Irreversible depigmentation of dark mouse hair by T-2 toxin (a metabolite ofFusarium sporotrichioides) and by calcium pantothenate

Summary T-2 toxin, a trichothecene metabolite of several Fusarium spp. causes depigmentation of dark mouse hair at the site of its application. Calcium pantothenate, though usually considered as antigreying factor, caused depigmentation at the site of its i.p. injections, at high concentration.     

Origin of ammonia excreted by trout gill (Salmo gairdneri)]

In the perfused head of Trout the gills are the site of ammonia clearance which corresponds exactly to the appearance rate of ammonia in the external medium. Thus metabolic production of ammonia by the gill apparently does not participate to its excretion. Under ammonia-free Ringer perfusion however, endogenous production is observed and ammonia is excreted in both external and internal media.     

Host recognition by toxigenic plant pathogens

Certain fungal pathogens release host-selective (or host-specific) toxins (HST) as a host recognition factor during spore germination at the infection site on plants. Prior to penetration of the pathogen into its host, the released toxin specifically binds to a putative receptor on the host cells and initiates signaling mechanisms leading to pleiotropic effects on cells. Of these, the crucial one negates the general and inducible defense reactions of the cells. This is accomplished by a signal from the HST, which is transduced through a path way at or near the step of plasma membrane modulation, which is directly or indirectly triggered by the HST. This mechanism operates even though the toxin may affect mitochondria or chloroplasts as the primary target organelle. The fungal spore is able to penetrate the so-called 'narcotized cell' and completes the initial colonization of the host. The host recognition process may take place without necessitating host cell death, even in the case of perthophytic parasites. At the molecular level, HST-mediated recognition of the host by a pathogen requires strict stereochemical precision like a lock and key.     

Sensitivity of follicular melanoblasts in newborn mouse skin to tritiated thymidine: Evidence for a long term retention of label

Summary Injection of tritiated thymidine into newborn mice results in a progressive greying of hair that does not begin until after the first hair coat is grown. After a year the depigmentation is appreciable (about 60% of the hair are white). The effect cannot be simulated by external irradiation of newborn mice or by the administration of radioactive uridine or methionine. The effect can best be explained by a long-term retention of radioactivity in the DNA of melanocyte stem cells (melanoblasts) in spite of several rounds of cell division. This could be achieved by labelling the strands of DNA destined to act as templates throughout life by being selectively retained in the stem line as described in Cairns' hypothesis.Acknowledgments. This work was supported by grants from the Cancer Research Campaign. I am indebted to Joan Bullock for her careful, patient help with these experiments. CSP is a fellow of the Cancer Research Campaign.     

Modification of the skin feeding site by tick saliva mediates virus transmission

A tick vector of Thogoto (THO) virus was shown to secrete a factor in saliva which potentiates the transmission of THO virus to uninfected ticks feeding on an apparently non-viraemic host. The effect of the saliva activated transmission (SAT) factor on the virus occurred at the site of inoculation in the skin and was apparent even when the virus was introduced 3 days after the SAT factor. The results suggest that tick saliva can play an important role in disease transmission by virtue of host modification at the site of feeding.     

High affinity of quinidine for a stereoselective microsomal binding site as determined by a radioreceptor assay

Summary The techniques of the radioreceptor binding assay were applied to detect stereoselective binding of quinidine and quinine to a site on human liver microsomes. Binding of³H-dihydroquinidine was 50% inhibited by 20–100 nM quinidine, while its enantiomer quinine did not displace the³H-ligand at concentrations up to 500 nM. This stereoselectivity agreed with the affinity values measured by functional enzyme assays of cytochrome P450 activity using sparteine or debrisoquine as substrates.Acknowledgments. We thank C. Ulpian for advice and assistance. We also thank Dr M. Robinette of Metro Organ Retrieval and Exchange and Dr T. Inaba for making human hepatic tissue available. This work was supported by grants from the Medical Research Council of Canada.     

Modification of the skin feeding site by tick saliva mediates virus transmission.

A tick vector of Thogoto (THO) virus was shown to secrete a factor in saliva which potentiates the transmission of THO virus to uninfected ticks feeding on an apparently non-viraemic host. The effect of the saliva activated transmission (SAT) factor on the virus occurred at the site of inoculation in the skin and was apparent even when the virus was introduced 3 days after the SAT factor. The results suggest that tick saliva can play an important role in disease transmission by virtue of host modification at the site of feeding.     

Colloidal carbon as a multilevel marker for experimental lesions

The use of colloidal carbon for the anatomical marking of experimental lesions is proposed. Visualization of the lesion site may be readily performed through this procedure at the macroscopic, light microscopic, and ultrastructural levels in the same specimen. The chemical inertness of the marker and its relative permanency greatly add to its usefulness.     

Colloidal carbon as a multilevel marker for experimental lesions

Summary The use of colloidal carbon for the anatomical marking of experimental lesions is proposed. Visualization of the lesion site may be readily performed through this procedure at the macroscopic, light microscopic, and ultrastructural levels in the same specimen. The chemical inertness of the marker and its relative permanency greatly add to its usefulness.     

Inhibition of 9-amino-2-methoxy-6-chloroacridine fluorescence by human serum albumin]

Study of the fluorescence quenching of 9-amino 2-methoxy 6-chloro acridine upon serum albumine additions reveals a single protein fixation site. Characteristic values of thermodynamic functions are obtained from experiments at different temperatures.     

Determinant of efficiency of a monomeric enzyme: acceleration by site-specific molecules for trypsin.

The interaction of a specific ligand at substrate binding site was shown to be responsible for the catalytic efficiency of trypsin. The reasoning of 'induced fit' theory was refined by kinetic analysis of characteristic properties of 'inverse' substrates.     

Degeneration of unmyelinated axons in the dental root canal induced by 6-OH-dopamine

Summary The pulpal nerve fibres of feline incisors were examined ultrastructurally after i.v. administration of 6-OH-dopamine. The presence of degenerating unmyelinated fibres at this site provides conclusive morphological evidence that sympathetic fibres enter the dental pulp.     

Functional, biochemical and genetic diversity of prokaryotic nitrate reductases

Prokaryotic nitrate reduction can serve a number of physiological roles and can be catalysed by a number of biochemically distinct nitrate reductases. Three distinct nitrate reductase classes can be indentified in prokaryotes, NAS, NAR and NAP. NAS is located in the cytoplasmic compartment and participates in nitrogen assimilation. NAR is usually a three-subunit complex anchored to the cytoplasmic face of the membrane with its active site located in the cytoplasmic compartment and is involved in anaerobic nitrate respiration. NAP is a two-subunit complex, located in the periplasmic compartment, that is coupled to quinol oxidation via a membrane anchored tetraheme cytochrome. It shows considerable functional flexibility by participating in anaerobic respiration or redox energy dissipation depending on the organism in which it is found. The members of all three classes of enzymes bind the bis-molybdopterin guanine dinucleotide cofactor at the active site, but they differ markedly in the number and nature of cofactors used to transfer electrons to this site. Analysis of prokaryotic genome sequences available at the time of writing reveals that the different nitrate reductases are phylogenetically widespread.     

Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine.

Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca++-protein activator (50% inhibition by 2 x 10(-5) M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca++ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.     

Walls of resonance: Institutional history and the buildings of the University of Manchester

The built environments of universities are useful for telling stories about their development. Exteriors – walls, windows, doorways, the relative positioning of different facilities – are particularly suited to broad institutional narratives: the rise and decline of scientific disciplines, for instance, or the institution’s changing relationship with benefactors and the wider public. Exteriors are also conveniently accessible to public audiences.This paper explores the possibilities through the case of the University of Manchester. The approach is in a sense the converse of industrial archaeology, which seeks to understand the functioning of a site from what survives of its material form: here, we have begun with knowledge gained largely from document sources, and aim to bring it to life for visitors by pointing to the material consequences. Connecting doors and architectural symmetries illustrate founding unifications and alliances; infilling and glassing-over, constrained expansion; grand but obscured frontages, displaced priorities.Populating the site with accounts of its lived existence is a powerful tool to communicate history, but it is important not to create an ‘official’ memorialisation: audiences often know the site at first hand, and may question any received version. I conclude by calling for a reflexive treatment, mapping the histories of the stories themselves.     

Inducement of blood vessel formation by ovarian extracts from mice injected with gonadotropins

Summary Ovarian extracts prepared from immature mice injected with human chorionic gonadotropin (hCG) and pregnant mare serum gonadotropin (PMSG) were assayed for angiogenic activity. The assay method consisted of implanting a film coated with ovarian extracts to the lateral wall of the m.rectus abdominus of a mouse for 20 days and examining the site for vascularization. The higher angiogenic activity obtained with PMSG-treated extract may be related to its follicle stimulating activity.Acknowledgment. Part of this work was supported by a grant from The Ministry of Education, Japan (No. 576165).     

Fragile site Xq27 and metabolism of monocarbons

After confirming the increase of the fragility of the site Xq27 by methotrexate and its decrease by 5-formyltetrahydrofolate, it is observed that L-serine, 5-amino-levulinate and L-4-hydroxy-proline at millimolar concentrations, reduce considerably the frequency of the anomaly in lymphocyte cultures. The possible relationships between this chromosomal marker, the one carbon cycle,and mental deficiency of the patients, are discussed.     

Host recognition by toxigenic plant pathogens

Certain fungal pathogens release host-selective (or host-specific) toxins (HST) as a host recognition factor during spore germination at the infection site on plants. Prior to penetration of the pathogen into its host, the released toxin specifically binds to a putative receptor on the host cells and initiates signaling mechanisms leading to pleiotropic effects on cells. Of these, the crucial one negates the general and inducible defense reactions of the cells. This is accomplished by a signal from the HSt, which is transduced through a path way at or near the step of plasma membrane modulation, which is directly or indirectly triggered by the HST. This mechanism operates even though the toxin may affect mitochondria or chloroplasts as the primary target organelle. The fungal spore is able to penetrate the so-called narcotized cell and completes the initial colonization of the host. The host recognition process may take place without necessitating host cell death, even in the case of perthophytic parasites. At the molecular level, HST-mediated recognition of the host by a pathogen requires strict stereochemical precision like a lock and key.     

Inhibition of the fluorescence of acridine, 9-aminoacridine, and 9-amino-6-chloroacridine by human serum albumin]

Study of fluorescence quenching of acridine and some 9 amino acridines upon human serum albumin additions reveals a single protein fixation site. Characteristic values of thermodynamic functions are obtained from experiments at different temperatures.     

Tropomodulins and tropomodulin/tropomyosin interactions

The tropomodulins are a family of proteins that cap the slow-growing (pointed) end of actin filaments and require tropomyosin for optimal function. Tropomodulin is an elongated molecule with a molecular mass of about 40 kDa. The C-terminal half of tropomodulin contains one compact cooperatively melting domain, whereas the N-terminal half has no cooperatively melting structure. The N-terminal half of tropomodulin contains two tropomysin-binding sites and a tropomyosin-dependent actin-binding site, the tropomyosin-independent actin-binding site being located at the C terminus. One tropomodulin molecule binds two tropomyosin molecules, and thus one molecule of tropomodulin is necessary and sufficient for capping at the pointed end. Tropomyosin/tropomodulin interactions are isoform specific. Differences in tropomyosin affinity for the two binding sites in tropomodulin may regulate its correct positioning at the pointed end as well as effectiveness of capping the actin filament. Received 30 July 2007; received after revision 2 October 2007; accepted 10 October 2007