Energy budget versus temporal discounting as determinants of preference in risky choice

Four pigeons and three ringneck doves responded on an operant simulation of natural foraging. After satisfying a schedule of reinforcement associated with search time, subjects could "accept" or "reject" another schedule of reinforcement associated with handling time. Two schedules of reinforcement were available, a variable interval, and a fixed interval with the same mean value. Food available in the session (a variable related to the energy budget) was manipulated in the different conditions either by increases of the value of the search state schedule of reinforcement, or by increases in the mean value of the handling state schedules. The results indicate that the amount of food available in the session did not affect the preference for variable schedules of reinforcement, as would be predicted by an influential theory of risk sensitive foraging. Instead, the preference for variability depended on the relationship between the time spent in the search and the handling states, as is predicted by a family of models of choice that are based on the temporal proximity to the reinforcer.     

CHLOROPLAST BIOGENESIS genes act cell and noncell autonomously in early chloroplast development

In order to identify nuclear genes required for early chloroplast development, a collection of photosynthetic pigment mutants of Arabidopsis was assembled and screened for lines with extremely low levels of chlorophyll. Nine chloroplast biogenesis (clb) mutants that affect proplastid growth and thylakoid membrane formation and result in an albino seedling phenotype were identified. These mutations identify six new genes as well as a novel allele of cla1. clb mutants have less than 2% of wild-type chlorophyll levels, and little or no expression of nuclear and plastid-encoded genes required for chloroplast development and function. In all but one mutant, proplastids do not differentiate enough to form elongated stroma thylakoid membranes. Analysis of mutants during embryogenesis allows differentiation between CLB genes that act noncell autonomously, where partial maternal complementation of chloroplast development is observed in embryos, and those that act cell autonomously, where complementation during embryogenesis is not observed. Molecular characterization of the noncell autonomous clb4 mutant established that the CLB4 gene encodes for hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (HDS), the next to the last enzyme of the methylerythritol 4-phosphate (MEP) pathway for the synthesis of plastidic isoprenoids. The noncell autonomous nature of the clb4 mutant suggests that products of the MEP pathway can travel between tissues, and provides in vivo evidence that some movement of MEP intermediates exists from the cytoplasm to the plastid. The isolation and characterization of clb mutants represents the first systematic study of genes required for early chloroplast development in Arabidopsis.     

Presence of Cochlodinium catenatum (Gymnodiniales: Gymnodiniaceae) in red tides of Bahía de Banderas, Mexican Pacific

The evolution of an ichthiotoxic algal bloom caused by the dinoflagellate Cochlodinium catenatum was studied from July to December 2000. The abnormal multiplication of this dinoflagellate occurred in the form of a discoloration spreading between a temperature and salinity interval of 25-32 degrees C and 33-35 ups, respectively. The density of C. catenatum reached 10 841 cells ml(-1). The event was observed in large areas of Banderas Bay affecting 13 fish species, whose massive killing was due to suffocation (gill obstruction and excessive mucus production). The human population around the area did not present respiratory affections or skin irritation. The C. catenatum measurements suggest a hologamic and heterothalic reproduction. Their morphological characteristics suggest that C. polykrikoides, C. heterolobatum and C. catenatum are the same species. It is estimated that the species could be a recent introduction in the Mexican Pacific.     

Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia

Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. These data are the first to document that ANG II can act at the pituitary level through the AT2 receptor subtype and that estrogens display a differential regulation of AT1 and AT2 receptors at this level.     

Dietary calcium deficiency increases Ca2+ uptake and Ca2+ extrusion mechanisms in chick enterocytes

Ca2+ uptake and Ca2+ extrusion mechanisms were studied in enterocytes with different degree of differentiation from chicks adapted to a low Ca2+ diet as compared to animals fed a normal diet. Chicks adapted to a low Ca2+ diet presented hypocalcemia, hypophosphatemia and increased serum 1,25(OH)2D3 and Ca2+ absorption. Low Ca2+ diet increased the alkaline phosphatase (AP) activity, independently of the cellular maturation, but it did not alter gamma-glutamyl-transpeptidase activity. Ca2+ uptake, Ca2+-ATPase and Na(+)/Ca2+ exchanger activities and expressions were increased by the mineral-deficient diet either in mature or immature enterocytes. Western blots analysis shows that vitamin D receptor (VDR) expression was much higher in crypt cells than in mature cells. Low Ca2+ diet decreased the number of vitamin D receptor units in both kinds of cells. In conclusion, changes in Ca2+ uptake and Ca2+ extrusion mechanisms in the enterocytes by a low Ca2+ diet appear to be a result of enhanced serum levels of 1,25(OH)2D3, which would promote cellular differentiation producing cells more efficient to express vitamin D dependent genes required for Ca2+ absorption.     

The -308 polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene and ex vivo lipopolysaccharide-induced TNF-alpha expression in patients with aggressive periodontitis and/or type 1 diabetes mellitus

Several single-nucleotide polymorphisms (SNPs) have been identified in the TNF-alpha gene promoter. The transition G-->A at position -308 generates the TNF-alpha1 (G/G) and TNF-alpha2 (G/A or A/A) alleles, where the polymorphic TNF-alpha2 allele is associated with a high, in vitro TNF-alpha expression and an increased susceptibility to diverse illnesses. Here we study the association of the -308 TNF-alpha SNP with the susceptibility for developing aggressive periodontitis (AP), AP combined with type 1 diabetes mellitus (DM) and DM. We also explore the TNF-alpha capability expression and the presence of the -308 polymorphism. For this purpose we recruited 27 individuals with AP (AP+ group), 27 individuals with AP combined with DM (AP+/DM+ group), and 27 individuals with DM without signs of periodontitis upon clinical examination (DM+ group). The control group was comprised of 30 subjects. Genotyping for TNF-alpha promoter was performed by PCR-RFLP analysis. For TNF-alpha expression we used a blood culture system.     

Passive antibody therapy for infectious diseases

Antibody-based therapies are currently undergoing a renaissance. After being developed and then largely abandoned in the twentieth century, many antibody preparations are now in clinical use. However, most of the reagents that are available target non-infectious diseases. Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that antibody-based therapies are the only means to provide immediate immunity against biological weapons. Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of antibody-based therapy for the prevention and treatment of infectious diseases.     

LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons

In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi localization and the PDZ domain for its presence at neuritic tips. Overexpression of wild-type LIMK1 suppresses the formation of trans-Golgi derived tubules, and prevents cytochalasin D-induced Golgi fragmentation, whereas that of a kinase-defective mutant has the opposite effect. Transfection of wild-type LIMK1 accelerates axon formation and enhances the accumulation of Par3/Par6, insulin-like growth factor (IGF)1 receptors, and neural cell adhesion molecule (NCAM) at growth cones, while inhibiting the Golgi export of synaptophysin-containing vesicles. These effects were dependent on the Golgi localization of LIMK1, paralleled by an increase in cofilin phosphorylation and phalloidin staining in the region of the Golgi apparatus, and prevented by coexpression of constitutive active cofilin. The long-term overexpression of LIMK1 produces growth cone collapse and axon retraction, an effect that is dependent on its growth cone localization. Together, our results suggest an important role for LIMK1 in axon formation that is related with its ability to regulate Golgi dynamics, membrane traffic, and actin cytoskeletal organization.     

Caspase-1 activation by Salmonella

Salmonella is an interesting example of how the selective pressure of host environments has led to the evolution of sophisticated bacterial virulence mechanisms. This microbe exploits the first-line of defence, the macrophage, as a crucial tool in the initiation of disease. After invasion of intestinal macrophages, a virulence protein secreted by Salmonella specifically induces apoptotic cell death by activating the cysteine protease caspase-1. The pro-apoptotic capability is necessary for successful pathogenesis. The study of mechanisms by which Salmonella induces programmed cell death offers new insights into how pathogens cause disease and into general mechanisms of activation of the innate immune system.     

More is not necessarily better: prozone-like effects in passive immunization with IgG

Despite a century of study, the relationship between Ag-specific Ig concentration and protection remains poorly understood for the majority of pathogens. In certain conditions, administration of high Ab doses before challenge with an infectious agent can be less effective than smaller Ab doses, a phenomenon which is consistent with a prozone-like effect. In this study, the relationship between IgG1, IgG2a, IgG2b, and IgG3 dose, infective inocula, and protection was investigated in a mouse model of Cryptococcus neoformans infection. The activity of each IgG subclass ranged from protective to disease-enhancing depending on both the Ab dose and infective inocula used. Enhanced dissemination to the brain was observed in mice given a high IgG2a dose and a relatively low inoculum. Ab administration had immunomodulatory effects, with cytokine expression in lung, brain, and spleen varying as a function of the infective inoculum Ab dose and IgG subclass. In vitro studies did not predict or explain the mechanism of in vivo prozone-like effects, because all isotypes were opsonic and elicited NO release from macrophages. IgG2a was most efficient in inducing a macrophage oxidative burst. These results reveal that an individual Ab can be protective, nonprotective, or disease-enhancing depending on its concentration relative to a challenge inoculum. Our findings have implications for the potential contribution of Ab responses to defense against microbial diseases because Ab-mediated immunity may be protective, nonprotective, or even deleterious to the host.