On the evolution of decoys in plant immune systems

The Guard-Guardee model for plant immunity describes how resistance proteins (guards) in host cells monitor host target proteins (guardees) that are manipulated by pathogen effector proteins. A recently suggested extension of this model includes decoys, which are duplicated copies of guardee proteins, and which have the sole function to attract the effector and, when modified by the effector, trigger the plant immune response. Here we present a proof-of-principle model for the functioning of decoys in plant immunity, quantitatively developing this experimentally-derived concept. Our model links the basic cellular chemistry to the outcomes of pathogen infection and resulting fitness costs for the host. In particular, the model allows identification of conditions under which it is optimal for decoys to act as triggers for the plant immune response, and of conditions under which it is optimal for decoys to act as sinks that bind the pathogen effectors but do not trigger an immune response.Comment: 15 pages, 6 figure

The energy budget in Rayleigh-Benard convection

It is shown using three series of Rayleigh number simulations of varying aspect ratio AR and Prandtl number Pr that the normalized dissipation at the wall, while significantly greater than 1, approaches a constant dependent upon AR and Pr. It is also found that the peak velocity, not the mean square velocity, obeys the experimental scaling of Ra^{0.5}. The scaling of the mean square velocity is closer to Ra^{0.46}, which is shown to be consistent with experimental measurements and the numerical results for the scaling of Nu and the temperature if there are strong correlations between the velocity and temperature.Comment: 5 pages, 3 figures, new version 13 Mar, 200

Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information

Measurement of polarization-transfer to bound protons in carbon and its virtuality dependence

We measured the ratio $P_{x}/P_{z}$ of the transverse to longitudinal components of polarization transferred from electrons to bound protons in $^{12}\mathrm{C}$ by the $^{12}\mathrm{C}(\vec{e},e'\vec{p})$ process at the Mainz Microtron (MAMI). We observed consistent deviations from unity of this ratio normalized to the free-proton ratio, $(P_{x}/P_{z})_{^{12}\mathrm{C}}/(P_{x}/P_{z})_{^{1}\mathrm{H}}$, for both $s$- and $p$-shell knocked out protons, even though they are embedded in averaged local densities that differ by about a factor of two. The dependence of the double ratio on proton virtuality is similar to the one for knocked out protons from $^{2}\mathrm{H}$ and $^{4}\mathrm{He}$, suggesting a universal behavior. It further implies no dependence on average local nuclear density

PI(5)P regulates autophagosome biogenesis.

Phosphatidylinositol 3-phosphate (PI(3)P), the product of class III PI3K VPS34, recruits specific autophagic effectors, like WIPI2, during the initial steps of autophagosome biogenesis and thereby regulates canonical autophagy. However, mammalian cells can produce autophagosomes through enigmatic noncanonical VPS34-independent pathways. Here we show that PI(5)P can regulate autophagy via PI(3)P effectors and thereby identify a mechanistic explanation for forms of noncanonical autophagy. PI(5)P synthesis by the phosphatidylinositol 5-kinase PIKfyve was required for autophagosome biogenesis, and it increased levels of PI(5)P, stimulated autophagy, and reduced the levels of autophagic substrates. Inactivation of VPS34 impaired recruitment of WIPI2 and DFCP1 to autophagic precursors, reduced ATG5-ATG12 conjugation, and compromised autophagosome formation. However, these phenotypes were rescued by PI(5)P in VPS34-inactivated cells. These findings provide a mechanistic framework for alternative VPS34-independent autophagy-initiating pathways, like glucose starvation, and unravel a cytoplasmic function for PI(5)P, which previously has been linked predominantly to nuclear roles.We are grateful for funding from a Wellcome Trust Principal Research Fellowship (095317/Z/11/Z to D.C.R.), a Wellcome Trust Strategic Award (100140/Z/ 12/Z), the NIHR Biomedical Research Centre in Dementia at Addenbrooke’s Hospital, an MRC Confidence in Concepts grant (D.C.R.), and a FEBS Long- Term Fellowship (A.A.).This article was originally published in Molecular Cell (M Vicinanza, VI Korolchuk, A Ashkenazi, C Puri, FM Menzies, JH Clarke, DC Rubinsztein, Molecular Cell 2015, 57, 219-234

Persistent global power fluctuations near a dynamic transition in electroconvection

This is a study of the global fluctuations in power dissipation and light transmission through a liquid crystal just above the onset of electroconvection. The source of the fluctuations is found to be the creation and annihilation of defects. They are spatially uncorrelated and yet temporally correlated. The temporal correlation is seen to persist for extremely long times. There seems to be an especially close relation between defect creation/annihilat ion in electroconvection and thermal plumes in Rayleigh-B\'enard convection

The effect of weaning diet type on grey mullet (Mugil cephalus) juvenile performance during the trophic shift from carnivory to omnivory

In captive grey mullet (Mugil cephalus) juveniles, the weaning stage overlaps the period where there are changes in the ontogeny of digestive enzymes as the fry transit from carnivory to omnivory. The aim of this study was to evaluate growth, survival, weight distribution and the activity of pancreatic and brush border digestive enzymes when fry are fed a carnivorous, herbivorous or omnivorous weaning diet. Fifteen 17-L aquaria in a flow through system with 40‰, UV treated, temperature (24.5 ± 0.5 °C) controlled seawater were stocked with eighty-five 23 dph grey mullet larvae per aquarium. This allowed the testing of three weaning dietary treatments, differing in their protein and carbohydrate content, in 5 replicate aquaria per treatment from 24 to 53 dph. Diet 1 was the dried macroalgal species Ulva lactuca and was designated as a low protein: high carbohydrate herbivorous diet. Diet 2 was a commercial microencapsulated starter feed designated as a high protein: low carbohydrate carnivorous diet. Diet 3 was a 1:1 ww mixture of diets 1 and diet 2 representing an omnivorous feeding regime. The average final weight of the omnivorous feeding fish was significantly (P .05). The activity levels of brush border alkaline phosphatase and intracellular leucine alanine peptidase were similar in grey mullet fry fed the carnivorous and omnivorous diets, but were higher than those in fish fed the herbivorous diet (P < .05). The intestinal maturation index exhibited the highest and lowest values in mullet fry fed the carnivorous and herbivorous diets, respectively, whereas those from the omnivorous group showed intermediate values (P = .03). This study broadly suggests that aquaculture feeds for juvenile grey mullet should be designed for omnivorous feeding habits.info:eu-repo/semantics/acceptedVersio

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved

In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments

The key neuroendocrine regulators of the onset of puberty in the Atlantic bluefin tuna (Thunnus thynnus)

Recently, significant progress on spawning induction in captive bluefin tuna (BFT, Thunnus thynnus), has been achieved providing the basis for the species' domestication. To further promote the development of a self- sustained BFT aquaculture, we investigated first sexual maturity in BFT reared from an immature stage in captivity. Accordingly, our major objectives were to evaluate: (i) maturational status of the brain-pituitary-gonadal (BPG) axis, and (ii) responsiveness of the BPG to exogenous hormones. Special emphasis was given to characterize the gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH) that act as central regulators of gonadal development and gamete maturation. The growth parameters recorded for the captive BFT juveniles are consistent with the length-weight relationship established for wild Mediterranean BFT stocks. The histological analyses of the gonads indicate advanced sexual maturation in BFT males compared to females, yet it is not yet clear whether this phenomenon typifies wild stocks or is induced due to the culture conditions. The hormone measurements show expression and accumulation of both gonadotropins in the pituitaries of immature and mature BFT. The pituitary LH content increased concomitantly with the age of the fish, exhibiting sex dimorphic patterns (i.e. 3-fold higher levels in females) in adult but not in juvenile BFT. The pituitary FSH levels, however, were elevated in 2Y immature males and in fully mature adults. Comparable to mammals, the intra-pituitary FSH/LH ratio was found to be higher (>1) in sexually immature than in maturing or pubertal BFT. Nevertheless, in the 3Y BFT females, which were all immature, the onset of puberty appears to require some other prerequisites, such as a rise in the LH storage above a minimal threshold. Our in vitro trials further demonstrated the capacity of rFSH and to a lesser extent that of rLH to stimulate cell proliferation in the immature ovarian and testicular fragments. Both rFSH and rLH have failed to stimulate steroidogenesis, yet pre-treatment with KiSS containing EVAc implants appeared to potentiate FSH-stimulated steroidogenesis in the immature testes. On the other hand, the expression levels of both the GtH-R and IGF I genes in the testicular fragments, derived from BFT juveniles and further exposed to the rLH treatment, showed dose-dependent pattern. Future studies testing the effects of captivity and hormone-based treatments on precocious maturity at relatively small body size are expected to facilitate the handling in confined environments, and to greatly improve the cost-efficiency of BFT farming.Postprin