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The cationic distribution is decisive for both the magnetic and electric properties of complex oxides. While it can be easily determined in bulk materials using classical methods such as X-ray or neutron diffraction, difficulties arise for thin films owing to the relatively small amount of material to probe. It is shown here that a full determination of the cationic site distribution in thin films is possible through an optimized processing of resonant elastic X-ray scattering experiments. The method is illustrated using gallium ferrite Ga2−xFexO3samples which have been the focus of an increasing number of studies this past decade. They indeed represent an alternative to the, to date, only room-temperature magnetoelectric compound BiFeO3. The methodology can be applied to determine the element distribution over the various crystallographic sites in any crystallized system.

Our research is exploiting the marsupial as a model to understand the signals required for lung development. Marsupials have a unique reproductive strategy, the mother gives birth to altricial neonate with an immature lung and the changes in milk composition during lactation in marsupials appears to provide bioactives that can regulate diverse aspects of lung development, including branching morphogenesis, cell proliferation and cell differentiation. These effects are seen with milk collected between 25 and 100 days postpartum. To better understand the temporal effects of milk composition on postnatal lung development we used a cross-fostering technique to restrict the tammar pouch young to milk composition not extending beyond day 25 for 45 days of its early postnatal life. These particular time points were selected as our previous study showed that milk protein collected prior to ~ day 25 had no developmental effect on mouse embryonic lungs in culture. The comparative analysis of the foster group and control young at day 45 postpartum demonstrated that foster pouch young had significantly reduced lung size. The lungs in fostered young were comprised of large intermediate tissue, had a reduced size of airway lumen and a higher percentage of parenchymal tissue. In addition, expression of marker genes for lung development (BMP4, WNT11, AQP-4, HOPX and SPB) were significantly reduced in lungs from fostered young. Further, to identify the potential bioactive expressed by mammary gland that may have developmental effect on pouch young lungs, we performed proteomics analysis on tammar milk through mass-spectrometry and listed the potential bioactives (PDGF, IGFBP5, IGFBPL1 and EGFL6) secreted in milk that may be involved in regulating pouch young lung development. The data suggest that postnatal lung development in the tammar young is most likely regulated by maternal signalling factors supplied through milk., Highlights • The temporal effects of milk composition on lung development is well demonstrated. • Fostered PY lungs were delayed in development due to change in milk composition. • Tammar milk secretes bioactives involved in lung development.

International audience; Patient-specific simulation of air flows in lungs is now straightforward using segmented airways trees from CT scans as the basis for Computational Fluid Dynamics (CFD) simulations. These models generally use static geometries, which do not account for the motion of the lungs and its influence on important clinical indicators, such as airway resistance. This paper is concerned with the simulation of tidal breathing, including the dynamic motion of the lungs, and the required analysis workflow. Geometries are based on CT scans obtained at the extremes of the breathing cycle, Total Lung Capacity (TLC) and Functional Residual Capacity (FRC). It describes how topologically consistent geometries are obtained at TLC and FRC, using a ‘skeleton’ of the network of airway branches. From this a 3D computational mesh which morphs between TLC and FRC is generated. CFD results for a number of patient-specific cases, healthy and asthmatic, are presented. Finally their potential use in evaluation of the progress of the disease is discussed, focusing on an important clinical indicator, the airway resistance.

It is now clear that milk has multiple functions; it provides the most appropriate nutrition for growth of the newborn, it delivers a range of bioactives with the potential to stimulate development of the young, it has the capacity to remodel the mammary gland (stimulate growth or signal cell death) and finally milk can provide protection from infection and inflammation when the mammary gland is susceptible to these challenges. There is increasing evidence to support studies using an Australian marsupial, the tammar wallaby (Macropus eugenii), as an interesting and unique model to study milk bioactives. Reproduction in the tammar wallaby is characterized by a short gestation, birth of immature young and a long lactation. All the major milk constituents change substantially and progressively during lactation and these changes have been shown to regulate growth and development of the tammar pouch young and to have roles in mammary gland biology. This review will focus on recent reports examining the control of lactation in the tammar wallaby and the timed delivery of milk bioactivity.

The recent upsurge in microbial genome data has revealed that hemoglobin-like (HbL) proteins may be widely distributed among bacteria and that some organisms may carry more than one HbL encoding gene. However, the discovery of HbL proteins has been limited to a small number of bacteria only. This study describes the prediction of HbL proteins and their domain classification using a machine learning approach. Support vector machine (SVM) models were developed for predicting HbL proteins based upon amino acid composition (AC), dipeptide composition (DC), hybrid method (AC + DC), and position specific scoring matrix (PSSM). In addition, we introduce for the first time a new prediction method based on max to min amino acid residue (MM) profiles. The average accuracy, standard deviation (SD), false positive rate (FPR), confusion matrix, and receiver operating characteristic (ROC) were analyzed. We also compared the performance of our proposed models in homology detection databases. The performance of the different approaches was estimated using fivefold cross-validation techniques. Prediction accuracy was further investigated through confusion matrix and ROC curve analysis. All experimental results indicate that the proposed BacHbpred can be a perspective predictor for determination of HbL related proteins. BacHbpred, a web tool, has been developed for HbL prediction.

International audience; Ni-Doped thin films of the room temperature ferrimagnetic oxide Ga0.6Fe1.4O3 were deposited by pulsed laser deposition and their electronic transport and structural and magnetic properties were studied. The actual insertion of the Ni cations within the Ga0.6Fe1.4O3 structure has been checked by resonant X-ray scattering. A clear extremum is noticed for all properties for the 2% Ni doping: extrema in the crystallographic cell parameters of the films, maximum in the Curie temperature, and maximum in the electric resistivity. We also observed a change of conductivity type for this dopant concentration, from n-type for Ni contents below 2% to p-type for Ni contents above 2%. We explain this behavior by the existence of oxygen vacancies in the pulsed laser deposited Ga0.6Fe1.4O3 thin films, which results in the reduction of some of the Fe3+ into Fe2+ cations, and n-type conduction via a hopping mechanism. The insertion of Ni2+ cations first deals with the presence of oxygen vacancies and reduces the number of n-type carriers in the films, in a compensation-like mechanism. When the number of introduced Ni2+ cations dominates the number of oxygen vacancies, conductivity becomes p-type and starts to increase again. We believe that the tunability of the conduction type and magnitude in thin films of a room temperature ferrimagnetic material paves the way towards new all oxide electronic devices.

The effect of the Fe-Ga ratio on the magnetic and electric properties of the multiferroic Ga2-xFexO3 compound has been studied in order to determine the composition range exhibiting magnetic and electric orders coexistence and their critical temperatures. A magnetoelectric phase diagram, showing the evolution of both the Neel magnetic ordering temperature and the electric ordering temperature, versus the iron content has been established for x values between 0.9 and 1.4. While the ferrimagnetic Neel temperature increases with the iron content, the electric ordering temperature shows an opposite trend. The electric polarization has been found to exist far above room temperature for the x value of 1.1 composition which shows the highest observed electric ordering temperature of approx. 580K. The compounds with x values of 1.3 and 1.4 are ferrimagnetic-electric relaxors with both properties coexisting at room temperature., Comment: Multiferroic GaFeO3

Lactation is a defining feature of mammals. The production of milk by the mammary gland during lactation is generally regarded as a mechanism required to supply nutrition to the neonate before it is able to digest other types of food. Increasing evidence suggests that components of milk have additional functions in addition to nutrition. Monotremes, marsupials and eutherians are all members of the class mammalia, but monotremes and marsupials have evolved a lactation pattern that is very different from eutherians. In eutherians, the gestation period is long relative to its lactation period. However, in marsupials and monotremes the gestation period is relatively short. As a result, the newborn is relatively small and undeveloped and most of the early development occurs postnatally. Eutherians produce milk of a constant composition after the expression of the initial colostrum, whereas marsupials such as the tammar wallaby ( Macropus eugenii ), have a short gestation, and give birth to a highly immature young and then commence a long lactation during which the milk production and composition progressively change in composition to suit the needs of the developing young. The comparative study of monotreme, marsupial and eutherian milk is of significant interest and may reveal bioactives required for developmental processes. These factors may have been either lost, down-regulated or altered/modified in eutherians since most development of eutherian young occurs in utero with nutrition and developmental signaling provided by the amniotic fluid and supplemented from the mother via the placenta.

Scandium rich cobalt ferrites Co y Fe 3− x − y Sc x O 4 with y ~1 never obtained in bulk could be stabilized in pulsed laser deposited thin films. Scandium contents of up to x =1 are reached. The cell parameter increases versus x as awaited when considering the size of scandium. It is equal to 0.8620 nm for x =1, significantly higher than that of CoFe 2 O 4 (0.8396 nm). The lattice mismatch between the MgO (100) substrate and the scandium-containing spinel leads to an increased roughness. Cobalt is displaced from the octahedral site by Sc and mainly occupies the tetrahedral sites for high x values.

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/.

The role of milk extends beyond simply providing nutrition to the suckled young. Milk has a comprehensive role in programming and regulating growth and development of the suckled young, and provides a number of potential autocrine factors so that the mammary gland functions appropriately during the lactation cycle. This central role of milk is best studied in animal models such as marsupials that have evolved a different lactation strategy to eutherians and allow researchers to more easily identify regulatory mechanisms that are not as readily apparent in eutherian species. For example, the tammar wallaby (Macropus eugenii) has evolved with a unique reproductive strategy of a short gestation, birth of an altricial young and a relatively long lactation during which the mother progressively changes the composition of the major, and many of the minor components of milk. Consequently, in contrast to eutherians, there is a far greater investment in development of the young during lactation and it is likely that many of the signals that regulate development of eutherian embryos in utero are delivered by the milk. This requires the co-ordinated development and function of the mammary gland since inappropriate timing of these signalling events may result in either limited or abnormal development of the young, and potentially a higher incidence of mature onset disease. Milk proteins play a significant role in these processes by providing timely presentation of signalling molecules and antibacterial protection for the young and the mammary gland at times when there is increased susceptibility to infection. This review describes studies exploiting the unique reproductive strategy of the tammar wallaby to investigate the role of several proteins secreted at specific times during the lactation cycle and that are correlated with potential roles in the young and mammary gland. Interestingly, alternative splicing of some milk protein genes has been utilised by the mammary gland to deliver domain-specific functions at specific times during lactation.

Microarrays and more recently RNA sequencing has led to an increase in available gene expression data. How to manage and store this data is becoming a key issue. In response we have developed EXP-PAC, a web based software package for storage, management and analysis of gene expression and sequence data. Unique to this package is SQL based querying of gene expression data sets, distributed normalization of raw gene expression data and analysis of gene expression data across experiments and species. This package has been populated with lactation data in the international milk genomic consortium web portal (http://milkgenomics.org/). Source code is also available which can be hosted on a Windows, Linux or Mac APACHE server connected to a private or public network (http://mamsap.it.deakin.edu.au/~pcc/Release/EXP_PAC.html)

Marsupials provide a suitable alternative model to studying mammary gland involution. They have evolved a different reproductive strategy from eutherians, giving birth to an altricial young and secreting milk that changes in composition during lactation. In this study, we used a marsupial-specific EST microarray to identify 47 up-regulated genes during mammary gland involution in the tammar wallaby (Macropus eugenii). These include the pro-apoptotic tumour necrosis factor receptor superfamily 21 (TNFRSF21) gene, whose expression in the mammary gland has not previously been reported. Genes encoding putative novel milk proteins which may protect the mammary gland from infection were also found to be up-regulated, such as amiloride binding protein 1 (ABP1), complement component 1QB (C1QB), complement component 4A (C4A) and colony stimulating factor 2 receptor β (CSF2Rβ). Our results show that the marsupial reproductive strategy was successfully exploited to identify genes and putative novel milk proteins implicated in mammary gland involution.

Most studies on the synthesis of nanoparticles are currently focused on the controlled synthesis of new morphologies, including core-shell structures, which are expected to exhibit new magnetic properties for uses in spintronics and recording media applications. In this study, the structure, morphology, and composition of cubic-shaped nanoparticles are carefully investigated and compared to those of spherically shaped nanoparticles through the use of a combination of techniques: X-ray diffraction (XRD) and transmission electronic microscopy (TEM) combined with more sensitive techniques such as scanning transmission electron microscopy-high-angle annular dark field (STEM-HAADF) imaging, electron tomography, and holography. While spherically shaped nanoparticles (NPs) crystallize with the spinel structure, cubic-shaped NPs can be described as a cubic core of w€ustite surrounded by a spinel shell. Stresses are observed at the core-shell interface and within the spinel shell due to the epitaxial growth and oxidation mechanisms of the wüstite phase. Furthermore, magnetic measurements displayed an exchange bias coupling between the antiferromagnetic (AFM) core and the ferrimagnetic (FIM) shell structure of cubic-shaped nanoparticles. It is shown that the magnetic properties are influenced by stresses generated by the oxidation of w€ustite and, also exhibit variations depending upon the evolution of this core-shell structure as a function of the oxidation time.

Changes in gene expression have been measured 24h after injury to mammalian spinal cords that can and cannot regenerate. In opossums there is a critical period of development when regeneration stops being possible: at 9 days postnatal cervical spinal cords regenerate, at 12 days they do not. By the use of marsupial cDNA microarrays, we detected 158 genes that respond differentially to injury at the two ages critical for regeneration. For selected candidates additional measurements were made by real-time PCR and sites of their expression were shown by immunostaining. Candidate genes have been classified so as to select those that promote or prevent regeneration. Up-regulated by injury at 8 days and/or down-regulated by injury at 13 days were genes known to promote growth, such as Mitogen-activated protein kinase kinase 1 or transcription factor TCF7L2. By contrast, at 13 days, up-regulation occurred of inhibitory molecules, including annexins, ephrins, and genes related to apoptosis and neurodegenerative diseases. Certain genes such as calmodulin 1 and NOGO, changed expression similarly in animals that could and could not regenerate without any additional changes in response to injury. These findings confirmed and extended changes of gene expression found in earlier screens on 9 and 12 ay preparations without lesions and provide a comprehensive list of genes that serve as a basis for testing how identified molecules, singly or in combination, promote and prevent central nervous system regeneration.

Substitution of Fe for Sc in CoFe2O4 spinel structure is presented. All CoFe2−xScxO4 compounds crystallize in the spinel type structure (space group Fd3m). By using X-ray diffraction studies, magnetic measurements and in-field 57Fe Mossbauer spectrometry, the limit of substitution has been determined to be equal to x=0.56. An increase in the cell parameter and the strains and a decrease in the apparent crystallites size are observed. For x>0.3, a partial oxidation of cobalt is evidenced and Co3+ is stabilized in the structure. A ferromagnetic behavior has been observed for all investigated compounds. As x increases, the Curie temperature and the hyperfine fields decrease. Following the Stephenson model, the diminution of TC is ascribed to a decrease of the main JAB interaction.

The contribution of cows&rsquo, milk containing beta-casein protein A1 variant to the development of type 1 diabetes (T1D) has been controversial for decades. Despite epidemiological data demonstrating a relationship between A1 beta-casein consumption and T1D incidence, direct evidence is limited. We demonstrate that early life exposure to A1 beta-casein through the diet can modify progression to diabetes in non-obese diabetic (NOD) mice, with the effect apparent in later generations. Adult NOD mice from the F0 generation and all subsequent generations (F1 to F4) were fed either A1 or A2 beta-casein supplemented diets. Diabetes incidence in F0&ndash, F2 generations was similar in both cohorts of mice. However, diabetes incidence doubled in the F3 generation NOD mice fed an A1 beta-casein supplemented diet. In F4 NOD mice, subclinical insulitis and altered glucose handling was evident as early as 10 weeks of age in A1 fed mice only. A significant decrease in the proportion of non-conventional regulatory T cell subset defined as CD4+CD25&minus, FoxP3+ was evident in the F4 generation of A1 fed mice. This feeding intervention study demonstrates that dietary A1 beta-casein may affect glucose homeostasis and T1D progression, although this effect takes generations to manifest.

Lactation, an important characteristic of mammalian reproduction, has evolved by exploiting a diversity of strategies across mammals. Comparative genomics and transcriptomics experiments have now allowed a more in-depth analysis of the molecular evolution of lactation. Milk cell and mammary gland genomic studies have started to reveal conserved milk proteins and other components of the lactation system of monotreme, marsupial, and eutherian lineages. These analyses confirm the ancient origin of the lactation system and provide useful insight into the function of specific milk proteins in the control of lactation. These studies also illuminate the role of milk in the regulation of growth and development of the young beyond simple nutritive aspects.

Local probe techniques, 57Fe in-field Mossbauer, and 57Fe NMR spectrometries have been combined to describe the magnetic structure of maghemite nanoparticles of 39 (±5) nm in size and commercial maghemite. Maghemite nanoparticles were obtained from oxidation of magnetite nanoparticles. Commercial maghemite consists of nanostructured rods, and the size of crystalline domain fairly compares to that of nanoparticles. The structure of the two samples is a partially disordered spinel structure. Both local probe techniques agree that Fe magnetic moments of octahedral and tetrahedral sites are canted in both systems. It was concluded that the canting originates not only from surface effects but also from the bulk resulting from the disordered spinel structure and the frustrated cationic topology, giving rise to reversed Fe moments.

Murine milk protein gene expression requires insulin, hydrocortisone, and prolactin; however, the role of insulin is not well understood. This study, therefore, examined the requirement of insulin for milk protein synthesis. Mammary explants were cultured in various combinations of the lactogenic hormones and global changes in gene expression analysed using Affymetrix microarray. The expression of 164 genes was responsive to insulin, and 18 were involved in protein synthesis at the level of transcription and posttranscription, as well as amino acid uptake and metabolism. The folate receptor gene was increased by fivefold, highlighting a potentially important role for the hormone in folate metabolism, a process that is emerging to be central for protein synthesis. Interestingly, gene expression of two milk protein transcription factors, Stat5a and Elf5, previously identified as key components of prolactin signalling, both showed an essential requirement for insulin. Subsequent experiments in HCll cells confirmed that Stat5a and Elf5 gene expression could be induced in the absence of prolactin but in the presence of insulin. Whereas prolactin plays an essential role in phosphorylating and activating Stat5a, gene expression is only induced when insulin is present. This indicates insulin plays a crucial role in the transcription of the milk protein genes.

J. Santoyo-Salazar*, M. A. Castellanos-Roman, B. Gomez-Looh, D. Ihiawakrim, C. Lefevre, G. Pourroy. 1 Institut de Physique et Chimie des Materiaux de Strasbourg, UMR CNRS-ULP-ECPM 7504, 23, rue du Loess, BP 43, 67034 Strasbourg cedex 2, France. 2 Facultad de Quimica, Departamento de Quimica Analitica, Universidad Nacional Autonoma de Mexico, Mexico D.F., 04510, Mexico. 3 Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico, AP 70-360, Mexico D.F. 04510, Mexico.

The immunological function of the metatherian mammary gland plays a crucial part in neonatal survival of the marsupial young. Marsupial pouch young do not develop adult like immune responses until just prior to leaving the pouch. The immune components of the maternal milk secretions are important during this vulnerable early post-partum period. In addition, infection of the mammary gland has not been recognized in metatherians, despite the ready availability of pathogens in the pouch. Regardless of which, little is known about the immunobiology of the mammary gland and the immune responses of mammary epithelial cells in metatherians. In this study, a molecular approach was utilized to examine the response of tammar ( Macropus eugenii ) mammary epithelial cells to Escherichia coli derived lipopolysaccharide (LPS) and Staphylococcus aureus derived lipoteichoic acid (LTA). Using custom-made cDNA microarrays, candidate genes were identified in the transciptome, which were involved in antigen presentation, inflammation, cell growth and proliferation, cellular damage and apoptosis. Quantification of mRNA expression of several of these candidate genes, along with seven other genes (TLR4, CD14, TNF-α, cathelicidin, PRDX1, IL-5 and ABCG2) associated with innate immunity in LPS and LTA challenged mammary epithelial cells and leukocytes, was assessed for up to 24 h. Differences in genes associated with cellular damage and pro-inflammatory cytokine production were seen between stimulated mammary epithelial cells and leukocytes. LTA challenge tended to result in lower level induction of pro-inflammatory cytokines, increased PRDX1 mRNA levels, suggesting increased oxidative stress, and increased CD14 expression, but in a non-TLR4-dependent manner. The use of functional genomic tools in the tammar identified differences in the response of tammar mammary epithelial cells (MEC) and leukocytes to challenge with LPS and LTA, and validates the utility of the approach. The results of this study are consistent with a model in which tammar mammary epithelial cells have the capacity to elicit a complex and robust immune response to pathogens.

The role of insulin in milk protein synthesis is unresolved in the bovine mammary gland. This study examined the potential role of insulin in the presence of two lactogenic hormones, hydrocortisone and prolactin, in milk protein synthesis. Insulin was shown to stimulate milk protein gene expression, casein synthesis and (14)C-lysine uptake in mammary explants from late pregnant cows. A global assessment of changes in gene expression in mammary explants in response to insulin was undertaken using Affymetrix microarray. The resulting data provided insight into the molecular mechanisms stimulated by insulin and showed that the hormone stimulated the expression of 28 genes directly involved in protein synthesis. These genes included the milk protein transcription factor, ELF5, translation factors, the folate metabolism genes, FOLR1 and MTHFR, as well as several genes encoding enzymes involved in catabolism of essential amino acids and biosynthesis of non-essential amino acids. These data show that insulin is not only essential for milk protein gene expression, but stimulates milk protein synthesis at multiple levels within bovine mammary epithelial cells.

SUMMARYMarsupials are born in a relatively underdeveloped state and develop during a period of intensive maturation in the postnatal period. During this period,the young marsupial lacks a competent immune system, but manages to survive despite the potential of exposure to environmental pathogens. Passive immune transfer via the milk is one well-recognised strategy to compensate the neonate, but there also may be innate immune mechanisms in place. In this study, CD14 and Toll-like receptor 4 (TLR4), integral molecular components of pathogen recognition, were identified and characterised for the first time in a marsupial, the tammar wallaby (Macropus eugenii). Functional motifs of tammar CD14 and the toll/interleukin receptor (TIR) domain of TLR4 were highly conserved. The lipopolysaccharide (LPS) binding residues and the TLR4 interaction site of CD14 were conserved in all marsupials. The TIR signalling domain had 84% identity within marsupials and 77% with eutherians. Stimulation of adult tammar leukocytes resulted in the induction of a biphasic pattern of CD14 and TLR4 expression, and coincided with increased production of the pro-inflammatory cytokine TNF-α. Differential patterns of expression of CD14 and TLR4 were observed in tammar pouch young early in development,suggesting that early maturation of the innate immune system in these animals may have developed as an immune survival strategy to protect the marsupial neonate from exposure to microbial pathogens.

Peroxiredoxin 1 (PRDX1) is a ubiquitously expressed antioxidant with vital roles in basal metabolic functions. In addition PRDX1 is involved in cell differentiation and proliferation, apoptosis and innate immunity. In this study, we have characterized PRDX1 from the tammar wallaby (Macropus eugenii). Tammar PRDX1 has high conservation of functional residues and motifs, and demonstrates a close homology with eutherian and vertebrate orthologues. Stimulation of adult tammar leukocytes with lipopolysaccharide and lipoteichoic acid suggests a role for PRDX1 in innate immune defences. PRDX1 expression in the organs of tammar pouch young was mildly elevated early in life possibly reflecting its role in basal metabolic processes. Later increases in PRDX1 expression correlated with functional maturation of several immune organs or with preparation for increased oxidative stress of emergence. The findings of the study are reflections of the complex integrated roles that PRDX1 has in regulation of oxidative stress, apoptosis, cell differentiation and proliferation, and innate immunity.

SUMMARY Whey acidic protein (WAP), a major whey protein present in milk of a number of mammalian species has characteristic cysteine-rich domains known as fourdisulfide cores (4-DSC). Eutherian WAP, expressed in the mammary gland throughout lactation, has two 4-DSC domains, (DI--DII) whereas marsupial WAP, expressed only during mid-late lactation, contains an additional 4-DSC (DIII), andhas a DIII--D1--DIIconfiguration. Wereport theexpression and evolution of echidna (Tachyglossus aculeatus) and platypus (Onithorhynchus anatinus) WAP cDNAs. Predicted translation of monotreme cDNAs showed echidna WAP contains two 4-DSC domains corresponding to DIII--DII, whereas platypus WAP contains an additional domain at the C-terminus with homology to DII and has the configuration DIII--DII--DII. Both monotreme WAPs represent new WAP protein configurations. We propose models for evolution of the WAP gene in the mammalian lineage either through exon loss from an ancient ancestor or by rapid evolution via the process of exon shuffling. This evolutionary outcome may reflect differences in lactation strategy between marsupials, monotremes, and eutherians, and give insight to biological function of the gene products. WAP four-disulfide core domain 2 (WFDC2) proteins were also identified in echidna, platypus and tammar wallaby (Macropus eugenii) lactating mammary cells. WFDC2 proteins are secreted proteins not previously associated with lactation. Mammary gland expression of tammar WFDC2 during the course of lactation showed WFDC2 was elevated during pregnancy, reduced in early lactation and absent in mid-late lactation.

Mammary development and function are regulated by systemic endocrine factors and by autocrine mechanisms intrinsic to the mammary gland, both of which act concurrently. The composition of milk includes nutritional and developmental factors that are crucial to the development of the suckled young, but it is becoming increasingly apparent that milk also has a role in regulating mammary function. This review examines the option of exploiting the comparative biology of species with extreme adaptation to lactation to examine regulatory mechanisms that are present but not readily apparent in other laboratory and livestock species. The tammar wallaby has adopted a reproductive strategy that includes a short gestation (26 d), birth of an immature young, and a relatively long lactation (300 d). The composition of milk changes progressively during the lactation cycle, and this is controlled by the mother and not the sucking pattern of the young. Furthermore, the tammar can practice concurrent asynchronous lactation; the mother provides a concentrated milk high in protein and fat for an older animal that is out of the pouch and a dilute milk low in fat and protein but high in carbohydrates from an adjacent mammary gland for a newborn pouch young. This phenomenon suggests that the mammary gland is controlled locally. The second study species, the Cape fur seal, has a lactation characterized by a repeated cycle of long at-sea foraging trips (up to 28 d) alternating with short suckling periods of 2 to 3 d ashore. Lactation almost ceases while the seal is off shore, but the mammary gland does not progress to apoptosis and involution, most likely because of local control of the mammary gland. Our studies have exploited the comparative biology of these models to investigate how mammary function is regulated by endocrine factors, and particularly by milk. This review reports 3 major findings using these model animals. First, the mammary epithelial cell has an extraordinary intrinsic capacity for survival in our culture model, and the path to either function or death by apoptosis is actively driven. The second outcome is that the route to apoptosis is most likely regulated by specific milk factors. Finally, whey acidic protein, a major milk protein in some species, may play a role in normal mammary development, but that role in vivo may be limited to marsupials. Evolutionary pressure has led to changes in the structure of the protein with an accompanying change in function. Therefore, we propose that a loss of function of this protein in eutherians may relate to a reproductive strategy that is less dependent on lactation.

International audience; The analysis of high-resolution computed tomography (CT) images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6-10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11) and asthmatic (n = 24) CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47). The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01) in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3-5) versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1) (Spearman ρ = -0.65, p < 0.001) and, at low flow rates (0.00017 L/s), FEV1 over forced vital capacity (FEV1/FVC) (ρ = -0.58, p < 0.001). We conclude that the pipeline and anatomical models can be used directly in mechanistic modelling studies and can form the basis for future patient-based modelling studies.

Nanostructures with controlled size, morphology, and composition represent a main challenge in materials science because controlling these parameters is fundamental to optimizing the subsequent functional properties. Aggregated nanostructures, combining both individual and collective properties of nanocrystals, offer interesting perspectives to design new magnetic nanomaterials. In that context, original porous raspberry shaped nanostructures consisting of oriented aggregates of ferrite nanocrystals have been synthesized by an one-pot polyol solvothermal method. Synthesis conditions have been optimized to obtain nanostructures featured by similar sizes of about 250 nm and nanocrystal sizes modulated from 5 to 60 nm, leading to porous structures with tunable specific surface area. Structural and magnetic studies of nanostructures as a function of the nanocrystal size evidenced their low oxidation state and enhanced magnetic properties. Indeed, the oriented aggregation of nanocrystals leads to high interface between nanograins reducing significantly their surface oxidation and enhancing their saturation magnetization in comparison to individual nanoparticles of similar sizes. Magnetic moments of each grain are also consequently strongly coupled by dipolar interactions which led to superspin glass effects.

International audience; Carbon nanostructured materials such as carbon nanotubes and graphene oxide are attracting much attention due to their outstanding chemical and physical properties. Metal nanoparticle-decoration can provide additional functionalities to these nanocarbons. Many chemical methods are being used for the synthesis of these metal nanoparticle-functionalized nanocarbon hybrids. On the other hand, the outstanding properties of spinelle iron oxide magnetic (MAG) nanoparticles have been efficiently used for a variety of applications such as manipulation of biomolecules and cells, cancer hyperthermia, and medical devices. Therefore, MAG nanoparticle decoration of carbon nanotubes and graphene oxide can provide promising nanohybrid materials for nanobiotechnological applications. In this work, we present a straightforward chemical route for MAG nanopartide decoration of nanocarbon supports including carbon nanotubes and graphene oxide using in situ high-temperature decomposition method. This chemical methodology allows precisely controlling the MAG nanoparticle content, the MAG nanopartide size leading to a uniform coating on the different carbon supports. The properties of these new hybrids have been thoroughly evaluated. Our results show that the MAG nanoparticle decoration process strongly affects the structural and magnetic characteristics of the hybrids. The combination of MAG nanopartide and nanocarbon materials will open the door to their use in different domains including nanocomposites, wastewater treatment, sensors, biomaterials, and cancer therapy. (C) 2015 Elsevier Ltd. All rights reserved.

Although single magnetic domain nanoparticles are very promising for many applications, size reduction usually results in low magnetic anisotropy and unblocked domain at room temperature, e.g., superparamagnetism. An alternative approach is core-shell nanoparticles featured by exchange bias coupling between ferro(i)magnetic [F(i)M] and antiferromagnetic (AFM) phases. Although exchange bias coupling has been reported for very diverse coreshell nanoparticles, it is difficult to compare these studies to rationalize the effect of many structural parameters on the magnetic properties. Herein, we report on a systematic study which consists of the modulation of the shell structure and its influence on the exchange bias coupling. A series of Fe-3-O-delta(4)@CoO core-shell nanoparticles has been synthesized by seed-mediated growth based on the thermal decomposition technique. The variation of Co reactant concentration resulted in the modulation of the shell structure for which thickness, crystallinity, and interface with the iron oxide core strongly affect the magnetic properties. The thickest CoO shell and the largest F(i)M/AFM interface led to the largest exchange bias coupling. Very high values of coercive field (19?000 Oe) and M-R/M-S ratio (0.86) were obtained. The most stricking results consist of the increase of the coercive field while exchange field vanishes when the CoO thickness decreases: it is ascribed to the diffusion of Co species in the surface layer of iron oxide which generates to some extent cobalt ferrite and induces hard/soft exchange coupling between ferrimagnetic phases.

The composition of milk includes factors required to provide appropriate nutrition for the growth of the neonate. However, it is now clear that milk has many functions and comprises bioactive molecules that play a central role in regulating developmental processes in the young while providing a protective function for both the suckled young and the mammary gland during the lactation cycle. Identifying these bioactives and their physiological function in eutherians can be difficult and requires extensive screening of milk components that may function to improve well-being and options for prevention and treatment of disease. New animal models with unique reproductive strategies are now becoming increasingly relevant to search for these factors.

International audience; The microwave properties of sheets containing silica-coated NiFeMo flakes are investigated and discussed according to the sheet structure, the silica layer uniformity and thickness. Commercial NiFeMo flakes are coated using the Stoeber method and embedded in polymer using the doctor blade process. The silica layer thickness is estimated by transmission electron microscopy (TEM) and the coating quality is probed by scanning electron microscopy (SEM). The in-plane orientation of magnetic moments within the sheet is evidenced by 57Fe Mössbauer spectrometry. As a result, the permittivity of composites is strongly reduced when the NiFeMo flakes are completely coated, whereas the permeability level is weakly and progressively altered when the silica thickness increases. We show that the frequency range for microwave absorption can be tuned according to the silica thickness and the flake loading. Reflection losses of −13 dB are obtained in the 1–2 GHz range for a normal incident electromagnetic wave interacting with 3 mm sheets backed by a perfect conductor and loaded with silica (90 nm width)-coated NiFeMo flakes.

Scandium rich cobalt ferrites Co y Fe 3− x − y Sc x O 4 with y ~1 never obtained in bulk could be stabilized in pulsed laser deposited thin films. Scandium contents of up to x =1 are reached. The cell parameter increases versus x as awaited when considering the size of scandium. It is equal to 0.8620 nm for x =1, significantly higher than that of CoFe 2 O 4 (0.8396 nm). The lattice mismatch between the MgO (100) substrate and the scandium-containing spinel leads to an increased roughness. Cobalt is displaced from the octahedral site by Sc and mainly occupies the tetrahedral sites for high x values.

We report the first isolation and sequencing of genomic BAC clones containing the marsupial milk protein genes Whey Acidic Protein (WAP) and Early Lactation Protein (ELP). The stripe-faced dunnart WAPgene sequence contained five exons, the middle three of which code for the WAPmotifs and four disulphide core domains which characterize WAP. The dunnart ELPgene sequence contained three exons encoding a protein with a Kunitz motif common to serine protease inhibitors. Fluorescence in situ hybridization located the WAPgene to chromosome 1p in the stripe-faced dunnart, and the ELPgene to 2q. Northern blot analysis of lactating mammary tissue of the closely related fat-tailed dunnart has shown asynchronous expression of these milk protein genes. ELPwas expressed at only the earlier phase of lactation and WAPonly at the later phase of lactation, in contrast to β-lactoglobulin (BLG) and α-lactalbumin (ALA) genes, which were expressed in both phases of lactation. This asynchronous expression during the lactation cycle in the fat-tailed dunnart is similar to other marsupials and it probably represents a pattern that is ancestral to Australian marsupials.

Comparing globin genes and their flanking sequences across many species has allowed globin gene evolution to be reconstructed in great detail. Marsupial globin sequences have proved to be of exceptional significance. A previous finding of a β(beta)-like ω(omega) gene in the α(alpha) cluster in the tammar wallaby suggested that the α and β cluster evolved via genome duplication and loss rather than tandem duplication. To confirm and extend this important finding we isolated and sequenced BACs containing the α and β loci from the distantly related Australian marsupial Sminthopsis macroura. We report that the α gene lies in the same BAC as the β-like ω gene, implying that the α-ω juxtaposition is likely to be conserved in all marsupials. The LUC7L gene was found 3′ of the S. macroura α locus, a gene order shared with humans but not mouse, chicken or fugu. Sequencing a BAC contig that contained the S. macroura β globin and Ε globin loci showed that the globin cluster is flanked by olfactory genes, demonstrating a gene arrangement conserved for over 180 MY. Analysis of the region 5′ to the S. macroura epsilon (Ε) globin gene revealed a region similar to the eutherian LCR, containing sequences and potential transcription factor binding sites with homology to eutherian hypersensitive sites 1 to 5. FISH mapping of BACs containing S. macroura α and β globin genes located the β globin cluster on chromosome 3q and the α locus close to the centromere on 1q, resolving contradictory map locations obtained by previous radioactive in situ hybridization.

Background Lactation is a key aspect of mammalian evolution for adaptation of various reproductive strategies along different mammalian lineages. Marsupials, such as tammar wallaby, adopted a short gestation and a relatively long lactation cycle, the newborn is immature at birth and significant development occurs postnatally during lactation. Continuous changes of tammar milk composition may contribute to development and immune protection of pouch young. Here, in order to address the putative contribution of newly identified secretory milk miRNA in these processes, high throughput sequencing of miRNAs collected from tammar milk at different time points of lactation was conducted. A comparative analysis was performed to find distribution of miRNA in milk and blood serum of lactating wallaby. Results Results showed that high levels of miRNA secreted in milk and allowed the identification of differentially expressed milk miRNAs during the lactation cycle as putative markers of mammary gland activity and functional candidate signals to assist growth and timed development of the young. Comparative analysis of miRNA distribution in milk and blood serum suggests that milk miRNAs are primarily expressed from mammary gland rather than transferred from maternal circulating blood, likely through a new putative exosomal secretory pathway. In contrast, highly expressed milk miRNAs could be detected at significantly higher levels in neonate blood serum in comparison to adult blood, suggesting milk miRNAs may be absorbed through the gut of the young. Conclusion The function of miRNA in mammary gland development and secretory activity has been proposed, but results from the current study also support a differential role of milk miRNA in regulation of development in the pouch young, revealing a new potential molecular communication between mother and young during mammalian lactation. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-1012) contains supplementary material, which is available to authorized users.

Background Marsupials such as the tammar wallaby (M.Eugenii) have a short gestation (29.3 days) and at birth the altricial young resembles a fetus, and the major development occurs postnatally while the young remains in the mother’s pouch. The essential functional factors for the maturation of the neonate are provided by the milk which changes in composition progressively throughout lactation (300 days). Morphologically the lungs of tammar pouch young are immature at birth and the majority of their development occurs during the first 100 days of lactation. Results In this study mouse embryonic lungs (E-12) were cultured in media with tammar skim milk collected at key time points of lactation to identify factors involved in regulating postnatal lung maturation. Remarkably the embryonic lungs showed increased branching morphogenesis and this effect was restricted to milk collected at specific time points between approximately day 40 to 100 lactation. Further analysis to assess lung development showed a significant increase in the expression of marker genes Sp-C, Sp-B, Wnt-7b, BMP4 and Id2 in lung cultures incubated with milk collected at day 60. Similarly, day 60 milk specifically stimulated proliferation and elongation of lung mesenchymal cells that invaded matrigel. In addition, this milk stimulated proliferation of lung epithelium cells on matrigel, and the cells formed 3-dimensional acini with an extended lumen. Conclusions This study has clearly demonstrated that tammar wallaby milk collected at specific times in early lactation contains bioactives that may have a significant role in lung maturation of pouch young. Electronic supplementary material The online version of this article (doi:10.1186/s12861-015-0063-z) contains supplementary material, which is available to authorized users.

Recent studies using the mouse showed an inverse correlation between the Caveolin 1 gene expression and lactation, and this was regulated by prolactin. However, current study using mammary explants from pregnant mice showed that while insulin (I), cortisol (F) and prolactin (P) resulted in maximum induction of the β-casein gene, FP and IFP resulted in the downregulation of Caveolin 1. Additionally, IF, FP and IFP resulted in the downregulation of Caveolin 2. Immunohistochemistry confirmed localisation of Caveolin 1 specific to myoepithelial cells and adipocytes. Comparative studies with the tammar wallaby showed Caveolin 1 and 2 had 70-80% homology with the mouse proteins. However, in contrast to the mouse, Caveolin 1 and 2 genes showed a significantly increased level of expression in the mammary gland during lactation. The regulation of tammar Caveolin 1 and 2 gene expression was examined in mammary explants from pregnant tammars, and no significant difference was observed either in the absence or in the presence of IFP.

Human milk contains both free and encapsulated RNA and microRNA in its cell, lipid and skim milk fractions. Recently, the microRNA content of human milk has attracted much attention due to its high...

Équipe 401 : Nanomatériaux pour la vie et développement durable; International audience; Iron oxide nanoparticles (NPs) with average sizes in the range 4-28 nm have been obtained by varying different synthesis parameters of the thermal decomposition of an iron precursor (iron stearate) in the presence of surfactants in high boiling solvents. The synthesis parameters affect the NPs nucleation and growth steps, by modifying the stability of iron stearate on which depend the monomer formation and concentration, in agreement with the LaMer model. The monomer formation, which is reaction time and/or temperature dependent, is thus found to vary mainly as a function of the nature of solvents and ligands. The structural and magnetic characterizations of NPs with sizes in the range 5-20 nm confirm that the composition of NPs evolves from the maghemite for small sizes (typically 12 nm) via a perturbed oxidized state for intermediate sizes. The values of saturation magnetization lower than those of bulk magnetite and maghemite were found to be related to this composition evolution and to the presence of oxidation defects, surface spin canting and volume spin canting as a function of NPs diameter. Small NPs presented mainly a surface spin canting. NPs with large sizes display M-s which depends on their oxidized shell thickness, defects and surface spin canting. NPs with intermediate sizes display a surface and in particular a volume spin canting due to a disordered structure induced by a perturbed oxidation state in these NPs.

Plasminogen (Pg), the precursor of the proteolytic and fibrinolytic enzyme of blood, is converted to the active enzyme plasmin (Pm) by different plasminogen activators (tissue plasminogen activators and urokinase), including the bacterial activators streptokinase and staphylokinase, which activate Pg to Pm and thus are used clinically for thrombolysis. The identification of Pg-activators is therefore an important step in understanding their functional mechanism and derives new therapies. In this study, different computational methods for predicting plasminogen activator peptide sequences with high accuracy were investigated, including support vector machines (SVM) based on amino acid (AC), dipeptide composition (DC), PSSM profile and Hybrid methods used to predict different Pg-activators from both prokaryotic and eukaryotic origins. Overall maximum accuracy, evaluated using the five-fold cross validation technique, was 88.37%, 84.32%, 87.61%, 85.63% in 0.87, 0.83,0.86 and 0.85 MCC with amino (AC) or dipeptide composition (DC), PSSM profile and Hybrid methods respectively. Through this study, we have found that the different subfamilies of Pg-activators are quite closely correlated in terms of amino, dipeptide, PSSM and Hybrid compositions. Therefore, our prediction results show that plasminogen activators are predictable with a high accuracy from their primary sequence. Prediction performance was also cross-checked by confusion matrix and ROC (Receiver operating characteristics) analysis. A web server to facilitate the prediction of Pg-activators from primary sequence data was implemented. The results show that dipeptide, PSSM profile, and Hybrid based methods perform better than single amino acid composition (AC). Furthermore, we also have developed a web server, which predicts the Pg-activators and their classification (available online at http://mamsap.it.deakin.edu.au/plas_pred/home.html ). Our experimental results show that our approaches are faster and achieve generally a good prediction performance.

The HfFe6Ge6-type ErMn6Ge6−xGax compounds (x=0.2, 0.4, 1.0) have been studied by powder neutron diffraction. The ErMn6Ge5.8Ga0.2 compound orders antiferromagnetically at 460 K in a collinear easy axis magnetic structure characterized by a doubling of the c-axis. Below Tt=270 K, a helimagnetic structure takes place and persists down to 50 K. Below this temperature, a ferrimagnetic structure with moments aligned along the c-axis is stable (μMn=2.21(5) μB and μEr=8.60(8) μB). The ErMn6Ge5.6Ga0.4 compound orders antiferromagnetically at 394 K. From 300 to 120 K, it is characterized by a helimagnetic arrangement. In both cases, the normal to the c-axis is perpendicular to the [001] direction. Below 110 K, a ferrimagnetic structure takes place and the direction of the ferromagnetic component is aligned along the c-axis. The Mn and Er moments refined at 2 K are μMn=2.21(6) μB and μEr=9.06(11) μB. The ErMn6Ge5Ga compound orders ferrimagnetically at 373 K and a moment reorientation takes place around 200 K. At high temperature the moments are close to the (001) plane whereas at low temperature they align along the c-axis. The Mn and Er moments refined at 2 K are μMn=2.23(6) μB and μEr=9.40(12) μB. Evolutions of the moment magnitudes, magnetocrystalline anisotropy and interlayer couplings, as a function of the Ga content and the nature of the rare earth element, are discussed.

Using a specifically designed diagnostic PCR assay with nested primers the following could be achieved: (1) a group of 22 clinically indistinguishable women attending an infertility clinic, 18 with repeated embryo transfer failure, and asymptomatic for HSV-1 could be divided into two subgroups after testing their menstrual blood. An HSV-DNA positive (50%) and HSV-DNA negative group (50%) could be distinguished. None of the four controls were positive; (2) semen from 154 infertile and 24 fertile men was tested in relation to infertility. In the group of infertile men 37 (24%) were HSV-DNA positive but none of the fertile control (0%) was positive; (3) treatment of both partners with an antiviral drug resulted in two pregnancies; (4) HLA data on four of the couples in which the wife's menstrual blood was HSV positive was compared to seven HSV negative couples and 22 infertile, as well as 22 fertile couples. Clustering of class I HLA (B61 and Cw3) was found with a significant increase in Cw3 in both partners.

Objective: To determine a possible link between herpes simplex virus 1 (HSV) and infertility. Method: A specifically designed polymerase chain reaction with nested primers, was developed and used to test for HSV in 153 men and 20 women attending an infertility clinic. Results: HSV DNA was detected in 37 (24%) out of 153 semen samples and in 11 (55%) out of 20 menstrual blood samples. However, HSV DNA (0%) was not detected in the semen of 16 males with children. A significant association between the evidence for infertility and an HSV positive test was observed in men (Fisher's exact test, p = 0.024), and a stronger effect was found in females after failed in vitro fertilization (Fisher's exact test p = 0.0086). Conclusion: This is the first report of the detection of herpes simplex virus DNA in semen and menstrual blood. Encouraging preliminary results justify antiviral therapy in case of a positive test.

Core-shell nanoparticles (NPs), which consist in a ferrimagnetic (FIM)/antiferromagnetic (AFM) interface and result in exchange bias coupling, became recently of primary importance in the field of magnetic nanoparticles. The enhancement of some applications such as hyperthermia or magnetic storage media based on the miniaturization of devices is correlated to the size reduction of NPs, which results in the decrease of the magnetocrystalline anisotropy and of the blocking temperature. We present here the synthesis of Fe3-delta O4@CoO core-shell NPs by a one-pot seed-mediated growth process based on the thermal decomposition of metal complexes at high temperature. A 2 nm thick CoO shell was grown homogeneously from the starting Fe3-delta O4 core surface. The Fe3-delta O4@CoO core-shell NP structure has been deeply investigated by performing XRD and advanced techniques based on TEM such as EELS and EFTEM. The high quality of the core-shell interface resulted in the large exchange bias coupling at 5 K (H-E approximate to 4.1 kOe) between the FIM and the AFM components. In comparison to starting Fe3-delta O4 NPs, the dramatic enhancement of the magnetic properties such as a high coercive field (at 5 K, H-C approximate to 15 kOe) were measured. Furthermore, the core-shell structure resulted in the enhancement of the magnetocrystalline anisotropy and the increase of the blocking temperature to 293 K.