D-Alanylation of Lipoteichoic Acids Confers Resistance to Cationic Peptides in Group B Streptococcus by Increasing the Cell Wall Density

Cationic antimicrobial peptides (CAMPs) serve as the first line of defense of the innate immune system against invading microbial pathogens. Gram-positive bacteria can resist CAMPs by modifying their anionic teichoic acids (TAs) with D-alanine, but the exact mechanism of resistance is not fully understood. Here, we utilized various functional and biophysical approaches to investigate the interactions of the human pathogen Group B Streptococcus (GBS) with a series of CAMPs having different properties. The data reveal that: (i) D-alanylation of lipoteichoic acids (LTAs) enhance GBS resistance only to a subset of CAMPs and there is a direct correlation between resistance and CAMPs length and charge density; (ii) resistance due to reduced anionic charge of LTAs is not attributed to decreased amounts of bound peptides to the bacteria; and (iii) D-alanylation most probably alters the conformation of LTAs which results in increasing the cell wall density, as seen by Transmission Electron Microscopy, and reduces the penetration of CAMPs through the cell wall. Furthermore, Atomic Force Microscopy reveals increased surface rigidity of the cell wall of the wild-type GBS strain to more than 20-fold that of the dltA mutant. We propose that D-alanylation of LTAs confers protection against linear CAMPs mainly by decreasing the flexibility and permeability of the cell wall, rather than by reducing the electrostatic interactions of the peptide with the cell surface. Overall, our findings uncover an important protective role of the cell wall against CAMPs and extend our understanding of mechanisms of bacterial resistance.     

Periodicity and time trends in the prevalence of total births and conceptions with congenital malformations among Jews and Muslims in Israel, 1999‐2006: A time series study of 823,966 births

BACKGROUND Congenital malformations (CMs) are a leading cause of infant disability. Geophysical patterns such as 2‐year, yearly, half‐year, 3‐month, and lunar cycles regulate much of the temporal biology of all life on Earth and may affect birth and birth outcomes in humans. Therefore, the aim of this study was to evaluate and compare trends and periodicity in total births and CM conceptions in two Israeli populations. METHODS Poisson nonlinear models (polynomial) were applied to study and compare trends and geophysical periodicity cycles of weekly births and weekly prevalence rate of CM (CMPR), in a time‐series design of conception date within and between Jews and Muslims. The population included all live births and stillbirths (n = 823,966) and CM (three anatomic systems, eight CM groups [n = 2193]) in Israel during 2000 to 2006. Data were obtained from the Ministry of Health. RESULTS We describe the trend and periodicity cycles for total birth conceptions. Of eight groups of CM, periodicity cycles were statistically significant in four CM groups for either Jews or Muslims. Lunar month and biennial periodicity cycles not previously investigated in the literature were found to be statistically significant. Biennial cycle was significant in total births (Jews and Muslims) and syndactyly (Muslims), whereas lunar month cycle was significant in total births (Muslims) and atresia of small intestine (Jews). CONCLUSION We encourage others to use the method we describe as an important tool to investigate the effects of different geophysical cycles on human health and pregnancy outcomes, especially CM, and to compare between populations. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.     

Systematics and phylogeography of Acanthodactylus schreiberi and its relationships with Acanthodactylus boskianus (Reptilia: Squamata: Lacertidae)

Acanthodactylus is a widespread lacertid genus occurring from the Iberian Peninsula and western North Africa to western India including the Middle East, Cyprus, and the Arabian Peninsula. The genus is in dire need of a taxonomic revision, and the phylogenetic relationships amongst and within its species remain unclear. In particular, the taxonomy and relationship of the allopatric, narrow‐ranged Acanthodactylus schreiberi and its close relative, the widespread Acanthodactylus boskianus asper, are poorly understood. We estimated the phylogenetic and phylogeographical structure of A. schreiberi across its distribution range, and evaluated its relationships to A. b. asper, using mitochondrial and nuclear data. The phylogenetic results indicate that both species are paraphyletic, with A. schreiberi nested within A. b. asper, and the subspecies A. schreiberi syriacus nested within a distinct lineage of A. b. asper. We suggest that the group is in need of a taxonomic revision because the identified lineages and genetic diversity are incongruent with the currently recognized taxonomy. We tentatively conclude that A. schreiberi is restricted to Cyprus and Turkey, reduced to a single form, and that the populations in Lebanon and Israel belong to A. b. asper. © 2014 The Linnean Society of London     

A guide to choosing and implementing reference models for social network analysis

Analysing social networks is challenging. Key features of relational data require the use of non-standard statistical methods such as developing system-specific null, or reference, models that randomize one or more components of the observed data. Here we review a variety of randomization procedures that generate reference models for social network analysis. Reference models provide an expectation for hypothesis testing when analysing network data. We outline the key stages in producing an effective reference model and detail four approaches for generating reference distributions: permutation, resampling, sampling from a distribution, and generative models. We highlight when each type of approach would be appropriate and note potential pitfalls for researchers to avoid. Throughout, we illustrate our points with examples from a simulated social system. Our aim is to provide social network researchers with a deeper understanding of analytical approaches to enhance their confidence when tailoring reference models to specific research questions.