The Major Yolk Protein Vitellogenin Interferes with the Anti-Plasmodium Response in the Malaria Mosquito Anopheles gambiae

When taking a blood meal on a person infected with malaria, female Anopheles gambiae mosquitoes, the major vector of human malaria, acquire nutrients that will activate egg development (oogenesis) in their ovaries. Simultaneously, they infect themselves with the malaria parasite. On traversing the mosquito midgut epithelium, invading Plasmodium ookinetes are met with a potent innate immune response predominantly controlled by mosquito blood cells. Whether the concomitant processes of mosquito reproduction and immunity affect each other remains controversial. Here, we show that proteins that deliver nutrients to maturing mosquito oocytes interfere with the antiparasitic response. Lipophorin (Lp) and vitellogenin (Vg), two nutrient transport proteins, reduce the parasite-killing efficiency of the antiparasitic factor TEP1. In the absence of either nutrient transport protein, TEP1 binding to the ookinete surface becomes more efficient. We also show that Lp is required for the normal expression of Vg, and for later Plasmodium development at the oocyst stage. Furthermore, our results uncover an inhibitory role of the Cactus/REL1/REL2 signaling cassette in the expression of Vg, but not of Lp. We reveal molecular links that connect reproduction and immunity at several levels and provide a molecular basis for a long-suspected trade-off between these two processes.     

Cationic lipids involved in gene transfer mobilize intracellular calcium

Cationic lipids are efficient tools to introduce nucleic acids and proteins into cells. Elucidation of the mechanism and cellular pathways associated with such transport has been relatively tedious, even though significant progress has been made in the characterization of the intracellular trafficking of lipid/DNA complexes. Surprisingly little is known about the effects of these delivery vectors on cell functioning. In this report, we show that both cationic lipids and cationic lipid/DNA complexes mobilize the intracellular calcium. Removal of extracellular calcium did not significantly abolish this effect and preincubating cells with thapsigargin led to a decrease in [Ca2+]i, indicating that calcium was released mainly from internal calcium stores sensitive to thapsigargin. Pretreatment of the cells with the phospholipase C inhibitor U73122, blocked the [Ca2+]i rise, suggesting an inositol dependent mechanism.     

Complexity and integration in the control of inner-eardevelopment

A report on the Sixth Molecular Biology of Hearing and Deafness Conference, Hinxton, UK, 11-14 July 2007.     

7-(4H-1,2,4-Triazol-3-yl)benzo[c][2,6]naphthyridines: a novel class of Pim kinase inhibitors with potent cell antiproliferative activity

A novel class of pan-Pim kinase inhibitors was designed by modifying the CK2 inhibitor CX-4945. Introduction of a triazole or secondary amide functionality on the C-7 position and 2'-halogenoanilines on C-5 resulted in potent inhibitors of the Pim-1 and Pim-2 isoforms, with many analogs active at single digit nanomolar concentrations. The molecules inhibited the phosphorylation at Serine 112 of the apoptosis effector BAD, and had potent antiproliferative effects on the AML cell line MV-4-11 (IC(50) <30 nM). This work delivers an excellent lead-optimization platform for Pim targeting anticancer therapies.     

Distribution of Sunn Pest,Eurygaster integriceps Puton (Hemiptera: Scutelleridae), in overwintering sites

Sunn Pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae), is the most serious pest of wheat in West and Central Asia. Following harvest, the pest migrates from wheat fields to high elevations to escape high summer temperatures and, the following spring, moves back to the fields. In this work, Sunn Pest populations were monitored in 21 overwintering sites located in seven provinces (with 800–2500 m elevation) in Iran. Litter samples were taken twice in each site, once in July–November 2002 and again in March 2003. At each site 60 Artemesia sp. bushes were selected at random and litter from each bush was collected and the number of live male and female adult Sunn Pest counted. More Sunn Pests were collected in higher elevations in the first sampling. Golestan (893 m), Kermanshah (1583 m), and Qazvin (1675 m), located in valleys and surrounded by mountainous areas, had < 5 adults/bush. However Azarbayejan (1750 m), Markazi (1883 m), Kordestan (2067 m), and Esfahan (2141 m), located in mountainous areas and/or close to mountains, had 10–52 adults/bush. No noticeable changes in Sunn Pest populations were observed in 17 overwintering sites among 21 between the two sampling times. These results suggest that, after Sunn Pest moves to more highly elevated sites at aestivation time, most of them remain in these sites during overwintering before migration to wheat fields in the spring. Sunn Pest can be targeted for management in these areas during the fall and/or early spring as their movement is clearly limited.     

Genetic diversity of nine faba bean (Vicia faba L.) populations revealed by isozyme markers

Seven isozyme systems (Sod, 6-Pgd, Me, Est, Skdh, Fdh and Gdh) representing nine loci were used to study the genetic diversity of nine faba bean populations. Seven loci revealed polymorphic bands and showed the same quaternary structure as that found in several species. They revealed a high number of phenotypes. Indeed, from 3 to 9 phenotypes per locus were investigated in this study. The percentage of polymorphic loci (P = 59.3 %) was higher than that mentioned in the autogamous species (P = 20.3 %) and less than the optimum (P=96 %) indicated for allogamous plants. Total genetic diversity (H _T) and within population genetic diversity (H _S) were estimated with the isozyme markers. The contribution of among population genetic diversity (D _ST) to total genetic diversity was 22%. Enzyme markers pointed out an average inbreeding level for whole population (F _IT) and within population (F _IS). Within population genetic diversity represents 78% of total diversity. Intra-population genetic diversity (H _S = 0.206) was ranged with the respect of allogamous species and was clearly higher than that of among population genetic diversity (D _ST = 0.057) indicating an out-crossing predominance in the studied populations. The expected heterozygosity was higher than that observed heterozygosity at the allogamous species was confirmed in this study. Although, the mean estimated gene flow was less than 1(Nm=0.814), the dendrogram based on Nei’s genetic distance of the 9 populations using UPGMA method showed some genetic drift between populations.     

Changes in leaf gas exchange, water relations, biomass production and solute accumulation in Phragmites australis under hypoxic conditions

The physiological responses to hypoxic stress were studied in the common reed, Phragmites australis (Cav.) Trin. ex Steudel. Growth, leaf gas exchange, water (and ion) relations and osmotic adjustment were determined in hydroponically grown plants exposed to 10, 20 and 30 days of oxygen deficiency. The highest growth of reed seedlings was found in normoxic (aerobic) conditions. Treatment effects on biomass production were relatively consistent within each harvest. Leaf water potential and osmotic potential declined significantly as hypoxia periods increased. However, leaf turgor pressure showed a consistent pattern of increase, suggesting that reed plants adjusted their water status by osmotic adjustment in response to root hypoxia. After 20 and 30 days in the low oxygen treatment, net CO₂ assimilation and stomatal conductance were positively associated and the former variable also had a strong positive relationship with transpiration. Short-term hypoxic stress had a slight effect on the ionic status (K⁺, Ca²⁺ and Mg²⁺) of reed plants. In contrast, soluble sugar concentrations increased more under hypoxic conditions as compared to normoxia. These findings indicate that hypoxia slightly affected the physiological behavior of reed plants.     

A human cancer-predisposing polymorphism in Cdc25A is embryonic lethal in the mouse and promotes ASK-1 mediated apoptosis

Background

Failure to regulate the levels of Cdc25A phosphatase during the cell cycle or during a checkpoint response causes bypass of DNA damage and replication checkpoints resulting in genomic instability and cancer. During G1 and S and in cellular response to DNA damage, Cdc25A is targeted for degradation through the Skp1-cullin-β-TrCP (SCF^β-TrCP) complex. This complex binds to the Cdc25A DSG motif which contains serine residues at positions 82 and 88. Phosphorylation of one or both residues is necessary for the binding and degradation to occur.

Results

We now show that mutation of serine 88 to phenylalanine, which is a cancer-predisposing polymorphic variant in humans, leads to early embryonic lethality in mice. The mutant protein retains its phosphatase activity both in vitro and in cultured cells. It fails to interact with the apoptosis signal-regulating kinase 1 (ASK1), however, and therefore does not suppress ASK1-mediated apoptosis.

Conclusions

These data suggest that the DSG motif, in addition to its function in Cdc25A-mediated degradation, plays a role in cell survival during early embyogenesis through suppression of ASK1-mediated apoptosis.