ATPase-Independent Type-III Protein Secretion in Salmonella enterica

Type-III protein secretion systems are utilized by gram-negative pathogens to secrete building blocks of the bacterial flagellum, virulence effectors from the cytoplasm into host cells, and structural subunits of the needle complex. The flagellar type-III secretion apparatus utilizes both the energy of the proton motive force and ATP hydrolysis to energize substrate unfolding and translocation. We report formation of functional flagella in the absence of type-III ATPase activity by mutations that increased the proton motive force and flagellar substrate levels. We additionally show that increased proton motive force bypassed the requirement of the Salmonella pathogenicity island 1 virulence-associated type-III ATPase for secretion. Our data support a role for type-III ATPases in enhancing secretion efficiency under limited secretion substrate concentrations and reveal the dispensability of ATPase activity in the type-III protein export process.     

Activation of a PKC is required for vanadate-induced phosphorylation of protein kinase B (Akt), but not p70S6k in mouse epidermal JB6 cells

Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms by which vanadate mediates adverse effects are not well understood. The present study investigated the vanadate-induced phosphorylation of Akt and p70S6K, two kinases known to be vital for cell survival, growth, transformation, and transition of the cell cycle in mammals. Exposure of mouse epidermal JB6 cells to vanadium led to phosphorylation of Akt and p70S6K in a time- and dose-dependent manner. Vanadium exposure also caused translocation of atypical isoforms of PKC (lambda, zeta) from the cytosol to the membrane, but had no effect on PKCalpha translocation, suggesting that the atypical PKCs (aPKC) were specifically involved in vanadium-induced cellular response. Importantly, overexpression of a dominant negative mutant PKClambda blocked Akt phosphorylation at Ser473 and Thr308, whereas it did not inhibit p70S6k phosphorylation at Thr389 and Thr421/Ser424, suggesting that aPKC activation is specifically involved in vanadium-induced activation of Akt, but not in activation of p70S6k. Furthermore, vanadium-induced p70S6k phosphorylation at Thr389 and Thr421/Ser424 and Akt phosphorylation at Thr308 occurred through a PI-3K-dependent pathway because a PI-3K dominant negative mutant inhibited induction as compared with vector control cells. These results indicate that there was a differential role of aPKC in vanadate-induced phosphorylation of Akt and p70S6k, suggesting that signal transduction pathways leading to the activation of Akt and p70S6k were different.     

HIFs and tumors--causes and consequences

For most organisms oxygen is essential fo life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counter act possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an alpha- and a beta-subunit. HIF-1 alpha protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.     

Interactions between the toxicity of the heavy metals cadmium,copper, zinc in combinations and the detoxifying role of calcium in the brown algaCystoseira barbata

The toxicity of three heavy metals, Cd, Cu and Zn, and the detoxifying role of Ca have been studied for the brown algaCystoseira barbata formaaurentia after a 4-week laboratory culture. The experimental design was based upon a complete factorial design 2^k, which seems to be the first time it has been used in algal physiology. It was demonstrated that these three elements, applied jointly, act on weight-growth, chlorophyll a, c and carotenoid synthesis and Cd, Cu and Zn uptake. Cd and Zn act in synergy or in antagony, depending on their exogenous concentrations, on chlorophyll a and on carotenoid synthesis. Zn is antagonistic towards Cd and Cu on weight-growth in the combination Cd-Cu-Zn. From different element combinations, the protective role of Ca appears evident on weight-growth (Cd-Zn-Ca and Cu-Ca), chlorophyll a (Cd-Cu-Ca and Cu-Zn-Ca), chlorophyll c (Cd-Ca), carotenoid synthesis (Cd-Cu-Ca and Cu-Zn-Ca), Cd and Cu uptake (Cd-Cu-Ca) and Zn uptake (Cu-Zn-Ca). This role is confirmed by cytological investigations. This is apparently the first report concerning a Ca interaction with toxicity of heavy metals applied in combinations. However, the mechanisms of tolerance remain unknown.     

National Agricultural Productivity & Reconciliation Ecology Centre conference

The National Agricultural Productivity & Reconciliation Ecology Centre (NAPREC) held its inaugural conference in Deniliquin in the southern Murray–Darling Basin, NSW, Australia, 4–5 October 2017, and attracted an engaged group of farmers, researchers, industry and government representatives. The theme of the conference was ‘Positive Partnerships for Pathways to Sustainable Agriculture and Biodiversity’. It explored the application of Reconciliation Ecology and the value of the human elements of natural resource management within the context of the southern Murray–Darling Basin.     

Molecular determinants of the binding specificity of BH3 ligands to BclXL apoptotic repressor

B‐cell lymphoma extra‐large protein (BclXL) serves as an apoptotic repressor by virtue of its ability to recognize and bind to BH3 domains found within a diverse array of proapoptotic regulators. Herein, we investigate the molecular basis of the specificity of the binding of proapoptotic BH3 ligands to BclXL. Our data reveal that while the BH3 ligands harboring the LXXX[A/S]D and [R/Q]XLXXXGD motif bind to BclXL with high affinity in the submicromolar range, those with the LXXXGD motif afford weak interactions. This suggests that the presence of a glycine at the fourth position (G+4)—relative to the N‐terminal leucine (L0) within the LXXXGD motif—mitigates binding, unless the LXXXGD motif also contains arginine/glutamine at the ?2 position. Of particular note is the observation that the residues at the +4 and ?2 positions within the LXXX[A/S]D and [R/Q]XLXXXGD motifs appear to be energetically coupled—replacement of either [A/S]+4 or [R/Q]‐2 with other residues has little bearing on the binding affinity of BH3 ligands harboring one of these motifs. Collectively, our study lends new molecular insights into understanding the binding specificity of BH3 ligands to BclXL with important consequences on the design of novel anticancer drugs. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 573–582, 2014.     

Genome‐wide scans to detect positive selection in Large White and Tongcheng pigs

Due to the direction, intensity, duration and consistency of genetic selection, especially recent artificial selection, the production performance of domestic pigs has been greatly changed. Therefore, we reasoned that there must be footprints or selection signatures that had been left during domestication. In this study, with porcine 60K BeadChip genotyping data from both commercial Large White and local Chinese Tongcheng pigs, we calculated the extended haplotype homozygosity values of the two breeds using the long‐range haplotype method to detect selection signatures. We found 34 candidate regions, including 61 known genes, from Large White pigs and 25 regions comprising 57 known genes from Tongcheng pigs. Many selection signatures were found on SSC1, SSC4, SSC7 and SSC14 regions in both populations. According to quantitative trait loci and network pathway analyses, most of the regions and genes were linked to growth, reproduction and immune responses. In addition, the average genetic differentiation coefficient F_ST was 0.254, which means that there had already been a significant differentiation between the breeds. The findings from this study can contribute to further research on molecular mechanisms of pig evolution and domestication and also provide valuable references for improvement of their breeding and cultivation.     

Early Warning Signals for Rate-induced Critical Transitions in Salt Marsh Ecosystems

Ecosystems - Intertidal ecosystems are important because of their function as coastal protection and ecological value. Sea level rise may lead to submergence of salt marshes worldwide. Salt marshes...     

Retinal Vascular Caliber Is Associated with Cardiovascular Biomarkers of Oxidative Stress and Inflammation: The POLA Study

Purpose

Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology.

Patients and Methods

Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid.

Results

In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003) whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001) and orosomucoid (p = 0.01).

Conclusion

In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.