New synaptic bouton formation is disrupted by misregulation of microtubule stability in aPKC mutants

The Baz/Par-3-Par-6-aPKC complex is an evolutionarily conserved cassette critical for the development of polarity in epithelial cells, neuroblasts, and oocytes. aPKC is also implicated in long-term synaptic plasticity in mammals and the persistence of memory in flies, suggesting a synaptic function for this cassette. Here we show that at Drosophila glutamatergic synapses, aPKC controls the formation and structure of synapses by regulating microtubule (MT) dynamics. At the presynapse, aPKC regulates the stability of MTs by promoting the association of the MAP1Brelated protein Futsch to MTs. At the postsynapse, aPKC regulates the synaptic cytoskeleton by controlling the extent of Actin-rich and MT-rich areas. In addition, we show that Baz and Par-6 are also expressed at synapses and that their synaptic localization depends on aPKC activity. Our findings establish a novel role for this complex during synapse development and provide a cellular context for understanding the role of aPKC in synaptic plasticity and memory.     

Group Colocation Behavior in Technological Social Networks

We analyze two large datasets from technological networks with location and social data: user location records from an online location-based social networking service, and anonymized telecommunications data from a European cellphone operator, in order to investigate the differences between individual and group behavior with respect to physical location. We discover agreements between the two datasets: firstly, that individuals are more likely to meet with one friend at a place they have not visited before, but tend to meet at familiar locations when with a larger group. We also find that groups of individuals are more likely to meet at places that their other friends have visited, and that the type of a place strongly affects the propensity for groups to meet there. These differences between group and solo mobility has potential technological applications, for example, in venue recommendation in location-based social networks.     

Resistant Starch Alters the Microbiota-Gut Brain Axis: Implications for Dietary Modulation of Behavior

The increasing recognition that the gut microbiota plays a central role in behavior and cognition suggests that the manipulation of microbial taxa through diet may provide a means by which behavior may be altered in a reproducible and consistent manner in order to achieve a beneficial outcome for the host. Resistant starch continues to receive attention as a dietary intervention that can benefit the host through mechanisms that include altering the intestinal microbiota. Given the interest in dietary approaches to improve health, the aim of this study was to investigate whether the use of dietary resistant starch in mice to alter the gut microbiota also results in a change in behavior. Forty-eight 6 week-old male Swiss-Webster mice were randomly assigned to 3 treatment groups (n = 16 per group) and fed either a normal corn starch diet (NCS) or diets rich in resistant starches HA7 diet (HA7) or octenyl-succinate HA7 diet (OS-HA7) for 6 week and monitored for weight, behavior and fecal microbiota composition. Animals fed an HA7 diet displayed comparable weight gain over the feeding period to that recorded for NCS-fed animals while OS-HA7 displayed a lower weight gain as compared to either NCS or HA7 animals (ANOVA p = 0.0001; NCS:HA7 p = 0.244; HA7:OS-HA7 p<0.0001; NCS:OS-HA7 p<0.0001). Analysis of fecal microbiota using 16s rRNA gene taxonomic profiling revealed that each diet corresponded with a unique gut microbiota. The distribution of taxonomic classes was dynamic over the 6 week feeding period for each of the diets. At the end of the feeding periods, the distribution of taxa included statistically significant increases in members of the phylum Proteobacteria in OS-HA7 fed mice, while the Verrucomicrobia increased in HA7 fed mice over that of mice fed OS-HA7. At the class level, members of the class Bacilli decreased in the OS-HA7 fed group, and Actinobacteria, which includes the genus Bifidobacteria, was enriched in the HA7 fed group compared to the control diet. Behavioral analysis revealed that animals demonstrated profound anxiety-like behavior as observed by performance on the elevated-plus maze with time spent by the mice in the open arm (ANOVA p = 0.000; NCS:HA7 p = 0.004; NCS:OS-HA7 p = 1.000; HA7:OS-HA7 p = 0.0001) as well as entries in the open arm (ANOVA p = 0.039; NCS:HA7 p = 0.041; HA7:OS-HA7 p = 0.221; NCS:OS-HA7 p = 1.000). Open-field behavior, a measure of general locomotion and exploration, revealed statistically significant differences between groups in locomotion as a measure of transitions across quadrant boundaries. Additionally, the open-field assay revealed decreased exploration as well as decreased rearing in HA7 and OS-HA7 fed mice demonstrating a consistent pattern of increased anxiety-like behavior among these groups. Critically, behavior was not correlated with weight. These results indicate that diets based on resistant starch can be utilized to produce quantifiable changes in the gut microbiota and should be useful to “dial-in” a specific microbiome that is unique to a particular starch composition. However, undesirable effects can also be associated with resistant starch, including lack of weight gain and increased anxiety-like behaviors. These observations warrant careful consideration when developing diets rich in resistant starch in humans and animal models.     

Abundance of common species,not species richness,drives delivery of a real‐world ecosystem service

Biodiversity‐ecosystem functioning experiments have established that species richness and composition are both important determinants of ecosystem function in an experimental context. Determining whether this result holds for real‐world ecosystem services has remained elusive, however, largely due to the lack of analytical methods appropriate for large‐scale, associational data. Here, we use a novel analytical approach, the Price equation, to partition the contribution to ecosystem services made by species richness, composition and abundance in four large‐scale data sets on crop pollination by native bees. We found that abundance fluctuations of dominant species drove ecosystem service delivery, whereas richness changes were relatively unimportant because they primarily involved rare species that contributed little to function. Thus, the mechanism behind our results was the skewed species‐abundance distribution. Our finding that a few common species, not species richness, drive ecosystem service delivery could have broad generality given the ubiquity of skewed species‐abundance distributions in nature.     

Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity

Oxidized lipids, such as 13-hydroperoxyoctadecadienoic acid (13-HPODE), have been implicated in the pathogenesis of atherosclerosis. 13-HPODE, a constituent of oxidized low-density lipoproteins, can induce cytotoxicity of vascular smooth muscle cells (SMC), which may facilitate plaque destabilization and/or rupture. 13-HPODE-induced cytotoxicity has been linked to oxidative stress, although the mechanisms by which this occurs are unknown. In the present study, we show that 13-HPODE and 9-HPODE (10-30 microM) increased superoxide (O2*-) production and induced cytotoxicity in SMC. The 13-HPODE-induced increase in O2*- was blocked by transfecting the cells with antisense oligonucleotides against p22phox, suggesting that the O2*- was produced by NAD(P)H oxidase. Similar concentrations of the corresponding HPODE reduction products, 13-hydroxyoctadecadienoic acid (13-HODE) and 9-HODE, neither increased O2*- production nor induced cytotoxicity, while 4-hydroxy nonenal (4-HNE), an unsaturated aldehyde lipid peroxidation product, induced cytotoxicity without increasing O2*- production. Treatment with superoxide dismutase or Tiron to scavenge O2*-, or transfection with p22phox antisense oligonucleotides to inhibit O2*- production, attenuated 13-HPODE-induced cytotoxicity, but not that induced by 4-HNE. These findings suggest that activation of NAD(P)H oxidase, and production of O2*-, play an important role in lipid hydroperoxide-induced smooth muscle cytotoxicity.     

Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria

Background

Effective mating between laboratory-reared males and wild females is paramount to the success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically modified male mosquitoes. However mosquito colonization and laboratory maintenance have the potential to negatively affect male genotypic and phenotypic quality through inbreeding and selection, which in turn can decrease male mating competitiveness in the field. To date, very little is known about the impact of those evolutionary forces on the reproductive biology of mosquito colonies and how they ultimately affect male reproductive fitness.

Methods

Here several male reproductive physiological traits likely to be affected by inbreeding and selection following colonization and laboratory rearing were examined. Sperm length, and accessory gland and testes size were compared in male progeny from field-collected females and laboratory strains of Anopheles gambiae sensu stricto colonized from one to over 25 years ago. These traits were also compared in the parental and sequentially derived, genetically modified strains produced using a two-phase genetic transformation system. Finally, genetic crosses were performed between strains in order to distinguish the effects of inbreeding and selection on reproductive traits.

Results

Sperm length was found to steadily decrease with the age of mosquito colonies but was recovered in refreshed strains and crosses between inbred strains therefore incriminating inbreeding costs. In contrast, testes size progressively increased with colony age, whilst accessory gland size quickly decreased in males from colonies of all ages. The lack of heterosis in response to crossing and strain refreshing in the latter two reproductive traits suggests selection for insectary conditions.

Conclusions

These results show that inbreeding and selection differentially affect reproductive traits in laboratory strains overtime and that heterotic ‘supermales’ could be used to rescue some male reproductive characteristics. Further experiments are needed to establish the exact relationship between sperm length, accessory gland and testes size, and male reproductive success in the laboratory and field settings.