Reduced KIR2DL1 recognition of MHC class I molecules presenting phosphorylated peptides

As initially described by K. Karre and colleagues in the missing self hypothesis, cells expressing self-MHC class I proteins are protected from NK cells attack. In contrast, reduction in the expression of MHC class I molecules due to viral infection or tumor transformation result in the killing of these "abnormal" cells by NK cells via NK-activating receptors. Thus, NK killing of target cells is determined by both negative signals coming from MHC class I proteins and by positive signals derived from the activating ligands. The bound peptide in MHC class I play an important role in the balanced recognition of NK cells. The peptide stabilizes the MHC complex and interacts directly with the NK inhibitory receptors, thus participating in the determination of the fate of the target cells. In this study we demonstrate that posttranslational modifications such as phosphorylation of the presented peptide altered the ability of NK cells to recognize MHC class I molecules. By using a consensus peptide (QYDDAVYKL) that binds HLA-Cw4 in which different positions in the bound peptide were modified by serine phosphorylation, we observed a reduction in KIR2DL1 binding that led to decreased protection from NK killing. Therefore, it might be possible that alteration in the phosphorylation pattern during tumor transformation or viral infection may result in less inhibition and, consequently, improved NK cell killing.     

Analysis of the human polynucleotide phosphorylase (PNPase) reveals differences in RNA binding and response to phosphate compared to its bacterial and chloroplast counterparts

PNPase is a major exoribonuclease that plays an important role in the degradation, processing, and polyadenylation of RNA in prokaryotes and organelles. This phosphorolytic processive enzyme uses inorganic phosphate and nucleotide diphosphate for degradation and polymerization activities, respectively. Its structure and activities are similar to the archaeal exosome complex. The human PNPase was recently localized to the intermembrane space (IMS) of the mitochondria, and is, therefore, most likely not directly involved in RNA metabolism, unlike in bacteria and other organelles. In this work, the degradation, polymerization, and RNA-binding properties of the human PNPase were analyzed and compared to its bacterial and organellar counterparts. Phosphorolytic activity was displayed at lower optimum concentrations of inorganic phosphate. Also, the RNA-binding properties to ribohomopolymers varied significantly from those of its bacterial and organellar enzymes. The purified enzyme did not preferentially bind RNA harboring a poly(A) tail at the 3' end, compared to a molecule lacking this tail. Several site-directed mutations at conserved amino acid positions either eliminated or modified degradation/polymerization activity in different manners than observed for the Escherichia coli PNPase and the archaeal and human exosomes. In light of these results, a possible function of the human PNPase in the mitochondrial IMS is discussed.     

Application of network methods for understanding evolutionary dynamics in discrete habitats

In populations occupying discrete habitat patches, gene flow between habitat patches may form an intricate population structure. In such structures, the evolutionary dynamics resulting from interaction of gene‐flow patterns with other evolutionary forces may be exceedingly complex. Several models describing gene flow between discrete habitat patches have been presented in the population‐genetics literature; however, these models have usually addressed relatively simple settings of habitable patches and have stopped short of providing general methodologies for addressing nontrivial gene‐flow patterns. In the last decades, network theory – a branch of discrete mathematics concerned with complex interactions between discrete elements – has been applied to address several problems in population genetics by modelling gene flow between habitat patches using networks. Here, we present the idea and concepts of modelling complex gene flows in discrete habitats using networks. Our goal is to raise awareness to existing network theory applications in molecular ecology studies, as well as to outline the current and potential contribution of network methods to the understanding of evolutionary dynamics in discrete habitats. We review the main branches of network theory that have been, or that we believe potentially could be, applied to population genetics and molecular ecology research. We address applications to theoretical modelling and to empirical population‐genetic studies, and we highlight future directions for extending the integration of network science with molecular ecology.     

Allelic Richness following Population Founding Events – A Stochastic Modeling Framework Incorporating Gene Flow and Genetic Drift

Allelic richness (number of alleles) is a measure of genetic diversity indicative of a population''s long-term potential for adaptability and persistence. It is used less commonly than heterozygosity as a genetic diversity measure, partially because it is more mathematically difficult to take into account the stochastic process of genetic drift for allelic richness. This paper presents a stochastic model for the allelic richness of a newly founded population experiencing genetic drift and gene flow. The model follows the dynamics of alleles lost during the founder event and simulates the effect of gene flow on maintenance and recovery of allelic richness. The probability of an allele''s presence in the population was identified as the relevant statistical property for a meaningful interpretation of allelic richness. A method is discussed that combines the probability of allele presence with a population''s allele frequency spectrum to provide predictions for allele recovery. The model''s analysis provides insights into the dynamics of allelic richness following a founder event, taking into account gene flow and the allele frequency spectrum. Furthermore, the model indicates that the “One Migrant per Generation” rule, a commonly used conservation guideline related to heterozygosity, may be inadequate for addressing preservation of diversity at the allelic level. This highlights the importance of distinguishing between heterozygosity and allelic richness as measures of genetic diversity, since focusing merely on the preservation of heterozygosity might not be enough to adequately preserve allelic richness, which is crucial for species persistence and evolution.     

Development of a gene knockout system for the halophilic archaeon Haloferax volcanii by use of the pyrE gene

So far, the extremely halophilic archaeon Haloferax volcanii has the best genetic tools among the archaea. However, the lack of an efficient gene knockout system for this organism has hampered further genetic studies. In this paper we describe the development of pyrE-based positive selection and counterselection systems to generate an efficient gene knockout system. The H. volacanii pyrE1 and pyrE2 genes were isolated, and the pyrE2 gene was shown to code for the physiological enzyme orotate phosphoribosyl transferase. A DeltapyrE2 strain was constructed and used to isolate deletion mutants by the following two steps: (i) integration of a nonreplicative plasmid carrying both the pyrE2 wild-type gene, as a selectable marker, and a cloned chromosomal DNA fragment containing a deletion in the desired gene; and (ii) excision of the integrated plasmid after selection with 5-fluoroorotic acid. Application of this gene knockout system is described.     

Streptococcus pneumoniae carriage in the Gaza strip

Background

Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs).

Methodology

In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction.

Principal Findings

S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively.

Conclusions

This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.     

Expanding intersubjective awareness: the anthropology of kinaesthetic diversity

When people with widely diverse bodily characteristics collaborate in dancing together, an exploration and communication of movement and embodied knowledge takes place through dialogue and shared practice. Engagement in these activities develops participants’ awareness of and appreciation for kinaesthetic complexities and diverse embodiments, promoting an understanding of bodily difference as contributing to, rather than detracting from, the realm of physical arts and society as a whole. Based on fieldwork conducted in Israel and the United States with integrated dance projects bringing together people with and without disabilities, this article offers an ethnographic analysis that continues the anthropological endeavour of revealing the ways kinaesthetic knowledge (awareness and knowledge of the movement and spatial orientation of one's body) is fostered. Introducing disability into movement theory, I offer an understanding of movement/stasis as a spectrum of ways of moving, looking at what happens when individuals who are different from one another engage in shared, critical reflection upon their movement practices.     

Applying cathodically polarised substrata to the restoration of a high value coral

Larval settlement of the high value red coral, Corallium rubrum, was studied on three different CaCO(3) substrata, viz. lithogenic (marble), electro-accreted calcium carbonate in the presence and in the absence of cathodic polarisation. The last two substrata consisted of stainless steel plates galvanically coupled with Zn anodes. The electrochemical characterization of the settlement device was studied in order to investigate correlations between cathodic parameters (polarisation potential, current density, calcareous deposit composition) and larval settlement. The results obtained in the natural habitat (at 35 m depth) showed that settlement was five times lower on the electro-accreted aragonite in the presence of low cathodic current densities (i≤1 μA cm(-2)) compared to both marble tiles and electro-accreted aragonite in the absence of polarisation. These last two substrata showed similar settlement values. The implications of these findings on restoration strategies for C. rubrum are discussed.     

Physiological performance of the cold-water coral Dendrophyllia cornigera reveals its preference for temperate environments

Cold-water corals (CWCs) are key ecosystem engineers in deep-sea benthic communities around the world. Their distribution patterns are related to several abiotic and biotic factors, of which seawater temperature is arguably one of the most important due to its role in coral physiological processes. The CWC Dendrophyllia cornigera has the particular ability to thrive in several locations in which temperatures range from 11 to 17 °C, but to be apparently absent from most CWC reefs at temperatures constantly below 11 °C. This study thus aimed to assess the thermal tolerance of this CWC species, collected in the Mediterranean Sea at 12 °C, and grown at the three relevant temperatures of 8, 12, and 16 °C. This species displayed thermal tolerance to the large range of seawater temperatures investigated, but growth, calcification, respiration, and total organic carbon (TOC) fluxes severely decreased at 8 °C compared to the in situ temperature of 12 °C. Conversely, no significant differences in calcification, respiration, and TOC fluxes were observed between corals maintained at 12 and 16 °C, suggesting that the fitness of this CWC is higher in temperate rather than cold environments. The capacity to maintain physiological functions between 12 and 16 °C allows D. cornigera to be the most abundant CWC species in deep-sea ecosystems where temperatures are too warm for other CWC species (e.g., Canary Islands). This study also shows that not all CWC species occurring in the Mediterranean Sea (at deep-water temperatures of 12–14 °C) are currently living at their upper thermal tolerance limit.