Monoclonal anti-I-A antibody reverses chronic paralysis and demyelination in Theiler's virus-infected mice: critical importance of timing of treatment

Susceptibility to demyelination caused by the WW isolate of Theiler's murine encephalomyelitis viruses is linked to class II genes of the major histocompatibility complex. SJL/J (H-2s) mice, expressing only I-As class II gene products of the major histocompatibility complex, are highly susceptible to Theiler's murine encephalomyelitis virus infection with the WW virus isolate, with chronic paralysis and severe inflammation and demyelination in the central nervous system. The effect of in vivo administration of anti-I-As monoclonal antibodies on Theiler's murine encephalomyelitis virus infection was observed. SJL/J mice were treated in various protocols pre- or postinfection. Anti-I-As monoclonal antibody reversed chronic paralysis and reduced inflammation and demyelination when given after the establishment of persistent infection. The effect was long lasting, but clinical signs, inflammation, and demyelination recurred 2 months after treatment ceased. Anti-I-As antibodies had no effect on viral titers within the central nervous system. The timing of the administration of monoclonal antibodies was critical. Administration of anti-I-As before the establishment of the persistent infection resulted in fatal encephalitis.     

Gametogenesis in Chlamydomonas eugametos: I. Light Requirements

Male and female mating types of Chlamydomonas eugametos Moewus show an absolute light requirement for gametogenesis. Increasing light intensity from 0.3 to 1.2 mw cm⁻² during nitrogen starvation (a precondition for gametogenesis) caused an increase in gametogenesis throughout a 28-hour period. Gametogenesis was measured by determining the percentage of paired cells after a 1-hour mixing period. Light requirements for the male and female differed. There was a 9-hour lag period in gametogenesis in the male, but no lag in the female. Gametogenesis was reduced 50% in the female and 90% in the male when 6.0 μm 3-(3,4-dichlorophenyl)-1, 1-dimethyl-urea was in the N-starvation medium. Sodium acetate, 1.8 mm, in the N-starvation medium increased gametogenesis in both mating types and eliminated the 9-hour lag in the male for cells irradiated for 3, 6, 9, 12, 15, 18, or 23 hours during the last part of a 23-hour N-starvation period. Sodium acetate concentrations higher than 1.8 mm inhibited the mating process. 3-(3,4-Dichlorophenyl)-1, 1-dimethylurea inhibition of gametogenesis was decreased in the male but increased in the female, when sodium acetate was added to the N-starvation medium. These results indicate a nonphotosynthetic as well as a photosynthetic role for light in the gametogenesis of both mating types. Also, the male will not undergo gametogenesis unless a required amount of energy is provided either in the medium or through photosynthesis.     

The rate of attachment of amoebae to the substratum: a study of nuclear-cytoplasmic relationships

The rate of attachment to the substratum was found to be a strain specific character of certain large free-living amoebae. Two strains, which differed significantly in this respect, were compared with regard to the rate of attachment of enucleated cytoplasm, nuclear-cytoplasmic hybrids and amoebae injected with cytoplasm from another strain. It was found that both the nucleus and the cytoplasm of the more rapidly attaching strain were able to transmit this character to amoebae of the more slowly attaching strain. The possible mechanisms underlying attachment and transmission of the rate of attachment are discussed.     

The ultrastructure of the spermatozoon and spermiogenesis in Cryptocotyle lingua (digenea: Heterophyidae)

During spermiogenesis two lateral flagellar processes and a median process arising from the apex of the zone of differentiation, fuse to form the elongated unipartite spermatozoon. Two axial units, therefore, with the ‘9+1’ pattern of microtubules are incorporated into the spermatozoon. The nucleus, in the head region, contains dense lamellar subunits arranged in a spiral in the long axis. These are formed by condensation of the chromatin during spermiogenesis. The single elongated mitochondrion, resulting from early fusion of small mitochondria, extends through the head and middle regions of the spermatozoon. Peripheral microtubules, present originally in the zone of differentiation, are arranged in straight dorsal and ventral rows, along the length. β glycogen particles accumulate in the spermatozoa after they have separated from the residual cytoplasm. Spermatozoa are present in the testes on the second day after infection of the bird host and accumulate in the vesicula seminalis from the third day onwards.     

In vitro studies of membrane protein folding.

The study of membrane protein folding is a new and challenging research field. Consequently, there are few direct studies on the in vitro folding of membrane proteins. This review covers work aimed at understanding folding mechanisms and the intermolecular forces that drive the folding of integral membrane proteins. We discuss the kinetic and thermodynamic studies that have been undertaken. Our review also draws on closely related research, mainly from purification studies of functional membrane proteins, and gives an overview of some of the successful methods. A brief survey is also given of the large body of mutagenesis and fragment work on membrane proteins, as this too has relevance to the folding problem. It is noticeable that the choice of solubilizing detergents and lipids can determine the success of the method, and indeed it appears that particular lipid properties can be used to control the rate and efficiency of folding. This has important ramifications for much in vitro folding work in that it aids our understanding of how to obtain and handle folded, functional protein. With this in mind, we also cover some relevant properties of model, lipid-bilayer systems.     

Evaluation of ultrafiltration cartridges for a water sampling apparatus

Aims:  To determine the efficiency of various ultrafiltration cartridges (UFC) in concentrating test micro-organisms from drinking water.
Methods and Results:  Replicate drinking water samples from three potable water supplies were dosed with Bacillus anthracis Sterne, Francisella tularensis LVS, Yersinia pestis CO92, bacteriophages MS2 and phi-X174, and Cryptosporidium parvum. The test micro-organisms were dosed together in 100 l of water, which was then recirculated through one of five different UFC until the retentate volume was reduced to c. 500 ml. The micro-organisms were assayed before and after ultrafiltration concentration and per cent recoveries were calculated. There were nine statistically significant differences among pairs of filters out of a possible 180 different combinations of UFC, test micro-organisms, and water types.
Conclusions:  No filter consistently performed better or worse than the others for each test micro-organism in all water samples tested.
Significance and Impact of the Study:  This study provides performance data on the ability of several different UFC to concentrate a panel of test micro-organisms from three sources of potable water. Water utilities and first responders may use these data when selecting UFC for use in emergency response protocols. This study also provides additional data as to the efficacy of ultrafiltration for recovering bacteria, virus-like particles, and protozoan oocysts from water samples.     

Early rise in inflammation and microcirculatory disorder determine the development of autoimmune pancreatitis in the MRL/Mp-mouse

Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis and mimics pancreatic cancer. Although there is strong interest in research, etiology and pathophysiology of AIP are still unknown. Therefore, we analyzed a total of 92 MRL/Mp-mice of either sex, which are prone to develop AIP, in four different age groups (8-12, 16-20, 24-28, and 32-40 wk). Using intravital fluorescence microscopy, histology, laboratory analysis, and Western blot, onset, severity, and pathophysiological mechanisms of AIP were evaluated. Female animals showed in vivo an age-dependent increase of intrapancreatic leukocyte accumulation, as well as a loss in functional capillary perfusion. In contrast, intrapancreatic inflammation in male mice was less pronounced and not age dependent. Furthermore, pancreatic tissue specimen of female animals exhibited major organ destruction with significantly higher values of mean pathological scores (1.5 +/- 0.3 vs. < or =0.2; P < 0.05), as well as significantly increased CD4-, CD8-, CD11b-, and CD138-positive cells compared with male animals of the same age. Interestingly, there was a significant positive correlation between intravascular leukocyte adherence and the histopathological score of the pancreas, indicating a determining role of the innate immune system for the late onset of AIP. The present study shows that the onset of AIP is characterized by an inflammatory response and microcirculatory failure, most probably constituting initiators and propagators of this autoimmune disease.     

Understanding reversals in the relative strength of sexual selection on males and females: a role for sperm competition?

Sperm competition affects sexual selection intensity on males, but models suggest it cannot affect the relative intensity of sexual selection on males compared to females. However, if sperm competition depresses the payoff for male multiple mating, it could affect the relative intensity of sexual selection and even cause sexual selection to be more intense on females than males (reversal of typical pattern). To evaluate how sperm competition, energy availability, and parental investment affect the intensity of sexual selection on each sex, I constructed a simulation model using the relationship between fecundity and number of mates to estimate sexual selection gradients. Unlike earlier models, I include a trade-off between paternal investment and sperm competition ability. The amount of energy available for reproduction affects the sexual selection gradient for each sex. Reversals in the sex experiencing stronger sexual selection do occur when additional paternal investment reduces a male's ability to compete for fertilizations within females. The shape of the distribution of mates for each sex (determined by mate competition) is also important. Output from the model is qualitatively similar to empirical data from insects with paternal investment. This model challenges previous thinking about the role of sperm competition in sex-role reversal.     

History of infection with different male-killing bacteria in the two-spot ladybird beetle Adalia bipunctata revealed through mitochondrial DNA sequence analysis

The two-spot ladybird beetle Adalia bipunctata (Coleoptera: Coccinellidae) is host to four different intracellular maternally inherited bacteria that kill male hosts during embryogenesis: one each of the genus Rickettsia (alpha-Proteobacteria) and Spiroplasma (Mollicutes) and two distinct strains of Wolbachia (alpha-Proteobacteria). The history of infection with these male-killers was explored using host mitochondrial DNA, which is linked with the bacteria due to joint maternal inheritance. Two variable regions, 610 bp of cytochrome oxidase subunit I and 563 bp of NADH dehydrogenase subunit 5, were isolated from 52 A. bipunctata with known infection status and different geographic origin from across Eurasia. Two outgroup taxa were also considered. DNA sequence analysis revealed that the distribution of mitochondrial haplotypes is not associated with geography. Rather, it correlates with infection status, confirming linkage disequilibrium between mitochondria and bacteria. The data strongly suggest that the Rickettsia male-killer invaded the host earlier than the other taxa. Further, the male-killing Spiroplasma is indicated to have undergone a recent and extensive spread through host populations. In general, male-killing in A. bipunctata seems to represent a highly dynamic system, which should prove useful in future studies on the evolutionary dynamics of this peculiar type of symbiont-host association.