Kevin R Nicholas

Publications of Kevin R Nicholas

• WFDC2 is differentially expressed in the mammary gland of the tammar wallaby and provides immune protection to the mammary gland and the developing pouch young.

  Authors: Ashalyn P Watt, Julie A Sharp, Christophe Lefevre, Kevin R Nicholas

  Developmental and comparative immunology. 03/2012; 36(3):584-90.

  WAP four disulfide core domain 2 (WFDC2) is a four disulfide core (4-DSC) protein secreted in the milk of the tammar wallaby. It is comprised of two 4-DSC domains assigned domain III at theWAP four disulfide core domain 2 (WFDC2) is a four disulfide core (4-DSC) protein secreted in the milk of the tammar wallaby. It is comprised of two 4-DSC domains assigned domain III at the NH2-terminal end and domain II at the COOH-terminal end. The WFDC2 gene was expressed only during pregnancy, early lactation, towards the end of lactation and involution. The WFDC2 protein showed antibacterial activity against Staphylococcus aureus, Salmonella enterica and Pseudomonas aeruginosa and this activity resided with domain II. There was no antibacterial activity detected against Enterococcus faecalis. The observed expression pattern of tammar WFDC2 and its antibacterial activity suggests a role to either reduce mastitis in the mammary gland caused by S. aureus or to protect the gut of the young at a time when it is not immune-competent. The latter effect could be achieved without disturbing the balance of commensal gut flora such as E. faecalis.

• Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

  Authors: Marilyn B Renfree, Anthony T Papenfuss, Janine E Deakin, James Lindsay, Thomas Heider, Katherine Belov, Willem Rens, Paul D Waters, Elizabeth A Pharo, Geoff Shaw [......] Tanya Levchenko, Richard A Gibbs, Desmond W Cooper, Terence P Speed, Asao Fujiyama, Jennifer A M Graves, Rachel J O'Neill, Andrew J Pask, Susan M Forrest, Kim C Worley

  Genome biology. 12/2011; 12(12):414.

• Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

  Authors: Marilyn B Renfree, Anthony T Papenfuss, Janine E Deakin, James Lindsay, Thomas Heider, Katherine Belov, Willem Rens, Paul D Waters, Elizabeth A Pharo, Geoff Shaw [......] Tanya Levchenko, Richard A Gibbs, Desmond W Cooper, Terence P Speed, Asao Fujiyama, Jennifer A M Graves, Rachel J O'Neill, Andrew J Pask, Susan M Forrest, Kim C Worley

  Genome biology. 08/2011; 12(8):R81.

  We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia toWe present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.

• Tammar wallaby mammary cathelicidins are differentially expressed during lactation and exhibit antimicrobial and cell proliferative activity.

  Authors: Stephen S Wanyonyi, Julie A Sharp, Elie Khalil, Christophe Lefevre, Kevin R Nicholas

  Comparative biochemistry and physiology. Part A, Molecular & integrative physiology. 07/2011; 160(3):431-9.

  Cathelicidins secreted in milk may be central to autocrine feedback in the mammary gland for optimal development in addition to conferring innate immunity to both the mammary gland and the neonate.Cathelicidins secreted in milk may be central to autocrine feedback in the mammary gland for optimal development in addition to conferring innate immunity to both the mammary gland and the neonate. This study exploits the unique reproductive strategy of the tammar wallaby (Macropus eugenii) model to analyse differential splicing of cathelicidin genes and to evaluate the bactericidal activity and effect of the protein on mammary epithelial cell proliferation. Two linear peptides, Con73 and Con218, derived from the heterogeneous carboxyl end of cathelicidin transcripts, MaeuCath1 and MaeuCath7 respectively, were evaluated for antimicrobial activity. Both Con73 and Con218 significantly inhibited the growth of Staphylococcus aureus, Pseudomonas aureginosa, Enterococcus faecalis and Salmonella enterica. In addition both MaeuCath1 and MaeuCath7 stimulated proliferation of primary tammar wallaby mammary epithelial cells (WallMEC). Lactation-phase specific alternate spliced transcripts were determined for MaeuCath1 showing utilisation of both antimicrobial and proliferative functions are required by the mammary gland and the suckled young. The study has shown for the first time that temporal regulation of milk cathelicidins may be crucial in antimicrobial protection of the mammary gland and suckled young and mammary cell proliferation.

• Conservation of the ST6Gal I gene and its expression in the mammary gland.

  Authors: Jovana Maksimovic, Julie A Sharp, Kevin R Nicholas, Benjamin G Cocks, Keith Savin

  Glycobiology. 11/2010; 21(4):467-81.

  Milk sialoglycoconjugates can protect the gastrointestinal tract of the suckling neonate by competitively binding to invading pathogens and promoting growth of beneficial flora, and their potentialMilk sialoglycoconjugates can protect the gastrointestinal tract of the suckling neonate by competitively binding to invading pathogens and promoting growth of beneficial flora, and their potential role in postnatal brain development is of particular interest in human infant nutrition. Although the concentration and the distribution of sialoglycoconjugates have been extensively studied in the milk of various species, the investigation of sialyltransferase gene expression in the mammary gland, in the context of lactation, has been limited. The sialyltransferase enzyme ST6Gal I transfers sialic acid from CMP-sialic acid to type 2 (Galβ1,4GlcNAc) free disaccharides or the termini of N- or O-linked oligosaccharides using an α2,6-linkage. Expression of the ST6Gal I gene is primarily regulated at the level of transcription through the use of several cell and development-specific promoters, producing transcripts with divergent 5' untranslated regions (UTR). In the mouse mammary gland, the novel 5'UTR exon (L) appears to be associated with a drastic increase in ST6Gal I gene expression during lactation. We find that rats also possess an exon (L), suggesting conservation of this regulatory mechanism in rodents. In contrast, an exon (L)-containing transcript was not detected in the lactating bovine or human mammary gland. We also observed a trend of increasing ST6Gal I gene expression in the bovine mammary gland, culminating in involution. This is in contrast to species such as mice where the greatest change in ST6Gal I gene expression occurs between pregnancy and lactation, suggesting different roles in rodents vs. other mammals for α2,6-sialylated oligosaccharides present in milk.

• Evolution of lactation: ancient origin and extreme adaptations of the lactation system.

  Authors: Christophe M Lefèvre, Julie A Sharp, Kevin R Nicholas

  Annual review of genomics and human genetics. 09/2010; 11:219-38.

  Lactation, an important characteristic of mammalian reproduction, has evolved by exploiting a diversity of strategies across mammals. Comparative genomics and transcriptomics experiments have nowLactation, 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.

• Mining protein-protein interactions from published abstracts with MontyLingua

  Authors: Maurice HT Ling, Christophe Lefevre, Kevin R Nicholas

  01/2010; iConcept Press Pty Ltd.

• Normal mammary gland growth and lactation capacity in pregnant relaxin-deficient mice.

  Authors: Laura J Parry, Lenka A Vodstrcil, Anna Madden, Stephanie H Amir, Katrina Baldwin, Mary E Wlodek, Kevin R Nicholas

  Reproduction, fertility, and development. 02/2009; 21(4):549-60.

  Pups born to mice with a targeted deletion of relaxin or its receptor (Rxfp1) die within 24 h postpartum. This has been attributed, in part, to abnormal mammary gland development in relaxin-mutantPups born to mice with a targeted deletion of relaxin or its receptor (Rxfp1) die within 24 h postpartum. This has been attributed, in part, to abnormal mammary gland development in relaxin-mutant mice (Rln(-/-)). However, mammary development is normal in relaxin receptor-mutant (Rxfp1(-/-)) mice. The present study aimed to verify the mammary phenotypes in late pregnant and early lactating Rln(-/-) mice and to test the hypothesis that relaxin is involved in milk protein synthesis. Comparisons between late pregnant and early lactating wildtype (Rln(+/+)) and Rln(-/-) mice showed no differences in lobuloalveolar structure or ductal branching in the mammary gland. Mammary explants from Rln(-/-) mice also expressed beta-casein and alpha-lactalbumin in response to lactogenic hormones at a similar level to Rln(+/+) mice, implying normal milk protein synthesis. Pregnant Rln(-/-) mice infused with relaxin for 6 days gave birth to live pups without difficulty, and 96% of pups survived beyond 7 days. This is in contrast with the 100% pup mortality in saline-treated Rln(-/-) mice or 3-day relaxin-treated Rln(-/-) mice. Pups born to relaxin-treated Rln(-/-) dams weighed significantly less than Rln(+/+) pups but had similar growth rates as their wildtype counterparts. In summary, relaxin is not critical for mammary gland development or beta-casein and alpha-lactalbumin expression in late pregnant mice. In addition, Rln(-/-) dams did not need to be treated with relaxin postpartum for the pups to survive, suggesting that relaxin has no role in the maintenance of lactation in mice.

• Cross-fostering of the tammar wallaby (Macropus eugenii) pouch young accelerates fore-stomach maturation.

  Authors: Joly H L Kwek, Robbert De Iongh, Matthew R Digby, Marilyn B Renfree, Kevin R Nicholas, Mary Familari

  Mechanisms of development. 02/2009;

  There are two phases of fore-stomach development during the first 200 days of pouch life in tammar wallaby. For the first 170 days, the mucosa displays an immature gastric glandular phenotype thatThere are two phases of fore-stomach development during the first 200 days of pouch life in tammar wallaby. For the first 170 days, the mucosa displays an immature gastric glandular phenotype that changes to a cardia glandular phenotype, which remains for the rest of the animal's life. During this 200-day period after birth, the pouch young (PY) is dependent on maternal milk, which progressively changes in composition. We showed previously that PY cross-fostered to host mothers at a later stage of lactation accelerated development. In this study, we investigated whether cross-fostering and exposure to late lactation stage milk affected the transition to cardia glandular phenotype. In fostered PY fore-stomach, there was increased apoptosis, but no change in cell proliferation. The parietal cell population was significantly reduced, and expression of gastric glandular phenotype marker genes (ATP4A, GKN2, GHRL and NDRG2) was down-regulated, suggesting down-regulation of gastric phenotype in fostered PY fore-stomach. The expression of cardia glandular phenotype genes (MUC4, KRT20, CSTB, ITLN2 and LPLUNC1) was not changed in fostered PY. These data suggest that fore-stomach maturation proceeds via two temporally distinct processes: down-regulation of gastric glandular phenotype and initiation of cardia glandular phenotype. In fostered PY, these two process appear uncoupled, as gastric glandular phenotype was down-regulated but cardia glandular phenotype was not initiated. We propose that milk from later stages of lactation and/or herbage consumed by the PY may play independent roles in regulating these two processes.

• Filtering Microarray Correlations by Statistical Literature Analysis Yields Potential Hypotheses for Lactation Research

  Authors: Maurice HT Ling, Christophe Lefevre, Kevin R Nicholas

  02/2009;

  Our results demonstrated that a previously reported protein name co-occurrence method (5-mention PubGene) which was not based on a hypothesis testing framework, it is generally statistically moreOur results demonstrated that a previously reported protein name co-occurrence method (5-mention PubGene) which was not based on a hypothesis testing framework, it is generally statistically more significant than the 99th percentile of Poisson distribution-based method of calculating co-occurrence. It agrees with previous methods using natural language processing to extract protein-protein interaction from text as more than 96% of the interactions found by natural language processing methods to overlap with the results from 5-mention PubGene method. However, less than 2% of the gene co-expressions analyzed by microarray were found from direct co-occurrence or interaction information extraction from the literature. At the same time, combining microarray and literature analyses, we derive a novel set of 7 potential functional protein-protein interactions that had not been previously described in the literature.

• Characterisation of monotreme caseins reveals lineage-specific expansion of an ancestral casein locus in mammals.

  Authors: Christophe M Lefèvre, Julie A Sharp, Kevin R Nicholas

  Reproduction, fertility, and development. 01/2009; 21(8):1015-27.

  Using a milk-cell cDNA sequencing approach we characterised milk-protein sequences from two monotreme species, platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus) and found aUsing a milk-cell cDNA sequencing approach we characterised milk-protein sequences from two monotreme species, platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus) and found a full set of caseins and casein variants. The genomic organisation of the platypus casein locus is compared with other mammalian genomes, including the marsupial opossum and several eutherians. Physical linkage of casein genes has been seen in the casein loci of all mammalian genomes examined and we confirm that this is also observed in platypus. However, we show that a recent duplication of beta-casein occurred in the monotreme lineage, as opposed to more ancient duplications of alpha-casein in the eutherian lineage, while marsupials possess only single copies of alpha- and beta-caseins. Despite this variability, the close proximity of the main alpha- and beta-casein genes in an inverted tail-tail orientation and the relative orientation of the more distant kappa-casein genes are similar in all mammalian genome sequences so far available. Overall, the conservation of the genomic organisation of the caseins indicates the early, pre-monotreme development of the fundamental role of caseins during lactation. In contrast, the lineage-specific gene duplications that have occurred within the casein locus of monotremes and eutherians but not marsupials, which may have lost part of the ancestral casein locus, emphasises the independent selection on milk provision strategies to the young, most likely linked to different developmental strategies. The monotremes therefore provide insight into the ancestral drivers for lactation and how these have adapted in different lineages.

• Biomedical literature analysis: current state and challenges

  Authors: Maurice HT Ling, Christophe Lefevre, Kevin R Nicholas

  01/2009; Nova Science Publishers, Inc..

• Molecular analysis of tammar (Macropus eugenii) mammary epithelial cells stimulated with lipopolysaccharide and lipoteichoic acid.

  Authors: Kerry A Daly, Sonia L Mailer, Matthew R Digby, Christophe Lefévre, Peter Thomson, Elizabeth Deane, Kevin R Nicholas, Peter Williamson

  Veterinary immunology and immunopathology. 01/2009;

  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 untilThe 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-alpha, 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 24h. 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.

• Genome analysis of the platypus reveals unique signatures of evolution.

  Authors: Wesley C Warren, Ladeana W Hillier, Jennifer A Marshall Graves, Ewan Birney, Chris P Ponting, Frank Grützner, Katherine Belov, Webb Miller, Laura Clarke, Asif T Chinwalla [......] Prathapan Thiru, Michael N Nhan, Craig S Pohl, Scott M Smith, Shunfeng Hou, Mikhail Nefedov, Pieter J de Jong, Marilyn B Renfree, Elaine R Mardis, Richard K Wilson

  Nature. 10/2008; 455(7210):256.

• Changes in milk protein composition during acute involution at different phases of tammar wallaby (Macropus eugenii) lactation.

  Authors: Elie Khalil, Matthew R Digby, Paul O'Donnell, Kevin R Nicholas

  Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 07/2008;

  This study exploited the unusual lactation cycle of the tammar wallaby (Macropus eugenii) to characterise milk composition during acute involution, a time when the mammary gland is subjected toThis study exploited the unusual lactation cycle of the tammar wallaby (Macropus eugenii) to characterise milk composition during acute involution, a time when the mammary gland is subjected to increased risk of infection. In early-lactation, tammar milk contains elevated levels of complex oligosaccharides and low protein and lipid content. Later in lactation, protein and lipid concentrations increase significantly, whereas carbohydrate content is reduced dramatically and changes to monosaccharides. Following initiation of involution at early-lactation, the carbohydrate concentration greatly decreased, while lipid and protein concentrations were elevated, suggesting that complex oligosaccharides are the major osmole in milk at this time. In contrast, involution at late lactation, when carbohydrate concentration was very low, led to an increase in the lipid concentration, but the concentration of protein was not significantly altered. This indicates that protein synthesis during acute involution at late lactation in the tammar may be down-regulated much more rapidly than during early-lactation. Analysis of milk at day 3 after the onset of involution at early-lactation identified a number of potential antimicrobials secreted at high concentrations, including lysozyme, dermcidin, polymeric immunoglobulin receptor and fragments of beta-lactoglobulin. These proteins may protect the mammary gland by minimising the risk of potential infection during involution.

• Genome analysis of the platypus reveals unique signatures of evolution.

  Authors: Wesley C Warren, Ladeana W Hillier, Jennifer A Marshall Graves, Ewan Birney, Chris P Ponting, Frank Grützner, Katherine Belov, Webb Miller, Laura Clarke, Asif T Chinwalla [......] Todd Wylie, Patricia Wohldmann, Prathapan Thiru, Michael N Nhan, Craig S Pohl, Scott M Smith, Shunfeng Hou, Marilyn B Renfree, Elaine R Mardis, Richard K Wilson

  Nature. 06/2008; 453(7192):175-83.

  We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have aWe present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.

• Parts-of-Speech Tagger Errors Do Not Necessarily Degrade Accuracy in Extracting Information from Biomedical Text

  Authors: Maurice HT Ling, Christophe Lefevre, Kevin R Nicholas

  05/2008;

  A recent study reported development of Muscorian, a generic text processing tool for extracting protein-protein interactions from text that achieved comparable performance to biomedical-specific textA recent study reported development of Muscorian, a generic text processing tool for extracting protein-protein interactions from text that achieved comparable performance to biomedical-specific text processing tools. This result was unexpected since potential errors from a series of text analysis processes is likely to adversely affect the outcome of the entire process. Most biomedical entity relationship extraction tools have used biomedical-specific parts-of-speech (POS) tagger as errors in POS tagging and are likely to affect subsequent semantic analysis of the text, such as shallow parsing. This study aims to evaluate the parts-of-speech (POS) tagging accuracy and attempts to explore whether a comparable performance is obtained when a generic POS tagger, MontyTagger, was used in place of MedPost, a tagger trained in biomedical text. Our results demonstrated that MontyTagger, Muscorian's POS tagger, has a POS tagging accuracy of 83.1% when tested on biomedical text. Replacing MontyTagger with MedPost did not result in a significant improvement in entity relationship extraction from text; precision of 55.6% from MontyTagger versus 56.8% from MedPost on directional relationships and 86.1% from MontyTagger compared to 81.8% from MedPost on nondirectional relationships. This is unexpected as the potential for poor POS tagging by MontyTagger is likely to affect the outcome of the information extraction. An analysis of POS tagging errors demonstrated that 78.5% of tagging errors are being compensated by shallow parsing. Thus, despite 83.1% tagging accuracy, MontyTagger has a functional tagging accuracy of 94.6%.

• A population of mammary epithelial cells do not require hormones or growth factors to survive.

  Authors: Amelia J Brennan, Julie A Sharp, Elie Khalil, Matthew R Digby, Sonia L Mailer, Christophe M Lefèvre, Kevin R Nicholas

  The Journal of endocrinology. 04/2008; 196(3):483-96.

  Hormonal stimulation of mammary explants mimics many of the biochemical changes observed during lactogenesis. Previous studies using eutherian species conclude that mammary explants require additionHormonal stimulation of mammary explants mimics many of the biochemical changes observed during lactogenesis. Previous studies using eutherian species conclude that mammary explants require addition of exogenous macromolecules to remain hormone responsive in culture. The present study examines the survival of mammary explants from the wallaby and mouse using milk protein gene expression as a functional marker of lactation and cell viability. Mammary explants from pregnant tammars and mice showed that milk protein gene expression was significantly elevated after 3 days of culture with lactogenic hormones. The subsequent removal of exogenous hormones from the media for 10 days resulted in the down-regulation of milk protein genes. Surprisingly, mammary explants remained hormone responsive and expression of milk protein genes was re-induced after a second challenge with lactogenic hormones. Furthermore, the alveolar architecture was maintained. Global functional microarray analysis showed that classic involution markers were not differentially expressed, although two stress-induced survival genes were significantly up-regulated. We report that a population of mammary epithelial cells have an intrinsic capacity to remain viable and hormone responsive for extended periods in chemically defined media without any exogenous macromolecules. We propose that the mammary explant culture model uncouples the first phase of involution, as milk accumulation that normally provides involution stimuli is absent in this culture model allowing a population of cells to survive.

• Identification, characterization and expression of cathelicidin in the pouch young of tammar wallaby (Macropus eugenii).

  Authors: Kerry A Daly, Matthew R Digby, Christophe Lefévre, Kevin R Nicholas, Elizabeth M Deane, Peter Williamson

  Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 04/2008; 149(3):524-33.

  Antimicrobial peptides, such as cathelicidin, are an evolutionarily old defense system. However they have more complex actions than just simply their antimicrobial effects, including immunoregulationAntimicrobial peptides, such as cathelicidin, are an evolutionarily old defense system. However they have more complex actions than just simply their antimicrobial effects, including immunoregulation and interaction with the adaptive immune system. In this study we have characterized several novel cathelicidin-like peptides from the tammar wallaby (Macropus eugenii). The tammar cathelicidin-like (MaeuCath) mRNA were isolated based on the conservation of the cathelin-like amino terminus. Mature MaeuCath peptides were positively charged with hydrophobic carboxyl tails, features that are fundamental for antimicrobial function. MaeuCath1 was induced in tammar leukocytes in response to pathogen-associated molecular patterns from both gram positive and negative bacteria. In addition, we also examined the expression of MaeuCath1 in the primary and secondary lymphoid organs of the tammar neonate throughout early pouch life. The results from this study demonstrate the importance that MaeuCath1 may play in innate defense of the marsupial young, especially in the mucosal organs. Such expression of antimicrobial peptides may form part of the immune strategies of marsupials for neonatal survival during their post-partum development.

• Uteroplacental insufficiency alters the mammary gland response to lactogenic hormones in vitro.

  Authors: Rachael O'Dowd, Mary E Wlodek, Kevin R Nicholas

  Reproduction, fertility, and development. 02/2008; 20(4):460-5.

  Adequate mammary development and coordinated actions of lactogenic hormones are essential for the initiation of lactation. Pregnancies compromised by uteroplacental insufficiency impair mammaryAdequate mammary development and coordinated actions of lactogenic hormones are essential for the initiation of lactation. Pregnancies compromised by uteroplacental insufficiency impair mammary development and lactation, further slowing postnatal growth. It is not known whether the initiation of lactation or galactopoesis is compromised. Uteroplacental insufficiency induced in rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on Day 18 of gestation preceded collection of mammary tissue on Day 20 of pregnancy. Mammary explants were cultured with combinations of insulin, cortisol and prolactin and analysed for alpha-lactalbumin and beta-casein gene expression. Mammary tissue from late pregnant Restricted rats had elevated alpha-lactalbumin, but not beta-casein, mRNA, which is consistent with premature lactogenesis resulting from an early decline in peripheral maternal progesterone. Explants from Restricted rats were more responsive to hormone stimulation after 3 days in culture, indicating that compromised galactopoesis, not lactogenesis, most likely leads to the reduced growth of suckled pups.