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Department of Animal Sciences
The Robert H. Smith Faculty
of Agricultural, Food & Environment

The Hebrew University of Jerusalem.

Herzl 229, Rehovot 7610001, Israel
Phone: +972-(0)8-9489119;
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e-mail: yaellew@savion.huji.ac.il

Publications

2021
Casey, T. ; Suarez-Trujillo, A. ; Cummings, S. ; Huff, K. ; Crodian, J. ; Bhide, K. ; Aduwari, C. ; Teeple, K. ; Shamay, A. ; Mabjeesh, S. ; et al. Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis. PLOS ONE 2021, 16.Abstract
The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). RT-qPCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr), Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.
Meir, Y. A. B. ; Nikbachat, M. ; Portnik, Y. ; Jacoby, S. ; Adin, G. ; Moallem, U. ; Halachmi, I. ; Miron, J. ; Mabjeesh, S. Effect of forage-to-concentrate ratio on production efficiency of low-efficient high-yielding lactating cows. ANIMAL 2021, 15.Abstract
Feed is usually the costliest input in lactating cow's farms. Therefore, the developing of methods for a better adjustment of feed intake to cow's energetic needs in order to improve efficiency is desired. The aim of this study was to improve feed efficiency of low-efficient (LE) cows through a moderate increase in diet forage-to-concentrate ratio. We studied the effects of replacing 8.2% corn grains in a control low-fiber (LF) diet that contained 17.5% forage neutral detergent fiber (NDF) with 7.5% wheat straw + 0.7% soybean meal for a high-fiber (HF) diet that contained 23.4% forage NDF. Based on efficiency data of individual cows from the Agricultural Research Organization's herd measured in our previous study, 15 pairs of pre-classified LE multiparous mid-lactating Israeli Holstein daily cows were selected, each pair with similar performance, intake, and efficiency data; each member of a pair was then adapted for 2 weeks to one or the other dietary treatment. Traits examined during the 5 weeks of the experiment were DM intake (DMI), eating behavior, milk production, in vivo digestibility, and estimation of feed efficiency (energy-corrected milk (ECM)/DMI and energy balance). Cows led the HF diet showed slower eating rate, smaller visit and meal sizes, longer daily eating time, higher visit frequency, and longer meal duration, compared to those fed the LF diet. The DMI of cows fed the HF diet was 9.1% lower, their DM digestibility decreased from 65.7 to 62.2%, and their ECM yield was 7.0% lower than in cows fed the LF diet Feed efficiency, measured as net energy captured/digestible energy intake, improved in the cows fed the HF vs. LF diet while feed efficiency measured as ECM/DMI remained similar. Our results thus show the potential of improving feed efficiency for milk production in LE cows by increasing the forage-to-concentrate ratio. (C) 2020 The Authors. Published by Elsevier Inc on behalf of The Animal Consortium.
Kalyesubula, M. ; Casey, T. M. ; Reicher, N. ; Sabastian, C. ; Wein, Y. ; Barshira, E. ; Hoang, N. ; George, U. Z. ; Shamay, A. ; Plaut, K. ; et al. Physiological state and photoperiod exposures differentially influence circadian rhythms of body temperature and prolactin and relate to changes in mammary PER1 expression in late pregnant and early lactation dairy goats. SMALL RUMINANT RESEARCH 2021, 200.Abstract
Short-day photoperiod (SDPP; 8 h light:16 h dark) during the dry period increases milk production compared with long-day photoperiod (LDPP; 16 h light:8 h dark). We hypothesized that the impact of photoperiod on lactation is mediated by alterations in the circadian system. Twelve Saanen goats were blocked at dry off into SDPP (n = 6) and LDPP (n = 6) treatments and mammary biopsies were taken in the middle of light and dark phases at 3 wk prepartum and 5 wk postpartum. Total RNA was isolated, and the expression of clock genes was analyzed by qPCR. SDPP goats produced more milk than LDPP goats (3.15 +/- 0.04 vs. 2.7 +/- 0.05 kg/d). In the 24 h period, LDPP goats had a greater body temperature than SDPP goats at 3 wk prepartum (39.6 +/- 0.06 vs. 39.3 +/- 0.1 degrees C) and 5 wk postpartum (40.1 +/- 0.15 vs. 39.7 +/- 0.1 degrees C). Cosinor analysis revealed that physiological state affected body temperature mesor (P< 0.001), peak (P< 0.01), amplitude (P< 0.05), and phase (P< 0.001). Plasma prolactin was 20, 10, and 17-fold higher in LDPP than in SDPP goats at 3 wk prepartum, 3 wk postpartum and 5 wk postpartum, respectively. Cosinor analysis revealed that photoperiod affected prolactin mesor (P< 0.0001), peak (P< 0.0001), trough (P< 0.001), amplitude (P< 0.01), and the peak to trough ratio (P< 0.01). Mammary expression of a core clock gene, PER1, was affected by the light-dark phase and the photoperiod treatment (P< 0.05). It also exhibited a photoperiod-physiological state interaction. Changes in the circadian rhythms with the onset of lactation and photoperiod manipulation support further studies of their role in the regulation of milk yield.
2019
Meir, Y. A. B. ; Nikbachat, M. ; Portnik, Y. ; Jacoby, S. ; Levit, H. ; Bikel, D. ; Adin, G. ; Moallem, U. ; Miron, J. ; Mabjeesh, S. ; et al. Dietary restriction improved feed efficiency of inefficient lactating cows. Journal of Dairy Science 2019, 102, 8898-8906. Publisher's VersionAbstract
The aim of this study was to reduce voluntary dry matter intake (DMI) to increase feeding efficiency of preclassified inefficient (INE) dairy cows through restricted feeding. We studied the effects of dietary restriction on eating behavior, milk and energy-corrected milk (ECM) production, in vivo digestibility, energy balance, and measures of feed efficiency [residual feed intake (RFI) and ECM/DMI]. Before the experiment, 12 pairs of cows were classified as INE. The 2 dietary treatments consisted of ad libitum feeding versus restricted feeding of the same total mixed ration containing 36.5% roughage. Inefficient cows fed the restricted total mixed ration had a shorter eating time and lower meal and visit frequency, but a similar rate of eating, meal size, and meal duration compared with INE cows fed ad libitum. Compared with the INE cows fed ad libitum, restricted INE cows had 12.8% lower intake, their dry matter and neutral detergent fiber digestibility remained similar, and their ECM yield was 5.3% lower. Feed efficiency, measured as RFI, ECM/DMI, and net energy retained divided by digestible energy intake, was improved in the restricted INE cows as compared with the ad libitum cows. Our results show that moderate DMI restriction has the potential to improve feed efficiency of preclassified INE cows. © 2019 American Dairy Science Association
Meir, Y. A. B. ; Nikbachat, M. ; Jacoby, S. ; Portnik, Y. ; Levit, H. ; Elazary, A. K. ; Gershon, E. ; Adin, G. ; Zinder, M. C. ; Shabtay, A. ; et al. Effect of lactation trimester and parity on eating behavior, milk production and efficiency traits of dairy cows. Animal 2019, 13, 1736-1743. Publisher's VersionAbstract
There is absence knowledge about the effects of lactation trimester and parity on eating behavior, production and efficiency of dairy cows. Objective of this study was to identify and characterize in 340 dairy cows, the 20% high efficient (HE), 20% low efficient (LE) and 60% mid efficient (ME) cows according to their individual residual feed intake (RFI) values, within and between lactation trimesters and between 1st and 2nd parities. Efficiency effect within each lactation trimester, was exhibited in daily dry matter intake (DMI), eating rate and meal size, that were the highest in LE cows, moderate in the ME cows and lowest in the HE group. Daily eating time, meal frequency, yields of milk and energy-corrected milk (ECM) and BW were similar in the three efficiency groups within each trimester. The lower efficiency of the LE cows in each trimester attributes to their larger metabolic energy intake, heat production and energy losses. In subgroup of 52 multiparous cows examined along their 1st and 2nd trimesters, milk and ECM production, DMI, eating behavior and efficiency traits were similar with high Pearson's correlation (r=0.78 to 0.89) between trimesters. In another subgroup of 42 multiparous cows measured at their 2nd and 3rd trimesters, milk and ECM yield, DMI and eating time were reduced (P<0.01) at the 3rd trimester, but eating rate, meal frequency and meal size remained similar with high Pearson's correlation (r=0.74 to 0.88) between trimesters. In subgroup of 26 cows measured in 1st and 2nd parities, DMI, BW, milk and ECM yield, and ECM/DMI increased in the 2nd lactation, but eating behavior and RFI traits were similar in both parities. These findings encourage accurate prediction of DMI based on a model that includes eating behavior parameters, together with individual measurement of ECM production. This can be further used to identify HE cows in commercial herd, a step necessary for potential genetic selection program aimed to improve herd efficiency. © The Animal Consortium 2019.
2018
Meir, Y. A. B. ; Nikbachat, M. ; Fortnik, Y. ; Jacoby, S. ; Levit, H. ; Adin, G. ; Zinder, M. C. ; Shabtay, A. ; Gershon, E. ; Zachut, M. ; et al. Eating behavior, milk production, rumination, and digestibility characteristics of high- and low-efficiency lactating cows fed a low-roughage diet. Journal of Dairy Science 2018, 101, 10973 - 10984. Publisher's VersionAbstract
ABSTRACT This study aimed to identify individual characteristics differing among high-efficiency (HEf; upper 20
Ovadia, Y. ; Chris Sabastian, C. ; Dahl, L. ; Troen, A. ; Mabjeesh, S. The Effect of Iodophor Post-Milking Teat Disinfection on Iodine Content in Goat Milk. Israel Journal of Veterinary Medicine 2018, 73, 14 - 22.Abstract
Iodine intake is important for thyroid function and human health. Goat milk can be an important source of iodine for human nutrition. However, data regarding the effect of iodophor post-milking teat disinfection on iodine content in goat milk is lacking. Our aim was to assess the iodine concentrations in raw milk of dairy goats and to investigate the effect of post-milking teat-dipping iodophor practice on iodine content in goat milk. Two groups of dairy goats (n=6 in each) were treated with different post-milking teat-dipping disinfection: iodine-free solution (iodine-free group) and iodine-based solution (4,000 μg/L) (iodophors group). Treatments were carried out for 19 experimental days, following a 14-day pre-experimental period, in which only iodine-free sanitizer was used for both groups. The results showed that Iodine concentrations in milk of all goats were 49 ± 23, 49, 17-86 μg/100g (mean ± SD, median, range) at days-3,-2,-1 and 45 ± 26, 42, 14-96 μg/100g (mean ± SD, median, range) at days 17, 18, 19 of treatment. Iodine concentration increased by 7 μg/100g (mean) in the iodophors group while iodine concentration decreased by 15 μg/100g by day 17-19 of treatment in the iodine free group. It was concluded that relatively high iodine concentrations were found in raw milk of dairy goats whose teats were dipped post-milking in disinfectants with or without iodine. Post-milking teat-dipping iodophor practice may increase iodine content in goat milk within an average period of 20 days. This information can help in controlling iodine content in goat milk and iodine intake in the public.
Casey, T. M. ; Plaut, K. ; Kalyesubula, M. ; Shamay, A. ; Sabastian, C. ; Wein, Y. ; Bar-Shira, E. ; Reicher, N. ; Mabjeesh, S. Mammary core clock gene expression is impacted by photoperiod exposure during the dry period in goats. Journal of Applied Animal Research 2018, 46, 1214 - 1219. Publisher's VersionAbstract
ABSTRACTShort-day photoperiod (SDPP) during the dry period increases milk production compared to long-day photoperiod (LDPP) in goats. Photoperiod information is sent to the master clock in the suprachiasmatic nuclei (SCN), which send temporal information to peripheral clocks located in every tissue of the body. We hypothesized photoperiod effects on milk production are mediated in part by changes in mammary clocks. Our objective was to determine the effect of photoperiod manipulation during the dry period in goats on core clock genes expression in mammary gland. Multiparous goats (n?=?6) were blocked at dry off into two treatments: LDPP and SDPP. Serial mammary biopsies were taken over a 24?h period during three weeks prepartum. Total RNA was isolated, and q-PCR analysis of the core clock genes CLOCK, ARNTL, PER1, CRY1, and CRY2 found exposure to LDPP significantly increased ARNTL (P?
Ovadia, Y. ; Gefel, D. ; Weizmann, N. ; Raizman, M. ; Goldsmith, R. ; Mabjeesh, S. ; Dahl, L. ; Troen, A. M. Low Iodine Intake from Dairy Foods Despite High Milk Iodine Content in Israel. Thyroid 2018, 28, 1042 - 1051. Publisher's VersionAbstract
Background: Milk is a major source of iodine in human nutrition. Because both iodine content and the consumption of milk and dairy vary widely over time and populations, their contribution to iodine intake must be evaluated regularly. A recent national iodine survey found Israel's population to be mildly iodine deficient, possibly due to unmonitored changes in the food content of dietary iodine. Accounting for dairy iodine content can help guide efforts to prevent iodine deficiency. Objectives: This study aimed to determine the iodine concentration of dairy products typically consumed in the Israeli diet, and to estimate iodine intake from dairy products among Israeli adults. Methods: Iodine was analyzed in 33 selected dairy products that account for 89% of the total population's dairy intake according to the ?MABAT? Israeli National Health and Nutrition survey. Based on these data, the distribution of iodine intake from milk, dairy, and dairy-based foods in the adult population was calculated. Results: Israeli milk is rich in iodine, with a mean concentration of 22??g/100?g. However, due to low dairy consumption, the mean iodine intake from milk and dairy was only 34??g/day (median 23??g/day; range: 0?337??g/day) or 22% of the recommended daily allowance. Self-reported intake among poor, male, and Arab subgroups was even lower. Conclusions: Because Israeli milk and dairy products are iodine rich, their contribution to the population's iodine intake would increase if they were consumed in greater amounts, particularly by high-risk groups. Dairy's potential contribution to iodine nutrition should be considered in recommendations for dairy consumption and iodine prophylaxis.Background: Milk is a major source of iodine in human nutrition. Because both iodine content and the consumption of milk and dairy vary widely over time and populations, their contribution to iodine intake must be evaluated regularly. A recent national iodine survey found Israel's population to be mildly iodine deficient, possibly due to unmonitored changes in the food content of dietary iodine. Accounting for dairy iodine content can help guide efforts to prevent iodine deficiency. Objectives: This study aimed to determine the iodine concentration of dairy products typically consumed in the Israeli diet, and to estimate iodine intake from dairy products among Israeli adults. Methods: Iodine was analyzed in 33 selected dairy products that account for 89% of the total population's dairy intake according to the ?MABAT? Israeli National Health and Nutrition survey. Based on these data, the distribution of iodine intake from milk, dairy, and dairy-based foods in the adult population was calculated. Results: Israeli milk is rich in iodine, with a mean concentration of 22??g/100?g. However, due to low dairy consumption, the mean iodine intake from milk and dairy was only 34??g/day (median 23??g/day; range: 0?337??g/day) or 22% of the recommended daily allowance. Self-reported intake among poor, male, and Arab subgroups was even lower. Conclusions: Because Israeli milk and dairy products are iodine rich, their contribution to the population's iodine intake would increase if they were consumed in greater amounts, particularly by high-risk groups. Dairy's potential contribution to iodine nutrition should be considered in recommendations for dairy consumption and iodine prophylaxis.
2016
Shaani, Y. ; Eliyahu, D. ; Mizrahi, I. ; Yosef, E. ; Ben-Meir, Y. ; Nikbachat, M. ; Solomon, R. ; Mabjeesh, S. ; Miron, J. Effect of feeding ensiled mixture of pomegranate pulp and drier feeds on digestibility and milk performance in dairy cows. Journal of Dairy Research 2016, 83, 35 - 41. Publisher's Version
Casey, T. ; Crodian, J. ; Suárez-Trujillo, A. ; Erickson, E. ; Weldon, B. ; Crow, K. ; Cummings, S. ; Chen, Y. ; Shamay, A. ; Mabjeesh, S. ; et al. CLOCK regulates mammary epithelial cell growth and differentiation. American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2016, 311, R1125 - R1134. Publisher's VersionAbstract
Circadian clocks influence virtually all physiological processes, including lactation. Here, we investigate the role of the CLOCK gene in regulation of mammary epithelial cell growth and differentiation. Comparison of mammary morphology in late-pregnant wild-type and Clock?19 mice, showed that gland development was negatively impacted by genetic loss of a functional timing system. To understand whether these effects were due, in part, to loss of CLOCK function in the gland, the mouse mammary epithelial cell line, HC11, was transfected with short hairpin RNA that targeted Clock (shClock). Cells transfected with shClock expressed 70% less Clock mRNA than wild-type (WT) HC11 cultures, which resulted in significantly depressed levels of CLOCK protein (P < 0.05). HC11 lines carrying shClock had four-fold higher growth rates (P < 0.05), and the percentage of cells in G1 phase was significantly higher (90.1 ± 1.1% of shClock vs. 71.3 ± 3.6% of WT-HC11) following serum starvation. Quantitative-PCR (qPCR) analysis showed shClock had significant effects (P < 0.0001) on relative expression levels of Ccnd1, Wee1, and Tp63. qPCR analysis of the effect of shClock on Fasn and Cdh1 expression in undifferentiated cultures and cultures treated 96 h with dexamethasone, insulin, and prolactin (differentiated) found levels were reduced by twofold and threefold, respectively (P < 0.05), in shClock line relative to WT cultures. Abundance of CDH1 and TP63 proteins were significantly reduced in cultures transfected with shClock. These data support how CLOCK plays a role in regulation of epithelial cell growth and differentiation in the mammary gland.Circadian clocks influence virtually all physiological processes, including lactation. Here, we investigate the role of the CLOCK gene in regulation of mammary epithelial cell growth and differentiation. Comparison of mammary morphology in late-pregnant wild-type and Clock?19 mice, showed that gland development was negatively impacted by genetic loss of a functional timing system. To understand whether these effects were due, in part, to loss of CLOCK function in the gland, the mouse mammary epithelial cell line, HC11, was transfected with short hairpin RNA that targeted Clock (shClock). Cells transfected with shClock expressed 70% less Clock mRNA than wild-type (WT) HC11 cultures, which resulted in significantly depressed levels of CLOCK protein (P < 0.05). HC11 lines carrying shClock had four-fold higher growth rates (P < 0.05), and the percentage of cells in G1 phase was significantly higher (90.1 ± 1.1% of shClock vs. 71.3 ± 3.6% of WT-HC11) following serum starvation. Quantitative-PCR (qPCR) analysis showed shClock had significant effects (P < 0.0001) on relative expression levels of Ccnd1, Wee1, and Tp63. qPCR analysis of the effect of shClock on Fasn and Cdh1 expression in undifferentiated cultures and cultures treated 96 h with dexamethasone, insulin, and prolactin (differentiated) found levels were reduced by twofold and threefold, respectively (P < 0.05), in shClock line relative to WT cultures. Abundance of CDH1 and TP63 proteins were significantly reduced in cultures transfected with shClock. These data support how CLOCK plays a role in regulation of epithelial cell growth and differentiation in the mammary gland.