Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection

An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I scavenger receptor (SR-BI) is the strongest regulator of Plasmodium infection among these factors. Inhibition of SR-BI function reduced P. berghei infection in Huh7 cells, and overexpression of SR-BI led to increased infection. In vivo silencing of liver SR-BI expression in mice and inhibition of SR-BI activity in human primary hepatocytes reduced infection by P. berghei and by P. falciparum, respectively. Heterozygous SR-BI(+/-) mice displayed reduced P. berghei infection rates correlating with liver SR-BI expression levels. Additional analyses revealed that SR-BI plays a dual role in Plasmodium infection, affecting both sporozoite invasion and intracellular parasite development, and may therefore constitute a good target for malaria prophylaxis.     

Genistein-supplemented diet decreases malaria liver infection in mice and constitutes a potential prophylactic strategy

In tropical regions millions of people still live at risk of malaria infection. Indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. Genistein is a naturally occurring compound that is widely used as a food supplement and is thought to be effective in countering several pathologies. Results presented here show that genistein inhibits liver infection by the Plasmodium parasite, the causative agent of malaria. In vitro, genistein decreased the infection rates of both mouse and human hepatoma cells by inhibiting the early stages of the parasite's intracellular development. Oral or intraperitoneal administration of genistein decreased the liver parasite load of P. berghei-infected mice. Moreover, mice fed on a genistein-supplemented diet showed a significant reduction in Plasmodium liver infection as well as a reduced blood parasitemia and partial protection from severe disease. Since genistein is a safe, low-cost, natural compound that can be used permanently in a diet, we propose its use as a prophylactic agent against malaria for endemic populations and long-time travelers.     

Fructans,but not the sucrosyl-galactosides,raffinose and loliose,are affected by drought stress in perennial ryegrass

The aim of this study was to evaluate the putative role of the sucrosyl-galactosides, loliose [alpha-D-Gal (1,3) alpha-D-Glc (1,2) beta-D-Fru] and raffinose [alpha-D-Gal (1,6) alpha-D-Glc (1,2) beta-D-Fru], in drought tolerance of perennial ryegrass and to compare it with that of fructans. To that end, the loliose biosynthetic pathway was first established and shown to operate by a UDP-Gal: sucrose (Suc) 3-galactosyltransferase, tentatively termed loliose synthase. Drought stress increased neither the concentrations of loliose and raffinose nor the activities of loliose synthase and raffinose synthase (EC 2.4.1.82). Moreover, the concentrations of the raffinose precursors, myoinositol and galactinol, as well as the gene expressions of myoinositol 1-phosphate synthase (EC 5.5.1.4) and galactinol synthase (EC 2.4.1.123) were either decreased or unaffected by drought stress. Taken together, these data are not in favor of an obvious role of sucrosyl-galactosides in drought tolerance of perennial ryegrass at the vegetative stage. By contrast, drought stress caused fructans to accumulate in leaf tissues, mainly in leaf sheaths and elongating leaf bases. This increase was mainly due to the accumulation of long-chain fructans (degree of polymerization > 8) and was not accompanied by a Suc increase. Interestingly, Suc but not fructan concentrations greatly increased in drought-stressed roots. Putative roles of fructans and sucrosyl-galactosides are discussed in relation to the acquisition of stress tolerance.     

A novel type of catalytic copper cluster in nitrous oxide reductase

Nitrous oxide (N20) is a greenhouse gas, the third most significant contributor to global warming. As a key process for N20 elimination from the biosphere, N20 reductases catalyze the two-electron reduction of N20 to N2. These 2 x 65 kDa copper enzymes are thought to contain a CuA electron entry site, similar to that of cytochrome c oxidase, and a CuZ catalytic center. The copper anomalous signal was used to solve the crystal structure of N20 reductase from Pseudomonas nautica by multiwavelength anomalous dispersion, to a resolution of 2.4 A. The structure reveals that the CuZ center belongs to a new type of metal cluster, in which four copper ions are liganded by seven histidine residues. N20 binds to this center via a single copper ion. The remaining copper ions might act as an electron reservoir, assuring a fast electron transfer and avoiding the formation of dead-end products.     

Maize (Zea mays L.) endogenous seed phosphorus remobilization is not influenced by exogenous phosphorus availability during germination and early growth stages

Background and aims

Phosphorus (P) nutrition is very important during early maize seedling growth. Remobilization of endogenous seed P and uptake of exogenous P are therefore of prime importance during this period. Our objectives were to study the effect of the availability of endogenous and exogenous P on i) remobilization of endogenous seed P, ii) the beginning of exogenous P uptake and its intensity, iii) their interaction and effect on seedling development.

Methods

Seeds with high and low reserves of endogenous seed P were cultivated at three rates of availability of exogenous P (0, 100, 1,000?μM) over a growth period of 530 cumulated degree days after sowing. Exogenous P was labeled with radioactive P (³²P) to distinguish the two fluxes of P in seedlings, one due to remobilization of seed P and the other to uptake of exogenous P.

Results

Initially, 86% of endogenous seed P was localized in the scutellum, mainly in the form of phytate, regardless of initial endogenous seed P. At 89 cumulated degree days after sowing (base temperature: 10°C), 98% of seed phytate was hydrolyzed in all treatments. In treatments with available exogenous P, significant uptake of exogenous P started at 71 cumulated degree days after sowing. Efficient uptake of exogenous P depended on its availability, but was independent of phytate hydrolysis and seedling P status. Significant loss of P from germinating seeds due to efflux was observed and was also independent of the availability of exogenous P.

Conclusions

Our results show that hydrolysis of seed P was not influenced by the availability of exogenous P, and conversely, that uptake of exogenous P was not influenced by endogenous P in the seed. This suggests that remobilization of endogenous seed P and uptake of exogenous P by seedling roots are controlled independently.     

The deletion of STOP/MAP6 protein in mice triggers highly altered mood and impaired cognitive performances

The microtubule-associated Stable Tubulie Only Polypeptide (STOP; also known as MAP6) protein plays a key role in neuron architecture and synaptic plasticity, the dysfunctions of which are thought to be implicated in the pathophysiology of psychiatric diseases. The deletion of STOP in mice leads to severe disorders reminiscent of several schizophrenia-like symptoms, which are also associated with differential alterations of the serotonergic tone in somas versus terminals. In STOP knockout (KO) compared with wild-type mice, serotonin (5-HT) markers are found to be markedly accumulated in the raphe nuclei and, in contrast, deeply depleted in all serotonergic projection areas. In the present study, we carefully examined whether the 5-HT imbalance would lead to behavioral consequences evocative of mood and/or cognitive disorders. We showed that STOP KO mice exhibited depression-like behavior, associated with a decreased anxiety-status in validated paradigms. In addition, although STOP KO mice had a preserved very short-term memory, they failed to perform well in all other learning and memory tasks. We also showed that STOP KO mice exhibited regional imbalance of the norepinephrine tone as observed for 5-HT. As a consequence, mutant mice were hypersensitive to acute antidepressants with different selectivity. Altogether, these data indicate that the deletion of STOP protein in mice caused deep alterations in mood and cognitive performances and that STOP protein might have a crucial role in the 5-HT and norepinephrine networks development.     

Phosphothioate oligodeoxynucleotides inhibit Plasmodium sporozoite gliding motility

Plasmodium sporozoites, transmitted to the mammalian host through a mosquito bite, travel to the liver, where they invade hepatocytes, and develop into a form that is then able to infect red blood cells. In spite of the importance of innate immunity in controlling microbial infections, almost nothing is known about its role during the liver stage of a malaria infection. Here, we tested whether synthetic CpG phosphothioate (PS) oligodeoxynucleotides (ODNs), which bind to Toll‐like receptor 9 (Tlr9), could have a protective effect on Plasmodium berghei infection in hepatocytes. Surprisingly, CpG PS‐ODNs potently impair P. berghei infection in hepatoma cell lines independently of Tlr9 activation. Indeed, not only CpG but also non‐CpG PS‐ODNs, which do not activate Tlr9, decreased parasite infection. Moreover, the ability of PS‐ODNs to impair infection was not due to an effect on the host but rather on the parasite itself. In fact, CpG PS‐ODNs, as well as non‐CpG PS‐ODNs, impair parasite gliding motility. Furthermore, our analysis reveals that PS‐ODNs inhibit parasite migration and invasion due to their negative charge, whereas development inside hepatocytes is undisturbed. Altogether, PS‐ODNs might represent a new class of prophylactic anti‐malaria agents, which hamper hepatocyte entry by Plasmodium sporozoites.     

Bio-fortification of minerals in crops: current scenario and future prospects for sustainable agriculture and human health

Plant Growth Regulation - Minerals are the key factor determining human beings’ optimum growth and development. The deficiencies of minerals and vitamins hinder the human normal growth and...     

Development of intervention behavior in Japanese macaques: Testing the targeting hypothesis

Matrilineal dominance systems, which characterize several species of cercopithecines, are determined largely by the patterning of third-party aggressive interventions in conflicts. Although the role of interventions in structuring rank relations has received much attention, very few studies have dealt specifically with the development of intervention behavior. In other words,most studies have focused on the interventions received and their effect on the recipients rather than on the interventions performed and the goals of the interveners. We analyzed the intervention behavior of 10 juvenile females in a colony of 40 Japanese macaques (Macaca fuscata)housed at the University of Montreal Laboratory of Behavioral Primatology. The analysis of 749 interventions performed by the juveniles over their first 4 years and 2425 interventions received over the same period reveals that (1) juvenile females intervened selectively against females ranking below their mother, (2) they began to intervene at about the same time that they began to challenge the latter females in dyadic contests, (3) they sided with females as well as with males against these females, (4) juvenile interveners incurred little risks in terms of aggressive retaliation from their targets, (5) they derived immediate benefits in terms of conflicts won over stronger targets, (6) interventions often did not take place when the possible recipients needed support, and (7) interveners did not conform to a pattern of mutually preferential support. These results support the view that interventions by juveniles are selfish (vs altruistic) and constitute a low-cost and effective means to target and to outrank prospectively subordinate females.