Identifying ‘firebreaks’ to fragment dispersal networks of a marine parasite

Marine ecosystems are beset by disease outbreaks, and efficient strategies to control dispersal of pathogens are scarce. We tested whether introducing no-farming areas or ‘firebreaks’ could disconnect dispersal networks of a parasitic disease affecting the world’s largest marine fish farming industry (～1000 farms). Larval salmon lice (Lepeophtheirus salmonis) are released from and transported among salmon farms by ocean currents, creating inter-farm networks of louse dispersal. We used a state-of-the-art biophysical model to predict louse movement along the Norwegian coastline and network analysis to identify firebreaks to dispersal. At least one firebreak that fragmented the network into two large unconnected groups of farms was identified for all seasons. During spring, when wild salmon migrate out into the ocean, and louse levels per fish at farms must be minimised, two effective firebreaks were created by removing 13 and 21 farms (1.3% and 2.2% of all farms in the system) at ～61°N and 67°N, respectively. We have demonstrated that dispersal models coupled with network analysis can identify no-farming zones that fragment dispersal networks. Reduced dispersal pathways should lower infection pressure at farms, slow the evolution of resistance to parasite control measures, and alleviate infection pressure on wild salmon populations.     

A distinctive set of genes is upregulated during the inflammation-carcinoma sequence in mouse stomach infected by Helicobacter felis.

Helicobacter pylori infects over half the population worldwide and is a leading cause of chronic gastritis and gastric cancer. However, the mechanism by which this organism induces inflammation and carcinogenesis is not fully understood. In the present study we used insulin-gastrin (INS-GAS) transgenic mice that fully develop gastric adenocarcinoma after infection of H. pylori-related Helicobacter felis. Histological examination revealed that more than half of those mice developed invasive adenocarcinoma after 8 months of infection. These carcinomas were stained by NCC-ST-439 and HECA-452 that recognize 6-sulfated and non-sulfated sialyl Lewis X. Lymphocytic infiltration predominantly to submucosa was observed in most H. felis-infected mice, and this was associated with the formation of peripheral lymph node addressin (PNAd) on high endothelial venule (HEV)-like vessels detected by MECA-79. Time-course analysis of gene expression by using gene microarray revealed upregulation of several inflammation-associated genes including chemokines, adhesion molecules, surfactant protein D (SP-D), and CD74 in the infected stomach. Immunohistochemical analysis demonstrated that SP-D is expressed in hyperplasia and adenocarcinoma whereas CD74 is expressed in adenocarcinoma in situ and invasive carcinoma. These results as a whole indicate that H. felis induces HEV-like vessels and inflammation-associated chemokines and chemokine receptors, followed by adenocarcinoma formation.     

The Siak, a tropical black water river in central Sumatra on the verge of anoxia

The Siak is a black water river in central Sumatra, Indonesia, which owes its brown color to dissolved organic matter (DOM) leached from surrounding, heavily disturbed peat soils. The dissolved organic carbon (DOC) concentrations measured during five expeditions in the Siak between 2004 and 2006 are among the highest reported world wide. The DOM decomposition appeared to be a main factor influencing the oxygen concentration in the Siak which showed values down to 12 μmol l⁻¹. Results derived from a box-diffusion model indicated that in addition to the DOC concentration and the associated DOM decomposition the water-depth also plays a crucial role in regulating the oxygen levels in the river because of its impact on the turbulence in the aquatic boundary layer and the surface/volume ratio of water in the river. Model results imply furthermore that a reduced water-depth could counteract an increased oxygen consumption caused by an enhanced DOM leaching during the transition from dry to wet periods. This buffer mechanism seems to be close to its limits as indicated by sensitivity studies which showed in line with measured data that an increase of the DOC concentrations by ~15% could already lead to anoxic conditions in the Siak. This emphasizes the sensitivity of the Siak against further peat soil degradation, which is assumed to increase DOC concentrations in the rivers.     

Inhibition of Mitogen-Activated Kinase Signaling Sensitizes HeLa Cells to Fas Receptor-Mediated Apoptosis

The Fas receptor (FasR) is an important physiological mediator of apoptosis in various tissues and cells. However, there are also many FasR-expressing cell types that are normally resistant to apoptotic signaling through this receptor. The mitogen-activated protein kinase (MAPK) signaling cascade has, apart from being a growth-stimulating factor, lately received attention as an inhibitory factor in apoptosis. In this study, we examined whether MAPK signaling could be involved in protecting FasR-insensitive cells. To this end, we used different approaches to inhibit MAPK signaling in HeLa cells, including treatment with the MAPK kinase inhibitor PD 98059, serum withdrawal, and expression of dominant-interfering MAPK kinase mutant protein. All of these treatments were effective in sensitizing the cells to FasR-induced apoptosis, demonstrating that MAPK indeed is involved in the control of FasR responses. The MAPK-mediated control seemed to occur at or upstream of caspase 8, the initiator caspase in apoptotic FasR responses. Transfection with the constitutively active MAPK kinase abrogated FasR-induced apoptosis also in the presence of cycloheximide, indicating that the MAPK-generated suppression of FasR-mediated apoptotic signaling is protein synthesis independent. In cells insensitive to FasR-induced apoptosis, stimulation of the FasR with an agonistic antibody resulted in significant MAPK activation, which was inhibited by PD 98059. When different cell types were compared, the FasR-mediated MAPK activation seemed proportional to the degree of FasR insensitivity. These results suggest that the FasR insensitivity is likely to be a consequence of FasR-induced MAPK activation, which in turn interferes with caspase activation.     

Partition of protein solvation into group contributions from molecular dynamics simulations

Linear response theory coupled to molecular dynamics simulations with an explicit solvent representation is used to derive fractional contributions of amino acid residues to the solvation of proteins. The new fractional methods developed here are compared with standard approaches based on empirical 1D and 3D statistical potentials, as well as with estimates obtained from the analysis of classical molecular interaction potentials. The new fractional methods, which have a clear physical basis and explicitly account for the effects due to protein structure and flexibility, provide an accurate picture of the contribution to solvation of different regions of the protein.     

Gene Expression-Based Classifiers Identify Staphylococcus aureus Infection in Mice and Humans

Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host’s inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.     

Mitogenomic phylogeny of Acanthocephala reveals novel Class relationships

The Acanthocephala is a phylum of obligate endoparasitic animals comprising four classes (Archiacanthocephala, Palaeacanthocephala, Eoacanthocephala and Polyacanthocephala), although the phylogenetic interrelationships of these classes still remains unresolved. To investigate phylogenetic relationships of major acanthocephalan groups, we characterized the complete mitochondrial genome sequences of two palaeacanthocephalan species Centrorhynchus aluconis and Prosthorhynchus transversus (representing two different families of the order Polymorphida), and Polyacanthorhynchus caballeroi (the first mitogenomic representative of the class Polyacanthocephala) and used these new sequences for phylogenetic analyses, along with 32 platyzoan mtDNAs, including 10 additional acanthocephalans. Phylogenetic analyses using concatenated amino acid sequences for 12 protein‐coding genes with maximum likelihood and Bayesian inference methods supported monophyly of Acanthocephala. Within the phylum, Archiacanthocephala was positioned as the sister to the clade containing all three other acanthocephalan classes, with the polyacanthocephalan species P. caballeroi nested within Eoacanthocephala. This result contradicts morphology‐based classification systems that treated polyacanthorhynchids as one of the palaeacanthocephalan families, and instead suggests Polyacanthocephala is a member of Eoacanthocephala. Within the Palaeacanthocephala, Polymorphida monophyly was strongly supported and this is inconsistent with nuclear rDNA‐based molecular hypotheses that suggest non‐monophyly.