Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents

Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Primary H. pylori susceptibility patterns, however, are becoming less predictable. Currently, high (≥20%) clarithromycin resistance rates have been observed in the USA and in developed countries in Europe and Asia, while the highest (≥80%) metronidazole-resistance rates have been reported in Africa, Asia and South America. Primary quinolone-resistance rates of 10% or more have already been reported in developed countries in Europe and Asia. Primary amoxicillin resistance has been low (0 to <2%) in Europe but higher (6–59%) in Africa, Asia and South America. Similarly, tetracycline resistance has been absent or low (<5%) in most countries and higher (9–27%) in Asia and South America. The increasing clarithromycin and quinolone resistance, and multidrug resistance detected in 0 to less than 5% in Europe and more often (14.2%) in Brazil are worrying. Growing resistance often parallels national antibiotic consumption and may vary within patient groups according to the geographic region, patient’s age and sex, type of disease, birthplace, other infections and other factors. The geographic map and evolution of primary H. pylori resistance are clinically important, should be considered when choosing eradication regimens, and should be monitored constantly at national and global levels in an attempt to reach the recently recommended goal of eradication of more than 95%.     

Learning from nature – Novel synthetic biology approaches for biomaterial design

Many biomaterials constructed today are complex chemical structures that incorporate biologically active components derived from nature, but the field can still be said to be in its infancy. The need for materials that bring sophisticated properties of structure, dynamics and function to medical and non-medical applications will only grow. Increasing appreciation of the functionality of biological systems has caused biomaterials researchers to consider nature for design inspiration, and many examples exist of the use of biomolecular motifs. Yet evolution, nature’s only engine for the creation of new designs, has been largely ignored by the biomaterials community. Molecular evolution is an emerging tool that enables one to apply nature’s engineering principles to non-natural situations using variation and selection. The purpose of this review is to highlight the most recent advances in the use of molecular evolution in synthetic biology applications for biomaterial engineering, and to discuss some of the areas in which this approach may be successfully applied in the future.     

The rediscovery of smallpox

Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts—variolation, quarantine, and the isolation of infected subjects—until Jenner’s discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease.     

The evo-devo origins of the nasopharynx

The process by which upper respiratory tract structures have changed over deep evolutionary time is, in part, reflected in the process of embryologic development. The nasopharynx in particular is a centrally located space bounded by components of the respiratory portion of the nasal cavity, cranial base, soft palate, and Eustachian tube. The development of these components can be understood both in terms of embryologic structures such as the branchial arches and paraxial mesoderm and through fossil evidence dating as far back as the earliest agnathan fish of the Cambrian Period. Understanding both the evolution and development of these structures has been an immeasurable benefit to the otolaryngologist seeking to model disease etiology of both common and rare conditions. This discussion is a primer for those who may be unfamiliar with the central importance of the nasopharynx both in terms of our evolutionary history and early embryological development of vital cranial and upper respiratory tract structures.     

Reproduction, social behavior, and aging trajectories in honeybee workers

While a negative correlation between reproduction and life span is commonly observed, specialized reproductive individuals outlive their non-reproductive nestmates in all eusocial species, including the honeybee, Apis mellifera (L). The consequences of reproduction for individual life expectancy can be studied directly by comparing reproductive and non-reproductive workers. We quantified the life span consequences of reproduction in honeybee workers by removal of the queen to trigger worker reproduction. Furthermore, we observed the social behavior of large cohorts of workers under experimental and control conditions to test for associations with individual life expectancy. Worker life expectancy was moderately increased by queen removal. Queenless colonies contained a few long-lived workers, and oviposition behavior was associated with a strong reduction in mortality risk, indicating that a reproductive role confers a significant survival advantage. This finding is further substantiated by an association between brood care behavior and worker longevity that depends on the social environment. In contrast, other in-hive activities, such as fanning, trophallaxis, and allogrooming did not consistently affect worker life expectancy. The influence of foraging varied among replicates. An earlier age of transitioning from in-hive tasks to outside foraging was always associated with shorter life spans, in accordance with previous studies. In sum, our studies quantify how individual mortality is affected by particular social roles and colony environments and demonstrate interactions between the two. The exceptional, positive association between reproduction and longevity in honeybees extends to within-caste plasticity, which may be exploited for mechanistic studies.     

Neural control of gene recruitment in metazoans

Gene recruitment played a critical role in metazoan evolution. Yet, there is no consensus on whether it is an accidental event or a result of an inherent “gene recruiting” mechanism. The prevailing opinion among biologists is that gene recruitment results from random changes in genes or their regulatory regions, but the supporting evidence is poor and controversial. Herein, I present a mechanism in which gene recruitment is a neurally determined event, an adaptive response to changes in environmental conditions. In support of the hypothesis, I present evidence on the manipulative expression of genes in the central nervous system, as well as neurally determined examples of gene recruitment in transgenerational developmental plasticity and in evolution of metazoans Developmental Dynamics 240:1–8, 2011. © 2010 Wiley‐Liss, Inc.     

Phenotypic plasticity facilitates recurrent rapid adaptation to introduced predators

A central role for phenotypic plasticity in adaptive evolution is often posited yet lacks empirical support. Selection for the stable production of an induced phenotype is hypothesized to modify the regulation of preexisting developmental pathways, producing rapid adaptive change. We examined the role of plasticity in rapid adaptation of the zooplankton Daphnia melanica to novel fish predators. Here we show that plastic up-regulation of the arthropod melanin gene dopa decarboxylase (Ddc) in the absence of UV radiation is associated with reduced pigmentation in D. melanica. Daphnia populations coexisting with recently introduced fish exhibit environmentally invariant up-regulation of Ddc, accompanied by constitutive up-regulation of the interacting arthropod melanin gene ebony. Both changes in regulation are associated with adaptive reduction in the plasticity and mean expression of melanin. Our results provide evidence that the developmental mechanism underlying ancestral plasticity in response to an environmental factor has been repeatedly co-opted to facilitate rapid adaptation to an introduced predator.     

Darwinian selection for sites of Asn-linked glycosylation in phylogenetically disparate eukaryotes and viruses

Numerous protists and rare fungi have truncated Asn-linked glycan precursors and lack N-glycan-dependent quality control (QC) systems for glycoprotein folding in the endoplasmic reticulum. Here, we show that the abundance of sequons (NXT or NXS), which are sites for N-glycosylation of secreted and membrane proteins, varies by more than a factor of 4 among phylogenetically diverse eukaryotes, based on a few variables. There is positive correlation between the density of sequons and the AT content of coding regions, although no causality can be inferred. In contrast, there appears to be Darwinian selection for sequons containing Thr, but not Ser, in eukaryotes that have N-glycan-dependent QC systems. Selection for sequons with Thr, which nearly doubles the sequon density in human secreted and membrane proteins, occurs by an increased conditional probability that Asn and Thr are present in sequons rather than elsewhere. Increasing sequon densities of the hemagglutinin (HA) of influenza viruses A/H3N2 and A/H1N1 during the past few decades of human infection also result from an increased conditional probability that Asn, Thr, and Ser are present in sequons rather than elsewhere. In contrast, there is no selection on sequons by this mechanism in HA of A/H5N1 or 2009 A/H1N1 (Swine flu). Very strong selection for sequons with both Thr and Ser in glycoprotein of M_r 120,000 (gp120) of HIV and related retroviruses results from this same mechanism, as well as amino acid composition bias and increases in AT content. We conclude that there is Darwinian selection for sequons in phylogenetically disparate eukaryotes and viruses.     

BMPs and Chordin regulate patterning of the directive axis in a sea anemone

The TGF-β molecules Dpp/BMP2/4/7 and their antagonist Sog/Chd play a conserved role in establishing the dorso-ventral (DV) axis in bilaterians. Homologues of BMPs and the antagonist, Chordin, have been isolated from Cnidaria and show a striking asymmetric expression pattern with respect to the primary oral-aboral (OA) axis. We used Morpholino knockdowns of Nematostella dpp (bmp2/4), bmp5-8, chordin, and tolloid to investigate their function during early development of the sea anemone Nematostella vectensis. Molecular analysis of the BMP Morpholino phenotypes revealed an upregulated and radialized expression of bmps and chordin in ectoderm and endoderm indicating a negative feedback loop. Our data further suggest that BMP signaling is required for symmetry breaking of bmp and chordin expression during gastrulation. While bmps and chordin marker genes of the ectodermal OA axis extended aborally, other ectodermal markers of the OA axis were not significantly affected. By contrast, expression of other endodermal marker genes marking both the OA and the directive axis were abolished. Our data suggest that the logic of BMP2/4 signaling and the BMP antagonist, Chordin, differs significantly between Cnidaria and Bilateria, yet the double negative feedback loop detected in Nematostella bears systemic similarities with part of the regulatory network of the DV axis patterning system in amphibians.