Inter-chromosomal Contact Properties in Live-Cell Imaging and in Hi-C

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Sheep Skin Odor Improves Trap Captures of Mosquito Vectors of Rift Valley Fever

In recent years, the East African region has seen an increase in arboviral diseases transmitted by blood-feeding arthropods. Effective surveillance to monitor and reduce incidence of these infections requires the use of appropriate vector sampling tools. Here, trapped skin volatiles on fur from sheep, a known preferred host of mosquito vectors of Rift Valley fever virus (RVFV), were used with a standard CDC light trap to improve catches of mosquito vectors. We tested the standard CDC light trap alone (L), and baited with (a) CO₂ (LC), (b) animal volatiles (LF), and (c) CO₂ plus animal volatiles (LCF) in two highly endemic areas for RVF in Kenya (Marigat and Ijara districts) from March–June and September–December 2010. The incidence rate ratios (IRR) that mosquito species chose traps baited with treatments (LCF, LC and LF) instead of the control (L) were estimated. Marigat was dominated by secondary vectors and host-seeking mosquitoes were 3–4 times more likely to enter LC and LCF traps [IRR = 3.1 and IRR = 3.8 respectively] than the L only trap. The LCF trap captured a greater number of mosquitoes than the LC trap (IRR = 1.23) although the difference was not significant. Analogous results were observed at Ijara, where species were dominated by key primary and primary RVFV vectors, with 1.6-, 6.5-, and 8.5-fold increases in trap captures recorded in LF, LC and LCF baited traps respectively, relative to the control. These catches all differed significantly from those trapped in L only. Further, there was a significant increase in trap captures in LCF compared to LC (IRR = 1.63). Mosquito species composition and trap counts differed between the RVF sites. However, within each site, catches differed in abundance only and no species preferences were noted in the different baited-traps. Identifying the attractive components present in these natural odors should lead to development of an effective odor-bait trapping system for population density-monitoring and result in improved RVF surveillance especially during the inter-epidemic period.     

A Nonintegrative Lentiviral Vector-Based Vaccine Provides Long-Term Sterile Protection against Malaria

Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated sporozoites (RAS) have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach. However, longer-term protection and higher protection rates are required to eradicate malaria from the endemic regions. It implies that there is still a need to explore new vaccine strategies. Lentiviral vectors are very potent at inducing strong immunological memory. However their integrative status challenges their safety profile. Eliminating the integration step obviates the risk of insertional oncogenesis. Providing they confer sterile immunity, nonintegrative lentiviral vectors (NILV) hold promise as mass pediatric vaccine by meeting high safety standards. In this study, we have assessed the protective efficacy of NILV against malaria in a robust pre-clinical model. Mice were immunized with NILV encoding Plasmodium yoelii Circumsporozoite Protein (Py CSP) and challenged with sporozoites one month later. In two independent protective efficacy studies, 50% (37.5–62.5) of the animals were fully protected (p = 0.0072 and p = 0.0008 respectively when compared to naive mice). The remaining mice with detectable parasitized red blood cells exhibited a prolonged patency and reduced parasitemia. Moreover, protection was long-lasting with 42.8% sterile protection six months after the last immunization (p = 0.0042). Post-challenge CD8+ T cells to CSP, in contrast to anti-CSP antibodies, were associated with protection (r = −0.6615 and p = 0.0004 between the frequency of IFN-g secreting specific T cells in spleen and parasitemia). However, while NILV and RAS immunizations elicited comparable immunity to CSP, only RAS conferred 100% of sterile protection. Given that a better protection can be anticipated from a multi-antigen vaccine and an optimized vector design, NILV appear as a promising malaria vaccine.     

New hypothesis elucidates self-incompatibility in the olive tree regarding S-alleles dominance relationships as in the sporophytic model

Most olive varieties are not strictly self-incompatible, nevertheless, they request foreign pollen to enhance fruit yield, and consequently orchards should contain pollinisers to ensure fruit set of the main variety. The best way to choose pollinisers is to experiment numerous crosses in a diallel design. Here, the genetic mode of inheritance of SI in the olive is deciphered and it does not correspond to the GSI type, but to the SSI type. It leaves S-allele dominance relationship expression in the male (pollen and pollen tube), but not in the female (stigma and style). Thus, a pair-wise combination of varieties may be inter-compatible in one direction (male to female, or female to male) and inter-incompatible in the other direction. Dominance relationships also explain different levels of self-pollination observed in varieties. Little efficient pollinisers were found and predicted in varieties; nevertheless, some new efficient pair-wise allele combinations are predicted and could be created. This model enables one to forecast compatibility without waiting for several years of yield records and to choose pollinisers in silico.     

Ceramic-based multisite microelectrode arrays for simultaneous measures of choline and acetylcholine in CNS

A ceramic-based microelectrode array (MEA) with enzyme coatings for the accurate measurement of acetylcholine (ACh) in brain tissues is presented. Novel design features allow for self-referencing recordings for improved limits of detection and highly selective measurements of ACh and choline (Ch), simultaneously. Design and fabrication features also result in minimal tissue damage during implantation and improved enzyme coatings due to isolated recording sites. In these studies we have used a recombinant human acetylcholinesterase enzyme coating, which has better reproducibility than other commercially available enzymes. The precisely patterned recording site dimensions, low limit of detection (0.2 micro M) and fast response time ( approximately 1s) allow for second-by-second measurements of ACh and Ch in brain tissues. An electropolymerized meta-phenylenediamine (mPD) layer was used to exclude interfering substances from being recorded at the platinum recording sites. Our studies support that the mPD layer was stable for over 24h under in vitro and in vivo recording conditions. In addition, our work supports that the current configuration of the MEAs produces a robust design, which is suited for measures of ACh and Ch in rat brain.     

Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task

The use of stimulants (methylphenidate and amphetamine) as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose) in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations) given with and without methylphenidate (20 mg, oral). Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less). This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering) was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering) or impaired (i.e., attention deficit hyperactivity disorder), but it could be detrimental when brain activity is already optimally focused. This would explain why methylphenidate has beneficial effects in some individuals and contexts and detrimental effects in others.     

Molecular classification of scrapie strains in mice using gene expression profiling

Transmissible spongiform encephalopathy strains demonstrate specific prion characteristics, each with specific incubation times, and strain-specific patterns of deposition of the misfolded isoform of prion, PrPSc, in the brains of infected individuals. Different biochemical properties, including glycosylation profiles and the degree of proteinase resistance, have been shown to be strain-specific. However, no relationship between these properties and the phenotypic differences in the subsequent diseases has as yet been determined. Here we explore the utility of gene expression profiles to identify differences in the host response to different strains of prion agent. We identify 114 genes that exhibit significantly different levels of expression in mice infected with three strains of scrapie. These genes represent a pool of genes involved in a strain-specific response to prion disease. We have identified the most discriminatory genes from this list utilizing a wrapper-based feature selection algorithm with external cross-validation.