Interdependencies between Biotic and Abiotic Ferrous Iron Oxidation and Influence of pH,Oxygen and Ferric Iron Deposits

The effect of pH, oxygen and ferrous iron on growth and oxidation rates of iron-oxidizing bacteria (Gallionella spp and Leptothrix spp) as well as indirect effects, the most prominent being catalytic activity of the produced ferric iron deposits, were investigated. Deposits of biotic origin exhibit slightly lower surface oxidation rates compared to abiotically produced ferric iron. It was shown that the required habitat conditions of the studied species hardly overlap, but increase the pH/oxygen range of potential Fe(II) oxidation conditions. The study highlights the combined effect of microbial iron oxidation and catalytic properties of the Mn and Fe oxidation products.     

Phantoms of Gondwana?—phylogeny of the spider subfamily Mynogleninae (Araneae: Linyphiidae)

This is the first genus‐level phylogeny of the subfamily Mynogleninae. It is based on 190 morphological characters scored for 44 taxa: 37 mynoglenine taxa (ingroup) representing 15 of the 17 known genera and seven outgroup taxa representing the subfamilies Stemonyphantinae, Linyphiinae (Linyphiini and Micronetini), and Erigoninae, and a representative of the family Pimoidae, the sister‐group to Linyphiidae. No fewer than 147 of the morphological characters used in this study are new and defined for this study, and come mainly from male and female genitalia. Parsimony analysis with equal weights resulted in three most parsimonious trees of length 871. The monophyly of the subfamily Mynogleninae and the genera Novafroneta, Parafroneta, Laminafroneta, Afroneta, Promynoglenes, Metamynoglenes, and Haplinis are supported, whereas Pseudafroneta is paraphyletic. The remaining seven mynoglenine genera are either monotypic or represented by only one taxon. Diagnoses are given for all genera included in the analysis. The evolution of morphological traits is discussed and we summarize the diversity and distribution patterns of the 124 known species of mynoglenines. The preferred topology suggests a single origin of mynoglenines in New Zealand with two dispersal events to Africa, and does not support Gondwana origin.     

Investigating filopodia sensing using arrays of defined nano-pits down to 35 nm diameter in size

In order for cells to react to topography, they must be able to sense shape. When considering nano-topography, these shapes are much smaller than the cell, but still strong responses to nano-topography have been seen. Filopodia, or microspikes, presented by cells at their leading edges are thought to be involved in gathering of special information. In order to investigate this, and to develop an understanding of what size of feature can be sensed by cells, morphological observation (electron and fluorescent microscopy) of fibroblasts reacting to nano-pits with 35, 75 and 120 nm diameters has been used in this study. The nano-pits are especially interesting because unlike many of the nanofeatures cited in the literature, they have no height for the cells to react to. The results showed that cell filopodia, and retraction fibres, interacted with all pit sizes, although direct interaction was hard to image on the 35 nm pits. This suggests that cells are extremely sensitive to their nanoevironment and that should be taken in to consideration when designing next-generation tissue engineering materials. We suggest that this may occur through nanocontact guidance as filopodia are moved over the pits.     

The mineralocorticoid receptor agonist,fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone

Whereas animal studies have shown a clear inhibitory effect of hippocampal mineralocorticoid receptors (MR) on hypothalamic-pituitary-adrenal (HPA) axis activity, investigations in humans revealed equivocal results. To further clarify the influence of MR in HPA activity we studied 10 healthy men during the circadian nadir of HPA activity (14:00 to 21:00) after pre-treatment with 3 g metyrapone to minimize the impact of basal endogenous cortisol secretion. On three separate occasions, in a placebo-controlled design, subjects received in a randomized order either 0.5 mg fludrocortisone p.o. or 0.2 mg aldosterone i.v. or placebo. Fludrocortisone exerted a significant inhibition of ACTH, cortisol and 11-desoxycortisol (p < 0.05), whereas no such effect was observed after aldosterone or placebo. These preliminary data suggest that MR are involved in the inhibition of the HPA axis during the circadian nadir of glucocorticoid concentrations in humans.     

Mesenchymal stem cells as all-round supporters in a normal and neoplastic microenvironment

ABSTRACT: Mesenchymal stem cells (MSC) represent a heterogeneous population exhibiting stem cell-like properties which are distributed almost ubiquitously among perivascular niches of various human tissues and organs. Organism requirements such as tissue damage determine interdisciplinary functions of resident MSC including self-renewal, migration and differentiation, whereby MSC support local tissue repair, angiogenesis and concomitant immunomodulating. However, growth of tumor cells and invasion also causes local tissue damage and injury which subsequently activates repair mechanisms and consequently, attracts MSC. Thereby, MSC exhibit a tissue-specific functional biodiversity which is mediated by direct cell-to-cell communication via adhesion molecule signaling and by a tightly regulated exchange of a multifactorial panel of cytokines, exosomes, and micro RNAs. Such interactions determine either tumor-promoting or tumor-inhibitory support by MSC. Moreover, fusion with necrotic/apoptotic tumor cell bodies contributes to re-program MSC into an aberrant phenotype also suggesting that tumor tissue in general represents different types of neoplastic cell populations including tumor-associated stem cell-like cells. The present work summarizes some functional characteristics and biodiversity of MSC and highlights certain controversial interactions with normal and tumorigenic cell populations, including associated modulations within the MSC microenvironment.     

Identification of Cytoskeleton-Associated Proteins Essential for Lysosomal Stability and Survival of Human Cancer Cells

Microtubule-disturbing drugs inhibit lysosomal trafficking and induce lysosomal membrane permeabilization followed by cathepsin-dependent cell death. To identify specific trafficking-related proteins that control cell survival and lysosomal stability, we screened a molecular motor siRNA library in human MCF7 breast cancer cells. SiRNAs targeting four kinesins (KIF11/Eg5, KIF20A, KIF21A, KIF25), myosin 1G (MYO1G), myosin heavy chain 1 (MYH1) and tropomyosin 2 (TPM2) were identified as effective inducers of non-apoptotic cell death. The cell death induced by KIF11, KIF21A, KIF25, MYH1 or TPM2 siRNAs was preceded by lysosomal membrane permeabilization, and all identified siRNAs induced several changes in the endo-lysosomal compartment, i.e. increased lysosomal volume (KIF11, KIF20A, KIF25, MYO1G, MYH1), increased cysteine cathepsin activity (KIF20A, KIF25), altered lysosomal localization (KIF25, MYH1, TPM2), increased dextran accumulation (KIF20A), or reduced autophagic flux (MYO1G, MYH1). Importantly, all seven siRNAs also killed human cervix cancer (HeLa) and osteosarcoma (U-2-OS) cells and sensitized cancer cells to other lysosome-destabilizing treatments, i.e. photo-oxidation, siramesine, etoposide or cisplatin. Similarly to KIF11 siRNA, the KIF11 inhibitor monastrol induced lysosomal membrane permeabilization and sensitized several cancer cell lines to siramesine. While KIF11 inhibitors are under clinical development as mitotic blockers, our data reveal a new function for KIF11 in controlling lysosomal stability and introduce six other molecular motors as putative cancer drug targets.     

The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation

Background and Aim

Non-alcoholic fatty liver disease (NAFLD) is a common condition, associated with hepatic insulin resistance and the metabolic syndrome including hyperglycaemia and dyslipidemia. We aimed at studying the potential impact of the NAFLD-associated PNPLA3 rs738409 G-allele on NAFLD-related metabolic traits in hyperglycaemic individuals.

Methods

The rs738409 variant was genotyped in the population-based Inter99 cohort examined by an oral glucose-tolerance test, and a combined study-sample consisting of 192 twins (96 twin pairs) and a sub-set of the Inter99 population (n = 63) examined by a hyperinsulinemic euglycemic clamp (n _total = 255). In Inter99, we analyzed associations of rs738409 with components of the WHO-defined metabolic syndrome (n = 5,847) and traits related to metabolic disease (n = 5,663). In the combined study sample we elucidated whether the rs738409 G-allele altered hepatic or peripheral insulin sensitivity. Study populations were divided into individuals with normal glucose-tolerance (NGT) and with impaired glucose regulation (IGR).

Results

The case-control study showed no associations with components of the metabolic syndrome or the metabolic syndrome. Among 1,357 IGR individuals, the rs738409 G-allele associated with decreased fasting serum triglyceride levels (per allele effect(β) = −9.9% [−14.4%;−4.0% (95% CI)], p = 5.1×10⁻⁵) and fasting total cholesterol (β = −0.2 mmol/l [−0.3;−0.01 mmol/l(95% CI)], p = 1.5×10⁻⁴). Meta-analyses showed no impact on hepatic or peripheral insulin resistance in carriers of the rs738409 G-allele.

Conclusion

Our findings suggest that the G-allele of PNPLA3 rs738409 associates with reduced fasting levels of cholesterol and triglyceride in individuals with IGR.