Paths to a malaria vaccine illuminated by parasite genomics.

More human death and disease is caused by malaria parasites than by all other eukaryotic pathogens combined. As early as the sequencing of the first human genome, malaria parasite genomics was prioritized to fuel the discovery of vaccine candidate antigens. This stimulated increased research on malaria, generating new understanding of the cellular and molecular mechanisms of infection and immunity. This review of recent developments illustrates how new approaches in parasite genomics, and increasingly large amounts of data from population studies, are helping to identify antigens that are promising lead targets. Although these results have been encouraging, effective discovery and characterization need to be coupled with more innovation and funding to translate findings into newly designed vaccine products for clinical trials

Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria.

BACKGROUND: Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity would allow higher levels of linkage disequilibrium (LD) than would exist in more highly endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: Assessment of LD was first made with 11 microsatellite loci widely dispersed in the parasite genome, and 16 microsatellite loci covering a approximately 140 kb region of chromosome 2 (an arbitrarily representative non-telomeric part of the genome), in a sample of 100 P. falciparum isolates. The dispersed loci showed minimal LD (Index of Association, I(S) (A) = 0.013, P = 0.10), while those on chromosome 2 showed significant LD values mostly between loci <5 kb apart. A disease association study was then performed comparing parasites in 113 severe malaria cases and 245 mild malaria controls. Genotyping was performed on almost all polymorphisms in the binding domains of three erythrocyte binding antigens (eba175, eba140 and eba181), and repeat sequence polymorphisms approximately 2 kb apart in each of three reticulocyte binding homologues (Rh1, Rh2a/b, and Rh4). Differences between cases and controls were seen for (i) codons 388-90 in eba175, and (ii) a repeat sequence centred on Rh1 codon 667. CONCLUSIONS/SIGNIFICANCE: Allelic association studies on P. falciparum require dense genotypic markers, even in a population of only moderate endemicity that has more extensive LD than highly endemic populations. Disease-associated polymorphisms in the eba175 and Rh1 genes encode differences in the middle of previously characterised erythrocyte binding domains, marking these for further investigation

Biophysical regulation of stem cell behavior within the niche.

Stem cells reside within most tissues throughout the lifetimes of mammalian organisms. To maintain their capacities for division and differentiation and thereby build, maintain, and regenerate organ structure and function, these cells require extensive and precise regulation, and a critical facet of this control is the local environment or niche surrounding the cell. It is well known that soluble biochemical signals play important roles within such niches, and a number of biophysical aspects of the microenvironment, including mechanical cues and spatiotemporally varying biochemical signals, have also been increasingly recognized to contribute to the repertoire of stimuli that regulate various stem cells in various tissues of both vertebrates and invertebrates. For example, biochemical factors immobilized to the extracellular matrix or the surface of neighboring cells can be spatially organized in their placement. Furthermore, the extracellular matrix provides mechanical support and regulatory information, such as its elastic modulus and interfacial topography, which modulate key aspects of stem cell behavior. Numerous examples of each of these modes of regulation indicate that biophysical aspects of the niche must be appreciated and studied in conjunction with its biochemical properties

Geological Mapping of the Debussy Quadrangle (H-14) - Preliminary Results

Geological mapping of Mercury is essential to build an understanding of the history of the planet and to set the context for observations by BepiColombo [1]. Geological mapping of the Debussy quadrangle (H-14) is now underway as part of a program to map the entire planet at a scale of 1:3M using MESSENGER data [2]. The quadrangle is located in the southern hemisphere of Mercury at 0o – 90o E and 22.5o – 65o S. This will be the first high resolution map of the quadrangle as it was not previously imaged by Mariner 10

The Strathclyde Brain Computer Interface (S-BCI) : the road to clinical translation

In this paper, we summarise the state of development of the Strathclyde Brain Computer Interface (S-BCI) and what has been so far achieved. We also briefly discuss our next steps for translation to spinal cord injured patients and the challenges we envisage in this process and how we plan to address some of them. Projections of the S-BCI project for the coming few years are also presented

Geological mapping of the Hokusai (H05) quadrangle of Mercury: Status update

[Introduction] MESSENGER data are being used to construct ~1:3M scale quadrangle geological maps of Mercury. Here, we present our progress mapping the Hokusai (H05) quadrangle

Post-deposition (and ongoing?) modification of Caloris ejecta blocks

Mercury’s circum-Caloris region hosts numerous kilometer-scale knobs. If these land-forms, peculiar to Caloris, are its ejecta, then they can provide insight into the deep materials of the planet

Primer

Discussion and history of public corruption statutes and the prosecution of public officials through McDonnell v. United States, 136 S. Ct. 2355 (2016)