Context‐specific effects of the identity of detrital mixtures on invertebrate communities

Many aquatic ecosystems are sustained by detrital subsidies of leaf litter derived from exogenous sources. Although numerous studies have examined the effects of litter species richness and identity on decomposition processes, it remains unclear how these effects extend to associated invertebrate communities or how these effects vary spatially according to local environmental context. Using field enrichment experiments, we assessed how the species richness, assemblage composition, and supply of detrital litter resources interact to affect benthic communities of three temperate Australian estuarine mudflats. Our experiments utilized eight litter sources that are presently experiencing human‐mediated changes in their supply to estuarine mudflats. Contrary to predictions, we did not detect effects of the species richness of detrital mixtures on benthic communities. Macroinvertebrate community structure and, in particular, abundance were, instead, influenced by the assemblage composition of detrital mixtures. At two of the three sites, plots receiving the most labile detrital mix, containing the ephemeral algae Chaetomorpha and Ulva, supported the fewest macroinvertebrates of all the experimental enrichments. The large effect of detrital mix identity on macroinvertebrate communities is of concern given present trends of proliferation of macroalgae at the expense of more refractory seagrasses and marsh grasses. As such environmental degradation continues, it will be important to more fully understand under what environmental contexts such compositional changes in detrital resources will have the most detrimental effects on important prey resources for commercially important fish and wading shorebirds.     

Nucleotide diversity of vernalization and flowering‐time‐related genes in a germplasm collection of meadow fescue (Festuca pratensis Huds. syn. Lolium pratense (Huds.) Darbysh.)

In plant species, control of flowering time is an important factor for adaptation to local natural environments. The Vrn1, CO, FT1 and CK2α genes are key components in the flowering‐specific signaling pathway of grass species. Meadow fescue is an agronomically important forage grass species, which is naturally distributed across Europe and Western Asia. In this study, meadow fescue flowering‐time‐related genes were resequenced to assess nucleotide diversity in European and Western Asian subpopulations. Identified sequence polymorphisms were then converted into PCR‐based molecular genetic markers, and a meadow fescue germplasm collection was genotyped to investigate global allelic variation. Lower nucleotide diversities were observed for the Vrn1 and CO orthologs, while relatively higher values were observed for the FT1 and casein kinase II α‐subunit (CK2α) orthologs. The nucleotide diversity for FT1 orthologs in the Western Asian subpopulation was significantly higher than those of the European subpopulation. Similarly, significant differences in nucleotide diversity for the remaining genes were observed between several combinations of subpopulation. The global allele distribution pattern was consistent with observed level of nucleotide diversity. These results suggested that the degree of purifying selection acting on the genes differs according to geographical location. As previously shown for model plant species, functional specificities of flowering‐time‐related genes may also vary according to environmental conditions.     

An Extensive Comparison of the Effect of Anthelmintic Classes on Diverse Nematodes

Soil-transmitted helminths are parasitic nematodes that inhabit the human intestine. These parasites, which include two hookworm species, Ancylostoma duodenale and Necator americanus, the whipworm Trichuris trichiura , and the large roundworm Ascaris lumbricoides , infect upwards of two billion people and are a major cause of disease burden in children and pregnant women. The challenge with treating these diseases is that poverty, safety, and inefficient public health policy have marginalized drug development and distribution to control infection in humans. Anthelmintics (anti-worm drugs) have historically been developed and tested for treatment of non-human parasitic nematodes that infect livestock and companion animals. Here we systematically compare the in vitro efficacy of all major anthelmintic classes currently used in human therapy (benzimidazoles, nicotinic acetylcholine receptor agonists, macrocyclic lactones, nitazoxanide) against species closely related to human parasitic nematodes-Ancylostoma ceylanicum, Trichuris muris , and Ascaris suum --- as well as a rodent parasitic nematode used in veterinary drug discovery, Heligmosomoides bakeri , and the free-living nematode Caenorhabditis elegans. Extensive in vitro data is complemented with single-dose in vivo data in three rodent models of parasitic diseases. We find that the effects of the drugs in vitro and in vivo can vary greatly among these nematode species, e.g., the efficacy of albendazole is strong on A. ceylanicum but weak on H . bakeri . Nonetheless, certain commonalities of the in vitro effects of the drugs can be seen, e.g., nitazoxanide consistently shows an all-or-nothing response. Our in vitro data suggest that further optimization of the clinical efficacy of some of these anthelmintics could be achieved by altering the treatment routine and/or dosing. Most importantly, our in vitro and in vivo data indicate that the hookworm A. ceylanicum is a particularly sensitive and useful model for anthelmintic studies and should be incorporated early on in drug screens for broad-spectrum human soil-transmitted helminth therapies.     

Rac2-Deficiency Leads to Exacerbated and Protracted Colitis in Response to Citrobacter rodentium Infection

Recent genetic-based studies have implicated a number of immune-related genes in the pathogenesis of inflammatory bowel disease (IBD). Our recent genetic studies showed that RAC2 is associated with human IBD; however, its role in disease pathogenesis is unclear. Given Rac2’s importance in various fundamental immune cell processes, we investigated whether a defect in Rac2 may impair host immune responses in the intestine and promote disease in the context of an infection-based (Citrobacter rodentium) model of colitis. In response to infection, Rac2^−/− mice showed i) worsened clinical symptoms (days 13–18), ii) increased crypt hyperplasia at days 11 and 22 (a time when crypt hyperplasia was largely resolved in wild-type mice; WT), and iii) marked mononuclear cell infiltration characterized by higher numbers of T (CD3⁺) cells (day 22), compared to WT-infected mice. Moreover, splenocytes harvested from infected Rac2^−/− mice and stimulated in vitro with C. rodentium lysate produced considerably higher levels of interferon-γ and interleukin-17A. The augmented responses observed in Rac2^−/− mice did not appear to stem from Rac2’s role in NADPH oxidase-driven reactive oxygen species production as no differences in crypt hyperplasia, nor inflammation, were observed in infected NOX2^−/− mice compared to WT. Collectively, our findings demonstrate that Rac2^−/− mice develop more severe disease when subjected to a C. rodentium-induced model of infectious colitis, and suggest that impaired Rac2 function may promote the development of IBD in humans.     

Evaluating Predictive Pharmacogenetic Signatures of Adverse Events in Colorectal Cancer Patients Treated with Fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers.     

Enterobacteriaceae Isolated from the River Danube: Antibiotic Resistances,with a Focus on the Presence of ESBL and Carbapenemases

In a clinical setting it seems to be normal these days that a relevant proportion or even the majority of different bacterial species has already one or more acquired antibiotic resistances. Unfortunately, the overuse of antibiotics for livestock breeding and medicine has also altered the wild-type resistance profiles of many bacterial species in different environmental settings. As a matter of fact, getting in contact with resistant bacteria is no longer restricted to hospitals. Beside food and food production, the aquatic environment might also play an important role as reservoir and carrier. The aim of this study was the assessment of the resistance patterns of Escherichia coli and Klebsiella spp. out of surface water without prior enrichment and under non-selective culture conditions (for antibiotic resistance). In addition, the presence of clinically important extended spectrum beta lactamase (ESBL) and carbapenmase harboring Enterobacteriaceae should be investigated. During Joint Danube Survey 3 (2013), water samples were taken over the total course of the River Danube. Resistance testing was performed for 21 different antibiotics. Samples were additionally screened for ESBL or carbapenmase harboring Enterobacteriaceae. 39% of all isolated Escherichia coli and 15% of all Klebsiella spp. from the river Danube had at least one acquired resistance. Resistance was found against all tested antibiotics except tigecycline. Taking a look on the whole stretch of the River Danube the proportion of multiresistances did not differ significantly. In total, 35 ESBL harboring Enterobacteriaceae, 17 Escherichia coli, 13 Klebsiella pneumoniae and five Enterobacter spp. were isolated. One Klebsiella pneumoniae harboring NMD-1 carbapenmases and two Enterobacteriaceae with KPC-2 could be identified. Human generated antibiotic resistance is very common in E. coli and Klebsiella spp. in the River Danube. Even isolates with resistance patterns normally associated with intensive care units are present.     

Pumping Iron in Australia: Prevalence,Trends and Sociodemographic Correlates of Muscle Strengthening Activity Participation from a National Sample of 195,926 Adults

ObjectiveThe current Australian Physical Activity Guidelines recommend that adults engage in regular muscle-strengthening activity (e.g. strength or resistance training). However, public health surveillance studies describing the patterns and trends of population-level muscle-strengthening activity participation are sparse. The aim of this study is to examine the prevalence, trends and sociodemographic correlates of muscle-strengthening activity participation in a national-representative sample of Australians aged 15 years and over.MethodsBetween 2001 and 2010, quarterly cross-sectional national telephone surveys were conducted as part of the Australian Sports Commission''s ''Exercise, Recreation and Sport Survey''. Pooled population-weighted proportions were calculated for reporting: [i] no muscle-strengthening activity; [ii] insufficient muscle-strengthening activity, and [iii] sufficient muscle-strengthening activity. Associations with sociodemographic variables were assessed using multiple logistic regression analyses.ResultsOut of 195,926 participants, aged 15–98 years, only 10.4% (95% CI: 10.1–10.7) and 9.3% (95% CI: 9.1–9.5) met the muscle-strengthening activity recommendations in the past two weeks and in the past year, respectively. Older adults (50+ years), and those living in socioeconomically disadvantaged, outer regional/remote areas and with lower education were less likely to report sufficient muscle-strengthening activity (p<0.001). Over the 10-year monitoring period, there was a significant increase in the prevalence of sufficient muscle-strengthening activity (6.4% to 12.0%, p-value for linear trend <0.001).ConclusionsA vast majority of Australian adults did not engage in sufficient muscle-strengthening activity. There is a need for public health strategies to support participation in muscle-strengthening activity in this population. Such strategies should target older and lower educated adults, and those living in socioeconomically disadvantaged, outer regional/remote and areas.     

Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections

The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1–3 distinct haplotypes per infestation.