A bibliometric overview of craniosynostosis research development.

This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the early development of the skull, when one or more of the sutures close too early, causing problems with normal brain and skull growth. Research in this field has developed from early clinical case descriptions, to genetic discoveries responsible for the occurring malformations and onwards to developing sophisticated surgical treatment. In this article we describe these developments, zoom in on publication trends and characteristics and visualize developing networks and topic shifts in this research field.

Dynamic histone H3 epigenome marking during the intraerythrocytic cycle of Plasmodium falciparum.

Epigenome profiling has led to the paradigm that promoters of active genes are decorated with H3K4me3 and H3K9ac marks. To explore the epigenome of Plasmodium falciparum asexual stages, we performed MS analysis of histone modifications and found a general preponderance of H3/H4 acetylation and H3K4me3. ChIP-on-chip profiling of H3, H3K4me3, H3K9me3, and H3K9ac from asynchronous parasites revealed an extensively euchromatic epigenome with heterochromatin restricted to variant surface antigen gene families (VSA) and a number of genes hitherto unlinked to VSA. Remarkably, the vast majority of the genome shows an unexpected pattern of enrichment of H3K4me3 and H3K9ac. Analysis of synchronized parasites revealed significant developmental stage specificity of the epigenome. In rings, H3K4me3 and H3K9ac are homogenous across the genes marking active and inactive genes equally, whereas in schizonts, they are enriched at the 5' end of active genes. This study reveals an unforeseen and unique plasticity in the use of the epigenetic marks and implies the presence of distinct epigenetic pathways in gene silencing/activation throughout the erythrocytic cycle.

Global histone analysis by mass spectrometry reveals a high content of acetylated lysine residues in the malaria parasite Plasmodium falciparum.

Post-translational modifications (PTMs) of histone tails play a key role in epigenetic regulation of gene expression in a range of organisms from yeast to human; however, little is known about histone proteins from the parasite that causes malaria in humans, Plasmodium falciparum. We characterized P. falciparum histone PTMs using advanced mass spectrometry driven proteomics. Acid-extracted proteins were resolved in SDS-PAGE, in-gel trypsin digested, and analyzed by reversed-phase LC-MS/MS. Through the combination of Q-TOF and LTQ-FT mass spectrometry we obtained high mass accuracy of both precursor and fragment ions, which is a prerequisite for high-confidence identifications of multisite peptide modifications. We utilize MS/MS fragment marker ions to validate the identification of histone modifications and report the m/z 143 ion as a novel MS/MS marker ion for monomethylated lysine. We identified all known P. falciparum histones and mapped 44 different modifications, providing a comprehensive view of epigenetic marks in the parasite. Interestingly, the parasite exhibits a histone modification pattern that is distinct from its human host. A general preponderance for modifications associated with a transcriptionally permissive state was observed. Additionally, a novel differentiation in the modification pattern of the two histone H2B variants (H2B and H2Bv) was observed, suggesting divergent functions of the two H2B variants in the parasite. Taken together, our results provide a first comprehensive map of histone modifications in P. falciparum and highlight the utility of tandem MS for detailed analysis of peptides containing multiple PTMs.

Identification and characterisation of high affinity nucleoside and nucleobase transporters in Toxoplasma gondii.

The protozoan parasite Toxoplasma gondii depends upon salvaging the purines that it requires. We have re-analysed purine transport in T. gondii and identified novel nucleoside and nucleobase transporters. The latter transports hypoxanthine (TgNBT1; K(m)=0.91+/-0.19 microM) and is inhibited by guanine and xanthine: it is the first high affinity nucleobase transporter to be identified in an apicomplexan parasite. The previously reported nucleoside transporter, TgAT1, is low affinity with K(m) values of 105 and 134 microM for adenosine and inosine, respectively. We have now identified a second nucleoside transporter, TgAT2, which is high affinity and inhibited by adenosine, inosine, guanosine, uridine and thymidine (K(m) values 0.28-1.5 microM) as well as cytidine (K(i)=32 microM). TgAT2 also recognises several nucleoside analogues with therapeutic potential. We have investigated the basis for the broad specificity of TgAT2 and found that hydrogen bonds are formed with the 3' and 5' hydroxyl groups and that the base groups are bound through H-bonds with either N3 of the purine ring or N(3)H of the pyrimidine ring, and most probably pi-pi-stacking as well. The identification of these high affinity purine nucleobase and nucleoside transporters reconciles for the first time the low abundance of free nucleosides and nucleobases in the intracellular environment with the efficient purine salvage carried out by T. gondii.