A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden,an Emerging Agent of Diarrheal Disease in Tropical Regions

Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies.     

Current Practice in the Referral of Individuals with Suspected Dementia for Neuroimaging by General Practitioners in Ireland and Wales

Objectives

While early diagnosis of dementia is important, the question arises whether general practitioners (GPs) should engage in direct referrals. The current study investigated current referral practices for neuroimaging in dementia, access to imaging modalities and investigated related GP training in Ireland and North Wales.

Methods

A questionnaire was distributed to GPs in the programme regions which included approximately two thirds of all GPs in the Republic of Ireland and all general practitioners in North Wales. A total of 2,093 questionnaires were issued.

Results

48.6% of Irish respondents and 24.3% of Welsh respondents directly referred patients with suspected dementia for neuroimaging. Irish GPs reported greater direct access to neuroimaging than their Welsh counterparts. A very small percentage of Irish and Welsh GPs (4.7% and 10% respectively) had received training in neuroimaging and the majority who referred patients for neuroimaging were not aware of any dementia-specific protocols for referrals (93.1% and 95% respectively).

Conclusions

The benefits of direct GP access to neuroimaging investigations for dementia have yet to be established. Our findings suggest that current GP speciality training in Ireland and Wales is deficient in dementia-specific and neuroimaging training with the concern being that inadequate training will lead to inadequate referrals. Further training would complement guidelines and provide a greater understanding of the role and appropriateness of neuroimaging techniques in the diagnosis of dementia.     

Positive correlation between superoxide dismutase and resistance to paraquat toxicity in the green alga Chlorella sorokiniana

Paraquat (10–30 μm) exerted a dose-dependent and light-dependent toxicity on Chlorella sorokiniana. Paraquat was also seen to increase the superoxide dismutase content of these cells and to cause the appearance of a new electrophoretically distinct isozyme. Cells grown in the absence of paraquat contained one manganese-superoxide dismutase and two iron-superoxide dismutases, while the paraquat-grown cells contained an additional manganese-superoxide dismutase. Cells which were grown in the presence of 25 μm Paraquat, and which therefore possessed elevated levels of superoxide dismutase, were resistant to 30 μm Paraquat, whereas control cells were bleached and killed by this level of Paraquat. Electron micrography and chemical analysis revealed that Paraquat decreased the starch content of the cells and caused a failure of dividing cells to separate. It appears that Paraquat increases the photoproduction of O₂^? in C. sorokiniana and that an increase in the cell content of superoxide dismutase is an adaptive response which provides protection against this herbicide.     

Archaeobotanical remains of hulled and naked cereals in the Iberian Peninsula

Archaeobotanical finds in Spain show differences in the representation of the different wheats and barleys. From the beginning of agriculture (around 5000 B.C.) onwards, all wheats and barleys can be found at the sites of the eastern Peninsula. But in later periods of the early Neolithic, free-threshing wheat becomes more important in the northeast and the southeast, compared to the hulled wheats (emmer and einkorn). Nevertheless, both naked and hulled barleys can be found in similar frequencies in this period. Seed analyses in the southeast and the east of Spain show the importance of naked barley compared with hulled barley in the third millenium uncal B.C. This is not the case in the northeast, where hulled barley has a similar frequency in this period until the Iron Age, when both hulled barley and free-threshing wheat are the most important taxa. The substitution of naked barley for hulled barley in the south-east Iberian Peninsula is very significant in the period of greatest growth of the Argar culture. Free-threshing wheat can be found at a similar frequency throughout the study area, and was an important human food source together with the barleys. Hulled wheats seem to have played a secondary role as food in all periods, although they are constantly present in our samples. Nevertheless spelt wheat does not appear until the Roman period, when it is only found on the Cantabrian north coast, where it is important.     

SUMO-targeted ubiquitin ligases in genome stability

We identify the SUMO-Targeted Ubiquitin Ligase (STUbL) family of proteins and propose that STUbLs selectively ubiquitinate sumoylated proteins and proteins that contain SUMO-like domains (SLDs). STUbL recruitment to sumoylated/SLD proteins is mediated by tandem SUMO interaction motifs (SIMs) within the STUbLs N-terminus. STUbL-mediated ubiquitination maintains sumoylation pathway homeostasis by promoting target protein desumoylation and/or degradation. Thus, STUbLs establish a novel mode of communication between the sumoylation and ubiquitination pathways. STUbLs are evolutionarily conserved and include: Schizosaccharomyces pombe Slx8-Rfp (founding member), Homo sapiens RNF4, Dictyostelium discoideum MIP1 and Saccharomyces cerevisiae Slx5-Slx8. Cells lacking Slx8-Rfp accumulate sumoylated proteins, display genomic instability, and are hypersensitive to genotoxic stress. These phenotypes are suppressed by deletion of the major SUMO ligase Pli1, demonstrating the specificity of STUbLs as regulators of sumoylated proteins. Notably, human RNF4 expression restores SUMO pathway homeostasis in fission yeast lacking Slx8-Rfp, underscoring the evolutionary functional conservation of STUbLs. The DNA repair factor Rad60 and its human homolog NIP45, which contain SLDs, are candidate STUbL targets. Consistently, Rad60 and Slx8-Rfp mutants have similar DNA repair defects.