Microbiology: a dangerous profession?

The history of science contains many cases of researchers who have died because of their professional activity. In the field of microbiology, some have died or have come close to death from infection by agents that were the subject of their research (Table 1). Infections that had a lethal outcome were usually accidental. Sometimes, however, researchers inoculated themselves with the pathogen or did not take preventive measures against the potential pathogen because they wanted to prove their hypotheses--or disprove someone else's--regarding the origin of the infection. Here is an overview of several episodes in the history of microbiology since the mid nineteenth century involving researchers or workers in fields related to microbiology who have become infected. They are considered here in their historical context to provide insights into some of the pillars of modern microbiology--The giants on whose shoulders several generations of microbiologists have stood to see further.     

Double fertilization: a personal view

 This year marks the 100th anniversary of the discovery of double fertilization by Nawaschin in St. Petersburg, Russia and, independently, Guignard in France. This discovery came at the end of a period of controversy about fertilization in angiosperms and ushered in a new period of intense research. Still, by 1950, there were many unanswered questions about double fertilization because of limitations of the light microscope. The introduction of the electron microscope stimulated new research and helped resolve some of the questions. My own research with the electron microscope and that of people who worked in my laboratory is recounted and some of the still unanswered questions raised. Received: 30 October 1997 / Accepted: 5 December 1997     

CAPRI: a Critical Assessment of PRedicted Interactions

CAPRI is a communitywide experiment to assess the capacity of protein-docking methods to predict protein-protein interactions. Nineteen groups participated in rounds 1 and 2 of CAPRI and submitted blind structure predictions for seven protein-protein complexes based on the known structure of the component proteins. The predictions were compared to the unpublished X-ray structures of the complexes. We describe here the motivations for launching CAPRI, the rules that we applied to select targets and run the experiment, and some conclusions that can already be drawn. The results stress the need for new scoring functions and for methods handling the conformation changes that were observed in some of the target systems. CAPRI has already been a powerful drive for the community of computational biologists who development docking algorithms. We hope that this issue of Proteins will also be of interest to the community of structural biologists, which we call upon to provide new targets for future rounds of CAPRI, and to all molecular biologists who view protein-protein recognition as an essential process.     

Olfactory functioning and callosotomy: a report of two cases

Two callosotomy patients with presumably intact anterior commissures were evaluated on a battery of olfactory tasks including sensitivity, discrimination, memory, identification, cross-modality matching, bilateral summation (dirhinic vs. monorhinic thresholds), and localization of odorants. One case was evaluated both pre- and post-surgery. He showed marked decrements after surgery in odor memory and in matching across modalities. After surgery, both patients were better able to name odorants presented to the left nostril than the right nostril. The patient who was asked to remember odorants that could be readily labeled was better able to remember those odorants presented to the left nostril. The findings that both cases performed equally well whether olfactory and tactile information was projected to the same hemisphere or a different one, that some bilateral summation was evident, and that the cases were unable to localize odorants suggests that the remaining neuronal pathways allow for some communication between hemispheres.     

The heart's Da Vinci code: a Renaissance at Keystone

At a recent Keystone symposium on "Molecular Pathways in Cardiac Development and Disease" in Colorado, significant advances in the understanding of heart development were discussed. The identification and isolation of cardiovascular progenitors, their modulation by secreted factors, and some tantalizing insights into cardiac regeneration were some of the highlights of what was characterized by some as a renaissance in cardiovascular development.     

Moving as a reason for pet relinquishment: a closer look

One of the most frequently given reasons for relinquishing a companion animal to an animal shelter is that the person or family is moving. Telephone interviews conducted with 57 caregivers who relinquished animal companions to a shelter in the midwestern United States covered details of the move, characteristics both of the caregivers and the animals, and efforts to avoid relinquishment. A human-nonhuman animal bonding scale also was administered. Although some participants had additional reasons for relinquishment, the majority had given up their pets solely because they were moving. Most had relatively low income, were moving for employment reasons, and were renting their homes. Landlord restrictions were an important factor in relinquishment. High scores on the bonding scale and spontaneous expressions of discomfort and sorrow suggest that external pressures overrode attachment to the animal and the pain of relinquishment.     

Membrane targeting: what a difference a G makes

Pleckstrin homology domains are modular domains that direct membrane targeting of their host proteins by binding to polyphosphoinositides; recent results have increased our appreciation of how some of these domains actually bind 3-phosphoinositides, and along the way thrown up some unexpected observations.     

Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas

We studied the expression of villin, a microfilament-associated, actin-binding protein typical of brush-border microvilli, in a variety of human carcinomas by applying immunofluorescence microscopy to frozen sections and immunoblotting methods to tissue extracts using a rabbit antiserum and a monoclonal antibody specific for villin. All of the 24 primary and metastatic colorectal adenocarcinomas tested were uniformly and strongly positive for villin, with the immunocytochemical labeling concentrated at the luminal cell margin. In poorly differentiated tumor areas, rudimentary tubules were stained. All of the six tubular adenocarcinomas of the stomach studied as well as two adenocarcinomas of the gall bladder and a hepatocellular carcinoma were also villin-positive. Villin was detectable in 12 of 14 adenocarcinomas of the pancreas; in some of these cases, its distribution was heterogeneous. Among 21 renal cell carcinomas investigated, positivity for villin was seen in nine of 13 clear cell tumors (especially those of grade II), and in all four chromophilic cell tumors; however, all four chromophobe cell tumors studied were negative. Four of 11 endometrial but none of nine ovarian carcinomas were (uniformly or focally) villin positive. Of 18 adenocarcinomas of the lung studied, one was uniformly and four focally positive for villin, while the remainder were negative. All of the other epithelial tumors studied, including 12 adenocarcinomas of the breast and seven epithelial or biphasic pleural mesotheliomas, were villin negative. Our results show that the expression of villin in intestinal epithelial cells is consistently maintained in their corresponding carcinomas, even when the organized brush-border structure has been lost. The presence of villin in some endometrial and pulmonary adenocarcinomas--in contrast to its absence in the respective normal epithelia--suggests that this protein is newly expressed during hyperplasia, dysplasia, or carcinogenesis. Determining the presence or absence of villin and its immunocytochemical staining pattern in metastatic adenocarcinomas may be of some help in determining the type and site of the primary tumor.     

Locomotor behaviour in Plio-Pleistocene sabre-tooth cats: a biomechanical analysis

The locomotor behaviour of some large extinct carnivores, including several species of Plio-Pleistocene sabre-tooth cats, is here reconstructed, based on a comparison of the cross-sectional geometric properties and linear dimensions of their femora and humeri with those of large modern carnivores. The long bones are modelled as simple beams, thereby allowing the use of basic beam theory in assessing relevant functional parameters such as second moments of area of the diaphyses when subjected to compressive and bending stresses. Three Pleistocene carnivores, Smilodon fatalis, Homotherium serum , and Panthera atrox seem to have had ecological and functional equivalents among the late Miocene-Early Pliocene genera, Barbourofelis, Machairodus , and Nimravides , respectively. Barbourofelis and Smilodon were 'cat-like'in dental morphology but some structural characteristics of their limb bones had 'bear-like'affinities. Machairodus and Homotherium were cursorial, whereas Nimravides and P. atrox display the limb morphology of true ambush predators. Various aspects of the postcranial skeleton of some of these extinct carnivores suggest that they may have employed locomotory gaits that lack modern analogs.     

Spontaneous insertions into cosmid vector: a warning

During the course of characterization of a human genomic library we found that some of the selected pNNL cosmid clones carried only very short inserts. In addition, several clones that did contain full-length inserts were found to be unstable and generated repeated deletions of various portions of their inserts. Moreover, all the clones examined displayed rearrangements in the vector portions. The rearranged clones that were characterized by restriction mapping were found to have deletions starting between ClaI and HindIII in the region of the cos segment of the pNNL vector used in the construction of the library. We determined the nucleotide sequence of the 1300-bp EcoRI-PvuII segment located in the cos region, and by the computer search we found that it contains Escherichia coli insertion elements IS1.     

Eo: a history of a mutation

Eighteen mouse t haplotype-carrying strains were found not to express cell-surface E molecules controlled by class II genes of the H-2 complex (= Eo strains). Northern and Southern blot analysis of these and other, non-t strains that also fail to express the E molecule, has revealed two kinds of defect. Three strains (CRO437, tw2, and presumably to) were found to transcribe the E alpha gene, but they were not able to convert the message into a functional protein. All other Eo strains fail to transcribe the E alpha gene because of a deletion encompassing the promoter region, the RNA initiation site, and the first exon. The length of the deletion is approximately 650 +/- 50 bp. These two defects closely resemble those found previously in standard inbred strains carrying the H-2f, H-2q (failure of E mRNA to be expressed functionally), H-2b, and H-2s (deletion of a part of the E alpha gene) haplotypes. In particular, the location and length of the E alpha deletion appear to be the same in the strains carrying this mutation. The E alpha deletion is in linkage disequilibrium with certain alleles at other H-2 loci in some of the strains. These observations, combined with the growing evidence that H-2 haplotypes associated with t chromosomes derive from a single ancestral haplotype, suggest that the E alpha deletion is an old mutation and that it has been disseminated in mouse populations by the t chromosomes.     

Size-biased dispersal prior to breeding in a damselfly: conflicting evidence from a natural population

Summary The sizes of adult damselflies (Coenagrion puella) that were marked at emergence and recaptured as mature adults at the natal pond and at the next nearest pond were compared. In addition the sizes of a much larger sample of animals that were never recaptured were compared with those that returned to breed at the natal pond. There was no statistically significant difference in mass or wing length between adults in either comparison. This result contrasts with a previous study on a coenagrionid species in which, from an equally small sample, some evidence of size-biased dispersal was detected (dispersing adults were larger than those returning).     

Large intra-individual variability of plasma cytokines in healthy young men: a two 24-h study over a month

Cytokine levels in blood are not yet fully considered as biomarkers for disease even if some significant progresses have been made in linking certain cytokines to some diseases. The aim of this study was to look for the stability of some cytokines in blood collected in two different days separated by one month. Fifteen healthy young men aged 20–30 years were selected for this study. Each subject participated in two 24-h sessions spaced a month apart. Blood sample was taken at 11:00, 17:00, 22:00, 01:00, 04:00, 06:00, and 08:00. Concentrations of interleukin-6, interleukin-1-receptor antagonist, soluble IL-2 receptor, interleukin-1 beta, and interleukin-2 were measured in serum. The circadian pattern of each variable was compared between the two days. The results show that there is no reliability for the measured cytokines. This study shows that cytokine levels measured in blood are neither reliable variables nor considered as stable markers in healthy subjects.     

Stobadine: bellwether of a broader view of drug actions

Stobadine was recognized early in its development as having antioxidant properties. A number of laboratories found associations between the antioxidant properties of stobadine and its potential beneficial effects. We found that stobadine acted as an antioxidant in a modification of an oxygen radical absorbance capacity (ORAC) assay. Similar results were observed with other drugs, including tirilazad and pramipexole. We suggest that stobadine and certain other drugs exhibit antioxidant properties in both hydrophilic and hydrophobic environments. Other drugs have been developed for their antioxidant properties and some currently marketed drugs have antioxidant properties. Although they may not have been explicitly sought during development, at least some of the beneficial effects may be related to antioxidant properties and/or scavenging of free radicals. Because stobadine was one of the first drugs for which useful properties were associated with its antioxidant actions, stobadine may be seen as a bellwether of a broader view of pharmacological actions--a view that encompasses antioxidant properties as a useful basis of therapeutic effects.     

Giardiasis in guinea pigs: a case report

During the quarantine of 15 guinea pigs acquired from a breeder in February 1983, several became weak and moribund, and one died. A tremendous number of Giardia sp. bodies were detected from stamp smear preparations of the duodenal contents of some necropsied animals in this group. Histopathological examinations of the intestine revealed slight inflammatory changes and cystic enlargement of the crypts in the duodenal and jejunal mucous membranes. From these findings and the fact that other major pathogenic organisms were not detected, this disease was diagnosed as giardiasis in guinea pigs.     

Tracking a fluctuating environment: a study of sampling

The problem of how animals keep track of unpredictable changes in the profitability of foraging sites was studied. An optimality model was used to predict the frequency with which a forager should sample a foraging site in which the probability of reward fluctuates randomly between high and low. The alternative foraging site is stable and offers an intermediate probability of reward. The model was tested with pigeons in a shuttle-box the two ends of which represented the two foraging sites. The pigeons succeeded in tracking the changes in the fluctuating site and the payoff attained was close to the optimum. Variations in the frequency of sampling between experimental treatments were in qualitative agreement with the model for some treatments but not others. The quantitative details of sampling behaviour were not as predicted by the optimality model, but many features could be accounted for by a mechanistic model of choice. The pigeons' choice rule, although different from that of the optimality model, is one that produces near-optimal payoffs under the conditions of this experiment.     

Spontaneous phospholipid transfer: development of a quantitative model

The effects of lipid structure on the kinetics of spontaneous transfer of a series of phosphatidylcholines have been determined. Donors, which were model-reassembled high-density lipoproteins composed of apo A-I, 1-palmitoyl-2-oleoylphosphatidylcholine, and a trace of a radiolabeled lipid, were mixed with acceptors, which were human low-density lipoproteins. Within a series of phosphatidylcholines, the addition of double bonds and methylene units, respectively, increased and decreased the rate of transfer in a predictable way. An equation that predicts the rates of transfer of a large number of diacylglycerides and phosphoglycerides from any lipoprotein has been empirically derived from these data. The transfers of phosphatidylcholines that contain superpolyunsaturated fatty acids (four or more double bonds) do not obey the derived equation, probably due to limitations on the number of conformational degrees of freedom in these lipids. The range of measured transfer halftimes extends from less than 2 h to more than 12 days. Thus, the spontaneous transfer halftimes of some (but not all) lipids are short compared to the lifetime of lipoproteins in plasma. These results suggest that some lipids transfer among lipoproteins and cells via a spontaneous mechanism while others require specific transfer factors or hydrolysis to achieve this within a physiologically significant time frame.     

Scraping a living: a review of littorinid grazing

Littorinid snails are predominantly herbivorous and the versatility of their radulae enables them to feed on a variety of macroscopic and microscopic plants in a diversity of habitats. Some are selective feeders preferring some species of algae to others, and rejecting some even after a prolonged period of starvation. Different species of snail exhibit different preferences. The factors affecting the attractiveness and edibility of food plants are discussed and food value considered.Foraging behaviour of littorinids is briefly reviewed in relation to the influence of chemical cues from the algae. Littorinids appear to be able to select or reject algae without having ingested them, having perceived the plants from a distance, moving towards favoured foods (or habitat-providing plants) and away from those that it rejects. The nature of the chemical cues emitted by the algae is discussed. Temporal patterns of foraging activity show some evidence of an endogenous component which can be overridden by responses to environmental conditions. These patterns place restraints on energy intake.The structural and chemical defences used by algae against littorinid grazing are considered. The importance of polyphenolic compounds is evaluated. The effects of grazing as a selective agency and a factor influencing algal populations are discussed. There is some evidence that life history patterns are a response to grazing. The influence of external physical factors, such as salinity on grazing pressure is demonstrated.Finally, the impact of littorinid snails on intertidal communities is assessed in relation to their abundance and biogeographical distribution. The relative importance of littorinids is contrasted on shores possessing or lacking limpets.     

Administration of a maple syrup extract to mitigate their hepatic inflammation induced by a high-fat diet: a transcriptome analysis

Effects of the administration of maple syrup extract (MSX) on hepatic gene expression were investigated in mice fed a high-fat diet. Gene annotation enrichment analysis based on gene ontology revealed some changes in the expression of genes related to lipid metabolism and the immune response in MSX-fed mice. Detailed analysis of these data indicated that MSX ingestion mitigates hepatic inflammation.