BNIP3 supports melanoma cell migration and vasculogenic mimicry by orchestrating the actin cytoskeleton

BNIP3 is an atypical BH3-only member of the BCL-2 family of proteins with reported pro-death as well as pro-autophagic and cytoprotective functions, depending on the type of stress and cellular context. In line with this, the role of BNIP3 in cancer is highly controversial and increased BNIP3 levels in cancer patients have been linked with both good as well as poor prognosis. In this study, using small hairpin RNA (shRNA) lentiviral transduction to stably knockdown BNIP3 (BNIP3-shRNA) expression levels in melanoma cells, we show that BNIP3 supports cancer cell survival and long-term clonogenic growth. Although BNIP3-shRNA increased mitochondrial mass and baseline levels of reactive oxygen species production, which are features associated with aggressive cancer cell behavior, it also prevented cell migration and completely abolished the ability to form a tubular-like network on matrigel, a hallmark of vasculogenic mimicry (VM). We found that this attenuated aggressive behavior of these melanoma cells was underscored by severe changes in cell morphology and remodeling of the actin cytoskeleton associated with loss of BNIP3. Indeed, BNIP3-silenced melanoma cells displayed enhanced formation of actin stress fibers and membrane ruffles, while lamellopodial protrusions and filopodia, tight junctions and adherens junctions were reduced. Moreover, loss of BNIP3 resulted in re-organization of focal adhesion sites associated with increased levels of phosphorylated focal adhesion kinase. Remarkably, BNIP3 silencing led to a drop of the protein levels of the integrin-associated protein CD47 and its downstream signaling effectors Rac1 and Cdc42. These observations underscore that BNIP3 is required to maintain steady-state levels of intracellular complexes orchestrating the plasticity of the actin cytoskeleton, which is integral to cell migration and other vital processes stimulating cancer progression. All together these results unveil an unprecedented pro-tumorigenic role of BNIP3 driving melanoma cell's aggressive features, like migration and VM

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Mitigating the carbon footprint and improving productivity of ruminant livestock agriculture using a red seaweed

Ruminants are responsible for a large proportion of agricultural greenhouse gas emissions in the form of methane. This can be managed. It is a global initiative to increase productivity of the livestock sector to meet a growing population, but with emphasis on decreasing enteric methane to achieve emissions targets. We investigated the marine red macroalga (seaweed) Asparagopsis taxiformis as a feed ingredient to fundamentally eliminate enteric methane in beef cattle fed a high grain diet and provide evidence of improved livestock production performance. Asparagopsis was included in the feed of Brahman-Angus cross steers at 0.00%, 0.05%, 0.10%, and 0.20% of feed organic matter. Emissions were monitored in respiration chambers fortnightly over 90 d of treatment, steers were weighed weekly prior to feeding, feed intake monitored daily, rumen fluid samples collected in conjunction with respiration chambers for assessment of rumen function, feces were collected for bromoform residue analysis, and meat, organ, and fat were collected post slaughter for residue analysis and sensory evaluation. Steers receiving 0.10% and 0.20% Asparagopsis demonstrated decreased methane up to 40% and 98%, and demonstrated weight gain improvements of 53% and 42%, respectively. There was no negative effect on daily feed intake, feed conversion efficiencies, or rumen function, and no residues or changes in meat eating quality were detected. Commercial production of Asparagopsis could create new economies, and with low inclusion rates of this seaweed in ruminant diets the industry has the potential to revolutionize management of greenhouse gas emissions across the ruminant livestock sector with complementary benefits to the environment, and economy of the wider agriculture sector

Developments in understanding and assessment of egg and egg product quality over the last century

The hen's egg, in the form of table eggs and egg products, forms a staple part of the world's total protein consumption. In the last century, there has been considerable research effort focusing on ways of improving egg production and enhancing the quality of eggs. More recently, and with the development and application of new molecular technologies, our understanding and knowledge of how an egg is formed, what it actually consists of, in terms of its major versus minor components, and what the functional roles of each of these components might be, have been greatly enhanced. For example, new previously unknown molecules with specific activity or functional properties have been discovered in the egg albumen and yolk, some of which have potential uses in pharmaceutical and other food related applications. This review paper, which is the collaborative effort of members of Working Group 4 - Quality of Eggs and Egg Products - of the European Federation of WPSA, describes the scientific research behind a number of these major advances and provides some insight to the focus of current research in this area

Ulvan: A systematic review of extraction, composition and function

Species of green macroalgae (Chlorophyta) of the genus Ulva are edible seaweeds with a range of health promoting bioactive components. Ulva is high in dietary fibre which promotes gastrointestinal health and is linked to a reduction in the incidence of chronic diseases. The fundamental active constituent of Ulva is the soluble fibre ulvan, a gelling sulfated polysaccharide with biological activities including immunomodulating, antiviral, antioxidant, antihyperlipidemic and anticancer. Ulvan also has the capacity to modulate cellular signalling processes in both plant and animal systems leading to beneficial effects on productivity and health. Consequently, ulvan is of significant interest as a constituent in human health, agricultural, and biomaterial products. This comprehensive systematic review investigates and recommends acid extraction, ultrafiltration, sugar constituent and molecular weight analysis for the extraction, purification, and characterisation of ulvan, respectively. The biological activities of ulvans are then critically reviewed

Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties.

The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity

A helminth-derived suppressor of ST2 blocks allergic responses.

The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor

Efficient photogeneration of charge carriers in silicon nanowires with a radial doping gradient

From electrodeless time-resolved microwave conductivity measurements, the efficiency of charge carrier generation, their mobility, and decay kinetics on photo-excitation were studied in arrays of Si nanowires grown by the vapor-liquid-solid mechanism. A large enhancement in the magnitude of the photoconductance and charge carrier lifetime are found depending on the incorporation of impurities during the growth. They are explained by the internal electric field that builds up, due to a higher doped sidewalls, as revealed by detailed analysis of the nanowire morphology and chemical composition