Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells
Mechanical ventilation (MV) of patients can cause damage to bronchoalveolar epithelium, leading to a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects of MV on the innate immune defense system in the human lung. In this study, we demonstrate that cyclic stretch of the human bronchial epithelial cell lines VA10 and BCi NS 1.1 leads to down-regulation of cathelicidin antimicrobial peptide (CAMP) gene expression. We show that treatment of VA10 cells with vitamin D3 and/or 4-phenyl butyric acid counteracted cyclic stretch mediated down-regulation of CAMP mRNA and protein expression (LL-37). Further, we observed an increase in pro-inflammatory responses in the VA10 cell line subjected to cyclic stretch. The mRNA expression of the genes encoding pro-inflammatory cytokines IL-8 and IL-1β was increased after cyclic stretching, where as a decrease in gene expression of chemokines IP-10 and RANTES was observed. Cyclic stretch enhanced oxidative stress in the VA10 cells. The mRNA expression of toll-like receptor (TLR) 3, TLR5 and TLR8 was reduced, while the gene expression of TLR2 was increased in VA10 cells after cyclic stretch. In conclusion, our in vitro results indicate that cyclic stretch may differentially modulate innate immunity by down-regulation of antimicrobial peptide expression and increase in pro-inflammatory responses.
Karadottir et al. (2015) Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells. PeerJ 3:e1483 https://doi.org/10.7717/peerj.1483
The first dromaeosaurid (Dinosauria: Theropoda) from the Lower Cretaceous Bayan Gobi Formation of Nei Mongol, China
The first dromaeosaurid theropod from the Lower Cretaceous Bayan Gobi Formation is identified based on an incompletely preserved partially-articulated left leg, increasing the known diversity of its understudied ecosystem. The leg belongs to specimen IVPP V22530 and includes a typical deinonychosaurian pedal phalanx II-2 with a distinct constriction between the enlarged proximal end and the distal condyle as well as a typical deinonychosaurian enlarged pedal phalanx II-3. It possesses a symmetric metatarsus and a slender and long MT V that together suggest it is a dromaeosaurid. Two anatomical traits suggest the leg is microraptorine-like, but a more precise taxonomic referral was not possible: metatarsals II, III and IV are closely appressed distally and the ventral margin of the medial ligament pit of phalanx II-2 is close to the centre of the rounded distal condyle. This taxonomic status invites future efforts to discover additional specimens at the study locality because—whether it is a microraptorine or a close relative—this animal is expected to make important contributions to our understanding of dromaeosaurid evolution and biology. IVPP V22530 also comprises of an isolated dromaeosaurid manual ungual, a proximal portion of a right theropod anterior dorsal rib and an indeterminate bone mass that includes a collection of ribs. Neither the rib fragment nor the bone mass can be confidently referred to Dromaeosauridae, although they may very well belong to the same individual to whom the left leg belongs.
Pittman et al. (2015) The first dromaeosaurid (Dinosauria: Theropoda) from the Lower Cretaceous Bayan Gobi Formation of Nei Mongol, China. PeerJ 3:e1480 https://doi.org/10.7717/peerj.1480
Wolbachia co-infection in a hybrid zone: discovery of horizontal gene transfers from two Wolbachia supergroups into an animal genome
Hybrid zones and the consequences of hybridization have contributed greatly to our understanding of evolutionary processes. Hybrid zones also provide valuable insight into the dynamics of symbiosis since each subspecies or species brings its unique microbial symbionts, including germline bacteria such as Wolbachia, to the hybrid zone. Here, we investigate a natural hybrid zone of two subspecies of the meadow grasshopper Chorthippus parallelus in the Pyrenees Mountains. We set out to test whether co-infections of B and F Wolbachia in hybrid grasshoppers enabled horizontal transfer of phage WO, similar to the numerous examples of phage WO transfer between A and B Wolbachia co-infections. While we found no evidence for transfer between the divergent co-infections, we discovered horizontal transfer of at least three phage WO haplotypes to the grasshopper genome. Subsequent genome sequencing of uninfected grasshoppers uncovered the first evidence for two discrete Wolbachia supergroups (B and F) contributing at least 448 kb and 144 kb of DNA, respectively, into the host nuclear genome. Fluorescent in situ hybridization verified the presence of Wolbachia DNA in C. parallelus chromosomes and revealed that some inserts are subspecies-specific while others are present in both subspecies. We discuss our findings in light of symbiont dynamics in an animal hybrid zone.
Funkhouser-Jones et al. (2015) Wolbachia co-infection in a hybrid zone: discovery of horizontal gene transfers from two Wolbachia supergroups into an animal genome. PeerJ 3:e1479 https://doi.org/10.7717/peerj.1479
Mismatched anti-predator behavioral responses in predator-naïve larval anurans
Organisms are adept at altering behaviors to balance the tradeoff between foraging and predation risk in spatially and temporally shifting predator environments. In order to optimize this tradeoff, prey need to be able to display an appropriate response based on degree of predation risk. To be most beneficial in the earliest life stages in which many prey are vulnerable to predation, innate anti-predator responses should scale to match the risk imposed by predators until learned anti-predator responses can occur. We conducted an experiment that examined whether tadpoles with no previous exposure to predators (i.e., predator-naive) exhibit innate antipredator behavioral responses (e.g., via refuge use and spatial avoidance) that match the actual risk posed by each predator. Using 7 treatments (6 free-roaming, lethal predators plus no-predator control), we determined the predation rates of each predator on Lithobates sphenocephalus tadpoles. We recorded behavioral observations on an additional 7 nonlethal treatments (6 caged predators plus no-predator control). Tadpoles exhibited innate responses to fish predators, but not non-fish predators, even though two non-fish predators (newt and crayfish) consumed the most tadpoles. Due to a mismatch between innate response and predator consumption, tadpoles may be vulnerable to greater rates of predation at the earliest life stages before learning can occur. Thus, naïve tadpoles in nature may be at a high risk to predation in the presence of a novel predator until learned anti-predator responses provide additional defenses to the surviving tadpoles.
Albecker et al. (2015) Mismatched anti-predator behavioral responses in predator-naïve larval anurans. PeerJ 3:e1472 https://doi.org/10.7717/peerj.1472
Production of fatty acids in Ralstonia eutropha H16 by engineering β-oxidation and carbon storage
Ralstonia eutropha H16 is a facultatively autotrophic hydrogen-oxidizing bacterium capable of producing polyhydroxybutyrate (PHB)-based bioplastics. As PHB’s physical properties may be improved by incorporation of medium-chain-length fatty acids (MCFAs), and MCFAs are valuable on their own as fuel and chemical intermediates, we engineered R. eutropha for MCFA production. Expression of UcFatB2, a medium-chain-length-specific acyl-ACP thioesterase, resulted in production of 14 mg/L laurate in wild-type R. eutropha. Total fatty acid production (22 mg/L) could be increased up to 2.5-fold by knocking out PHB synthesis, a major sink for acetyl-CoA, or by knocking out the acyl-CoA ligase fadD3, an entry point for fatty acids into β-oxidation. As ΔfadD3 mutants still consumed laurate, and because the R. eutropha genome is predicted to encode over 50 acyl-CoA ligases, we employed RNA-Seq to identify acyl-CoA ligases upregulated during growth on laurate. Knockouts of the three most highly upregulated acyl-CoA ligases increased fatty acid yield significantly, with one strain (ΔA2794) producing up to 62 mg/L free fatty acid. This study demonstrates that homologous β-oxidation systems can be rationally engineered to enhance fatty acid production, a strategy that may be employed to increase yield for a range of fuels, chemicals, and PHB derivatives in R. eutropha.
Chen et al. (2015) Production of fatty acids in Ralstonia eutropha H16 by engineering β-oxidation and carbon storage. PeerJ 3:e1468 https://doi.org/10.7717/peerj.1468
Triple therapy in type 2 diabetes; a systematic review and network meta-analysis
Aims. The purpose was to evaluate the evidence for triple therapy regimen using medicines available in Australia for type 2 diabetes. Methods. A systematic literature review was performed to update the relevant evidence from 2002 to 2014 on triple therapy for type 2 diabetes. A multiple-treatments network meta-analysis was undertaken to summarise the comparative efficacy and harms of different triple therapies. Results. Twenty seven trials were identified, most were six months of duration. The following combinations were included in the network meta-analysis: metformin (MET) + sulfonylureas (SU) (used as reference combination); MET + SU+ dipeptidyl peptidase 4 inhibitors (DPP-4-i); MET + SU+ thiazolidinediones (TZD); MET + SU+ glucagon-like peptide-1 receptor agonists (GLP-1-RA); MET + SU+ insulins; MET + TZD + DPP-4-i; and MET + SU+ sodium/glucose cotransporter 2 inhibitors (SGLT2-i). For HbA1c reduction, all triple therapies were statistically superior to MET+SU dual therapy, except for MET + TZD + DPP-4-i. None of the triple therapy combinations demonstrated differences in HbA1c compared with other triple therapies. MET + SU + SGLT2-i and MET + SU + GLP-1-RA resulted in significantly lower body weight than MET + SU + DPP-4-i, MET+SU+insulin and MET + SU + TZDs; MET + SU + DPP-4-i resulted in significantly lower body weight than MET + SU + insulin and MET + SU + TZD. MET + SU + insulin, MET + SU + TZD and MET + SU + DPP-4-i increased the odds of hypoglycaemia when compared to MET + SU. MET + SU + GLP-1-RA reduced the odds of hypoglycaemia compared to MET + SU + insulin. Conclusion. Care when choosing a triple therapy combination is needed as there is often a risk of increased hypoglycaemia events associated with this regimen and there are very limited data surrounding the long-term effectiveness and safety of combined therapies.
Downes et al. (2015) Triple therapy in type 2 diabetes; a systematic review and network meta-analysis. PeerJ 3:e1461 https://doi.org/10.7717/peerj.1461
Large-scale structure of brown rat (Rattus norvegicus) populations in England: effects on rodenticide resistance
The brown rat (Rattus norvegicus) is a relatively recent (<300 years) addition to the British fauna, but by association with negative impacts on public health, animal health and agriculture, it is regarded as one of the most important vertebrate pest species. Anticoagulant rodenticides were introduced for brown rat control in the 1950s and are widely used for rat control in the UK, but long-standing resistance has been linked to control failures in some regions. One thus far ignored aspect of resistance biology is the population structure of the brown rat. This paper investigates the role population structure has on the development of anticoagulant resistance. Using mitochondrial and microsatellite DNA, we examined 186 individuals (from 15 counties in England and one location in Wales near the Wales–England border) to investigate the population structure of rural brown rat populations. We also examined individual rats for variations of the VKORC1 gene previously associated with resistance to anticoagulant rodenticides. We show that the populations were structured to some degree, but that this was only apparent in the microsatellite data and not the mtDNA data. We discuss various reasons why this is the case. We show that the population as a whole appears not to be at equilibrium. The relative lack of diversity in the mtDNA sequences examined can be explained by founder effects and a subsequent spatial expansion of a species introduced to the UK relatively recently. We found there was a geographical distribution of resistance mutations, and relatively low rate of gene flow between populations, which has implications for the development and management of anticoagulant resistance.
Haniza et al. (2015) Large-scale structure of brown rat (Rattus norvegicus) populations in England: effects on rodenticide resistance. PeerJ 3:e1458 https://doi.org/10.7717/peerj.1458
Low effect of young afforestations on bird communities inhabiting heterogeneous Mediterranean cropland
Afforestation programs such as the one promoted by the EU Common Agricultural Policy have spread tree plantations on former cropland. These afforestations attract generalist forest and ubiquitous species but may cause severe damage to open habitat species, especially birds of high conservation value. We investigated the effects of young (<20 yr) tree plantations dominated by pine P. halepensis on bird communities inhabiting the adjacent open farmland habitat in central Spain. We hypothesize that pine plantations located at shorter distances from open fields and with larger surface would affect species richness and conservation value of bird communities. Regression models controlling for the influence of land use types around plantations revealed positive effects of higher distance to pine plantation edge on community species richness in winter, and negative effects on an index of conservation concern (SPEC) during the breeding season. However, plantation area did not have any effect on species richness or community conservation value. Our results indicate that the effects of pine afforestation on bird communities inhabiting Mediterranean cropland are diluted by heterogeneous agricultural landscapes.
Sánchez-Oliver et al. (2015) Low effect of young afforestations on bird communities inhabiting heterogeneous Mediterranean cropland. PeerJ 3:e1453 https://doi.org/10.7717/peerj.1453
Palaeogeographic implications of a new iocrinid crinoid (Disparida) from the Ordovician (Darriwillian) of Morocco
Complete, articulated crinoids from the Ordovician peri-Gondwanan margin are rare. Here, we describe a new species, Iocrinus africanus sp. nov., from the Darriwilian-age Taddrist Formation of Morocco. The anatomy of this species was studied using a combination of traditional palaeontological methods and non-destructive X-ray micro-tomography (micro-CT). This revealed critical features of the column, distal arms, and aboral cup, which were hidden in the surrounding rock and would have been inaccessible without the application of micro-CT. Iocrinus africanus sp. nov. is characterized by the presence of seven to thirteen tertibrachials, three in-line bifurcations per ray, and an anal sac that is predominantly unplated or very lightly plated. Iocrinus is a common genus in North America (Laurentia) and has also been reported from the United Kingdom (Avalonia) and Oman (middle east Gondwana). Together with Merocrinus, it represents one of the few geographically widespread crinoids during the Ordovician and serves to demonstrate that faunal exchanges between Laurentia and Gondwana occurred at this time. This study highlights the advantages of using both conventional and cutting-edge techniques (such as micro-CT) to describe the morphology of new fossil specimens.
Zamora et al. (2015) Palaeogeographic implications of a new iocrinid crinoid (Disparida) from the Ordovician (Darriwillian) of Morocco. PeerJ 3:e1450 https://doi.org/10.7717/peerj.1450
Biofouling of inlet pipes affects water quality in running seawater aquaria and compromises sponge cell proliferation
Marine organism are often kept, cultured, and experimented on in running seawater aquaria. However, surprisingly little attention is given to the nutrient composition of the water flowing through these systems, which is generally assumed to equal in situ conditions, but may change due to the presence of biofouling organisms. Significantly lower bacterial abundances and higher inorganic nitrogen species (nitrate, nitrite, and ammonium) were measured in aquarium water when biofouling organisms were present within a 7-year old inlet pipe feeding a tropical reef running seawater aquaria system, compared with aquarium water fed by a new, biofouling-free inlet pipe. These water quality changes are indicative of the feeding activity and waste production of the suspension- and filter-feeding communities found in the old pipe, which included sponges, bivalves, barnacles, and ascidians. To illustrate the physiological consequences of these water quality changes on a model organism kept in the aquaria system, we investigated the influence of the presence and absence of the biofouling community on the functioning of the filter-feeding sponge Halisarca caerulea, by determining its choanocyte (filter cell) proliferation rates. We found a 34% increase in choanocyte proliferation rates following the replacement of the inlet pipe (i.e., removal of the biofouling community). This indicates that the physiological functioning of the sponge was compromised due to suboptimal food conditions within the aquarium resulting from the presence of the biofouling organisms in the inlet pipe. This study has implications for the husbandry and performance of experiments with marine organisms in running seawater aquaria systems. Inlet pipes should be checked regularly, and replaced if necessary, in order to avoid excessive biofouling and to approach in situ water quality.
Alexander et al. (2015) Biofouling of inlet pipes affects water quality in running seawater aquaria and compromises sponge cell proliferation. PeerJ 3:e1430 https://doi.org/10.7717/peerj.1430