Role of NK cells in protection of mice against herpes simplex virus-1 infection

Natural killer (NK) cells have been implicated in the recognition and killing of a variety of virus infected target cells in vitro, yet their role in vivo remains uncertain. In these experiments, the role of NK cells in the regulation of resistance to herpes simplex virus-1 (HSV-1) was studied. Adult C57BL/6 mice are resistant to HSV-1 (HFEM strain), but are rendered highly susceptible by treatment with cyclophosphamide 24 hr prior to infection. In this model, passive transfer of 10(8) normal spleen cells or 10(7) poly I:C-treated spleen cells provided protection for 72% of the recipients. Spleen cells from NK cell-deficient beige mice similarly treated failed to engender passive protection. The phenotype of the cells responsible for transferring protection was NK1.1+, and asialo GM1+. Transfer of NK cells resulted in marked reduction of HSV titers in the livers and brains of recipients. These experiments provide direct evidence for a role for NK cells in protection against development of fatal HSV infection in mice.     

Microsporogenesis and tapetal development in fertile and cytoplasmic male-sterile sugar beet (Beta vulgaris L.)

Summary The development of sporogenous and tapetal cells in the anthers of male-fertile and cytoplasmic male-sterile sugar beet (Beta vulgaris L.) plants was studied using light and transmission electron microscopy. In general, male-sterile anthers showed a much greater variability in developmental pattern than male-fertile anthers. The earliest deviation from normal anther development was observed to occur in sterile anthers at meiotic early prophase: there was a degeneration or irregular proliferation of the tapetal cells. Other early aberrant events were the occurrence of numerous small vesicles in the microspore mother cells (MMC) and a disorganized chromatin condensation. Deviations that occurred in sterile anthers at later developmental stages included: (1) less distinct inner structures in the mitochondria of both MMC and tapetal cells from middle prophase onwards. (2) dilated ER and nuclear membranes at MMC prophase, in some cases associated with the formation of protein bodies. (3) breakdown of cell walls in MMCs and tapetal cells at late meiotic prophase. (4) no massive increase in tapetal ER at the tetrad stage. (5) a general dissolution of membranes, first in the MMC, then in the tapetum. (6) abortion of microspores and the occurrence of a plasmodial tapetum in anthers reaching the microspore stage. (7) no distinct degeneration of tapetal cells after microspore formation. Thus, it seems that the factors that lead to abortive microsporogenesis are structurally expressed at widely different times during anther development. Aberrant patterns are not restricted to the tetrad stage but occur at early prophase.     

Constitutional del(5)(q23.3q31.1)

A 4-month-old male infant with muscular hypotonia, growth and psychomotor retardation, large low-set ears, hypoplastic genitalia, right hip luxation and bilateral equinovarus, was found to have a constitutional 46,XY,del(5)(q23.3q31.1) karyotype. From the comparison with 12 similar cases, a rather characteristic clinical phenotype emerges.     

Testosterone effects on the immune system and parasite infestations in the barn swallow (Hirundo rustica): an experimental test of the immunocompetence hypothesis

The immunocompetence hypothesis predicts that testosterone (T)enhances the expression of male secondary sexual characterswhile exerting a suppressive effect on the immune system therebyexposing hosts to higher intensities of parasite infestations.In a natural population of barn swallow (Hirundo rustica) males,the intensity of infestation by some ectoparasites was negativelycorrelated with tail length and was positively correlated withimmunoglobulin levels, but no clear relationship was observedbetween immune responses (leukocyte counts, immunoglobulins)and tail length. Males implanted with T had higher intensitiesof parasite infestations at the time of recapture than controlmales, and T-implanted males experienced an increase in countsof eosinophils. In T-implanted males, immunoglobulin levelsinitially decreased and then increased as time from implantationelapsed. Among T-implanted males, those with longer tails hada smaller increase in eosinophil counts, tended to experiencea smaller increase of parasite infestations, and were more likelyto survive until the following breeding season than those withshorter tails. The relationships between parasite burden, immunesystem, and exaggeration of tail length in the natural populationof males are consistent with some aspects of the immunocompetencehandicap hypothesis. The results from the manipulation of Tplasma levels are also partly consistent with the hypothesis,since T-implantation resulted in higher levels of parasite infestations,but contradict the assumption of an obligatory immunosuppressiveeffect of T. Higher activation of the immune system of T-implantedmales indicate that high T plasma levels imposed a two-foldcost because of the effects on parasites and the immune responseto parasites, and this suggests that the effect of T on parasitesmight not be mediated by the immune system of the host. Theresults of the manipulation of T plasma levels support the handicapversion of the immunocompetence hypothesis since high quality,long-tailed males paid less in terms of activation of the immunesystem, change in parasite infestations, and chances of survivalthan low-quality, short-tailed males.     

Design and synthesis of potent and subtype-selective PPARalpha agonists

Beginning with a moderately potent PPARgamma agonist 9, a series of potent and highly subtype-selective PPARalpha agonists was identified through a systematic SAR study. Based on the results of the efficacy studies in the hamster and dog models of dyslipidemia and the desired pharmacokinetic data, the optimized compound 39 was selected for further profiling.     

Sex ratio and male sexual characters in a population of blue tits, Parus caeruleus

Sex allocation theory proposes that parents should bias thesex ratio of their offspring if the reproductive value of onesex is greater than that of the other. In the monogamous bluetit (Parus caeruleus), males have a greater variance in reproductivesuccess than females, and high-quality males have higher reproductivesuccess than high-quality females due to extrapair paternity.Consequently, females mating with attractive males are expectedto produce broods biased toward sons, as sons benefit more thandaughters from inheriting their father's characteristics. Songand plumage color in birds are secondary sexual characters indicatingmale quality and involved in female choice. We used these malesexual traits in blue tits to investigate adaptive sex ratiomanipulation by females. We did not find any relationship betweenmale color ornamentation and brood sex ratio, contrary to previousstudies. On the other hand, the length of the strophe bout (i.e.,the mean number of strophes per strophe bout) of fathers waspositively related with the proportion of sons in their broods.The length of the strophe bout is supposed to reflect male qualityin terms of neuromuscular performance. We further showed thatsons produced in experimentally enlarged broods had shorterstrophe bouts than sons raised in reduced broods. These resultsare consistent with the hypothesis that females adjust the sexratio of their broods in response to the phenotype of theirmate.     

Maternal allocation of androgens and antagonistic effects of yolk androgens on sons and daughters

Mothers can influence the phenotype of their offspring by adjustingthe quality of their eggs in relation to sex and reproductivevalue of the progeny. Maternal androgens in the eggs of vertebratesmay mediate such adaptive early maternal effects. However, theevolution of early maternal effects mediated by egg androgensmay be constrained by the inability of mothers to differentiallyallocate androgens to eggs with a male or a female if androgenshave different effects on sons and daughters. In this study,we increased the concentration of androgens in the eggs of barnswallows (Hirundo rustica) within the physiological range ofvariation and analyzed the effect on nestling growth and beggingbehavior. Egg androgens increased body size and mass of sonsbut reduced these characters in daughters when compared to twocontrol groups in a repeated-measures analysis of variance ofdata collected at different ages. However, the differentialeffect of androgen on the two sexes was no longer significantwhen the analysis was restricted to the age of 12 days, whenfinal body size is attained. In a second experiment, we testedwhether mothers differentially allocated androgens to eggs withsons rather than daughters while manipulating a paternal secondarysexual character. Androgen concentration did not vary in relationto paternal ornamentation or embryo sex. Hence, antagonisticeffects of egg androgens on sons and daughters may exist inthe very early posthatching life and may constrain the evolutionof adaptive maternal effects because mothers do not differentiallyallocate androgens in relation to embryo sex.