Phenotypic Plasticity of Southern Ocean Diatoms: Key to Success in the Sea Ice Habitat?

Diatoms are the primary source of nutrition and energy for the Southern Ocean ecosystem. Microalgae, including diatoms, synthesise biological macromolecules such as lipids, proteins and carbohydrates for growth, reproduction and acclimation to prevailing environmental conditions. Here we show that three key species of Southern Ocean diatom (Fragilariopsis cylindrus, Chaetoceros simplex and Pseudo-nitzschia subcurvata) exhibited phenotypic plasticity in response to salinity and temperature regimes experienced during the seasonal formation and decay of sea ice. The degree of phenotypic plasticity, in terms of changes in macromolecular composition, was highly species-specific and consistent with each species’ known distribution and abundance throughout sea ice, meltwater and pelagic habitats, suggesting that phenotypic plasticity may have been selected for by the extreme variability of the polar marine environment. We argue that changes in diatom macromolecular composition and shifts in species dominance in response to a changing climate have the potential to alter nutrient and energy fluxes throughout the Southern Ocean ecosystem.     

Phosphorylation of C-terminal polycystin-2 influences the interaction with PIGEA14: A QCM study based on solid supported membranes

Polycystin-2 (PC2) trafficking has been proposed to be a result of the interaction of PIGEA14 with PC2 as a function of the phosphorylation state of PC2. Here, we investigated the interaction of PIGEA14 with the C-terminal part of polycystin-2 wild type (cPC2wt) and the pseudophosphorylated mutant (cPC2S812D) to first, quantify the binding affinity between cPC2 and PIGEA14 and second, to elucidate the influence of PC2 phosphorylation on PIGEA14 binding. Solid supported membranes composed of octanethiol/1,2-dioleoyl-sn-glycero-3-phosphocholine doped with the receptor lipid DOGS–NTA–Ni were used to attach PIGEA14 to the membrane via its hexahistidine tag. By means of the quartz crystal microbalance technique, binding affinities as well as kinetic constants of the interaction were extracted in a label-free manner by applying the scaled particle theory. The results show that the dissociation constant of cPC2 to PIGEA14 is in the 10 nM regime providing strong evidence of a very specific interaction of cPC2 with PIGEA14. The interaction of cPC2wt is twofold larger than that of cPC2S812D. The moderate higher binding affinity of cPC2wt to PIGEA14 is discussed in light of PC2 trafficking to the plasma membrane.     

The catalytic domain CysPc of the DEK1 calpain is functionally conserved in land plants

DEK1, the single calpain of land plants, is a member of the ancient membrane bound TML–CysPc–C2L calpain family that dates back 1.5 billion years. Here we show that the CysPc–C2L domains of land plant calpains form a separate sub‐clade in the DEK1 clade of the phylogenetic tree of plants. The charophycean alga Mesostigma viride DEK1‐like gene is clearly divergent from those in land plants, suggesting that a major evolutionary shift in DEK1 occurred during the transition to land plants. Based on genetic complementation of the Arabidopsis thaliana dek1‐3 mutant using CysPc–C2L domains of various origins, we show that these two domains have been functionally conserved within land plants for at least 450 million years. This conclusion is based on the observation that the CysPc–C2L domains of DEK1 from the moss Physcomitrella patens complements the A. thaliana dek1‐3 mutant phenotype. In contrast, neither the CysPc–C2L domains from M. viride nor chimeric animal–plant calpains complement this mutant. Co‐evolution analysis identified differences in the interactions between the CysPc–C2L residues of DEK1 and classical calpains, supporting the view that the two enzymes are regulated by fundamentally different mechanisms. Using the A. thaliana dek1‐3 complementation assay, we show that four conserved amino acid residues of two Ca²⁺‐binding sites in the CysPc domain of classical calpains are conserved in land plants and functionally essential in A. thaliana DEK1.     

Structure of a translocation signal domain mediating conjugative transfer by type IV secretion systems

Relaxases are proteins responsible for the transfer of plasmid and chromosomal DNA from one bacterium to another during conjugation. They covalently react with a specific phosphodiester bond within DNA origin of transfer sequences, forming a nucleo‐protein complex which is subsequently recruited for transport by a plasmid‐encoded type IV secretion system. In previous work we identified the targeting translocation signals presented by the conjugative relaxase TraI of plasmid R1. Here we report the structure of TraI translocation signal TSA. In contrast to known translocation signals we show that TSA is an independent folding unit and thus forms a bona fide structural domain. This domain can be further divided into three subdomains with striking structural homology with helicase subdomains of the SF1B family. We also show that TSA is part of a larger vestigial helicase domain which has lost its helicase activity but not its single‐stranded DNA binding capability. Finally, we further delineate the binding site responsible for translocation activity of TSA by targeting single residues for mutations. Overall, this study provides the first evidence that translocation signals can be part of larger structural scaffolds, overlapping with translocation‐independent activities.     

Glucose Augments Killing Efficiency of Daptomycin Challenged Staphylococcus aureus Persisters

Treatment of Staphylococcus aureus in stationary growth phase with high doses of the antibiotic daptomycin (DAP) eradicates the vast majority of the culture and leaves persister cells behind. Despite resting in a drug-tolerant and dormant state, persister cells exhibit metabolic activity which might be exploited for their elimination. We here report that the addition of glucose to S. aureus persisters treated with DAP increased killing by up to five-fold within one hour. This glucose-DAP effect also occurred with strains less sensitive to the drug. The underlying mechanism is independent of the proton motive force and was not observed with non-metabolizable 2-deoxy-glucose. Our results are consistent with two hypotheses on the glucose-DAP interplay. The first is based upon glucose-induced carbohydrate transport proteins that may influence DAP and the second suggests that glucose may trigger the release or activity of cell-lytic proteins to augment DAP’s mode of action.     

Epidemiology,Diagnosis and Management of Extra-Pulmonary Tuberculosis in a Low-Prevalence Country: A Four Year Retrospective Study in an Australian Tertiary Infectious Diseases Unit

Objectives

Extra-pulmonary tuberculosis (EPTB) is relatively neglected and increasing in incidence, in comparison to pulmonary tuberculosis (PTB) in low-burden settings. It poses particular diagnostic and management challenges. We aimed to determine the characteristics of EPTB in Western Sydney, Australia, and to conduct a quality assurance investigation of adherence to guidelines among Infectious Diseases (ID) practitioners managing EPTB cases.

Methods

All adult EPTB cases managed by a large ID service during 01/01/2008–31/12/2011 were eligible for inclusion in the retrospective review. Data were extracted from patient medical records on demographic, diagnostic, clinical and management details, and on clinician adherence to local and international TB guidelines.

Results

129 cases managed by the ID service were identified, with files available for 117. 98 cases were managed by the Respiratory service and were excluded. 98.2%(112/114) had been born in a country other than Australia. HIV status was tested or previously known in 97 people, and positive in 4 (4%). Microbiological confirmation was obtained in 68/117 (58.1%), an additional 24 had histopathological findings considered confirmatory (92/117, 78.6%), with the remainder diagnosed on clinical and/or radiological grounds. Median time to diagnosis post-migration from a high TB-burden country was 5 years (range 0–41). 95 cases were successfully treated, 11 cases defaulted, refused therapy or transferred, 2 cases relapsed and outcomes unknown or pending in 9 cases. No deaths occurred in the sample analysed. Clinician adherence to guidelines was high, but with scope for improvement in offering testing for co-infections, performing eye checks, monitoring blood glucose in patients receiving adjunctive corticosteroids, and considering drug interactions.

Conclusions

Despite excellent TB outcomes in this setting, the low proportion of cases with susceptibility data is worrying in this era of increasing drug resistance, and illustrates the diagnostic difficulties faced even in a well-resourced setting. Vigilance for EPTB needs to remain high in those moving from high prevalence countries to Australia, even decades after immigration.     

Opposing the veil in the name of liberalism: popular attitudes to liberalism and Muslim veiling in the Netherlands

Is popular antagonism towards Muslim veils in Europe rooted in an exclusionary ‘enlightenment liberalism’? By examining different conceptions of liberalism and readings of veiling in a Dutch survey from 2014, we present the first study that investigates this question empirically. We thus bring together two hitherto largely unconnected literatures. The first is the work on immigration and ethnicity, which has shown the centrality of enlightenment liberalism in anti-Muslim media and policy discourses. The second is the literature on anti-Muslim attitudes in public opinion, which explains support for veil bans as the result of perceiving veils as threatening the respondent's own, supposedly liberal, values – but has failed to distinguish between different conceptions of liberalism and thus reached inconclusive results. This, we show, can be remedied by distinguishing between ‘enlightenment liberals’, who hold negative attitudes, and ‘reformation liberals’, who hold positive attitudes towards Muslim veils.     

The G protein Gαs acts as a tumor suppressor in sonic hedgehog signaling-driven tumorigenesis

G protein-coupled receptors (GPCRs) are critical players in tumor growth and progression. The redundant roles of GPCRs in tumor development confound effective treatment; therefore, targeting a single common signaling component downstream of these receptors may be efficacious. GPCRs transmit signals through heterotrimeric G proteins composed of Gα and Gβγ subunits. Hyperactive Gα_s signaling can mediate tumor progression in some tissues; however, recent work in medulloblastoma and basal cell carcinoma revealed that Gα_s can also function as a tumor suppressor in neoplasms derived from ectoderm cells including neural and epidermal stem/progenitor cells. In these stem-cell compartments, signaling through Gα_s suppresses self-renewal by inhibiting the Sonic Hedgehog (SHH) and Hippo pathways. The loss of GNAS, which encodes Gα_s, leads to activation of these pathways, over-proliferation of progenitor cells, and tumor formation. Gα_s activates the cAMP-dependent protein kinase A (PKA) signaling pathway and inhibits activation of SHH effectors Smoothened-Gli. In addition, Gα_s-cAMP-PKA activation negatively regulates the Hippo pathway by blocking the NF2-LATS1/2-Yap signaling. In this review, we will address the novel function of the signaling network regulated by Gα_s in suppression of SHH-driven tumorigenesis and the therapeutic approaches that can be envisioned to harness this pathway to inhibit tumor growth and progression.     

A Comparison Between Bonobos and Chimpanzees: A Review and Update

Chimpanzees (Pan troglodytes) and bonobos (P. paniscus) are our closest living relatives, with the human lineage diverging from the Pan lineage only around five to seven Mya, but possibly as early as eight Mya.^1–2 Chimpanzees and bonobos even share genetic similarities with humans that they do not share with each other.² Given their close genetic relationship to humans, both Pan species represent crucial living models for reconstructing our last common ancestor (LCA) and identifying uniquely human features. Comparing the similarities and differences of the two Pan is thus essential for constructing balanced models of human evolution.³