Equilibrium partitioning and isotopic fractionation of nitrogen between biotite, plagioclase, and K-feldspar during magmatic differentiation

Funding: UK Natural Environment Research Council (NE/R012253/1, NE/V010824/1, NE/P012167/1)A significant portion of the continental crust is composed of plutonic igneous rocks. However, little is known about the geochemical behaviour of N between the different minerals during magmatic differentiation. To provide new constraints for the behaviour of N during crust formation, we have characterised the geochemistry of nitrogen (N) in the compositionally zoned calc-alkaline pluton at Loch Doon, SW Scotland. We present N concentration and N isotope values for whole-rock data alongside biotite, plagioclase and K-feldspar mineral separates and assess the degree to which these data preserve equilibrium partitioning during magmatic differentiation. We show that whole rock likely inherited its N contents and δ15N signatures from the initial source composition and that this signature is homogenous at a pluton scale. Whilst the whole-rock data are best explained as crust-derived N in the source, the degree of homogenisation across a pluton scale is inconsistent with empirical N diffusivities, ruling out syn-emplacement crustal assimilation as the source of N. Instead, our data suggest a crustal signature inherited from depth associated with the Iapetus subduction zone. At a mineral scale, we find that N preferentially partitions into the feldspars over mica in this system in the order K-feldspar > plagioclase ≈ biotite > quartz, with average mineral-mineral distribution coefficients of DNplagioclase-biotite = 1.3 ± 0.6 and DNKspar-biotite = 2.8 ± 0.6. Partitioning is accompanied by a large and near constant equilibrium isotope fractionation factor between biotite and both feldspars (averages are Δ15NPlag-Biotite = +7.8 ± 1.2 ‰ and Δ15NKspar-Biotite = +7.9 ± 1.0 ‰), whereas Δ15NKspar-Plagioclase closely approximates 0 ‰, where both minerals show δ15N overlapping with the bulk rock δ15N values. These results show that mica crystallisation generates in a large negative Δ15N resulting a 15N-depleted reservoir within plutonic rocks. Moreover, our dataset suggests that feldspars might be a more significant host of N in the igneous portion of Earth’s continental and oceanic crust than previous thought.Publisher PDFPeer reviewe

The evaluation criteria used by venture capitalists:evidence from a UK fund

GRAHAM BOOCOCK AND MARGARET WOODS are Lecturers in Banking and Finance, and Financial Management, respectively, at Loughborough University Business School, England. The paper examines how venture fund managers select their investee companies, by exploring the evaluation criteria and the decision-making process adopted at one United Kingdom regional venture fund (henceforth referred to as the Fund). The analysis confirms that relatively consistent evaluation criteria are applied across the industry and corroborates previous models which suggest that the venture capitalist's decision-making consists of several stages. With the benefit of access to the Fund's internal records, however, this paper adds to the current literature by differentiating the evaluation criteria used at each successive stage of the decision-making process. The paper presents a model of the Fund's activities which demonstrates that the relative importance attached to the evaluation criteria changes as applications are systematically processed. Proposals have to satsfy different criteria at each stage of the decision-making process before they receive funding. In the vast majority of cases, applications are rejected by the fund managers. In addition, the length of time taken by the fund managers in appraising propositions can lead to withdrawal of applications at an advanced stage

β2-adrenergic signalling promotes cell migration by upregulating expression of the metastasis-associated molecule LYPD3

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line models of basal-type and oestrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and β2-adrenoceptor mediated cell behaviour including migration, invasion, adhesion, and survival in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified biomarkers and drug targets. Baseline levels of adrenoceptor gene expression are higher in basal-type rather than oestrogen receptor-positive cancer cells. Norepinephrine (NE) treatment increased invasive capacity in all cell lines but did not increase proliferation/survival. Protein profiling revealed the upregulation of the pro-metastatic gene Ly6/PLAUR Domain-Containing Protein 3 (LYPD3) in norepinephrine-treated MDA-MB-468 cells. Histology confirmed selective LYPD3 expression in primary and metastatic breast tumour samples. These findings demonstrate that basal-type cancer cells show a more aggressive adrenoceptor-β2-activated phenotype in the resting and stimulated state, which is attenuated by adrenoceptor-β2 inhibition. This study also highlights the first association between ADRβ2 signalling and LYPD3; its knockdown significantly reduced the basal and norepinephrine-induced activity of MCF-7 cells in vitro. The regulation of ADRβ2 signalling by LYPD3 and its metastasis promoting activities, reveal LYPD3 as a promising therapeutic target in the treatment of breast and other cancers

Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation

Organophosphate compounds (OPs) induce both acute and delayed neurotoxic effects, the latter of which is believed to involve their interaction with proteins other than acetylcholinesterase. However, few OP-binding proteins have been identified that may have a direct role in OP-induced delayed neurotoxicity. Given their ability to disrupt Ca2+ homeostasis, a key aim of the current work was to investigate the effects of sub-lethal neurite outgrowth inhibitory levels of OPs on the Ca2+-dependent enzyme tissue transglutaminase (TG2). At 1–10 µM, the OPs phenyl saligenin phosphate (PSP) and chlorpyrifos oxon (CPO) had no effect cell viability but induced concentration-dependent decreases in neurite outgrowth in differentiating N2a neuroblastoma cells. The activity of TG2 increased in cell lysates of differentiating cells exposed for 24 h to PSP and chlorpyrifos oxon CPO (10 µM), as determined by biotin-cadaverine incorporation assays. Exposure to both OPs (3 and/or 10 µM) also enhanced in situ incorporation of the membrane permeable substrate biotin-X-cadaverine, as indicated by Western blot analysis of treated cell lysates probed with ExtrAvidin peroxidase and fluorescence microscopy of cell monolayers incubated with FITC-streptavidin. Both OPs (10 µM) stimulated the activity of human and mouse recombinant TG2 and covalent labelling of TG2 with dansylamine-labelled PSP was demonstrated by fluorescence imaging following SDS-PAGE. A number of TG2 substrates were tentatively identified by mass spectrometry, including cytoskeletal proteins, chaperones and proteins involved protein synthesis and gene regulation. We propose that the elevated TG2 activity observed is due to the formation of a novel covalent adduct between TG2 and OPs

Ancient and modern mitogenomes from Central Argentina: New insights into population continuity, temporal depth and migration in South America

The inverted triangle shape of South America places Argentina territory as a geographical crossroads between the two principal peopling streams that followed either the Pacific or the Atlantic coasts, which could have then merged in Central Argentina (CA). Although the genetic diversity from this region is therefore crucial to decipher past population movements in South America, its characterization has been overlooked so far. We report 92 modern and 22 ancient mitogenomes spanning a temporal range of 5000 years, which were compared with a large set of previously reported data. Leveraging this dataset representative of the mitochondrial diversity of the subcontinent, we investigate the maternal history of CA populations within a wider geographical context. We describe a large number of novel clades within the mitochondrial DNA tree, thus providing new phylogenetic interpretations for South America. We also identify several local clades of great temporal depth with continuity until the present time, which stem directly from the founder haplotypes, suggesting that they originated in the region and expanded from there. Moreover, the presence of lineages characteristic of other South American regions reveals the existence of gene flow to CA. Finally, we report some lineages with discontinuous distribution across the Americas, which suggest the persistence of relic lineages likely linked to the first population arrivals. The present study represents to date the most exhaustive attempt to elaborate a Native American genetic map from modern and ancient complete mitochondrial genomes in Argentina and provides relevant information about the general process of settlement in South America.This work was supported by Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (PICT 2007-1549, PICT 2012-711 and PICT 2015-3155), Secretaría de Ciencia y Tecnología (Universidad Nacional de Córdoba), Ministerio de Ciencia y Tecnología de la Provincia de Córdoba (PID 2018-79) and Consejo Nacional de Investigaciones Científicas y Técnicas (2015-11220150100953CO). M.P. is a postdoctoral fellow and A.G., R.N., J.M.B.M, C.M.B., M.F. and D.A.D. are research career members of CONICET, Argentina

Small extracellular vesicles released from germinated kiwi pollen (pollensomes) present characteristics similar to mammalian exosomes and carry a plant homolog of ALIX

Introduction: In the last decade, it has been discovered that allergen-bearing extracellular nanovesicles, termed “pollensomes”, are released by pollen during germination. These extracellular vesicles (EVs) may play an important role in pollen-pistil interaction during fertilization, stabilizing the secreted bioactive molecules and allowing long-distance signaling. However, the molecular composition and the biological role of these EVs are still unclear. The present study had two main aims: (I) to clarify whether pollen germination is needed to release pollensomes, or if they can be secreted also in high humidity conditions; and (II) to investigate the molecular features of pollensomes following the most recent guidelines for EVs isolation and identification. Methods: To do so, pollensomes were isolated from hydrated and germinated kiwi (Actinidia chinensis Planch.) pollen, and characterized using imaging techniques, immunoblotting, and proteomics. Results: These analyses revealed that only germinated kiwi pollen released detectable concentrations of nanoparticles compatible with small EVs for shape and protein content. Moreover, a plant homolog of ALIX, which is a well-recognized and accepted marker of small EVs and exosomes in mammals, was found in pollensomes. Discussion: The presence of this protein, along with other proteins involved in endocytosis, is consistent with the hypothesis that pollensomes could comprehend a prominent subpopulation of plant exosome-like vesicles

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

At present, little is known about the effect(s) of organophosphorous compounds (OPs) on cardiomyocytes. In this study we have investigated the effects of phenyl saligenin phosphate (PSP), two organophosphorothioate insecticides (diazinon and chlorpyrifos) and their acutely toxic metabolites (diazoxon and chlorpyrifos oxon) on mitotic and differentiated H9c2 cardiomyoblasts. OP-induced cytotoxicity was assessed by monitoring MTT reduction, LDH release and caspase-3 activity. Cytotoxicity was not observed with diazinon, diazoxon or chlorpyrifos oxon (48 h exposure; 200 μM). Chlorpyrifos-induced cytotoxicity was only evident at concentrations >100 μM. In marked contrast, PSP displayed pronounced cytotoxicity towards mitotic and differentiated H9c2 cells. PSP triggered the activation of JNK1/2, but not ERK1/2, p38 MAPK or PKB, suggesting a role for this pro-apoptotic protein kinase in PSP-induced cell death. The JNK1/2 inhibitor SP 600125 attenuated PSP-induced caspase-3 and JNK1/2 activation, confirming the role of JNK1/2 in PSP-induced cytotoxicity. Fluorescently labelled PSP (dansylated PSP) was used to identify novel PSP binding proteins. Dansylated PSP displayed cytotoxicity towards differentiated H9c2 cells. 2D-gel electrophoresis profiles of cells treated with dansylated PSP (25 μM) were used to identify proteins fluorescently labelled with dansylated PSP. Proteomic analysis identified tropomyosin, heat shock protein β-1 and nucleolar protein 58 as novel protein targets for PSP. In summary, PSP triggers cytotoxicity in differentiated H9c2 cardiomyoblasts via JNK1/2-mediated activation of caspase-3. Further studies are required to investigate whether the identified novel protein targets of PSP play a role in the cytotoxicity of this OP, which is usually associated with the development of OP-induced delayed neuropathy