specific and nonspecific binding of agonists to these receptors and to the lipid; (c) alpha-bungarotoxin can be used to distinguish between specific and nonspecific binding to the receptor; (d) the receptor--substrate interaction causes a large change in the selective relaxation time of the agonists even at concentrations 100x greater than that of the receptor. This last observation means that these measurements provide a rapid method to monitor drug binding when only small amounts of receptor are available. Furthermore, the binding strategies presented here may be useful for the NMR determination of the conformation of the ligand in its bound state.     

First report on new evidence for the occurrence of Podocarpus and possible human presence at the mouth of the Amazon during the Late-glacial

Palynological studies on late Quaternary lake sediments from the region of the Amazon estuary, 100 km north-east of Belém, Pará State, Brazil, enable reconstruction of lowland Amazonian rain forest during the Late-glacial and Holocene periods. Late-glacial forests included populations of Podocarpus which suggests a distinct climatic cooling. Ilex was abundant in the early Holocene. Records of the mangrove taxon, Rhizophora, indicate rapid Atlantic sea-level rise in the beginning of the Holocene. High charcoal representation may reflect the first arrival of Amerindians in the Amazon coastal area, probably about 10 800 B.P.     

Stroboscopic nuclear magnetic resonance microscopy of arterial blood flow.

NMR microscopy was used to obtain transverse flow profiles of arterial blood flow in the rat carotid artery at 33 microns resolution. The images were gated to the EKG and correspond to identified regions of diastole. The profiles show that flow is laminar during this part of the heart cycle. These results provide the first direct view of blood flow profiles in arteries of submillimeter diameter and suggest that animals as small as juvenile rodents will serve as valuable models for hemodynamic studies. Extensions to flow during systole, stenoses, and flow in the vicinity of the carotid bifurcation are discussed.     

Four millennia of vegetation and environmental history above the Hyrcanian forest,northern Iran

Vegetation History and Archaeobotany - Past vegetation, fire, and climate dynamics, as well as human impact, have been reconstructed for the first time in the highlands of the Gilan province in the...     

Intensification of agriculture in southwestern Germany between the Bronze Age and Medieval period,based on archaeobotanical data from Baden-Württemberg

Vegetation History and Archaeobotany - A system of farming with an alternation of land use between being cultivated or left fallow as grassland (Feldgraswirtschaft) developed in southwestern...     

Late Holocene environmental change and human impact inferred from three soil monoliths and the Laguna Zurita multi-proxi record in the southeastern Ecuadorian Andes

Late Holocene vegetation, climate and fire dynamics of mountain forest and paramo ecosystems, as well as human impact, are presented from the upper Rio San Francisco valley, southeastern Ecuadorian Andes. Palaeoenvironmental changes, inferred from three soil monoliths, spanning an altitudinal gradient between 1,990 and 3,200 m and the high resolution multi-proxy sediment record from Laguna Zurita (2,590 m), were investigated by pollen, spore and charcoal analyses, in combination with XRF- and magnetic susceptibility-scanning. Three of the four pollen records show a marked change in the floristic composition between ca. 900 and 350 cal b.p. (interpolated age). Past fires have strongly influenced the floristic composition of the mountain rainforest ecosystem. Frequent fires, together with the relatively high occurrence of grasses and some Zea mays plantations document past human activities in the upper Rio San Francisco valley. A large number of areas of probably ancient Z. mays cultivation in the upper Rio San Francisco valley has been identified, using GIS-based calculation. High occurrences of Cyperaceae and Isoetes indicate the development of marshy lake shores in response to a lower lake level at Laguna Zurita before ca. 700 cal b.p. The decrease of Isoetes and Cyperaceae after ca. 1200 cal b.p. reflects a lake level rise, due to increasing moisture and/or human activities.     

Prior exposure to indole-3-carbinol decreases the incidence of specific cyclophosphamide-induced developmental defects in mice

BACKGROUND: Indole-3-carbinol (I3C) is a product of the hydrolysis of glucobrassicin that is found in cruciferous vegetables. I3C can intervene in toxic processes that are mediated by oxidative mechanisms because it possesses the chemical and pharmacokinetic properties necessary to provide a free radical trap. Cyclophosphamide (CP) is a bifunctional alkylating agent known to produce DNA damage and to cause developmental toxicity, including malformations, in laboratory animals. METHODS: Pregnant CD-1 mice were given a 100 mg/kg dose of I3C 24 or 48 hr before administration of 20 mg/kg CP on gestation day 10 (GD 10). Controls were given the vehicle (DMSO), I3C, or CP. This regimen was carried out to determine if I3C could protect against the developmental toxicity of alkylating agents, such as CP. Dams were sacrificed on GD 17 and their litters were examined for adverse effects. RESULTS: Treatment with I3C 48 hr before CP administration was associated with decreased fetal limb and tail malformations. Limb malformation incidences were reduced from 42% litters affected in the CP control to 16% in the I3C/CP 48-hr treatment group, and tail malformations were reduced from 45% in the CP control to 16% in the I3C/CP 48-hr treatment group, indicating a protective effect of prior exposure to I3C. I3C given 24 hr before CP had no significant protective effect, while having an apparently adverse consequence with regard to the incidence of talipes. CONCLUSIONS: Exposure of a developing mammal to indole-3-carbinol before exposure to cyclophosphamide during organogenesis can influence the teratogenicity of cyclophosphamide.