SciLactis Ltd.

Hamilton, New Zealand

SciLactis Ltd.

Hamilton, New Zealand

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Stelwagen K.,SciLactis Ltd. | Phyn C.V.C.,DairyNZ Ltd. | Davis S.R.,LIC | Guinard-Flament J.,Agrocampus Ouest | And 3 more authors.
Journal of Dairy Science | Year: 2013

Most dairy cows throughout the world are milked twice daily. In intensive dairying systems, however, it is not uncommon to increase milking frequency to between 3 and 6 times daily to increase milk production. Reducing milking frequency is much less common; however, once-daily milking of dairy cows, practiced either strategically during certain parts of the lactation or for the entire lactation, is not uncommon in key dairying countries where less emphasis is placed on milk production per cow. The practice fits well with more extensive dairy production systems, particularly those based on grazed pasture. A feature of once-daily milking is that it reduces milk yield by approximately 22%, depending on stage of lactation, breed, and parity, and it may adversely affect lactation length and persistency. However, it can offer several positive farm management options, especially related to labor requirements and farm working expenses. In addition, it may provide a tool to better manage the metabolism and energy balance of cows during early lactation or during periods of pasture deficit, and it may help to improve reproductive performance and animal health and welfare. Once-daily milking, representing one extreme of the mammary function spectrum, has attracted considerable research interest over the years. Consequently, substantial scientific information is available on its effects on mammary function, at both the physiological and molecular levels. This review focuses instead on the management of the cow milked once daily, covering the production response in relation to breed, stage of lactation, and parity, and its effect on energy status, reproduction, health and welfare, as well as on milk composition and processability. © 2013 American Dairy Science Association.


Singh K.,Agresearch Ltd. | Molenaar A.J.,Agresearch Ltd. | Swanson K.M.,Agresearch Ltd. | Gudex B.,Livestock Improvement Corporation | And 3 more authors.
Animal | Year: 2012

A potential role for epigenetic mechanisms in the regulation of mammary function in the dairy cow is emerging. Epigenetics is the study of heritable changes in genome function that occur because of chemical changes rather than DNA sequence changes. DNA methylation is an epigenetic event that results in the silencing of gene expression and may be passed on to the next generation. However, recent studies investigating different physiological states and changes in milk protein gene expression suggest that DNA methylation may also play an acute, regulatory, role in gene transcription. This overview will highlight the role of DNA methylation in the silencing of milk protein gene expression during mastitis and mammary involution. Moreover, environmental factors such as nutrition may induce epigenetic modifications of gene expression. The current research investigating the possibility of in utero, hence cross-generational, epigenetic modifications in dairy cows will also be discussed. Understanding how the mammary gland responds to environmental cues provides a potential to enhance milk production not only of the dairy cow but also of her daughter. © Copyright The Animal Consortium 2012.


Wheeler T.T.,Agresearch Ltd. | Smolenski G.A.,Agresearch Ltd. | Harris D.P.,Agresearch Ltd. | Gupta S.K.,Agresearch Ltd. | And 4 more authors.
Animal | Year: 2012

Milk is a source of bioactive molecules with wide-ranging functions. Among these, the immune properties have been the best characterised. In recent years, it has become apparent that besides the immunoglobulins, milk also contains a range of minor immune-related proteins that collectively form a significant first line of defence against pathogens, acting both within the mammary gland itself as well as in the digestive tract of the suckling neonate. We have used proteomics technologies to characterise the repertoire of host-defence-related milk proteins in detail, revealing more than 100 distinct gene products in milk, of which at least 15 are known host-defence-related proteins. Those having intrinsic antimicrobial activity likely function as effector proteins of the local mucosal immune defence (e.g. defensins, cathelicidins and the calgranulins). Here, we focus on the activities and biological roles of the cathelicidins and mammary serum amyloid A. The function of the immune-related milk proteins that do not have intrinsic antimicrobial activity is also discussed, notably lipopolysaccharide-binding protein, RNase4, RNase5/angiogenin and cartilage-glycoprotein 39 kDa. Evidence is shown that at least some of these facilitate recognition of microbes, resulting in the activation of innate immune signalling pathways in cells associated with the mammary and/or gut mucosal surface. Finally, the contribution of the bacteria in milk to its functionality is discussed. These investigations are elucidating how an effective first line of defence is achieved in the bovine mammary gland and how milk contributes to optimal digestive function in the suckling calf. This study will contribute to a better understanding of the health benefits of milk, as well as to the development of high-value ingredients from milk. © Copyright The Animal Consortium 2011.


Stelwagen K.,SciLactis Ltd | Singh K.,Agresearch Ltd.
Journal of Mammary Gland Biology and Neoplasia | Year: 2014

Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species. © 2013 Springer Science+Business Media New York.


Smolenski G.A.,Agresearch Ltd. | Broadhurst M.K.,Agresearch Ltd. | Stelwagen K.,SciLactis Ltd | Haigh B.J.,Agresearch Ltd. | Wheeler T.T.,Agresearch Ltd.
Proteome Science | Year: 2014

Background: Milk contains a range of proteins of moderate or low abundance that contribute to host defence. Characterisation of these proteins, the extent to which their abundance is regulated by pathogenic stimuli, and the variability of their response between and within individual animals would facilitate a better understanding of the molecular basis for this important function of milk.Results: We have characterised the host defence proteins in bovine milk and their responses to intra-mammary infection by a common Gram positive mastitis pathogen, Streptococcus uberis, using a combination of 2D gel electrophoresis and GeLC mass spectrometry. In total, 68 host defence-associated proteins were identified, 18 of which have a direct antimicrobial function, 23 of which have a pathogen-recognition function, and 27 of which have a role in modulating inflammatory or immune signalling. The responsiveness of seven proteins was quantified by western blotting; validating the proteomic analyses, quantifying the within- and between animal variability of the responses, and demonstrating the complexity and specificity of the responses to this pathogen.Conclusions: These data provide a foundation for understanding the role of milk in host-microbe interaction. Furthermore they provide candidate biomarkers for mastitis diagnosis, and will inform efforts to develop dairy products with improved health-promoting properties. © 2014 Smolenski et al.; licensee BioMed Central Ltd.


Murney R.,Agresearch Ltd. | Murney R.,Massey University | Stelwagen K.,SciLactis Ltd. | Wheeler T.T.,Agresearch Ltd. | And 2 more authors.
Journal of Dairy Science | Year: 2015

In dairy cows, short-term changes of milking frequency in early lactation have been shown to produce an immediate and a long-term effect on milk yield in stall-fed cows. The effect is controlled locally within mammary glands and could be a function of either secretory mammary epithelial cell number or activity. To resolve this and determine its applicability in other feed management systems, a unilateral milking frequency experiment was conducted with udder halves of 17 multiparous, pasture-fed dairy cows milked either 4 times (4×) or once a day (1×) for 14d from 5 ± 2d in milk. Mean half-udder milk yield during the treatment period was higher from the 4× compared with 1× udder halves and continued to be higher until 200d in milk once returned to twice a day milking. Mammary biopsies were obtained on d 14 of treatment from both udder halves of 10 cows. Proliferation of mammary cells was higher in 4× udder halves compared with 1×, whereas no difference in apoptosis levels was detected. Abundance of αS1-casein, β-casein, α-lactalbumin, and β-lactoglobulin mRNA was higher in tissue samples from 4× udder halves compared with 1×, whereas lactoferrin mRNA abundance was lower in 4× udder halves. In summary, change in milking frequency during early lactation affects proliferation of mammary cells as well as expression of the major milk protein genes, which both contribute to the observed changes in milk yield during and after unilateral milking frequency treatment. © 2015 American Dairy Science Association.


PubMed | Agresearch Ltd., SciLactis Ltd. and University of Maryland College Park
Type: Journal Article | Journal: Journal of dairy science | Year: 2015

In dairy cows, extended periods of nonmilking results in reduced milk secretion, modifications in milk composition, and eventually involution of the mammary glands. The aim of this study was to determine the effect of extended nonmilking periods on the recovery of milk yield and composition, and levels of prolactin and insulin-like growth factor-I in pasture-fed cows after resuming milking. Pasture-fed, primiparous, nonpregnant, Friesian dairy cows at mid lactation (mean standard deviation, 97 2d in milk, 14.0 2.5 L/d) were divided into 3 groups (n=6 per group). The cows were subjected to nonmilking periods of 7, 14, or 28d. Twice-daily milking was resumed for 7d following the nonmilking periods. Milk yield recoveries at the end of the 7-d remilking period were 91, 51, and 29% for the 7, 14, and 28-d nonmilked groups, respectively. The somatic cell count declined to less than 400,000 cells/mL by d 3 and 6 of remilking for the 7- and 14-d-nonmilked groups, respectively, but remained greater than 800,000 cells/mL in the 28-d-nonmilked group through the 7-d remilking period. By d 7 of remilking, the somatic cell count for the 7-d-nonmilked group was not different from pretrial values. Upon remilking, the milk fat content returned to pretrial values for the 7- and 14-d-nonmilked groups, although it remained lower than pretrial for the 28-d-nonmilked group. All 3 nonmilked groups had a higher milk protein content following 7d of remilking, compared with pretrial values. The lactose content returned to pretrial values for the 7-d-nonmilked group but remained lower for the 14- and 28-d-nonmilked groups. Circulating prolactin concentrations increased once remilking was resumed, compared with the pretrial and nonmilking periods. Prolactin concentrations did not majorly differ between the groups, with the levels upon 7d of remilking remaining higher than the pretrial concentrations and the nonmilked periods. Plasma concentrations of insulin-like growth factor-I increased during the nonmilking period and were greater in all 3 nonmilked groups on d 1 of remilking than pretrial values and returned to pretrial concentrations following remilking for the 7-d-nonmilked group, whereas the 14- and 28-d-nonmilked groups remained higher than the pretrial values. These data indicate that the process of involution is fully reversed after remilking following 7d of milk stasis but more extended periods of nonmilking prevent the complete recovery of lactation. However, even after 28d of milk stasis, the milk synthesis capacity of the mammary gland could still be partially recovered.


PubMed | Massey University, Agresearch Ltd. and SciLactis Ltd.
Type: Journal Article | Journal: Journal of dairy science | Year: 2015

Prolactin (PRL) is important in the regulation of milk synthesis in mammary epithelial cells (MEC). In cattle, circulating levels of PRL are not limiting, suggesting the possible involvement of other factors that may control the response to PRL at the cellular level. The effects of milking frequency (MF) on milk synthesis are controlled locally within mammary glands and involve PRL signaling. To further investigate this relationship between MF and PRL signaling, udder halves of 17 dairy cows were milked either 4 times a day (4) or once a day (1) for 14 d in early lactation. Mammary biopsies were obtained 3 to 5h following milking from both udder halves of 10 cows, and changes in PRL and associated pathways were measured. The abundance of STAT5A mRNA was higher after 4 milking, whereas that of the PRL receptor (PRLR) and STAT3 were lower relative to that after 1 milking. In 4 mammary tissues, the protein levels of STAT5, activated STAT5, and 1-integrin were higher, whereas the those of the long isoform of PRL receptor and activated STAT3 were lower than 1 tissues. The activation of STAT5 correlated strongly with major milk protein mRNA abundance (r=0.86 to 0.94) and 1-integrin protein levels (r=0.91). These results confirm that major milk protein gene expression is associated with STAT5 activation and suggests that the STAT5 and 1-integrin signaling pathways are linked. Modulation of 1-integrin abundance in response to changes in MF may be a mechanism that controls the MEC ability to respond to PRL and therefore its secretory activity.


PubMed | Agresearch Ltd. and SciLactis Ltd.
Type: Journal Article | Journal: Journal of dairy science | Year: 2016

In dairy cows, mammary gland involution, and thus a decline in milk production, occurs following peak lactation. To examine the cell signaling pathways regulating involution of the mammary gland, signal transducer and activator of transcription factors (STAT5 and 3), suppressors of cytokine signaling (SOCS1-3 and CIS), insulin-like growth factors (IGF1 and 2), and protein kinase B (Akt) were examined. Mammary involution was induced by termination of milking, and alveolar tissue was collected from 52 nonpregnant, primiparous, mid-lactation Holstein-Friesian cows killed at 0, 6, 12, 18, 24, 36, 72, and 192h postmilking. Qualitative immunohistochemistry showed that activated (phosphorylated) STAT5-P was localized in nuclei of mammary epithelial cells at the early time points, with detection levels decreasing by 24h postmilking. In contrast, STAT3-P was barely detectable at the early time points, with detection levels increasing following longer postmilking periods. This was supported by Western analysis, which showed a decline in STAT5 and STAT5-P protein levels by 24h postmilking, no change in STAT3 levels, and an increase in STAT3-P protein (barely detectable at the early time points) by 72h postmilking. Quantitative real-time reverse transcription PCR analysis showed SOCS1 and SOCS3 mRNA increased by 72h postmilking compared with 6h postmilking. The SOCS2 mRNA remained unchanged across the time series, whereas CIS decreased by 18h postmilking and remained lower compared with that at 6h postmilking until 72h postmilking. The IGF1 mRNA increased by 192h postmilking, whereas IGF2 mRNA decreased by 18h postmilking compared with 6h postmilking. The IGFBP5 mRNA and protein levels of Akt and Akt-P remained unchanged over the time series. These results show that reciprocal activation of STAT5 and STAT3 occurs at the onset of mammary gland involution in the bovine, albeit at a slower rate than in rodents. Mathematical modeling of the pathways indicated that activated STAT3 could block the STAT5 pathway by upregulating SOCS3. The regulation of IGF1-Akt signaling suggests that by 192h postmilking in dairy cows, the involution process is still in the reversible phase, with quiescent mammary epithelial cells not yet in the senescent phase.


PubMed | Massey University, Agresearch Ltd. and SciLactis Ltd.
Type: Journal Article | Journal: Journal of dairy science | Year: 2015

In dairy cows, short-term changes in milking frequency (MF) in early lactation have been shown to produce both an immediate and a long-term effect on milk yield. The effect of MF on milk yield is controlled locally within mammary glands and could be a function of changes in either number or activity of secretory mammary epithelial cells (MEC). Insulin-like growth factor I (IGF-I) signaling is one candidate factor that could mediate these effects, as it can be controlled locally within mammary glands. Both MEC number and activity can be affected by IGF-I signaling by activating the phosphoinositide 3-kinase (PI3K)/Akt and extracellular-signal-regulated kinase (ERK)1/2 pathways. To investigate the relationship between MF and IGF-I signaling, udder halves of 17 dairy cows were milked either 4 times a day (4) or once a day (1) for 14 d in early lactation. On d 14, between 3 and 5 h following milking, mammary biopsies were obtained from 10 cows from both udder halves, and changes in the expression of genes associated with IGF-I signaling and the activation of the PI3K/Akt and ERK1/2 pathways were measured. The mRNA abundance of IGF type I receptor, IGF binding protein (IGFBP)-3, and IGFBP-5 were lower following 4 milking relative to 1 milking. However, the mRNA abundance of IGF-I was not affected by MF. Both IGFBP3 and IGFBP5 are thought to inhibit IGF-I; therefore, decreases in their mRNA abundance may serve to stimulate the IGF-I signal in the 4-milked mammary gland. The activation of PI3K/Akt pathway was lower in response to 4 milking relative to 1, and the activation of the ERK1/2 was unaffected by MF, suggesting that they do not mediate the effects of MF.

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