Mapping the in vivo distribution of herpes simplex virions

We describe a method for labeling enveloped viral particles with a radiotracer, indium-111, allowing labeled viruses to be traced in vivo by nuclear imaging. After initial optimization experiments, a labeling efficiency of 83% (incorporation yield) was achieved for herpes simplex virus (HSV), resulting in a specific activity of 30 microCi/10(9) PFU. The labeling procedure did not significantly reduce the infectivity of the labeled virus and the virus did not release any significant amounts of the radionuclide within 12 hr after labeling. Sequential imaging of animals after intravenous administration of the labeled virus showed fast accumulation in the liver and redistribution from the blood pool (immediately after injection) to liver and spleen (12-24 hr after injection). At 12 hr after injection 7% of the virus-associated (111)In had been eliminated from the body and the remaining organ distribution of the virus was as follows: spleen 2.87 +/- 0.54% ID/g; liver, 2.60 +/- 0.51% ID/g; kidney, 0.98 +/- 0.31% ID/g; lung, 0.57 +/- 0.10% ID/g; [corrected] and lower amounts in other organs. Our results indicate that the described method allows qualitative and quantitative assessment of viral biodistribution in vivo by nuclear imaging.     

Internal versus external determinants of Schistosoma japonicum transmission in irrigated agricultural villages

Currently schistosomiasis transmission has been suppressed to low levels in many historically endemic areas of China by widespread use of praziquantel in human and bovine populations and application of niclosamide for snail control. However, re-emergent transmission has signalled the need for sustainable interventions beyond these repeated chemical interventions. To take advantage of ongoing investment in rural infrastructure, an index of schistosomiasis transmission potential is needed to identify villages where environmental modifications would be particularly effective. Based on a retrospective analysis of data from 10 villages in Sichuan Province, an index linked to the basic reproductive number is shown to have promise in meeting this need. However, a lack of methods for estimating the spatial components of the proposed metric and for estimating the import of cercariae and miracidia from neighbouring villages leads to significant uncertainty in its estimation. These findings suggest a priority effort to develop methods for measuring the free-swimming forms of the parasite in surface waters. This need is underscored by the high cost and limited sensitivity of current methods for diagnosing human infection and mounting evidence of the inadequacy of snail surveys to identify environments supporting low levels of transmission.     

Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor

A human member of the immunoglobulin superfamily was shown to mediate entry of several alphaherpesviruses, including herpes simplex viruses (HSV) 1 and 2, porcine pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). This membrane glycoprotein is poliovirus receptor-related protein 1 (Prr1), designated here as HveC. Incubation of HSV-1 with a secreted form of HveC inhibited subsequent infection of a variety of cell lines, suggesting that HveC interacts directly with the virus. Poliovirus receptor (Pvr) itself mediated entry of PRV and BHV-1 but not of the HSV strains tested. HveC was expressed in human cells of epithelial and neuronal origin; it is the prime candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect epithelial cells on mucosal surfaces and spread to cells of the nervous system.     

Characteristics and consequences of free-feeding ethanol ingestion during the first two postnatal weeks of the rat

In many smooth muscle tissues a minor M3-muscarinic acetylcholine (mACh) receptor population mediates contraction, despite the presence of a larger M2-mACh receptor population. However, this is not the case for guinea-pig uterus where radioligand binding and functional studies exclude a dominant role for M3-mACh receptors. Using tissue from animals pre-treated with diethylstilboestrol, estimates of antagonist affinity were made before and after selective alkylation procedures, together with estimates of agonist affinity to characterise the mACh receptor population mediating carbachol-induced contraction of guinea-pig isolated uterus. Antagonist affinity estimates made at 'protected' receptors were not significantly different from those made in untreated tissues. However all estimations were significantly different from those reported in guinea-pig ileum and atria. The rank order of affinities were atropine>zamifenacin=tripitramine> methoctramine. Carbachol-induced contractions were insensitive to the M4-selective muscarinic toxin MTx-3, or PD102807 (0.1 microM) ruling out a role for M4-mACh receptors. The agonist affinity value for L-660,863, a putative 'M2-selective' agonist of 5.44+/-0.30 (n=6) was significantly different from that reported in guinea-pig atria. In contrast, the pKA value for carbachol (4.22+/-0.17 n = 8) agrees with that reported for guinea-pig ileum. Carbachol-induced contractions were insensitive to pertussis toxin although carbachol-induced inhibition of forskolin-stimulated cyclic AMP production was attenuated, ruling out the involvement of Gi-proteins in contraction. Radioligand binding studies revealed a KD for N-[3H]-methylscopolamine of 0.12+/-0.05 nM and a Bmax of 147+/-18 fmol mg protein(-1). Antagonist affinity estimates made using competition binding studies supported previous data suggesting the presence of a homogenous population of M2-mACh receptors. These data suggest a small population of mACh receptors with an atypical operational profile which can not be distinguished using radioligand binding studies may mediate carbachol-induced contraction of guinea-pig isolated uterus.     

Technical problems in determining safe re-entry intervals

Organophosphate pesticide residues have been responsible for periodic outbreaks of acute intoxication among California fieldworkers for over 30 years. In 1971, California established 're-entry intervals' to protect workers against overexposure to these residues. These intervals are stipulated times which must elapse between pesticide application and entry into the field for work involving substantial foliar or soil contact. The re-entry strategy depends upon a relatively predictable relation between time post-application and the level of the pesticide residue. It now appears that there are thiophosphates for which the residue hazard is not related to time in a stable way. This circumstance and the continued occurrence of poisoning incidents have focused attention on the quantitative aspects of the relationships between pesticide residue and toxicological response in humans. In the last decade, considerable progress has been made in elucidating these relationships and it now appears to be possible to outline the data requirements for a comprehensive regulatory solution to this longstanding occupational health problem.     

Behaviours that indicate memory: Levels of expression.

Presents examples of research topics that require better criteria as to whether an individual has or has not expressed memory for a particular episode. Some historical reasons as to why this question has not been answered and some contemporary reasons why it is important to answer it now are suggested. Associated implications for fundamental issues of the memory process such as its ontogeny, selectivity, and physiological determinants are discussed. The fundamental observation is that an acquired memory affects relatively subtle behaviors even when having no effect on conventional indices of retention. Examples are drawn from a variety of memory experiments, some using animals and some using humans as Ss. It is concluded that an inevitable step in the study of memory would seem to be more explicit analysis of behavioral reflections of acquired memories, perhaps in terms of different levels at which a memory may be expressed. (French abstract) (65 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Planning art museum exhibitions

In this paper, we develop an integer programming model for use by art museums to plan cost effective temporary special exhibitions. By using a model based plan for organizing the changing exhibitions, the museum's professional staff can identify the timing and selection of exhibits to maximize attendance. We consider both the fixed and variable costs incurred in designing and organizing an exhibition as well as revenues generated by admission charges and museum shop sales after its installation.     

Suckling behavior in neonatal rats: Psychopharmacological investigations.

Examined the effects of various neurotransmitter antagonists on suckling behavior of 370 3- and 4-day-old Sprague-Dawley rat pups. Peripheral administration of 3 serotonergic antagonists (methysergide, methiothepin, and metergoline) and a cholinergic antagonist (scopolamine) were observed to markedly reduce suckling behavior of neonatal Ss. These effects appear to be centrally mediated, since intracisternal administration of small doses of all these drugs was observed to suppress suckling. The reduction in suckling induced by these antagonists did not appear to be a result of a debilitating effect of the drugs or to be due to any alteration in body temperature. In contrast, the opiate antagonist naloxone, the dopaminergic antagonist haloperidol, the alpha-noradrenergic antagonist phentolamine, and the beta-noradrenergic antagonist propranolol did not consistently produce any alteration in suckling behavior. Results suggest that the serotonergic and cholinergic systems may be functioning much earlier in ontogeny than previously suggested and may be involved in modulating suckling behavior in the early neonatal period. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eutrophication in peel inlet—II. Identification of critical uncertainties via generalized sensitivity analysis

A generalized sensitivity analysis was carried out on a phosphorous based model of cultural eutrophication processes in the Peel Inlet of Western Australia. The object of the analysis was to identify critical uncertainties in present knowledge of the system for the direction and planning of future research. The main hypothesis suggested by the results is that the nuisance alga, Cladophora aff. battersii, have access to nutrients in the interstitial water of the sediments in the Inlet and that a significant quantity of nutrient is deposited in the major area of Cladophora growth by river-borne sediment. Suggested areas for future research include investigation of mechanisms of deposition, release and remineralization of nutrients in the sediment, and of certain aspects of the physiology of Cladophora.