Cysteine proteinase C1A paralog profiles correspond with phylogenetic lineages of pathogenic piroplasmids

Piroplasmid parasites comprising of Babesia, Theileria, and Cytauxzoon are transmitted by ticks to farm and pet animals and have a significant impact on livestock industries and animal health in tropical and subtropical regions worldwide. In addition, diverse Babesia spp. infect humans as opportunistic hosts. Molecular phylogeny has demonstrated at least six piroplasmid lineages exemplified by B. microti, B. duncani, C. felis, T. equi, Theileria sensu stricto (T. annulata, T. parva, and T. orientalis) and Babesia sensu stricto (B. bovis, B. bigemina, and B. ovis). C1A cysteine-proteinases (C1A-Cp) are papain-like enzymes implicated in pathogenic and vital steps of the parasite life cycle such as nutrition and host cell egress. An expansion of C1A-Cp of T. annulata and T. parva with respect to B. bovis and B. ovis was previously described. In the present work, C1A-Cp paralogs were identified in available genomes of species pertaining to each piroplasmid lineage. Phylogenetic analysis revealed eight C1A-Cp groups. The profile of C1A-Cp paralogs across these groups corroborates and defines the existence of six piroplasmid lineages. C. felis, T. equi and Theileria s.s. each showed characteristic expansions into extensive families of C1A-Cp paralogs in two of the eight groups. Underlying gene duplications have occurred as independent unique evolutionary events that allow distinguishing these three piroplasmid lineages. We hypothesize that C1A-Cp paralog families may be associated with the advent of the schizont stage. Differences in the invertebrate tick host specificity and/or mode of transmission in piroplasmid lineages might also be associated with the observed C1A-Cp paralog profiles

Highly syntenic and yet divergent: a tale of two Theilerias

The published genomic sequences of the two major host-transforming Theileria species of cattle represent a rich resource of information that has allowed novel bioinformatic and experimental studies into these important apicomplexan parasites. Since their publication in 2005, the genomes of T. annulata and T. parva have been utilised for a diverse range of applications, ranging from candidate antigen discovery to the identification of genetic markers for population analysis. This has led to advancements in the quest for a sub-unit vaccine, while providing a greater understanding of variation among parasite populations in the field. The unique ability of these Theileria species to induce host cell transformation is the subject of considerable scientific interest and the availability of full genomic sequences has provided new insights into this area of research. This article reviews the data underlying published comparative analyses, focussing on the general features of gene expression, the major Tpr/Tar multi-copy gene family and a re-examination of the predicted macroschizont secretome. Codon usage between the Theileria species is reviewed in detail, as this underpins ongoing comparative studies investigating selection at the intra- and inter-species level. The TashAT/TpshAT family of genes, conserved between T. annulata and T. parva, encodes products targeted to the host nucleus and has been implicated in contributing to the transformed bovine phenotype. Species-specific expansion and diversification at this critical locus is discussed with reference to the availability, in the near future, of genomic datasets which are based on non-transforming Theileria species

Identification of molecular markers of delayed graft function based on the regulation of biological ageing

Introduction: Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications. Methodology: The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts. Results: Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation. Conclusion: These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Trait-based plant mortality and preference for native versus non-native seedlings by invasive slug and snail herbivores in Hawaii

Non-native herbivores may alter plant communities through their preferential consumption of seedlings of different species. We assessed seedling herbivory by two invasive gastropod species in Hawaii, the giant African snail (Achatina fulica) and the Cuban brown slug (Veronicella cubensis). We hypothesized that six native species would suffer greater gastropod herbivory than four non-native species, and that species with short stature, thin leaves, and lacking physical defenses would suffer the greatest mortality from gastropods. Herbivory was measured during 13-day preference trials using enclosures that each contained four different woody species (two native, two non-native) and were assigned to one of three treatments: giant African snail, Cuban brown slug, or control (no gastropod). Discriminant function analysis was used to predict gastropod-induced seedling mortality from a suite of seedling characteristics. Native species did not always experience greater herbivory than non-natives species, and seedling mortality was 0–100 %. Native Pipturus albidus and Clermontia parviflora suffered 100 % mortality from V. cubensis herbivory, and P. albidus, Psychotria hawaiiensis, and Myrsine lessertiana suffered C80 % mortality from A. fulica. Two non-natives (Fraxinus uhdei, Clidemia hirta), and two natives (Metrosideros polymorpha, Diospyros sandwicensis), suffered little damage and no mortality. Non-native Ardisia elliptica suffered 10–30 %gastropod mortality, and non-native Psidium cattleianum mortality was 0–50 %. Leaf thickness best predicted species mortality caused by slugs and snails; some thicker-leaved species suffered most. Invasive snails and slugs threaten some native and non-native seedlings by directly consuming them. Current and future plant community structure in Hawaii may in part reflect the feeding preferences of invasive gastropods

Trait-based plant mortality and preference for native versus non-native seedlings by invasive slug and snail herbivores in Hawaii

Non-native herbivores may alter plant communities through their preferential consumption of seedlings of different species. We assessed seedling herbivory by two invasive gastropod species in Hawaii, the giant African snail (Achatina fulica) and the Cuban brown slug (Veronicella cubensis). We hypothesized that six native species would suffer greater gastropod herbivory than four non-native species, and that species with short stature, thin leaves, and lacking physical defenses would suffer the greatest mortality from gastropods. Herbivory was measured during 13-day preference trials using enclosures that each contained four different woody species (two native, two non-native) and were assigned to one of three treatments: giant African snail, Cuban brown slug, or control (no gastropod). Discriminant function analysis was used to predict gastropod-induced seedling mortality from a suite of seedling characteristics. Native species did not always experience greater herbivory than non-natives species, and seedling mortality was 0–100 %. Native Pipturus albidus and Clermontia parviflora suffered 100 % mortality from V. cubensis herbivory, and P. albidus, Psychotria hawaiiensis, and Myrsine lessertiana suffered C80 % mortality from A. fulica. Two non-natives (Fraxinus uhdei, Clidemia hirta), and two natives (Metrosideros polymorpha, Diospyros sandwicensis), suffered little damage and no mortality. Non-native Ardisia elliptica suffered 10–30 %gastropod mortality, and non-native Psidium cattleianum mortality was 0–50 %. Leaf thickness best predicted species mortality caused by slugs and snails; some thicker-leaved species suffered most. Invasive snails and slugs threaten some native and non-native seedlings by directly consuming them. Current and future plant community structure in Hawaii may in part reflect the feeding preferences of invasive gastropods

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Invasive rodent responses to experimental and natural hurricanes with implications for global climate change

Hurricanes cause dramatic changes to forests by opening the canopy and depositing debris onto the forest floor. How invasive rodent populations respond to hurricanes is not well understood, but shifts in rodent abundance and foraging may result from scarce fruit and seed resources that follow hurricanes. We conducted studies in a wet tropical forest in Puerto Rico to better understand how experimental (canopy trimming experiment) and natural (Hurricane Maria) hurricane effects alter populations of invasive rodents (Rattus rattus [rats] and Mus musculus [mice]) and their foraging behaviors. To monitor rodent populations, we used tracking tunnels (inked and baited cards inside tunnels enabling identification of animal visitors’ footprints) within experimental hurricane plots (arborist trimmed in 2014) and reference plots (closed canopy forest). To assess shifts in rodent foraging, we compared seed removal of two tree species (Guarea guidonia and Prestoea acuminata) between vertebrate-excluded and free-access treatments in the same experimental and reference plots, and did so 3 months before and 9 months after Hurricane Maria (2017). Trail cameras were used to identify animals responsible for seed removal. Rat incidences generated from tracking tunnel surveys indicated that rat populations were not significantly affected by experimental or natural hurricanes. Before Hurricane Maria there were no mice in the forest interior, yet mice were present in forest plots closest to the road after the hurricane, and their forest invasion coincided with increased grass cover resulting from open forest canopy. Seed removal of Guarea and Prestoea across all plots was rat dominated (75%–100% rat-removed) and was significantly less after than before Hurricane Maria. However, following Hurricane Maria, the experimental hurricane treatment plots of 2014 had 3.6 times greater seed removal by invasive rats than did the reference plots, which may have resulted from rats selecting post-hurricane forest patches with greater understory cover for foraging. Invasive rodents are resistant to hurricane disturbance in this forest. Predictions of increased hurricane frequency from expected climate change should result in forest with more frequent periods of grassy understories and mouse presence, as well as with heightened rat foraging for fruit and seed in preexisting areas of disturbance