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This paper presents inserexs, an open-source computer program that aims to pre-evaluate the different reflections for resonant elastic X-ray scattering (REXS) diffraction experiments. REXS is an extremely versatile technique that can provide positional and occupational information about the atoms present in a crystal. inserexs was conceived to help REXS experimentalists know beforehand which reflections to choose to determine a parameter of interest. Prior work has already proven this to be useful in the determination of atomic positions in oxide thin films. inserexs allows generalization to any given system and aims to popularize resonant diffraction as an alternative technique to improve the resolution of crystalline structures.

Precisely locating oxygen atoms in nanosized systems is a real challenge. The traditional strategies used for bulk samples fail at probing samples with much less matter. Resonant elastic X-ray scattering (REXS) experiments in the X-ray absorption near-edge structure (XANES) domain have already proved their efficiency in probing transition metal cations in thin films, but it is not feasible to perform such experiments at the low-energy edges of lighter atoms – such as oxygen. In this study, the adequacy of using REXS in the extended X-ray absorption fine structure (EXAFS) domain, also known as extended diffraction absorption fine structure (EDAFS), to solve this issue is shown. The technique has been validated on a bulk FeV2O4 sample, through comparison with results obtained with conventional X-ray diffraction measurements. Subsequently, the positions of oxygen atoms in a thin film were unveiled by using the same strategy. The approach described in this study can henceforth be applied to solve the crystallographic structure of oxides, and will help in better understanding the properties and functionalities which are dictated by the positions of the oxygen atoms in functional nanosized materials.

Materials Chemistry and Physics, 276, ISSN:0254-0584

International audience; The low power manipulation of magnetization is currently a highly sought-after objective in spintronics. Non ferromagnetic large spin-orbit coupling heavy metal (NM) / ferromagnet (FM) heterostructures offer interesting elements of response to this issue, by granting the manipulation of the FM magnetization by the NM spin Hall effect (SHE) generated spin current. Additional functionalities, such as the electric field control of the spin current generation, can be offered using multifunctional ferromagnets. We have studied the spin current transfer processes between Pt and the multifunctional magnetoelectric Ga0.6Fe1.4O3 (GFO). In particular, via angular dependent magnetotransport measurements, we were able to differentiate between magnetic proximity effect (MPE)-induced anisotropic magnetoresistance (AMR) and spin Hall magnetoresistance (SMR). Our analysis shows that SMR is the dominant phenomenon at all temperatures and is the only one to be considered near room temperature, with a magnitude comparable to those observed in Pd/YIG or Pt/YIG heterostructures. These results indicate that magnetoelectric GFO thin films show promises for achieving an electric-field control of the spin current generation in NM/FM oxide-based heterostructures.

The electric field control of $d$-electron magnetism in multiferroic transition metal oxides is attracting widespread interest for the underlying fundamental physics and for next generation spintronic devices. Here, we report an extensive study of the $3d$ magnetism in magnetoelectric ${\mathrm{Ga}}_{0.6}{\mathrm{Fe}}_{1.4}{\mathrm{O}}_{3}$ (GFO) epitaxial films by polarization-dependent x-ray absorption spectroscopy. We found a nonzero integral of the x-ray magnetic circular dichroism (XMCD), with the sign depending upon the relative orientation between the external magnetic field and the crystallographic axes. This finding translates into a sign reversal between the average Fe magnetic orbital and spin moments. Large Fe displacements, among inequivalent octahedral sites, lower the symmetry of the system producing anisotropic paths for the Fe-O bondings giving rise to a large orbital-lattice interaction akin to a preferential crystallographic direction for the uncompensated, or averaged among different sites, magnetic orbital moment. The latter may lead to a partial reorientation of the magnetic orbital moment under an external magnetic field that, combined with the ferrimagnetic nature of the GFO, can qualitatively explain the observed sign reversal of the XMCD integral. The results suggest that control over the local symmetry of the oxygen octahedra in transition metal oxides can offer a suitable leverage over the manipulation of the effective orbital and spin moments in magnetoelectric systems.

Thin deposits of aligned semiconducting titanium oxide and of zinc oxide nanowires are prepared by grazing incidence spraying on transparent substrates. By measuring the transmittance of linearly polarized light of these anisotropic assemblies as compared to that of randomly oriented nanowires and of spherical nanoparticles, we find that titanium oxide nanowires exhibit an orientation-dependent variation of the apparent optical band gap energy at room temperature (>100 meV), depending on the direction of the polarization of the light with respect to the direction of alignment of the nanowires.

Ti-modified LaFeO

Ti-modified LaFeO3/β-SiC alveolar foams were used as immobilized, highly robust dual catalysts with combined photocatalytic wet peroxide oxidation and photocatalytic activity under UV-A light. They were prepared by incipient wetness impregnation of a β-SiC foam support, by implementing a sol-gel Pechini synthesis at the foam surface in the presence of dried amorphous sol-gel titania as a titanium source. The physicochemical and catalytic features suggest the stabilization at the foam surface of a substituted La1-xTixFeO3 catalyst analogous to its powdery counterpart. Taking 4-chlorophenol removal in water as a model reaction, its dual nature enables both high reaction rates and full total organic carbon (TOC) conversion because of a synergy effect, while its macroscopic structure overcomes the drawback of working with powdery catalysts. Further, it yields photonic efficiencies for degradation and mineralization of ca. 9.4 and 38%, respectively, that strongly outperform those obtained with a reference TiO2 P25/β-SiC foam photocatalyst. The enhancement of the catalyst robustness upon Ti modification prevents any Fe leaching to the solution, and therefore, the optimized macroscopic foam catalyst with 10 wt % catalyst loading operates through pure heterogeneous surface reactions, without any activity loss during reusability test cycles.

International audience; The composition of metal oxide nanoparticles is of great importance for their applications because defects and/or deviation from stoechiometry strongly affect their physical properties. We report here on the crucial role of synthesis parameters such as solvent, ligand and iron precursors on the composition of spinel iron oxide nanoparticles synthesized by the thermal decomposition method. At first, the investigation of the thermal decomposition of iron stearates bearing either two or three stearate chains by thermogravimetric analysis, IR spectroscopy and Mössbauer spectrometry as a function of temperature and syntheses with only oleic acid and iron stearate confirmed that the composition of the first nuclei is wüstite Fe 1-x O. The synthesis of nanoparticles with high sizes requires the use of very high boiling point solvents to ensure an effective growth step. We observed that, when the grain growth and oxidation kinetics are similar, nanoparticles with a spinel composition and quite no defects are produced. An oxidation rate slower than the nuclei growth rate favours the formation of core-shell Fe 1-x O@Fe 3-x O 4 NPs. The oxidation kinetics is shown to be influenced by surfactant and solvent natures. Indeed, surfactants such as oleic acid form a dense monolayer at the nuclei surface which oxidation kinetics will depend on this monolayer permeability. Temperature, solvents with high surfactant affinity, deprotonated surfactants or decomposition products of solvents affect the monolayer stability and thus the nanoparticle composition. The solvents' nature and solvent mediated ligand-ligand interactions are thus evidenced to be important parameters to control the formation of defectsfree and stoechiometric oxide nanoparticles.

Assessing the role of lactogenic hormones in human mammary gland development is limited due to issues accessing tissue samples and so development of a human in vitro three-dimensional mammosphere model with functions similar to secretory alveoli in the mammary gland can aid to overcome this shortfall. In this study, a mammosphere model has been characterised using human mammary epithelial cells grown on either mouse extracellular matrix or agarose and showed insulin is essential for formation of mammospheres. Insulin was shown to up-regulate extracellular matrix genes. Microarray analysis of these mammospheres revealed an up-regulation of differentiation, cell-cell junctions, and cytoskeleton organisation functions, suggesting mammosphere formation may be regulated through ILK signalling. Comparison of insulin and IGF-1 effects on mammosphere signalling showed that although IGF-1 could induce spherical structures, the cells did not polarise correctly as shown by the absence of up-regulation of polarisation genes and did not induce the expression of milk protein genes. This study demonstrated a major role for insulin in mammary acinar development for secretory differentiation and function indicating the potential for reduced lactational efficiency in women with obesity and gestational diabetes.

International audience; A strategy combining both heterogenized photo-Fenton and photocatalysis advanced oxidation processes in a single dual catalyst is developed for simultaneously benefiting from the higher reaction rate of photo-Fenton and the higher mineralization yield of photocatalysis in water treatment, while overcoming the strong drawbacks still limiting their viability as single processes. We prepared via a facile Pechini sol-gel route a highly efficient and stable Ti-substituted LaFeO3 dual catalyst, active simultaneously as reusable photo-Fenton solid catalyst and photocatalyst in water treatment. The partial substitution of La by Ti ions in the crystalline network led to pure heterogeneous surface reactions with an increase in the catalyst robustness by more than two orders of magnitude, symbolized by the absence of any Fe release and the stability of catalytic performance with test cycles. It further strongly enhanced the reaction rates, due to both an increased availability of the photogenerated charge carriers at the surface and the electronic enrichment of surface Fe, and allowed full mineralization of the pollutant to be achieved at circumneutral pH through combined advanced oxidation processes.

International audience; Static and dynamic magnetic properties of Zn0.4Fe2.6O4 nanoparticles synthesized by thermal decomposition have been investigated. Two ranges of diameter have been used: small particles (diameter about 6.2 nm) and larger ones (diameter about 22.4 nm). The nanoparticle microstructure has been characterized by transmission electron microscopy. The temperature dependence of the zero-field dynamic permeability for both nanoparticle sizes has been studied, revealing a superparamagnetic state for the small ones. Effects of the nanoparticle size on the dynamic permeability have been studied, and linked to the superparamagnetic state. A dynamic susceptibility model has been found to reproduce the experimental behavior as well as its temperature dependence.

Recent advances in technology for both describing and interrogating the sequence and structure of animal genomes and their functional variation have presented opportunities for scientists to more clearly understand the complexity of bovine milk protein structure and utility and the control of milk protein gene expression. Using these technologies in conjunction with protein sequence data, we can begin to understand the significance of naturally occurring genetic variation influencing milk protein production and composition and how the proteins in colostrum and milk are processed/digested into biologically active peptides. The challenge is to translate this information into useful nutritional and nutraceutical products that help to underpin the commercial viability of the dairy industry. Recent advances in genetic technologies provide the potential for accurate selection of desirable traits in dairy cow populations through genomic methods. Milk composition may also be modified through gene editing, although consumer acceptance of genetically modified foods is still an issue. We present a review of the current status of bovine milk genomics, including functional genomics and gene editing approaches, and discuss the roles, characteristics, and key bioactivities of the major bovine milk proteins and their encrypted peptides.

Background After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray short-tailed opossum (Monodelphis domestica). Results Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis. Conclusion The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung. Electronic supplementary material The online version of this article (10.1186/s12864-018-5102-2) contains supplementary material, which is available to authorized users.

Physical Review Materials, 3 (12), ISSN:2475-9953

Background The unique lactation strategy of the tammar wallaby (Macropus eugeni) has been invaluable in evaluating the role of lactogenic hormones and the extracellular matrix (ECM) in the local control of mammary gland function. However molecular pathways through which hormones and ECM exert their effect on wallaby mammary gland function remain unclear. This study undertakes transcriptome analysis of wallaby mammary epithelial cells (WallMEC) following treatment with mammary ECM from two distinct stages of lactation. Methods WallMEC from MID lactation mammary glands were cultured on ECM from MID or LATE lactation and treated for 5 days with 1 μg/ml cortisol, 1 μg/ml insulin, 0.2 µg/ml prolactin, 650 pg/ml triodothyronine and 1 pg/ml estradiol to induce lactation. WallMEC RNA from triplicate ECM treatments was used to perform RNAseq. Results ECM from MID and LATE lactation differentially regulated key genes in sugar and lipid metabolism. Seven pathways including galactose metabolism, lysosome, cell adhesion molecules (CAM), p53 signaling, the complement and coagulation and Nod-like receptor signaling pathways were only significantly responsive to ECM in the presence of hormones. The raw RNA-seq data for this project are available on the NCBI Gene Expression Omnibus (GEO) browser (accession number GSE81210). Conclusions A potential role of ECM in regulation of the caloric content of milk, among other functions including apoptosis, cell proliferation and differentiation has been identified. General significance This study has used a non-eutherian lactation model to demonstrate the synergy between ECM and hormones in the local regulation of mammary function., Highlights • RNAseq was used to suggest novel roles of ECM in the control of mammary epithelial function. • ECM from MID and LATE lactation differentially regulated key genes in carbohydrate and lipid metabolism. • ECM-mediated changes in galactose metabolism, lysosome, cell adhesion molecules (CAM), p53 signaling, the complement and coagulation and Nod-like receptor signaling pathways were dependent on lactogenic hormones.

Endocrine regulation of milk protein gene expression in marsupials and eutherians is well studied. However, the evolution of this complex regulation that began with monotremes is unknown. Monotremes represent the oldest lineage of extant mammals and the endocrine regulation of lactation in these mammals has not been investigated. Here we characterised the proximal promoter and hormonal regulation of two platypus milk protein genes, Beta-lactoglobulin (BLG), a whey protein and monotreme lactation protein (MLP), a monotreme specific milk protein, using in vitro reporter assays and a bovine mammary epithelial cell line (BME-UV1). Insulin and dexamethasone alone provided partial induction of MLP, while the combination of insulin, dexamethasone and prolactin was required for maximal induction. Partial induction of BLG was achieved by insulin, dexamethasone and prolactin alone, with maximal induction using all three hormones. Platypus MLP and BLG core promoter regions comprised transcription factor binding sites (e.g. STAT5, NF-1 and C/EBPα) that were conserved in marsupial and eutherian lineages that regulate caseins and whey protein gene expression. Our analysis suggests that insulin, dexamethasone and/or prolactin alone can regulate the platypus MLP and BLG gene expression, unlike those of therian lineage. The induction of platypus milk protein genes by lactogenic hormones suggests they originated before the divergence of marsupial and eutherians.

International audience; A highly robust Ti-substituted LaFeO3 dual catalyst was synthesized via a facile Pechini sol-gel route using a dried amorphous sol-gel titania as titanium source and a final calcination at 800 °C that enabled solid-solid diffusion of titanium atoms within the perovskite network. Using an amorphous precursor instead of crystallized titania nanocrystals increased the Ti → La atomic substitution degree in the crystalline network from 5 at% to 11 at%, together with a strong increase in the catalytic activity. The partially substituted La1-xTixFeO3 catalyst with a 11 at% substitution degree allowed pure heterogeneous surface reactions to take place under pure visible light (λ > 420 nm), with an increase in the catalyst robustness by more than two orders of magnitude compared to the unmodified LaFeO3 counterpart, evidenced by the absence of any Fe release, the structural stability of the substituted catalyst and the absence of any loss of catalytic activity with test cycles. Further, the strategy of combining both photocatalysis and H2O2-mediated heterogeneous photo-Fenton advanced oxidation processes within one single heterogeneous catalyst allowed the dual La1-xTixFeO3 catalyst to simultaneously take advantage from the higher reaction rate of photo-Fenton and from the higher mineralization yield of photocatalysis in water treatment. As a result, the dual 11 at% Ti-substituted La1-xTixFeO3 catalyst clearly outperformed its unmodified LaFeO3 counterpart and led to a complete mineralization of the 4-chlorophenol substrate under pure visible light, with strongly enhanced H2O2 decomposition, 4-chlorophenol and TOC conversion rates. Finally, the activity of the La1-xTixFeO3 catalyst under visible light contributed significantly to its overall activity obtained using the full solar spectra.

New Ti-substituted LaFeO3 perovskites have been synthesized via a sol-gel method with partial substitution of La by Ti and used as catalyst in the photoassisted CWPO for the removal of 4-Cl-Phenol in water. The influence of the calcination temperature and the Ti at.% content was evaluated in terms of activity and stability. The Ti-substituted LaFeO3 catalyst calcined at 800 °C showed an activity optimum for a 3.2 at.% content of Ti in the presence of the stoichiometric dose of H2O2, with a higher mineralization rate and yield than its LaFeO3 counterpart, while achieving complete Cl-phenol removal and 100% mineralization at circumneutral pH, ambient pressure and temperature. The La partial substitution by Ti and the increase in the calcination temperature strongly improved the catalyst stability in terms of Fe leaching, and the Ti-substituted LaFeO3 catalyst calcined at 800 °C displayed stable performances over 5 cycles of reaction, with a limited Fe leaching lower than 0.1% of its total content. The catalyst was active simultaneously in both photoassisted CWPO and photocatalysis under UV-A light. Thus, the photoassisted CWPO with Ti-substituted LaFeO3 catalysts may overcome some drawbacks of single AOPs by combining higher rates at complete mineralization.

Significantly preterm and low-birthweight (LBW) babies have diminished lung and gut development, generally fail to thrive, have increased mortality and higher frequency of mature-onset disease. Mothers often cannot breastfeed, and babies receive either formula or pasteurized donor milk, which may further limit the baby's recovery. New approaches are required to manage the early stages of neonatal development. The tammar wallaby, an Australian marsupial, has a short gestation and a simple placenta, and gives birth to an altricial young equivalent to a final trimester human embryo. The neonate remains in the pouch and attached to the teat for 100 days postpartum. The mother slows growth of the young and progressively changes the composition of the milk to deliver signals for organ development, including the lung and gut. This closely resembles the relationship between the human fetus and delivery of placental and uterine bioactives. Datasets comprised of differentially expressed genes coding for secreted proteins in early lactation in the tammar mammary gland have been compared to databases produced from human placenta, amniotic fluid, colostrum and milk to identify human homologues for the putative signaling molecules for organ development. These data will be used to develop milk fortifiers for treatment of preterm and LBW babies in both the developed and the developing world.

Significantly preterm and low-birthweight (LBW) babies have diminished lung and gut development, generally fail to thrive, have increased mortality and higher frequency of mature-onset disease. Mothers often cannot breastfeed, and babies receive either formula or pasteurized donor milk, which may further limit the baby's recovery. New approaches are required to manage the early stages of neonatal development. The tammar wallaby, an Australian marsupial, has a short gestation and a simple placenta, and gives birth to an altricial young equivalent to a final trimester human embryo. The neonate remains in the pouch and attached to the teat for 100 days postpartum. The mother slows growth of the young and progressively changes the composition of the milk to deliver signals for organ development, including the lung and gut. This closely resembles the relationship between the human fetus and delivery of placental and uterine bioactives. Datasets comprised of differentially expressed genes coding for secreted proteins in early lactation in the tammar mammary gland have been compared to databases produced from human placenta, amniotic fluid, colostrum and milk to identify human homologues for the putative signaling molecules for organ development. These data will be used to develop milk fortifiers for treatment of preterm and LBW babies in both the developed and the developing world.

The molecular processes underlying human milk production and the effects of mastitic infection are largely unknown because of limitations in obtaining tissue samples. Determination of gene expression in normal lactating women would be a significant step toward understanding why some women display poor lactation outcomes. Here, we demonstrate the utility of RNA obtained directly from human milk cells to detect mammary epithelial cell (MEC)-specific gene expression. Milk cell RNA was collected from five time points (24 h prepartum during the colostrum period, midlactation, two involutions, and during a bout of mastitis) in addition to an involution series comprising three time points. Gene expression profiles were determined by use of human Affymetrix arrays. Milk cells collected during milk production showed that the most highly expressed genes were involved in milk synthesis (e.g., CEL, OLAH, FOLR1, BTN1A1, and ARG2), while milk cells collected during involution showed a significant downregulation of milk synthesis genes and activation of involution associated genes (e.g., STAT3, NF-kB, IRF5, and IRF7). Milk cells collected during mastitic infection revealed regulation of a unique set of genes specific to this disease state, while maintaining regulation of milk synthesis genes. Use of conventional epithelial cell markers was used to determine the population of MECs within each sample. This paper is the first to describe the milk cell transcriptome across the human lactation cycle and during mastitic infection, providing valuable insight into gene expression of the human mammary gland.

Iron oxide nanoparticles are widely used as a contrast agent in magnetic resonance imaging (MRI), and may be used as therapeutic agent for magnetic hyperthermia if they display in particular high magnetic anisotropy. Considering the effect of nanoparticles shape on anisotropy, a reproducible shape control of nanoparticles is a current synthesis challenge. By investigating reaction parameters, such as the iron precursor structure, its water content, but also the amount of the surfactant (sodium oleate) reported to control the shape, iron oxide nanoparticles with different shape and composition were obtained, in particular, iron oxide nanoplates. The effect of the surfactant coming from precursor was taking into account by using in house iron stearates bearing either two or three stearate chains and the negative effect of water on shape was confirmed by considering these precursors after their dehydration. Iron stearates with three chains in presence of a ratio sodium oleate/oleic acid 1:1 led mainly to nanocubes presenting a core-shell Fe1&minus, xO@Fe3&minus, xO4 composition. Nanocubes with straight faces were only obtained with dehydrated precursors. Meanwhile, iron stearates with two chains led preferentially to the formation of nanoplates with a ratio sodium oleate/oleic acid 4:1. The rarely reported flat shape of the plates was confirmed with 3D transmission electronic microscopy (TEM) tomography. The investigation of the synthesis mechanisms confirmed the major role of chelating ligand and of the heating rate to drive the cubic shape of nanoparticles and showed that the nanoplate formation would depend mainly on the nucleation step and possibly on the presence of a given ratio of oleic acid and chelating ligand (oleate and/or stearate).

International audience

Extracellular matrix (ECM) plays an important role in the normal physiology of tissues and progression to disease. Earlier studies and our external microarray data analysis indicated that mammary matrix from involuting tissue showed upregulation of genes involved in ECM remodeling. The present study examines the fate of mammary and oral cancer cells grown in the ECM from lactating mammary gland. Our findings show that non-tumorigenic cells, MCF10A and DOK cells did not proliferate but the tumorigenic and metastatic cells, SCC25 and MDA-MB-231, underwent apoptosis when grown on mammary ECM isolated from lactating mice. In addition, the cytokinesis marker, CEP55, was repressed in the oral and breast cancer cells. In contrast, these cells proliferated normally on mammary ECM isolated from mice undergoing involution. External microarray data analysis of mammary tissue further revealed over expression (~16 fold) of QSOX1 gene, which promotes cellular quiescence, in lactating mammary gland. A recent study has indicated that QSOX1 overexpression in breast cancer cells led to reduced proliferation and tumorigenic properties. This extracellular protein in mammary ECM may be responsible for reduced cellular proliferation. The present study has shown that ECM from lactating mammary gland can regulate signals to oral and breast cancer cells to halt cell division. This preliminary observation provided insights into the potential role of ECM factors present in lactating mammary gland as therapeutic targets to control cancer cell division. This preliminary study is an attempt to understand not only the requirement of ECM remodeling factors essential for the growth and survival of cancer cells but also the factors present in the lactation matrix that simultaneously halts cell division and selectively inhibits the growth of cancer cells.

MicroRNA have been recently discovered in human milk signifying potentially important functions for both the lactating breast and the infant. Whilst human milk microRNA have started to be explored, little data exist on the evaluation of sample processing, and analysis to ensure that a full spectrum of microRNA can be obtained. Human milk comprises three main fractions: cells, skim milk, and lipids. Typically, the skim milk fraction has been measured in isolation despite evidence that the lipid fraction may contain more microRNA. This study aimed to standardize isolation of microRNA and total RNA from all three fractions of human milk to determine the most appropriate sampling and analysis procedure for future studies. Three different methods from eight commercially available kits were tested for their efficacy in extracting total RNA and microRNA from the lipid, skim, and cell fractions of human milk. Each fraction yielded different concentrations of RNA and microRNA, with the highest quantities found in the cell and lipid fractions, and the lowest in skim milk. The column‐based phenol‐free method was the most efficient extraction method for all three milk fractions. Two microRNAs were expressed and validated in the three milk fractions by qPCR using the three recommended extraction kits for each fraction. High expression levels were identified in the skim and lipid milk factions for these microRNAs. These results suggest that careful consideration of both the human milk sample preparation and extraction protocols should be made prior to embarking upon research in this area. J. Cell. Biochem. 116: 2397–2407, 2015. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

Cloud and service computing has started to change the way research in science, in particular biology and medicine, is being carried out. Researchers that have taken advantage of this technology (making use of public and private cloud compute resources) can process large amounts of data (big data) and speed up discovery. However, this requires researchers to acquire a solid knowledge and skills in the development of sequential and high performance computing (HPC), and cloud development and deployment background. In response a technology exposing HPC applications as services through the development and deployment of a SaaS cloud, and its proof of concept in the form of implementation of a cloud environment, Uncinus, has been developed and implemented to allow researchers easy access to cloud computing resources. The new technology offers and Uncinus supports the development of applications as services and the sharing of compute resources to speed up applications' execution. Users access these cloud resources and services through web interfaces. Using the Uncinus platform, a bio-informatics workflow was executed on a private (HPC) cloud, server and public cloud (Amazon EC2) resources, performance results showing a 3 fold improvement compared to local resources' performance. Biology and medicine specialists with no programming and application deployment on clouds background could run the case study applications with ease. A framework for the deployment of SaaS clouds aimed at supporting scientific research.A novel resource selection approach which can automate complex deployment methodologies such as cloud bursting.Simplified deployment of Software as a Services through the publication of attributes.The automated development of hybrid HPC clouds.Framework and cloud feasibility and performance proofs demonstrated through a bio-informatics workflow.

With the aim of producing Au–FexOy dimers with outstanding heating performances under magnetic hyperthermia conditions applicable to human patients, here we report two synthesis routes, a two-pot and a one-pot method. The addition of chloride ions and the absence of 1,2-hexadecanediol (HDDOL), a commonly used chemical in this synthesis, are the key factors that enable us to produce dimers at low temperature with crystalline iron oxide domains in the size range between 18–39 nm that is ideal for magnetic hyperthermia. In the case of two-pot synthesis, in which no chloride ions are initially present in the reaction pot, dimers are obtained only at 300 1C. In order to lower the reaction temperature to 200 1C and to tune the size of the iron oxide domain, the addition of chloride ions becomes the crucial parameter. In the one-pot method, the presence of chloride ions from the start of the synthesis (as counter ions of the gold salt precursor) enables a prompt formation of dimers directly at 200 1C. In this case, the reaction time is the main parameter used to tune the iron oxide size. A record value of specific absorption rates (SARs) up to 1300 W gFe1 at 330 kHz and 24 kA m1 was measured for dimers with an iron oxide domain of 24 nm in size.

Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female’s abdomen. Milk is the sole source of nutrition and immune protection for the developing young until weaning. Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples.

The current challenge in the field of nano-medicine is the design of multifunctional nano-objects effective both for the diagnosis and treatment of diseases. Here, dendronized FeO1-x@Fe3-xO4 nanoparticles with spherical, cubic, and octopode shapes and oxidized Fe3-xO4 nanocubes have been synthesized and structurally and magnetically characterized. Strong exchange bias properties are highlighted in core shell nanoparticles (NPs) due to magnetic interactions between their antiferromagnetic core and ferrimagnetic shell. Both in vitro relaxivity measurements and nuclear magnetic resonance (NMR) distribution profiles have confirmed the very good in vitro magnetic resonance imaging (Mm) properties of core shell and cubic shape NPs, especially at low concentration. This might be related to the supplementary anisotropy introduced by the exchange bias properties and the cubic shape. The high heating values of core shell NPs and oxidized nanocubes at low concentration are attributed to dipolar interactions inducing different clustering states, as a function of concentration. In vivo MRI studies have also evidenced a clustering effect at the injection point, depending on the concentration, and confirmed the very good in vivo MRI properties of core shell NPs and oxidized nanocubes in particular at low concentration. These results show that these core shell and cubic shape dendronized nano-objects are very suitable to combine MRI and hyperthermia properties at low injected doses.

Contains fulltext : 137671.pdf (Publisher’s version ) (Open Access) The {VESSEL12} ({VES}sel {SE}mentation in the {L}ung) challenge objectively compares the performance of different algorithms to identify vessels in thoracic computed tomography ({CT}) scans. Vessel segmentation is fundamental in computer aided processing of data generated by 3D imaging modalities. As manual vessel segmentation is prohibitively time consuming, any real world application requires some form of automation. Several approaches exist for automated vessel segmentation, but judging their relative merits is difficult due to a lack of standardized evaluation. We present an annotated reference dataset containing 20 {CT} scans and propose nine categories to perform a comprehensive evaluation of vessel segmentation algorithms from both academia and industry. Twenty algorithms participated in the {VESSEL12} challenge, held at International Symposium on Biomedical Imaging ({ISBI}) 2012. All results have been published at the {VESSEL12} website http://{VESSEL12}.grand-challenge.org. The challenge remains ongoing and open to new participants. Our three contributions are: (1) an annotated reference dataset available online for evaluation of new algorithms; (2) a quantitative scoring system for objective comparison of algorithms; and (3) performance analysis of the strengths and weaknesses of the various vessel segmentation methods in the presence of various lung diseases.

α-lactalbumin is a protein of dual function found in milk of most mammals. α-lactalbumin binds β-1,4-galactosyltransferase to form the regulatory subunit for lactose synthesis and has also been shown to cause cell death. This study shows, for the first time, that α-lactalbumin isolated in a rare 28kDa dimeric form induces cell death, while 14kDa monomeric α-lactalbumin is inactive. In contrast to the casein derived and chemically induced α-lactalbumin variants, MAL and HAMLET/BAMLET, the effects of 28kDa α-lactalbumin are calcium independent and, unlike MAL and HAMLET, 28kDa α-lactalbumin dimer causes cell death of primary mammary cells and a variety of immortalised cell lines, which are committed to cell death pathways within 1-4h of exposure. Microarray analysis confirmed that cell death was the result of an apoptotic response. Functional assays determined that the mechanism by which 28kDa α-lactalbumin kills cells involved inhibition of histone deacetylase activity mediated by NF-kB. We also show that 28kDa α-lactalbumin occurs naturally in the milk of cows, goats and sheep, is low in concentration during mid-lactation, but accumulates during milk stasis, consistent with a role in involution.

Milk is a complex secretion that has an important role in mammalian reproduction. It is only recently that sequencing technologies have allowed the identification and quantification of microRNA (miRNA) in milk of a growing number of mammalian species. This provides a novel window on the study of the evolution and functionality of milk through the comparative analysis of milk miRNA content. Here, milk miRNA sequencing data from five species (one marsupial (tammar wallaby) and four eutherians (human, mouse, cow and pig)) have been retrieved from public depositories and integrated in order to perform a comparison of milk miRNA profiles. The study shows that milk miRNA composition varies widely between species, except for a few miRNAs that are ubiquitously expressed in the milk of all mammals and indicates that milk miRNA secretion has broadly evolved during mammalian evolution. The putative functions of the most abundant milk miRNAs are also discussed.

A method has been developed for predicting blood proteins using the SVM based machine learning approach. In this prediction method a two-step strategy was deployed to predict blood proteins and their subclasses. We have developed models of blood proteins and achieved the maximum accuracies of 90.57% and 91.39% with Matthews correlation coefficient (MCC) of 0.89 and 0.90 using single amino acid and dipeptide composition respectively. Furthermore, the method is able to predict major subclasses of blood proteins; developed based on amino acid (AC) and dipeptide composition (DC) with a maximum accuracy 90.38%, 92.83%, 87.41%, 92.52% and 85.27%, 89.07%, 94.82%, 86.31 for albumin, globulin, fibrinogen, and regulatory proteins respectively. All modules were trained, tested, and evaluated using the five-fold cross-validation technique.

S100 proteins are calcium-binding proteins involved in controlling diverse intracellular and extracellular processes such as cell growth, differentiation, and antimicrobial function. We recently identified a S100-like cDNA from the tammar wallaby (Macropus eugenii) stomach. Phylogentic analysis shows wallaby S100A19 forms a new clade with other marsupial and monotreme S100A19, while this group shows similarity to eutherian S100A7 and S100A15 genes. This is also supported by amino acid and domain comparisons. We show S100A19 is developmentally-regulated in the tammar wallaby gut by demonstrating the gene is expressed in the forestomach of young animals at a time when the diet consists of only milk, but is absent in older animals when the diet is supplemented with herbage. During this transition the forestomach phenotype changes from a gastric stomach into a fermentation sac and intestinal flora changes with diet. We also show that S100A19 is expressed in the mammary gland of the tammar wallaby only during specific stages of lactation; the gene is up-regulated during pregnancy and involution and not expressed during the milk production phase of lactation. Comparison of the tammar wallaby S100A19 protein sequence with S100 protein sequences from eutherian, monotreme and other marsupial species suggest the marsupial S100A19 has two functional EF hand domains, and an extended His tail. An evolutionary analysis of S100 family proteins was carried out to gain a better understanding of the relationship between the S100 family member functions. We propose that S100A19 gene/protein is the ancestor of the eutherian S100A7 gene/protein, which has subsequently modified its original function in eutherians. This modified function may have arisen due to differentiation of evolutionary pressures placed on gut and mammary gland developmental during mammal evolution. The highly regulated differential expression patterns of S100A19 in the tammar wallaby suggests that S100A19 may play a role in gut development, which differs between metatherians and eutherians, and/or include a potential antibacterial role in order to establish the correct flora and protect against spiral bacteria in the immature forestomach. In the mammary gland it may protect the tissue from infection at times of vulnerability during the lactation cycle.

Asynchronous concurrent lactation (ACL) is an extreme lactation strategy in macropod marsupials including the tammar wallaby, that may hold the key to understanding local control of mammary epithelial cell function. Marsupials have a short gestation and a long lactation consisting of three phases; P2A, P2B and P3, representing early, mid and late lactation respectively and characterised by profound changes in milk composition. A lactating tammar is able to concurrently produce phase 2A and 3 milk from adjacent glands in order to feed a young newborn and an older sibling at heel. Physiological effectors of ACL remain unknown and in this study the extracellular matrix (ECM) is investigated for its role in switching mammary phenotypes between phases of tammar wallaby lactation. Using the level of expression of the genes for the phase specific markers tELP, tWAP, and tLLP-B representing phases 2A, 2B and 3 respectively we show for the first time that tammar wallaby mammary epithelial cells (WallMECs) extracted from P2B acquire P3 phenotype when cultured on P3 ECM. Similarly P2A cells acquire P2B phenotype when cultured on P2B ECM. We further demonstrate that changes in phase phenotype correlate with phase-specific changes in ECM composition. This study shows that progressive changes in ECM composition in individual mammary glands provide a local regulatory mechanism for milk protein gene expression thereby enabling the mammary glands to lactate independently.

The influence of the iron content on the magnetic, polar, and magnetoelectric properties of Ga2-xFexO3 (x = 1.0; x = 1.4) polycrystalline samples was studied by a combined magnetic (SQUID) and structural (X-ray and temperature-dependent neutrons diffraction) study. As expected, the samples showed a ferrimagnetic structure, with moments aligned along the c axis. The Neel temperature increases with x, from 210 K for GaFeO3 to 360 K for Ga0.6Fe1.4O3. The magnetic moment is close to 3.8 mu B per iron atom for all compositions. The structural investigations show a decrease in the distortion parameters with increasing iron content, and computation of the polarization with a point-charge model gives a similar significant and temperature-independent value of approximate to 20 mu C/cm(2) for both compositions. This study clearly indicates that magnetic properties can be strongly enhanced by increasing the Fe content in the cell, while the non-negligible polarization value is preserved. Because the magnetoelectric coupling is also predicted to be preserved when increasing the iron content to x = 1.4, this composition is the most appropriate for applications.

The physicochemical and rheological properties of yoghurt made from unstandardised unhomogenised buffalo milk were investigated during fermentation and 28 days of storage and compared to the properties of yoghurt made from homogenised fortified bovine milk. A number of differences observed in the gel network can be linked to differences in milk composition. The microstructure of buffalo yoghurt, as assessed by confocal laser scanning microscopy (CLSM) and cryo scanning electron microscopy (cryo-SEM), was interrupted by large fat globules and featured more serum pores. These fat globules have a lower surface area and bind less protein than the homogenised fat globules in bovine milk. These microstructural differences likely lead to the higher syneresis observed for buffalo yoghurt with an increase from 17.4 % (w/w) to 19.7 % (w/w) in the weight of whey generated at days 1 and 28 of the storage. The higher concentration of total calcium in buffalo milk resulted in the release of more ionic calcium during fermentation. Gelation was also slower but the strength of the two gels was similar due to similar protein and total solids concentrations. Buffalo yoghurt was more viscous, less able to recover from deformation and less Newtonian than bovine yoghurt with a thixotropy of 3,035 Pa.s−1 measured for buffalo yoghurt at the end of the storage, at least four times higher than the thixotropy of bovine yoghurt. While the titratable acidity, lactose consumption and changes in organic acid concentrations were similar, differences were recorded in the viability of probiotic bacteria with a lower viability of Lactobacillus acidophilus of 5.17 log (CFU/g) recorded for buffalo yoghurt at day 28 of the storage. Our results show that factors other than the total solids content and protein concentration of milk affect the structural properties of yoghurt. They also illustrate the physicochemical reasons why buffalo and bovine yoghurt are reported to have different sensory properties and provide insight into how compositional changes can be used to alter the microstructure and properties of dairy products.

MicroRNAs (miRNAs) are small non-coding RNAs that play a role in post-transcriptional regulation of gene expression in most eukaryotes. They help in fine-tuning gene expression by targeting messenger RNAs (mRNA). The interactions of miRNAs and mRNAs are sequence specific and computational tools have been developed to predict miRNA target sites on mRNAs, but miRNA research has been mainly focused on target sites within 3′ untranslated regions (UTRs) of genes. There is a need for an easily accessible repository of genome wide full length mRNA — miRNA target predictions with versatile search capabilities and visualization tools. We have created a web accessible database of miRNA target predictions for human, mouse, cow, chicken, Zebra fish, fruit fly and Caenorhabditis elegans using two different target prediction algorithms, The database has target predictions for miRNA's on 5′ UTRs, coding region and 3′ UTRs of all mRNAs. This database can be freely accessed at http://mamsap.it.deakin.edu.au/mirna_targets/.