The serine/threonine phosphatases of apicomplexan parasites

The balance between phosphorylation and de-phosphorylation, which is delicately regulated by protein kinases and phosphatases, is critical for nearly all biological processes. The Apicomplexa are a large phylum which contains various parasitic protists, including human pathogens, such as Plasmodium, Toxoplasma, Cryptosporidium and Babesia species. The diverse life cycles of these parasites are highly complex and, not surprisingly, many of their key steps are exquisitely regulated by phosphorylation. Interestingly, many of the kinases and phosphatases, as well as the substrates involved in these events are unique to the parasites and therefore phosphorylation constitutes a viable target for antiparasitic intervention. Most progress on this realm has come from studies in Toxoplasma and Plasmodium of their respective kinomes and phosphoproteomes. Nonetheless, given their likely importance, phosphatases have recently become the focus of research within the apicomplexan parasites. In this review, we concentrate on serine/threonine phosphatases in apicomplexan parasites, with the focus on comprehensively identifying and naming protein phosphatases in available apicomplexan genomes, and summarizing the progress of their functional analyses in recent years

Normal families and shared values of meromorphic functions

AbstractLet k(⩾2) be a positive integer, let F be a family of meromorphic functions in a domain D, all of whose zeros have multiplicity at least k+1, and let a(z)(≠0), h(z)(≢0) be two holomorphic functions on D. If, for each f∈F, f=a(z)⇔f(k)=h(z), then F is normal in D

RNA polymerase II CTD Evolutionary Diversity and Associated Protein Identification in Green and Red Algae

In model eukaryotes, the C-terminal domain (CTD) of the largest subunit (RPB1) of DNA-dependent RNA polymerase II is composed of tandemly repeated heptads with the consensus sequence YSPTSPS. Both the core motif and tandem structure generally are highly conserved across many model taxa, including animals, yeasts and higher plants. Broader investigations quickly revealed that the CTDs of many organisms deviate substantially from this canonical structure; however, limited sampling made it difficult to determine whether disordered sequences represent the CTD's ancestral state, or reflect degeneration from an originally repetitive structure. Therefore, I undertook the broadest investigation to date of the evolution of the RNAP II CTD across eukaryotic diversity. The results indicate that a tandem heptad CTD-structure existed in the ancestors of each major taxon, and that degeneration and reinvention of this ordered structure are common features of CTD evolution. Lineage specific modifications of heptads that were amplified initially appear to be associated with greater developmental complexity in multicellular taxa. The pattern has been taken to an extreme in both fungi and red algae. Overall, loss and reinvention of varied repeats have punctuated CTD evolution, occurring independently and sometimes repeatedly in various groups.    Although present in simple, ancestral red algae, CTD tandem repeats have undergone extensive modifications and degeneration during the evolutionary transition to developmentally complex rhodophytes. In contrast, CTD repeats are conserved in both green algae and their more complex land plant relatives. Understanding the mechanistic differences that underlie these variant patterns of CTD evolution requires knowledge of CTD-associated proteins in these two lineages. To provide an initial baseline comparison, potential phospho-CTD associated proteins (PCAPs) were bound to artificially synthesized and phosphorylated CTD repeats from the unicellular green alga Chlamydomonas reinhardtii and red alga Cyanidioschyzon merolae. My results indicate that red and green algae share a number of PCAPs, including kinases and proteins involved in mRNA export. There also are important taxon-specific differences, including mRNA splicing-related PCAPs recovered from Chlamydomonas but not Cyanidioschyzon, consistent with the relative intron densities in green and red algae. This work also offers the first experimental indication that different proteins bind the two types of repeats in Cyanidioschyzon, suggesting a division of function between the proximal and distal CTD, similar to patterns identified in more developmentally complex model organisms.  Ph.D

Preliminary study of beta-blocker therapy on modulation of interleukin-33/ST2 signaling during ventricular remodeling after acute myocardial infarction

Background: This study aimed to evaluate the role of b-blocker therapy on modulating interleukin (IL)-33/ST2 (interleukin-1 receptor-like 1) signaling during ventricular remodeling related to heart failure (HF) after acute myocardial infarction (AMI). Methods: Sprague-Dawley rats that survived surgery to induce AMI were randomly divided into the placebo group and the b-blocker treatment group. A sham group was used as a control. Left ventricular (LV) function variables, the myocardial infarct size, fibrosis and IL-33/ST2 protein expression was measured. Results: Compared with the placebo group, b-blocker treatment significantly improved LV function and reduced infarct size (p < 0.05). There was higher protein expression of IL-33 (p < 0.05) and sST2 (p < 0.05), as well as higher expression of fibrosis (p < 0.05), compared to the sham group. Notably, the high expression of cardioprotective IL-33 was not affected by b-blocker treatment (p > 0.05), however, treatment with b-blocker enhanced IL-33/ST2 signaling, with lower expression of sST2 (p < 0.05) and significantly attenuated fibrosis (p < 0.05). Conclusions: Our study suggested that b-blocker therapy might play a beneficial role in the modula­tion of IL-33/ST2 signaling during ventricular remodeling. These results may be helpful in identifying IL-33/ST2 systems as putative b-blocker targets at an early stage after AMI. (Cardiol J 2017; 24, 2: 188–194

Consistent dissection of the protein interaction network by combining global and local metrics

A new network decomposition method is proposed that uses both a global metric and a local metric to identify protein interaction modules in the protein interaction network