Skip to main content Accessibility help
×
×
Home

Does the circadian system regulate lactation?

  • K. Plaut (a1) and T. Casey (a1)
Abstract

Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the ‘setting’ of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition.

Copyright
Corresponding author
E-mail: kplaut@purdue.edu
References
Hide All
Aharoni, Y, Brosh, A, Ezra, E 2000. Short communication: prepartum photoperiod effect on milk yield and composition in dairy cows. Journal of Dairy Science 83, 27792781.
Akhtar, RA, Reddy, AB, Maywood, ES, Clayton, JD, King, VM, Smith, AG, Gant, TW, Hastings, MH, Kyriacou, CP 2002. Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Current Biology 12, 540550.
Andersson, H, Johnston, JD, Messager, S, Hazlerigg, D, Lincoln, G 2005. Photoperiod regulates clock gene rhythms in the ovine liver. General and Comparative Endocrinology 142, 357363.
Ando, H, Yanagihara, H, Hayashi, Y, Obi, Y, Tsuruoka, S, Takamura, T, Kaneko, S, Fujimura, A 2005. Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146, 56315636.
Andrade, BR, Salama, AA, Caja, G, Castillo, V, Albanell, E, Such, X 2008. Response to lactation induction differs by season of year and breed of dairy ewes. Journal of Dairy Science 91, 22992306.
Auchtung, TL, Kendall, PE, Salak-Johnson, JL, McFadden, TB, Dahl, GE 2003. Photoperiod and bromocriptine treatment effects on expression of prolactin receptor mRNA in bovine liver, mammary gland and peripheral blood lymphocytes. Journal of Endocrinology 179, 347356.
Auchtung, TL, Rius, AG, Kendall, PE, McFadden, TB, Dahl, GE 2005. Effects of photoperiod during the dry period on prolactin, prolactin receptor, and milk production of dairy cows. Journal of Dairy Science 88, 121127.
Auldist, MJ, Turner, SA, McMahon, CD, Prosser, CG 2007. Effects of melatonin on the yield and composition of milk from grazing dairy cows in New Zealand. Journal of Dairy Research 74, 5257.
Balsalobre, A, Damiola, F, Schibler, U 1998. A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93, 929937.
Barkova, EN, Nazarenko, EV, Zhdanova, EV 2005. Diurnal variations in qualitative composition of breast milk in women with iron deficiency. Bulletin of Experimental Biology and Medicine 140, 394396.
Bass, J, Takahashi, JS 2010. Circadian integration of metabolism and energetics. Science 330, 13491354.
Bauman, DE, Currie, WB 1980. Partitioning of nutrients during pregnancy and lactation: a review of mechanisms involving homeostasis and homeorhesis. Journal of Dairy Science 63, 15141529.
Bell, A, Bauman, D 1997. Adaptations of glucose metabolism during pregnancy and lactation. Journal of Mammary Gland Biology and Neoplasia 2, 265278.
Bell, AW, Bauman, DE, Currie, WB 1987. Regulation of nutrient partitioning and metabolism during pre- and postnatal growth. Journal of Animal Science 65, 186212.
Bernabucci, U, Basirico, L, Lacetera, N, Morera, P, Ronchi, B, Accorsi, PA, Seren, E, Nardone, A 2006. Photoperiod affects gene expression of leptin and leptin receptors in adipose tissue from lactating dairy cows. Journal of Dairy Science 89, 46784686.
Bitman, J, Wood, DL, Lefcourt, AM 1990. Rhythms in cholesterol, cholesteryl esters, free fatty acids, and triglycerides in blood of lactating dairy cows. Journal of Dairy Science 73, 948955.
Bitman, J, Kahl, S, Wood, DL, Lefcourt, AM 1994. Circadian and ultradian rhythms of plasma thyroid hormone concentrations in lactating dairy cows. American Journal of Physiology 266, R1797R1803.
Bosler, O, Beaudet, A 1985. VIP neurons as prime synaptic targets for serotonin afferents in rat suprachiasmatic nucleus: a combined radioautographic and immunocytochemical study. Journal of Neurocytology 14, 749763.
Brewer, M, Lange, D, Baler, R, Anzulovich, A 2005. SREBP-1 as a transcriptional integrator of circadian and nutritional cues in the liver. Journal of Biological Rhythms 20, 195205.
Brown, SA, Schibler, U 1999. The ins and outs of circadian timekeeping. Current Opinion in Genetics & Development 9, 588594.
Buhr, ED, Yoo, S-H, Takahashi, JS 2010. Temperature as a universal resetting cue for mammalian circadian oscillators. Science 330, 379385.
Casey, T, Patel, O, Dykema, K, Dover, H, Furge, K, Plaut, K 2009. Molecular signatures reveal the homeorhetic response to lactation may be orchestrated by circadian clocks. PLoS One 4, e7395.
Collier, RJ, Miller, MA, McLaughlin, CL, Johnson, HD, Baile, CA 2008. Effects of recombinant bovine somatotropin (rbST) and season on plasma and milk insulin-like growth factors I (IGF-I) and II (IGF-II) in lactating dairy cows. Domestic Animal Endocrinology 35, 1623.
Cubero, J, Narciso, D, Terron, P, Rial, R, Esteban, S, Rivero, M, Parvez, H, Rodriguez, AB, Barriga, C 2007. Chrononutrition applied to formula milks to consolidate infants’ sleep/wake cycle. Neuro Endocrinology Letters 28, 360366.
Dahl, GE 2008. Effects of short day photoperiod on prolactin signaling in dry cows: a common mechanism among tissues and environments?. Journal of Animal Science 86, 1014.
Dahl, GE, Petitclerc, D 2003. Management of photoperiod in the dairy herd for improved production and health. Journal of Animal Science 81 (suppl. 3), 1117.
Dahl, GE, Buchanan, BA, Tucker, HA 2000. Photoperiodic effects on dairy cattle: a review. Journal of Dairy Science 83, 885893.
Dahl, GE, Auchtung, TL, Kendall, PE 2002. Photoperiodic effects on endocrine and immune function in cattle. Reproduction Supplement 59, 191201.
Dahl, GE, Auchtung, TL, Reid, ED 2004. Manipulating milk production in early lactation through photoperiod changes and milking frequency. Veterinary Clinics of North America: Food Animal Practice 20, 675685.
Dahl, GE, Elsasser, TH, Capuco, AV, Erdman, RA, Peters, RR 1997. Effects of a long daily photoperiod on milk yield and circulating concentrations of insulin-like growth factor-I. Journal of Dairy Science 80, 27842789.
Damiola, F 2000. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes and Developement 14, 29502961.
Darlington, TK 1998. Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science 280, 15991600.
Darul, K, Kruczynska, H 2004. Effect of melatonin on biochemical variables of the blood in dairy cows. Acta Veterinaria Hungarica 52, 361367.
DeVries, TJ, von Keyserlingk, MA, Beauchemin, KA 2003. Short communication: diurnal feeding pattern of lactating dairy cows. Journal of Dairy Science 86, 40794082.
Drackley, JK 1999. ADSA Foundation Scholar Award. Biology of dairy cows during the transition period: the final frontier?. Journal of Dairy Science 82, 22592273.
Eleswarapu, S, Jiang, H 2005. Growth hormone regulates the expression of hepatocyte nuclear factor-3 gamma and other liver-enriched transcription factors in the bovine liver. Journal of Endocrinology 184, 95105.
Froy, O 2007. The relationship between nutrition and circadian rhythms in mammals. Frontiers in Neuroendocrinology 28, 6171.
Gekakis, N 1998. Role of the CLOCK protein in the mammalian circadian mechanism. Science 280, 15641569.
Green, CB, Takahashi, JS, Bass, J 2008. The meter of metabolism. Cell 134, 728742.
Grummer, RR, Wiltbank, MC, Fricke, PM, Watters, RD, Silva-Del-Rio, N 2010. Management of dry and transition cows to improve energy balance and reproduction. The Journal of Reproduction and Development 56 (suppl.), S22S28.
Guillaumond, F, Dardente, H, Giguère, V, Cermakian, N 2005. Differential control of Bmal1 circadian transcription by REV–ERB and ROR nuclear receptors. Journal Biological Rhythms 20, 391403.
Hadsell, DL, Parlow, AF, Torres, D, George, J, Olea, W 2008. Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression. Journal of Endocrinology 198, 6170.
Hastings, M, O'Neill, JS, Maywood, ES 2007. Circadian clocks: regulators of endocrine and metabolic rhythms. Journal of Endocrinology 195, 187198.
Hedlund, L, Lischko, MM, Rollag, MD, Niswender, GD 1977a. Melatonin: daily cycle in plasma and cerebrospinal fluid of calves. Science 195, 686687.
Hedlund, L, Doelger, SG, Tollerton, AJ, Lischko, MM, Johnson, HD 1977b. Plasma growth hormone concentrations after cerebroventricular and jugular injection of thyrotropin-releasing hormone. Proceedings of the Society for Experimental Biology and Medicine 156, 422425.
Hernandez, LL, Stiening, CM, Wheelock, JB, Baumgard, LH, Parkhurst, AM, Collier, RJ 2008. Evaluation of serotonin as a feedback inhibitor of lactation in the bovine. Journal of Dairy Science 91, 18341844.
Jacobs, B, Martin-Cora, F, Fornal, C 2002. Activity of medullary serotonergic neurons in freely moving animals. Brain Research Reviews 40, 4552.
Kennaway, DJ, Owens, JA, Voultsios, A, Varcoe, TJ 2006. Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are clock independent. American Journal of Physiology Regulation, Integration, and Comparative Physiology 291, R1172R1180.
Kohsaka, A, Bass, J 2007. A sense of time: how molecular clocks organize metabolism. Trends in Endocrinology and Metabolism 18, 411.
Kohsaka, A, Laposky, AD, Ramsey, KM, Estrada, C, Joshu, C, Kobayashi, Y, Turek, FW, Bass, J 2007. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metabolism 6, 414421.
Kuhn, NJ, Carrick, DT, Wilde, CJ 1980. Symposium: milk synthesis : lactose synthesis: The possibilities of regulation. Journal of Dairy Science 63, 328336.
Kume, K 1999. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98, 193205.
LeBlanc, S 2010. Monitoring metabolic health of dairy cattle in the transition period. The Journal of Reproduction and Development 56 (suppl.), S29S35.
Lefcourt, AM, Bitman, J, Kahl, S, Wood, DL 1993. Circadian and ultradian rhythms of peripheral cortisol concentrations in lactating dairy cows. Journal of Dairy Science 76, 26072612.
Lefcourt, AM, Akers, RM, Wood, DL, Bitman, J 1994. Circadian and ultradian rhythms of peripheral prolactin concentrations in lactating dairy cows. American Journal of Physiology 267, R1461R1466.
Lefcourt, AM, Bitman, J, Wood, DL, Akers, RM 1995. Circadian and ultradian rhythms of peripheral growth hormone concentrations in lactating dairy cows. Domestic Animal Endocrinology 12, 247256.
Lefcourt, AM, Huntington, JB, Akers, RM, Wood, DL, Bitman, J 1999. Circadian and ultradian rhythms of body temperature and peripheral concentrations of insulin and nitrogen in lactating dairy cows. Domestic Animal Endocrinology 16, 4155.
Lubetzky, R, Littner, Y, Mimouni, FB, Dollberg, S, Mandel, D 2006. Circadian variations in fat content of expressed breast milk from mothers of preterm infants. Journal of the American College of Nutrition 25, 151154.
Lubetzky, R, Mimouni, FB, Dollberg, S, Salomon, M, Mandel, D 2007. Consistent circadian variations in creamatocrit over the first 7 weeks of lactation: a longitudinal study. Breastfeeding Medicine 2, 1518.
Maningat, PD, Sen, P, Rijnkels, M, Sunehag, AL, Hadsell, DL, Bray, M, Haymond, MW 2009. Gene expression in the human mammary epithelium during lactation: the milk fat globule transcriptome. Physiological Genomics 37, 1222.
Matsuda, M, Imaoka, T, Vomachka, AJ, Gudelsky, GA, Hou, Z, Mistry, M, Bailey, JP, Nieport, KM, Walther, DJ, Bader, M, Horseman, ND 2004. Serotonin regulates mammary gland development via an autocrine–paracrine loop. Developmental Cell 6, 193203.
Mendoza, J 2007. Circadian clocks: setting time by food. Journal of Neuroendocrinology 19, 127137.
Metz, R, Qu, X, Laffin, B, Earnest, DJ, Porter, W 2006. Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary gland. Developmental Dynamics 235, 263271.
Meyer-Bernstein, E, Morin, L 1996. Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. Journal of Neuroscience 16, 20972111.
Mikolayunas, CM, Thomas, DL, Dahl, GE, Gressley, TF, Berger, YM 2008. Effect of prepartum photoperiod on milk production and prolactin concentration of dairy ewes. Journal of Dairy Science 91, 8590.
Moore, RY, Speh, JC 2004. Serotonin innervation of the primate suprachiasmatic nucleus. Brain Research 1010, 169173.
Moore, R, Halaris, A, Jones, B 1978. Serotonin neurons of the midbrain raphe: ascending projections. Journal of Comparative Neurology 180, 417438.
Mulligan, FJ, Doherty, ML 2008. Production diseases of the transition cow. The Veterinary Journal 176, 39.
Nielsen, NI, Ingvartsen, KL, Larsen, T 2003. Diurnal variation and the effect of feed restriction on plasma and milk metabolites in TMR-fed dairy cows. Journal of Veterinary Medicine Series A – Physiology Pathology Clinical Medicine 50, 8897.
Noshiro, M, Usui, E, Kawamoto, T, Kubo, H, Fujimoto, K, Furukawa, M, Honma, S, Makishima, M, Honma, K, Kato, Y 2007. Multiple mechanisms regulate circadian expression of the gene for cholesterol 7alpha-hydroxylase (Cyp7a), a key enzyme in hepatic bile acid biosynthesis. Journal of Biological Rhythms 22, 299311.
Oates, JE, Bradshaw, FJ, Bradshaw, SD, Stead-Richardson, EJ, Philippe, DL 2007. Reproduction and embryonic diapause in a marsupial: insights from captive female Honey possums, Tarsipes rostratus (Tarsipedidae). General and Comparative Endocrinology 150, 445461.
Oishi, K, Fukui, H, Ishida, N 2000. Rhythmic expression of BMAL1 mRNA is altered in clock mutant mice: differential regulation in the suprachiasmatic nucleus and peripheral tissues. Biochemical and Biophysical Research Communications 268, 164171.
Panda, S 2002. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109, 307320.
Peters, RR, Tucker, HA 1978. Prolactin and growth hormone responses to photoperiod in heifers. Endocrinology 103, 229234.
Peters, RR, Chapin, LT, Leining, KB, Tucker, HA 1978. Supplemental lighting stimulates growth and lactation in cattle. Science 199, 911912.
Peters, RR, Chapin, LT, Emery, RS, Tucker, HA 1981. Milk yield, feed intake, prolactin, growth hormone, and glucocorticoid response of cows to supplemented light. Journal of Dairy Science 64, 16711678.
Petitclerc, D, Chapin, LT, Tucker, HA 1984. Carcass composition and mammary development responses to photoperiod and plane of nutrition in holstein heifers. Journal of Animal Science 58, 913919.
Petitclerc, D, Kineman, RD, Zinn, SA, Tucker, HA 1985. Mammary growth response of Holstein heifers to photoperiod. Journal of Dairy Science 68, 8690.
Piccione, G, Caolaa, G, Refinetti, R 2003. Circadian rhythms of body temperature and liver function in fed and food-deprived goats. Comparative Biochemistry and Physiology 134, 563572.
Plaut, K, Bauman, DE, Agergaard, N, Akers, RM 1987. Effect of exogenous prolactin administration on lactational performance of dairy cows. Domestic Animal Endocrinology 4, 279290.
Pohjanvirta, R, Boutros, PC, Moffat, ID, Linden, J, Wendelin, D, Okey, AB 2008. Genome-wide effects of acute progressive feed restriction in liver and white adipose tissue. Toxicology and Applied Pharmacology 230, 4156.
Preitner, N, Damiola, F, Luis Lopez, M, Zakany, J, Duboule, D, Albrecht, U, Schibler, U 2002. The orphan nuclear receptor REV–ERB[alpha] controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110, 251260.
Reppert, SM, Weaver, DR 2002. Coordination of circadian timing in mammals. Nature 418, 935941.
Rius, AG, Dahl, GE 2006. Exposure to long-day photoperiod prepubertally may increase milk yield in first-lactation cows. Journal of Dairy Science 89, 20802083.
Rudic, RD, McNamara, P, Curtis, AM, Boston, RC, Panda, S, Hogenesch, JB, Fitzgerald, GA 2004. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biology 2, e377.
Ruiter, M, La Fleur, SE, van Heijningen, C, van der Vliet, J, Kalsbeek, A, Buijs, RM 2003. The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior. Diabetes 52, 17091715.
Sanchez-Barcelo, EJ, Mediavilla, MD, Zinn, SA, Buchanan, BA, Chapin, LT, Tucker, HA 1991. Melatonin suppression of mammary growth in heifers. Biology of Reproduction 44, 875879.
Schibler, U, Ripperger, J, Brown, SA 2003. Peripheral circadian oscillators in mammals: time and food. Journal of Biological Rhythms 18, 250260.
Sheward, WJ, Maywood, ES, French, KL, Horn, JM, Hastings, MH, Seckl, JR, Holmes, MC, Harmar, AJ 2007. Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice. Journal of Neuroscience 27, 43514358.
Simonneaux, V, Ribelayga, C 2003. Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacologic Reviews 55, 325395.
Sookoian, S, Castano, G, Gemma, C, Gianotti, TF, Pirola, CJ 2007. Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease. World Journal of Gastroenterology 13, 42424248.
Stanisiewski, EP, Ames, NK, Chapin, LT, Blaze, CA, Tucker, HA 1988a. Effect of pinealectomy on prolactin, testosterone and luteinizing hormone concentration in plasma of bull calves exposed to 8 or 16 hours of light per day. Journal of Animal Science 66, 464469.
Stanisiewski, EP, Chapin, LT, Ames, NK, Zinn, SA, Tucker, HA 1988b. Melatonin and prolactin concentrations in blood of cattle exposed to 8, 16 or 24 hours of daily light. Journal of Animal Science 66, 727734.
Stokkan, K-A, Yamazaki, S, Tei, H, Sakaki, Y, Menaker, M 2001. Entrainment of the circadian clock in the liver by feeding. Science 291, 490493.
Storch, K, Lipan, O, Leykin, I, Viswanathan, N, Davis, F, Wong, W, Weitz, C 2002. Extensive and divergent circadian gene expression in liver and heart. Nature 417, 7883.
Stull, MA, Pai, V, Vomachka, AJ, Marshall, AM, Jacob, GA, Horseman, ND 2007. Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions. Proceedings Of The National Academy Of Sciences of The United States Of America 104, 1670816713.
Turek, FW, Joshu, C, Kohsaka, A, Lin, E, Ivanova, G, McDearmon, E, Laposky, A, Losee-Olson, S, Easton, A, Jensen, DR, Eckel, RH, Takahashi, JS, Bass, J 2005. Obesity and metabolic syndrome in circadian clock mutant mice. Science 308, 10431045.
Vollmers, C, Gill, S, DiTacchio, L, Pulivarthy, SR, Le, HD, Panda, S 2009. Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proceedings of the National Academy of Sciences 106, 2145321458.
Wall, EH, Auchtung-Montgomery, TL, Dahl, GE, McFadden, TB 2005. Short communication: Short-day photoperiod during the dry period decreases expression of suppressors of cytokine signaling in mammary gland of dairy cows. Journal of Dairy Science 88, 31453148.
Welsh, DK, Logothetis, DE, Meister, M, Reppert, SM 1995. Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms. Neuron 14, 697706.
Wirz-Justice, A 2006. Biological rhythm disturbances in mood disorders. International Clinical Psychopharmacology 21 (suppl. 1), S11S15.
Woon, PY, Kaisaki, PJ, Braganca, J, Bihoreau, MT, Levy, JC, Farrall, M, Gauguier, D 2007. Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proceedings of the National Academy of Science of the United States of America 104, 1441214417.
Yagita, K 2000. Dimerization and nuclear entry of mPER proteins in mammalian cells. Genes and Development 14, 13531363.
Yamazaki, S, Numano, R, Abe, M, Hida, A, Takahashi, R, Ueda, M, Block, G, Sakaki, Y, Menaker, M, Tei, H 2000. Resetting central and peripheral circadian oscillators in transgenic rats. Science 288, 682685.
Yang, Q, Kurotani, R, Yamada, A, Kimura, S, Gonzalez, FJ 2006. Peroxisome proliferator-activated receptor alpha activation during pregnancy severely impairs mammary lobuloalveolar development in mice. Endocrinology 147, 47724780.
Zinn, SA, Chapin, LT, Tucker, HA 1986. Response of body weight and clearance and secretion rates of growth hormone to photoperiod in holstein heifers. Journal of Animal Science 62, 12731278.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

animal
  • ISSN: 1751-7311
  • EISSN: 1751-732X
  • URL: /core/journals/animal
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed