LPS antagonism of TGF‐β signaling results in prolonged survival and activation of rat primary microglia

Accumulating evidence indicates that activated microglia contribute to the neuropathology involved in many neurodegenerative diseases and after traumatic injury to the CNS. The cytokine transforming growth factor‐beta 1 (TGF‐β1), a potent deactivator of microglia, should have the potential to reduce microglial‐mediated neurodegeneration. It is therefore perplexing that high levels of TGF‐β1 are found in conditions where microglia are chronically activated. We hypothesized that TGF‐β1 signaling is suppressed in activated microglia. We therefore activated primary rat microglia with lipopolysaccharide (LPS) and determined the expression of proteins important to TGF‐β1 signaling. We found that LPS treatment decreased the expression of the TGF‐β receptors, TβR1 and TβR2, and reduced protein levels of Smad2, a key mediator of TGF‐β signaling. LPS treatment also antagonized the ability of TGF‐β to suppress expression of pro‐inflammatory cytokines and to induce microglial cell death. LPS treatment similarly inhibited the ability of the TGF‐β related cytokine, Activin‐A, to down‐regulate expression of pro‐inflammatory cytokines and to induce microglial cell death. Together, these data suggest that microglial activators may oppose the actions of TGF‐β1, ensuring continued microglial activation and survival that eventually may contribute to the neurodegeneration prevalent in chronic neuroinflammatory conditions.

     

The stroke trial - can we predict clinical outcome of patients with ischemic stroke by measuring soluble cell adhesion molecules (CAM)?

BACKGROUND: Several studies have found that an increased concentration of haemostatic or inflammation markers was associated with worse prognosis in vascular disease. The inflammatory components in ischemic stroke are of current interest, and there is some experimental evidence that they may be linked. HYPOTHESIS: The study was performed to determine the association between the neurological clinical outcome and levels of cell adhesion molecules in the first four days of hospitalization in patients with acute ischemic event. METHODS: This prospective, pilot, case-controlled study examined the association between the clinical outcome and inflammatory markers within the first few days of hospitalization. The neurological evaluation was performed using the NIH score on admission and four days later, and levels of cell adhesion molecules were measured by ELISA methods on admission and four days later. RESULTS: Twenty three patients with an acute cerebral event (mean age 71 +/- 15 y, 12 women and 11 men) were examined neurologically on admission and four days later. Among 19 patients who improved, there was a significant decrease in the NIH neurological scale, from 3.8 +/- 3.2 to 1.3 +/- 1.8 (p = 0.01), which was accompanied by a significant decrease in the cell adhesion molecules that were measured (E-selectin, ICAM-1 and VCAM-1). Of the four patients who did not improve, their mean clinical NIH score was 10 +/- 4.6 and worsened or remained unchanged after four days of follow-up. In this group, we could not demonstrate a significant change in levels of cell adhesion molecules between days one and four. CONCLUSIONS: Patients who improved clinically within the first four days of hospitalization demonstrated a remarkable inhibition of all three cell adhesion molecules that were measured (E-selectin, ICAM-1, and VCAM-1). Patients who did not improve had more severe cerebral infarcts, a higher NIH score on admission (10 +/- 4.6), and no change was observed in levels of cell adhesion molecules during the follow-up period. Measuring cell adhesion molecule levels may predict objectively the clinical outcome in hospitalized patients with acute ischemic stroke.     

Sexual specialization in two tropical dioecious figs

Ficus species (figs) and their species-specific pollinator wasps are involved in an intimate mutualism in which wasps lay eggs in some ovaries of the closed inflorescences (syconia), and mature, inseminated offspring carry pollen from mature syconia to fertilize receptive inflorescences. In monoecious species, each syconium produces seeds and wasps. In functionally dioecious fig species, making up approximately half the figs worldwide, male and female functions are separated; hermaphrodite (functionally male) trees produce wasps and pollen only, while female trees produce seeds only. This sexual separation allows selection to act independently on the reproductive biology of each sex. Examining sexual specialization in a tight mutualism allows us to determine aspects of the mutualism that are flexible and those that are canalized. In this study, we quantified the phenology of two species of dioecious figs, F. exasperata and F. hispida, for 2 years by following the fates of several thousand syconia over time. In studying each of these species in a dry and a wet site in south India, we tested specific predictions of how dioecious figs might optimize sexual function. On female trees of both species, more inflorescences matured during the wet (monsoon) season than in any other season; this fruiting period enabled seeds to be produced during the season most suitable for germination. In F. exasperata, functionally male trees released most wasps from mature syconia in the dry season, during peak production of receptive female syconia, and thus maximized successful pollination. In F. hispida, “male” trees produced more syconia in the dry and monsoon seasons than in the post-monsoon season. In both species, male and female trees abscised more unpollinated, young inflorescences than pollinated inflorescences, but abscission appeared to be more likely due to resource- rather than pollinator- limitation. The phenology of F. exasperata requires that male inflorescences wait in receptive phase for scarce pollinators to arrive. As expected, male inflorescences of this species had a longer receptive phase than female inflorescences. In F. hispida, where pollinators are rarely scarce, duration of receptive phase was the same for both sexes. Duration of developing phase was longer in female syconia of both species than in male syconia, most likely because they need a longer period of investment in a fleshy fruit. Variation in developing phase of female syconia in one species (F. exasperata) was also greater than that in male syconia, and enabled female trees to sample a variety of germination environments in time. The strong sexual differences in both fig species support the hypothesis that selection for sexual specialization has strongly influenced the reproductive biology of these species. Received: 28 May 1997 / Accepted: 2 February 1998     

B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

1. Download : Download high-res image (215KB)
2. Download : Download full-size image

     

Nest Hydrocarbons as Cues for Philopatry in a Paper Wasp

Philopatric behavior has been demonstrated in a wide taxonomic spread of animals. In temperate environments, overwintered Polistes wasp foundresses often return to their natal nest prior to initiating colony construction. Previous research has shown that these spring foundresses can identify the natal nest in the absence of landmark and gross morphological cues. Hydrocarbons are essential recognition cues for Polistes nest and nestmate discrimination, but cuticular hydrocarbon profiles can become homogenized when foundresses overwinter in mixed colony groups. We examined the hydrocarbon profiles of Polistes dominulus foundresses and nests before and after an overwintering period, and found that the hydrocarbon profiles of nests remain unique over time and that this uniqueness is influenced by the original foundresses. Our data raise the possibility that in returning to the natal nest, foundresses reacquire their colony‐specific signature, which may play a role in the formation of cooperative associations.     

Strangler fig-host associations in roadside and deciduous forest sites, South India

Abstract. Understanding the regeneration niche of animal-dispersed epiphytes is important in understanding forest community structure, maintenance of species richness in plant communities, animal movements and distributions, and in managing plant and animal communities for conservation. Strangler figs are particularly interesting for studying epiphyte-host relations because they are hemiepiphytes, implying that strangler and host can potentially belong to the same species and either fuse together or strangle each other, and because all stranglers have many-seeded, animal-dispersed fruit, providing many opportunities for seed dispersal to other stranglers. A study was conducted at a roadside and at a forest site in Karnataka State, south India, to determine factors influencing host choice of strangler figs. Stranglers were found more frequently at the roadside site than at the forest site. At the roadside site, stranglers were found much more abundantly on Ficus hosts than on non-Ficus hosts, whereas at the forest site, stranglers were found more abundantly on non- Ficus hosts. Host tree species with animal-dispersed fruit bore significantly more stranglers than those with mechanically dispersed fruit. More stranglers were found on hosts in large d.b.h. size classes (>80 cm d.b.h.) than on those in small d.b.h. classes. Prior studies of strangler-host relations have never found stranglers growing on other stranglers. The results of this study suggest that stranglers are fully capable of regenerating on other stranglers, including conspecifics, but these regeneration events are not observed in forests because of relatively low strangler seed rain, due to lack of clumping of strangler hosts, and low insolation in these habitats.     

Ion selectivity of the anthrax toxin channel and its effect on protein translocation

Anthrax toxin consists of three ∼85-kD proteins: lethal factor (LF), edema factor (EF), and protective antigen (PA). PA₆₃ (the 63-kD, C-terminal portion of PA) forms heptameric channels ((PA₆₃)₇) in planar phospholipid bilayer membranes that enable the translocation of LF and EF across the membrane. These mushroom-shaped channels consist of a globular cap domain and a 14-stranded β-barrel stem domain, with six anionic residues lining the interior of the stem to form rings of negative charges. (PA₆₃)₇ channels are highly cation selective, and, here, we investigate the effects on both cation selectivity and protein translocation of mutating each of these anionic residues to a serine. We find that although some of these mutations reduce cation selectivity, selectivity alone does not directly predict the rate of protein translocation; local changes in electrostatic forces must be considered as well.     

Increased spindle resistance to antimicrotubule agents in women of high risk for meiotic nondisjunction

Summary Spindle sensitivity of phytohemagglutinin (PHA)-stimulated lymphocytes to three antimicrotubule drugs was compared in two groups of women who differ in their predisposition to meiotic aneuploidy: young women of low-risk age (ranging from 22 to 34 years) and middle-aged women of high-risk age (ranging from 40 to 52 years). Numerical sensitivity values for the antimicrotubule drugs, colchicine, podophyllotoxin, and vinblastine were obtained for each woman by recording the percentage of fully arrested metaphases out of the total metaphase cell population, i.e., cells exhibiting short, thick, and condensed chromosomes with sister chromatids clearly separated at their distal parts. Sensitivity increased linearly with increasing drug concentrations and was highly correlated with youth: its rate was significantly higher for women of the low-risk group. In addition, dividing lymphocytes of young mothers (26–33 years old) of Down syndrome children revealed significantly lower sensitivity to colchicine and podophyllotoxin than those of all young women of the low-risk group and similar sensitivity to that of the middle-aged women, i.e., the high-risk age group. The data are consistent with the theory that factors involved in meiotic nondisjunction may be concurrently operating in somatic cells. These factors presumably shift the equilibrium between tubulin and microtubules towards microtubules stabilization and thereby affect some of their functions.