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Shannon L. Kelleher - One of the best experts on this subject based on the ideXlab platform.
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A common genetic variant in zinc transporter ZnT2 (Thr288Ser) is present in women with low milk volume and alters lysosome Function and cell energetics
American journal of physiology. Cell physiology, 2020Co-Authors: Olivia C. Rivera, Annie Gagnon, Donna T. Geddes, Shiran Barber-zucker, Raz Zarivach, David I. Soybel, Shannon L. KelleherAbstract:Suboptimal lactation is a common, yet underappreciated cause for early cessation of breastfeeding. Molecular regulation of Mammary Gland Function is critical to the process lactation; however, physiological factors underlying insufficient milk production are poorly understood. The zinc (Zn) transporter ZnT2 is critical for regulation of Mammary Gland development and maturation during puberty, lactation, and postlactation Gland remodeling. Numerous genetic variants in the gene encoding ZnT2 (SLC30A2) are associated with low milk Zn concentration and result in severe Zn deficiency in exclusively breastfed infants. However, the Functional impacts of genetic variation in ZnT2 on key Mammary epithelial cell Functions have not yet been systematically explored at the cellular level. Here we determined a common mutation in SLC30A2/ZnT2 substituting serine for threonine at amino acid 288 (Thr288Ser) was found in 20% of women producing low milk volume (n = 2/10) but was not identified in women producing normal volume. Exploration of cellular consequences in vitro using phosphomimetics showed the serine substitution promoted preferential phosphorylation of ZnT2, driving localization to the lysosome and increasing lysosome biogenesis and acidification. While the substitution did not initiate lysosome-mediated cell death, cellular ATP levels were significantly reduced. Our findings demonstrate the Thr288Ser mutation in SLC30A2/ZnT2 impairs critical Functions of Mammary epithelial cells and suggest a role for genetic variation in the regulation of milk production and lactation performance.
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Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysFunction in women with common genetic variants in SLC30A2
Scientific reports, 2019Co-Authors: Shannon L. Kelleher, Annie Gagnon, Olivia C. Rivera, Steven D. Hicks, Molly C. Carney, Samina AlamAbstract:Studies in humans and pre-clinical animal models show milk-derived miRNAs reflect Mammary Gland Function during lactation. The zinc transporter SLC30A2/ZnT2 plays a critical role in Mammary Gland Function; ZnT2-null mice have profound defects in Mammary epithelial cell (MEC) polarity and secretion, resulting in sub-optimal lactation. Non-synonymous genetic variation in SLC30A2 is common in humans, and several common ZnT2 variants are associated with changes in milk components that suggest breast dysFunction in women. To identify novel mechanisms through which dysFunction might occur, milk-derived miRNA profiles were characterized in women harboring three common genetic variants in SLC30A2 (D103E, T288S, and Exon 7). Expression of ten miRNAs differed between genotypes, and contributed to distinct spatial separation. Studies in breast milk and cultured MECs confirmed expression of ZnT2 variants alters abundance of protein levels of several predicted mRNA targets critical for breast Function (PRLR, VAMP7, and SOX4). Moreover, bioinformatic analysis identified two novel gene networks that may underlie normal MEC Function. Thus, we propose that genetic variation in genes critical for normal breast Function such as SLC30A2 has important implications for lactation performance in women, and that milk-derived miRNAs can be used to identify novel mechanisms and for diagnostic potential.
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Molecular regulation of lactation: The complex and requisite roles for zinc.
Archives of biochemistry and biophysics, 2016Co-Authors: Sooyeon Lee, Shannon L. KelleherAbstract:Lactation provides many health benefits to the nursing infant and breastfeeding mother. In order to successfully breastfeed, the Mammary Gland must expand and differentiate to activate numerous processes that regulate milk production and secretion. This involves a complex series of molecular, biochemical and cellular events driven largely by lactogenic hormones. Recent advances implicate zinc as a critical modulator of Mammary Gland Function. Here, we provide an overview of our current understanding of the role and regulation of zinc in promoting proliferation, differentiation and secretion in the Mammary Gland during lactation, and highlight critical gaps in knowledge.
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Exome Sequencing of SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants Associated with Breast Cell DysFunction
Journal of Mammary Gland Biology and Neoplasia, 2015Co-Authors: Samina Alam, David I. Soybel, Stephen R Hennigar, Carla Gallagher, Shannon L. KelleherAbstract:The zinc (Zn) transporter ZnT2 ( SLC30A2 ) is expressed in specialized secretory cells including breast, pancreas and prostate, and imports Zn into mitochondria and vesicles. Mutations in SLC30A2 substantially reduce milk Zn concentration ([Zn]) and cause severe Zn deficiency in exclusively breastfed infants. Recent studies show that ZnT2-null mice have low milk [Zn], in addition to profound defects in Mammary Gland Function during lactation. Here, we used breast milk [Zn] to identify novel non-synonymous ZnT2 variants in a population of lactating women. We also asked whether specific variants induce disturbances in intracellular Zn management or cause cellular dysFunction in Mammary epithelial cells. Healthy, breastfeeding women were stratified into quartiles by milk [Zn] and exonic sequencing of SLC30A2 was performed. We found that 36 % of women tested carried non-synonymous ZnT2 variants, all of whom had milk Zn levels that were distinctly above or below those in women without variants. We identified 12 novel heterozygous variants. Two variants (D^103E and T^288S) were identified with high frequency (9 and 16 %, respectively) and expression of T^288S was associated with a known hallmark of breast dysFunction (elevated milk sodium/potassium ratio). Select variants (A^28D, K^66N, Q^71H, D^103E, A^105P, Q^137H, T^288S and T^312K) were characterized in vitro. Compared with wild-type ZnT2, these variants were inappropriately localized, and most resulted in either ‘loss-of-Function’ or ‘gain-of-Function’, and altered sub-cellular Zn pools, Zn secretion, and cell cycle check-points. Our study indicates that SLC30A2 variants are common in this population, dysregulate Zn management and can lead to breast cell dysFunction. This suggests that genetic variation in ZnT2 could be an important modifier of infant growth/development and reproductive health/disease. Importantly, milk [Zn] level may serve as a bio-reporter of breast Function during lactation.
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essential role for zinc transporter 2 znt2 mediated zinc transport in Mammary Gland development and Function during lactation
Journal of Biological Chemistry, 2015Co-Authors: Sooyeon Lee, Samina Alam, Stephen R Hennigar, Keigo Nishida, Shannon L. KelleherAbstract:The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting Mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating Mammary Gland and non-secreting MECs, highlighting the importance of ZnT2 in general Mammary Gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on Mammary Gland development, Function during lactation, and milk composition. We found that ZnT2 was primarily expressed in MECs and to a limited extent in macrophages in the nulliparous Mammary Gland and loss of ZnT2 impaired Mammary expansion during development. Secondly, we found that lactating ZnT2-null mice had substantial defects in Mammary Gland architecture and MEC Function during secretion, including fewer, condensed and disorganized alveoli, impaired Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume and milk containing less protein, fat, and lactose compared with wild-type littermates, implicating ZnT2 in the regulation of Mammary differentiation and optimal milk production during lactation. Together, these results demonstrate that ZnT2-mediated zinc transport is critical for Mammary Gland Function, suggesting that defects in ZnT2 not only reduce milk zinc concentration but may compromise breast health and increase the risk for lactation insufficiency in lactating women.
Samina Alam - One of the best experts on this subject based on the ideXlab platform.
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Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysFunction in women with common genetic variants in SLC30A2
Scientific reports, 2019Co-Authors: Shannon L. Kelleher, Annie Gagnon, Olivia C. Rivera, Steven D. Hicks, Molly C. Carney, Samina AlamAbstract:Studies in humans and pre-clinical animal models show milk-derived miRNAs reflect Mammary Gland Function during lactation. The zinc transporter SLC30A2/ZnT2 plays a critical role in Mammary Gland Function; ZnT2-null mice have profound defects in Mammary epithelial cell (MEC) polarity and secretion, resulting in sub-optimal lactation. Non-synonymous genetic variation in SLC30A2 is common in humans, and several common ZnT2 variants are associated with changes in milk components that suggest breast dysFunction in women. To identify novel mechanisms through which dysFunction might occur, milk-derived miRNA profiles were characterized in women harboring three common genetic variants in SLC30A2 (D103E, T288S, and Exon 7). Expression of ten miRNAs differed between genotypes, and contributed to distinct spatial separation. Studies in breast milk and cultured MECs confirmed expression of ZnT2 variants alters abundance of protein levels of several predicted mRNA targets critical for breast Function (PRLR, VAMP7, and SOX4). Moreover, bioinformatic analysis identified two novel gene networks that may underlie normal MEC Function. Thus, we propose that genetic variation in genes critical for normal breast Function such as SLC30A2 has important implications for lactation performance in women, and that milk-derived miRNAs can be used to identify novel mechanisms and for diagnostic potential.
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Exome Sequencing of SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants Associated with Breast Cell DysFunction
Journal of Mammary Gland Biology and Neoplasia, 2015Co-Authors: Samina Alam, David I. Soybel, Stephen R Hennigar, Carla Gallagher, Shannon L. KelleherAbstract:The zinc (Zn) transporter ZnT2 ( SLC30A2 ) is expressed in specialized secretory cells including breast, pancreas and prostate, and imports Zn into mitochondria and vesicles. Mutations in SLC30A2 substantially reduce milk Zn concentration ([Zn]) and cause severe Zn deficiency in exclusively breastfed infants. Recent studies show that ZnT2-null mice have low milk [Zn], in addition to profound defects in Mammary Gland Function during lactation. Here, we used breast milk [Zn] to identify novel non-synonymous ZnT2 variants in a population of lactating women. We also asked whether specific variants induce disturbances in intracellular Zn management or cause cellular dysFunction in Mammary epithelial cells. Healthy, breastfeeding women were stratified into quartiles by milk [Zn] and exonic sequencing of SLC30A2 was performed. We found that 36 % of women tested carried non-synonymous ZnT2 variants, all of whom had milk Zn levels that were distinctly above or below those in women without variants. We identified 12 novel heterozygous variants. Two variants (D^103E and T^288S) were identified with high frequency (9 and 16 %, respectively) and expression of T^288S was associated with a known hallmark of breast dysFunction (elevated milk sodium/potassium ratio). Select variants (A^28D, K^66N, Q^71H, D^103E, A^105P, Q^137H, T^288S and T^312K) were characterized in vitro. Compared with wild-type ZnT2, these variants were inappropriately localized, and most resulted in either ‘loss-of-Function’ or ‘gain-of-Function’, and altered sub-cellular Zn pools, Zn secretion, and cell cycle check-points. Our study indicates that SLC30A2 variants are common in this population, dysregulate Zn management and can lead to breast cell dysFunction. This suggests that genetic variation in ZnT2 could be an important modifier of infant growth/development and reproductive health/disease. Importantly, milk [Zn] level may serve as a bio-reporter of breast Function during lactation.
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essential role for zinc transporter 2 znt2 mediated zinc transport in Mammary Gland development and Function during lactation
Journal of Biological Chemistry, 2015Co-Authors: Sooyeon Lee, Samina Alam, Stephen R Hennigar, Keigo Nishida, Shannon L. KelleherAbstract:The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting Mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating Mammary Gland and non-secreting MECs, highlighting the importance of ZnT2 in general Mammary Gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on Mammary Gland development, Function during lactation, and milk composition. We found that ZnT2 was primarily expressed in MECs and to a limited extent in macrophages in the nulliparous Mammary Gland and loss of ZnT2 impaired Mammary expansion during development. Secondly, we found that lactating ZnT2-null mice had substantial defects in Mammary Gland architecture and MEC Function during secretion, including fewer, condensed and disorganized alveoli, impaired Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume and milk containing less protein, fat, and lactose compared with wild-type littermates, implicating ZnT2 in the regulation of Mammary differentiation and optimal milk production during lactation. Together, these results demonstrate that ZnT2-mediated zinc transport is critical for Mammary Gland Function, suggesting that defects in ZnT2 not only reduce milk zinc concentration but may compromise breast health and increase the risk for lactation insufficiency in lactating women.
Young Ah Seo - One of the best experts on this subject based on the ideXlab platform.
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Marginal Maternal Zinc Deficiency in Lactating Mice Reduces Secretory Capacity and Alters Milk Composition
The Journal of nutrition, 2012Co-Authors: Colleen Dempsey, Young Ah Seo, Nicholas H. Mccormick, Thomas P. Croxford, Arthur Grider, Shannon L. KelleherAbstract:Dietary analysis predicts that marginal Zn deficiency is common in women of reproductive age. The lack of reliable biomarkers limits the capacity to assess Zn status and consequently understand effects of maternal Zn deficiency. We determined effects of marginal maternal Zn deficiency on Mammary Gland Function, milk secretion, and milk composition in mice. Mice (n = 12/diet) were fed marginal (ZD; 15 mg Zn/kg diet) or adequate (ZA; 30 mg Zn/kg diet) Zn diets for 30 d prior to conception through mid-lactation. Mice fed the ZD had a higher plasma Zn concentration (~20%; P < 0.05) but lower milk Zn concentration (~15%; P < 0.05) compared with mice fed the ZA. ZnT2 abundance was higher (P < 0.05) in mice fed the ZD compared with mice fed the ZA; no effect on ZnT4 abundance was detected. The Zn concentration of Mammary Gland mitochondria tended to be ~40% greater in mice fed ZD (P = 0.07); this was associated with apoptosis and lower milk secretion (~80%; P < 0.01). Total milk protein was ~25% higher (P < 0.05), although the abundance of the major milk proteins (caseins and whey acidic protein) was lower (P < 0.05) in mice fed the ZD. Proteomic analysis of milk proteins revealed an increase (P < 0.05) in four proteins in mice fed the ZD. These findings illustrate that marginal maternal Zn deficiency compromises Mammary Gland Function and milk secretion and alters milk composition. This suggests that lactating women who consume inadequate Zn may not produce and/or secrete an adequate amount of high quality milk to provide optimal nutrition to their developing infant.
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Functional analysis of two single nucleotide polymorphisms in slc30a2 znt2 implications for Mammary Gland Function and breast disease in women
Physiological Genomics, 2010Co-Authors: Young Ah Seo, Shannon L. KelleherAbstract:Zinc transporter 2 (ZnT2) plays a major role in zinc (Zn) export from the Mammary Gland. Recently, we determined that ZnT2 is associated with secretory vesicles reflecting its role in Zn secretion ...
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Functional analysis of two single nucleotide polymorphisms in SLC30A2 (ZnT2): implications for Mammary Gland Function and breast disease in women
Physiological genomics, 2010Co-Authors: Young Ah Seo, Shannon L. KelleherAbstract:Zinc transporter 2 (ZnT2) plays a major role in zinc (Zn) export from the Mammary Gland. Recently, we determined that ZnT2 is associated with secretory vesicles reflecting its role in Zn secretion during lactation. Herein, we identified two distinct single nucleotide polymorphisms (SNPs) in SLC30A2, which encodes ZnT2. SNP1 (rs35235055) results in a leucine-to-proline substitution (Leu23Pro), while SNP2 (rs35623192) results in an arginine-to-cysteine substitution (Arg340Cys). We examined the localization and Function of each SNP in cells generated to express these polymorphic variants. SNP1 was mislocalized to lysosomes, while SNP2 was mislocalized to the Golgi apparatus. FluoZin-3 fluorescence illustrated increased lysosomal accumulation of Zn in cells expressing SNP1 concomitant with the abrogation of Zn secretion. In contrast, ectopic expression of SNP2 was associated with the expansion of cytoplasmic Zn pools, elevated reactive oxygen species, and increased Zn efflux. Taken together, our data indicate that polymorphic variants in ZnT2 distinctly alter Mammary cell Zn metabolism. We speculate that these SNPs may compromise Mammary cell Function, which may have important implications in human health and breast disease.
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(ZnT2): implications for Mammary Gland Function and breast disease in women
2010Co-Authors: Young Ah Seo, Shannon L. KelleherAbstract:leucine-to-proline substitution (Leu 23 Pro), while SNP2 (rs35623192) results in an arginine-to-cysteine substitution (Arg 340 Cys). We examined the localization and Function of each SNP in cells generated to express these polymorphic variants. SNP1 was mislocalized to lysosomes, while SNP2 was mislocalized to the Golgi apparatus. FluoZin-3 fluorescence illustrated increased lysosomal accumulation of Zn in cells expressing SNP1 concomitant with the abrogation of Zn secretion. In contrast, ectopic expression of SNP2 was associated with the expansion of cytoplasmic Zn pools, elevated reactive oxygen species, and increased Zn efflux. Taken together, our data indicate that polymorphic variants in ZnT2 distinctly alter Mammary cell Zn metabolism. We speculate that these SNPs may compromise Mammary cell Function, which may have important implications in human health and breast disease.
Kevin R. Nicholas - One of the best experts on this subject based on the ideXlab platform.
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Transcriptome analysis of Mammary epithelial cell gene expression reveals novel roles of the extracellular matrix.
Biochemistry and biophysics reports, 2017Co-Authors: Stephen Wanyonyi, Christophe Lefevre, Amit Kumar, Ryan Du Preez, Kevin R. NicholasAbstract:Abstract Background The unique lactation strategy of the tammar wallaby (Macropus eugeni) has been invaluable in evaluating the role of lactogenic hormones and the extracellular matrix (ECM) in the local control of Mammary Gland Function. However molecular pathways through which hormones and ECM exert their effect on wallaby Mammary Gland Function remain unclear. This study undertakes transcriptome analysis of wallaby Mammary epithelial cells (WallMEC) following treatment with Mammary ECM from two distinct stages of lactation. Methods WallMEC from MID lactation Mammary Glands were cultured on ECM from MID or LATE lactation and treated for 5 days with 1 μg/ml cortisol, 1 μg/ml insulin, 0.2 µg/ml prolactin, 650 pg/ml triodothyronine and 1 pg/ml estradiol to induce lactation. WallMEC RNA from triplicate ECM treatments was used to perform RNAseq. Results ECM from MID and LATE lactation differentially regulated key genes in sugar and lipid metabolism. Seven pathways including galactose metabolism, lysosome, cell adhesion molecules (CAM), p53 signaling, the complement and coagulation and Nod-like receptor signaling pathways were only significantly responsive to ECM in the presence of hormones. The raw RNA-seq data for this project are available on the NCBI Gene Expression Omnibus (GEO) browser (accession number GSE81210). Conclusions A potential role of ECM in regulation of the caloric content of milk, among other Functions including apoptosis, cell proliferation and differentiation has been identified. General significance This study has used a non-eutherian lactation model to demonstrate the synergy between ECM and hormones in the local regulation of Mammary Function.
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Comparative analysis of caveolins in mouse and tammar wallaby: Role in regulating Mammary Gland Function
Gene, 2014Co-Authors: Sanjana Kuruppath, Julie A. Sharp, Christophe Lefevre, Robyn M. Murphy, Kevin R. NicholasAbstract: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.
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Acute involution in the tammar wallaby: Identification of genes and putative novel milk proteins implicated in Mammary Gland Function
Genomics, 2011Co-Authors: Elie Khalil, Christophe Lefevre, Matthew R. Digby, Peter C. Thomson, Sonia L. Mailer, Cate Pooley, Kevin R. NicholasAbstract: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.
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Fur seal adaptations to lactation: insights into Mammary Gland Function.
Current topics in developmental biology, 2006Co-Authors: Julie A. Sharp, Kylie N. Cane, Christophe Lefevre, John P. Y. Arnould, Kevin R. NicholasAbstract:The fur seal ( Arctocephalus spp. and Callorhinus spp., members of the pinniped family) is a mammal with the unusual capability to modulate its lactation cycle by turning milk production on and off without the typical mammalian regression and involution of the Mammary Gland. Lactation has evolved from constraints arising from the spatial and temporal separation of infant nursing and maternal foraging as the mother gives birth and feeds the pup on land while acquisition of nutrients for milk production occurs at sea. The lactation cycle begins with the female fur seal undergoing a perinatal fast of approximately 1 wk, after which time she departs the breeding colony to forage at sea. For the remainder of the long lactation period (116–540 days), the mother alternates between short periods ashore suckling the young with longer periods of up to 4 wk of foraging at sea. Milk production continues while foraging at sea, but at less than 20% the rate of production on land. Fur seals produce one of the richest milk reported, with a very high lipid content contributing up to 85% of total energy. This feature serves as an adaptation to the young's need to produce an insulating blubber layer against heat loss and to serve as an energy store when the mother is away foraging at sea. This atypical pattern of lactation means mothers have long periods with no suckling stimulus and can transfer high-energy milk rapidly while on land to minimize time away from foraging grounds. The absence of suckling stimulus and milk removal during foraging does not result in the onset of involution with associated apoptosis of Mammary secretory cells and a subsequent progressive breakdown of the cellular structure of the Mammary Gland. The mechanisms controlling lactation in the fur seal Mammary Gland have been investigated using molecular and cellular techniques. These findings have shed light on the processes by which the unique features of lactation in the fur seal are regulated.
Giovanni Bittante - One of the best experts on this subject based on the ideXlab platform.
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Integrated PTR-ToF-MS, GWAS and biological pathway analyses reveal the contribution of cow’s genome to cheese volatilome
Scientific Reports, 2018Co-Authors: Sara Pegolo, Matteo Bergamaschi, Flavia Gasperi, Franco Biasioli, Alessio Cecchinato, Giovanni BittanteAbstract:Volatile organic compounds (VOCs) are small molecules that contribute to the distinctive flavour of cheese which is an important attribute for consumer acceptability. To investigate whether cow’s genetic background might contribute to cheese volatilome, we carried out genome-wide association studies (GWAS) and pathway–based analyses for 173 spectrometric peaks tentatively associated with several VOCs obtained from proton-transfer-reaction mass spectrometry (PTR-ToF-MS) analyses of 1,075 model cheeses produced using raw whole-milk from Brown Swiss cows. Overall, we detected 186 SNPs associated with 120 traits, several of which mapped close to genes involved in protein ( e.g. CSN3 , GNRHR and FAM169A ), fat ( e.g. AGPAT3 , SCD5 , and GPAM ) and carbohydrate ( e.g. B3GNT2 , B4GALT1 , and PHKB ) metabolism. Gene set enrichment analysis showed that pathways connected with proteolysis/amino acid metabolism (purine and nitrogen metabolism) as well as fat metabolism (long-term potentiation) and Mammary Gland Function (tight junction) were overrepresented. Our results provide the first evidence of a putative link between cow’s genes and cheese flavour and offer new insights into the role of potential candidate loci and the biological Functions contributing to the cheese volatilome.
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Integrated PTR-ToF-MS, GWAS and biological pathway analyses reveal the contribution of cow's genome to cheese volatilome.
Scientific reports, 2018Co-Authors: Sara Pegolo, Matteo Bergamaschi, Flavia Gasperi, Franco Biasioli, Alessio Cecchinato, Giovanni BittanteAbstract:Volatile organic compounds (VOCs) are small molecules that contribute to the distinctive flavour of cheese which is an important attribute for consumer acceptability. To investigate whether cow’s genetic background might contribute to cheese volatilome, we carried out genome-wide association studies (GWAS) and pathway–based analyses for 173 spectrometric peaks tentatively associated with several VOCs obtained from proton-transfer-reaction mass spectrometry (PTR-ToF-MS) analyses of 1,075 model cheeses produced using raw whole-milk from Brown Swiss cows. Overall, we detected 186 SNPs associated with 120 traits, several of which mapped close to genes involved in protein (e.g. CSN3, GNRHR and FAM169A), fat (e.g. AGPAT3, SCD5, and GPAM) and carbohydrate (e.g. B3GNT2, B4GALT1, and PHKB) metabolism. Gene set enrichment analysis showed that pathways connected with proteolysis/amino acid metabolism (purine and nitrogen metabolism) as well as fat metabolism (long-term potentiation) and Mammary Gland Function (tight junction) were overrepresented. Our results provide the first evidence of a putative link between cow’s genes and cheese flavour and offer new insights into the role of potential candidate loci and the biological Functions contributing to the cheese volatilome.
