The ratio of germanium to silicon in plant phytoliths: quantification of biological discrimination under controlled experimental conditions

Slight differences in the chemical behavior of germanium (Ge) and silicon (Si) during soil weathering enable Ge/Si ratios to be used as a tracer of Si pathways. Mineral weathering and biogenic silicon cycling are the primary modifiers of Ge/Si ratios, but knowledge of the biogenic cycling component is based on relatively few studies. We conducted two sets of greenhouse experiments in order to better quantify the range and variability in Ge discrimination by plants. Graminoid species commonly found in North American grassland systems, Agropyron smithii, Schizachyrium scoparium, and Andropogon gerardii were grown under controlled hydroponic environmental conditions. Silicon leaf contents were positively correlated with solution Si and ambient temperature but not with nutrient solution pH, electrical conductivity, or species. The Ge/Si ratio incorporated into phytoliths shows a distribution coefficient [(Ge/Si)_phytolith/(Ge/Si)_solution] of about 0.2 and is remarkably invariant between species, photosynthetic pathway, and solution temperature. Ge seems to be discriminated against during the uptake and translocation of Si to the opal deposition sites by about a factor of five. In the second experiment, a wider range of graminoid species (Agropyron smithii, Bouteloua gracilis, Buchloe dactyloides, Oryzopsis hymenoides, Schizachyrium scoparium and Andropogon gerardii) were grown in two different soil mediums. Plant phytoliths showed a distribution factor of about 0.4 for field grown grasses, and 0.6 for potting soil grown grasses with no clear trends among the species. Evidence of the direction and degree of biological Ge discrimination during plant uptake provides a geochemical finger print for plants and improves the utility of Ge/Si ratios in studies of terrestrial weathering and links between Si cycles in terrestrial and marine systems.     

Importance of microbial colonization of the gut in early life to the development of immunity

The mammalian gastrointestinal tract harbors a complex microbiota consisting of between 500 and 1000 distinct microbial species. Comparative studies based on the germ-free gut have provided clear evidence that the gut microbiota is instrumental in promoting the development of both the gut and systemic immune systems. Early microbial exposure of the gut is thought to dramatically reduce the incidence of inflammatory, autoimmune and atopic diseases further fuelling the scientific viewpoint, that microbial colonization plays an important role in regulating and fine-tuning the immune system throughout life. Recent molecular diversity studies have provided additional evidence that the human gut microbiota is compositionally altered in individuals suffering from inflammatory bowel disorders, suggesting that specific bacterial species are important to maintaining immunological balance and health. New and exciting insights into how gut bacteria modulate the mammalian immune system are emerging. However, much remains to be elucidated about how commensal bacteria influence the function of cells of both the innate and adaptive immune systems in health and disease.     

When is breeding for drought tolerance optimal if drought is random?

* Increasing climatic unpredictability associated with characteristics of some species makes plant drought-tolerance an important drought-adaptation strategy. Using norm-of-reaction functions, or empirically determined functions that enable us to predict the state of a trait given the state of an environmental variable, allows modelling of plant performance when water availability varies randomly. * A mathematical model is proposed to evaluate drought-tolerance and growth strategies given a set of environmental parameters: the frequency of rainy days, the soil water-storage capacity, plant water use and plant growth rates. This model compares the performance of genotypes that differ in drought tolerance expressed as the ability to grow in drier soils, and assumes a general trade-off function between drought tolerance and maximum plant growth rate. * It is worth selecting plants with a greater degree of drought tolerance, expressed by the ability to grow in drier soils whenever the frequency of rains is smaller than the rate of soil water depletion. Otherwise, maximizing growth rate at the expense of drought tolerance is the best strategy. The nature of the trade-off between drought tolerance and plant growth rate also constrains the selection for optimal drought-adapted genotypes. * Breeders will have to consider these aspects of plant-environment interactions before establishing selection programs for drought adaptation.     

Antigen, in the presence of TGF-beta, induces up-regulation of FoxP3gfp+ in CD4+ TCR transgenic T cells that mediate linked suppression of CD8+ T cell responses

CD4(+)CD25(+) regulatory T cells (Tregs) inhibit immune responses to a variety of Ags, but their specificity and mechanism of suppression are controversial. This controversy is largely because many studies focused on natural Tregs with undefined specificities and suppression has frequently been measured on polyclonal T cell responses. To address the issue of specificity further, we have bred K(d)-specific, CD4(+) TCR (TCR75) transgenic mice to Foxp3(gfp) knockin reporter mice to permit sorting of Tregs with a known specificity. Foxp3(gfp).TCR75 mice did not express significant numbers of natural FoxP3(+) Tregs expressing the TCR75 transgenes, but FoxP3 expression was induced by stimulating with K(d) plus TGF-beta. The resulting GFP(+) TCR75 cells were anergic, whereas the GFP(-) TCR75 cells proliferated upon restimulation with K(d) peptide. Yet both exhibited severely reduced expression of intracellular IFN-gamma and TNF-alpha upon restimulation. GFP(+), but not GFP(-), TCR75 T cells suppressed responses by naive TCR75 T cells and by nontransgenic spleen cells stimulated with anti-CD3. GFP(+) TCR75 cells also inhibited polyclonal C57BL/6 anti-K(d) CTL responses if the APC expressed K(d) and both MHC class I and class II, and responses by OT1 T cells to B6.K(d).OVA but not B6.K(d) plus OVA expressing APC, demonstrating linked-suppression of CD8 responses. Thus, Tregs exhibit a greater degree of specificity in vitro than previously appreciated. The observation that Tregs and responder T cells must recognize the same APC provides a mechanistic explanation for the observation that Tregs must be in direct contact with effector T cells to suppress their responses.     

Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host

Peripheral blood CD4+ T cell counts are a key measure for assessing disease progression and need for antiretroviral therapy in HIV-infected patients. More recently, studies have demonstrated a dramatic depletion of mucosal CD4+ T cells during acute infection that is maintained during chronic pathogenic HIV as well as SIV infection. A different clinical disease course is observed during the infection of natural hosts of SIV infection, such as sooty mangabeys (Cercocebus atys), which typically do not progress to AIDS. Previous studies have determined that SIV+ mangabeys generally maintain healthy levels of CD4+ T cells despite having viral replication comparable to HIV-infected patients. In this study, we identify the emergence of a multitropic (R5/X4/R8-using) SIV infection after 43 or 71 wk postinfection in two mangabeys that is associated with an extreme, persistent (>5.5 years), and generalized loss of CD4+ T cells (5-80 cells/microl of blood) in the absence of clinical signs of AIDS. This study demonstrates that generalized CD4+ T cell depletion from the blood and mucosal tissues is not sufficient to induce AIDS in this natural host species. Rather, AIDS pathogenesis appears to be the cumulative result of multiple aberrant immunologic parameters that include CD4+ T cell depletion, generalized immune activation, and depletion/dysfunction of non-CD4+ T cells. Therefore, these data provide a rationale for investigating multifaceted therapeutic strategies to prevent progression to AIDS, even following dramatic CD4 depletion, such that HIV+ humans can survive normal life spans analogous to what occurs naturally in SIV+ mangabeys.     

Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein

The CA domain of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein plays critical roles in both the early and late phases of viral replication and is therefore an attractive antiviral target. Compounds with antiviral activity were recently identified that bind to the N-terminal domain of CA (CA^N) and inhibit capsid assembly during viral maturation. We have determined the structure of the complex between CA^N and the antiviral assembly inhibitor N-(3-chloro-4-methylphenyl)-N′-{2-[({5-[(dimethylamino)-methyl]-2-furyl}-methyl)-sulfanyl]ethyl}-urea) (CAP-1) using a combination of NMR spectroscopy and X-ray crystallography. The protein undergoes a remarkable conformational change upon CAP-1 binding, in which Phe32 is displaced from its buried position in the protein core to open a deep hydrophobic cavity that serves as the ligand binding site. The aromatic ring of CAP-1 inserts into the cavity, with the urea NH groups forming hydrogen bonds with the backbone oxygen of Val59 and the dimethylamonium group interacting with the side-chains of Glu28 and Glu29. Elements that could be exploited to improve binding affinity are apparent in the structure. The displacement of Phe32 by CAP-1 appears to be facilitated by a strained main-chain conformation, which suggests a potential role for a Phe32 conformational switch during normal capsid assembly.