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Expression of the classical interferon (IFN) stimulated genes (ISGs) increases in the endometrial stroma and glandular epithelium (GE) through activation of signal transducer and activator of transcription (STAT) signaling in response to the secretion of IFN tau (IFNT) and IFN gamma (IFNG) by the conceptuses of ruminants, including cattle and sheep, and pigs, respectively. The first of the classical ISGs to be characterized was ISG15 in cattle. Classical ISGs are not expressed by the endometrial luminal epithelium (LE) due to the expression of interferon regulatory factor 2 (IRF2) in the LE that prevents the expression of ISGs in the LE. Classical ISG expression in the endometrium serves as a reliable indicator of conceptus health and elongation in cattle. There are also nonclassical ISGs that are upregulated in endometrial LE in response to progesterone (P4) that are further stimulated by IFNT in sheep, the intracellular signaling pathway responsible for IFN effects on expression is unknown. ISGs are also upregulated in extrauterine tissues including CL and peripheral blood mononuclear cells (PBMCs). The expression of ISGs by the PBMCs of cattle serves as an early prognosticator of pregnancy. The physiological roles of ISGs remain obscure, but evidence suggests that they are at least in part involved in modifying the immune system to support endometrial remodeling necessary for the successful implantation of the conceptus. Our understanding of these ISGs is primarily the result of work from the laboratories of Drs Fuller Bazer, Thomas (Tod) Hansen, Gregory Johnson, Hakhyun Ka, Patrick Lonergan, Troy Ott, and Thomas Spencer. [ABSTRACT FROM AUTHOR]

Deep and abyssal layer decadal temperature trends from the mid‐1980s to the mid‐2010s are mapped globally using Deep Argo and historical ship‐based Conductivity‐Temperature‐Depth (CTD) instrument data. Abyssal warming trends are widespread, with the strongest warming observed around Antarctic Bottom Water (AABW) formation regions. The warming strength follows deep western boundary currents transporting abyssal waters north and decreases with distance from Antarctica. Abyssal cooling trends are found in the North Atlantic and eastern South Atlantic, regions primarily ventilated by North Atlantic Deep Water (NADW). Deep warming trends are prominent in the Southern Ocean south of about 50°S, the Greenland‐Iceland‐Norwegian (GIN) Seas and the western subpolar North Atlantic, with cooling in the eastern subpolar North Atlantic and the subtropical and tropical western North Atlantic. Globally integrated decadal heat content trends of 21.6 (±6.5) TW in the deep and 12.9 (±1.8) TW in the abyssal layer are more certain than previous estimates. Plain Language Summary: Even the deepest waters in the ocean, which sink to the abyss around Antarctica after being cooled and made saltier by heat exchange with the atmosphere and sea ice formation, have been shown to be warming around much of the globe in recent decades. The net warming rate below 2000‐m depth accounts for about 10% of total ocean heat uptake, but uncertainties in prior estimates have been about half the size of the signal owing to sparse sampling in the deep ocean. However, new observations from Deep Argo floats, capable of profiling to the ocean floor in most locations, have improved that situation in some regions. Here we analyze these new observations together with historical observations collected from ships since the 1970s to map decadal ocean temperature trends around the globe. As a result, we use more historical data than previous estimates. We refine the local patterns of warming and cooling in the waters deeper than 2,000 m. We confirm the amplitude of the net warming below 2,000 m estimated in previous studies, and extend the time covered by those estimates. The increased data coverage substantially reduces the uncertainty of the net warming estimate. Key Points: Analysis of Deep Argo float and historical ship‐based CTD data reveal global patterns in deep and abyssal layer decadal temperature trendsHigh resolution maps reveal spreading of abyssal warming from Antarctica and cooling from the North Atlantic on sub‐basin spatial scalesGlobally integrated decadal heat content trends are 21.6 (±6.5) TW in the deep and 12.9 (±1.8) TW in the abyssal layer [ABSTRACT FROM AUTHOR]

Antarctic Bottom Water has been warming in recent decades throughout most of the oceans and freshening in regions close to its Indian and Pacific sector sources. We assess warming rates on isobars in the eastern Pacific sector of the Southern Ocean using CTD data collected from shipboard surveys from the early 1990s through the late 2010s together with CTD data collected from Deep Argo floats deployed in the region in January 2023. We show cooling and freshening in the temperature‐salinity relation for water colder than ∼0.4°C. We further find a recent acceleration in the regional bottom water warming rate vertically averaged for pressures exceeding 3,700 dbar, with the 2017/18 to 2023/24 trend of 7.5 (±0.9) m°C yr−1 nearly triple the 1992/95 to 2023/24 trend of 2.8 (±0.2) m°C yr−1. The 0.2°C isotherm descent rate for these same time periods nearly quadruples from 7.8 to 28 m yr−1. Plain Language Summary: Cold winds blowing over polynyas (areas of ice‐free water) on the Antarctic continental shelf create sea ice, forming very cold and somewhat salty, hence very dense, waters. These dense shelf waters descend the continental slope to the abyss, mixing with adjacent waters to form Antarctic Bottom Water (AABW). AABW spreads northward from there, filling much of the global abyssal ocean as it mixes with warmer, lighter waters above. AABW has been warming on pressure surfaces, freshening and cooling on density surfaces, and reducing in volume (contracting). These changes are likely a result of melting Antarctic ice sheets, which freshen the shelf waters, making them less dense, hence less able to sink to the bottom. We compare profiles of ocean temperature and salinity in the eastern Pacific sector of the Southern Ocean collected in 2023 and 2024 by robotic freely drifting profilers to data collected from ships from the early 1990s to the late 2010s. We find all of the above listed changes, but also acceleration of the warming, with the rate from 2017/18 to 2023/24 being nearly triple the rate from 1992/95 to 2023/24. The contraction rate has nearly quadrupled. This acceleration has been predicted by high‐resolution climate model simulations. Key Points: Antarctic Bottom Water (AABW) changes in the east Pacific sector of the Southern Ocean are assessed using Deep Argo and ship‐based CTD profilesBottom water warming rates from 2017/18 to 2023/24 nearly triple compared to 1992/95 to 2023/24 rates, contraction rates nearly quadrupleAABW cooling and freshening on isopycnals is also observed in the region, relative to older Circumpolar Deep Water [ABSTRACT FROM AUTHOR]

Background: Tissue non-specific alkaline phosphatase (TNSALP; encoded by the ALPL gene) has a critical role in the postnatal regulation of phosphate homeostasis, yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown. This study tested the hypothesis that progesterone (P4) and/or interferon tau (IFNT) regulate TNSALP activity during pregnancy in sheep. Methods: In Exp. 1, ewes were bred and received daily intramuscular injections of either corn oil vehicle (CO) or 25 mg progesterone in CO (P4) for the first 8 days of pregnancy and were hysterectomized on either Day 9, 12, or 125 of gestation. In Exp. 2, ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist (RU486) in CO from Days 8 to 15, and twice daily intrauterine injections of either control proteins (CX) or IFNT (25 µg/uterine horn/d) from Days 11 to 15 (treatment groups: P4 + CX; P4 + IFNT; RU486 + P4 + CX; and RU486 + P4 + IFNT) and were hysterectomized on Day 16. Results: In Exp. 1, endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12. TNSALP activity appeared greater in the epithelia, stratum compactum stroma, and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12. On Day 125, TNSALP activity localized to uterine epithelial and endothelial cells, independent of P4 treatment. TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes. In Exp. 2, endometrial homogenates from ewes administered RU486 + P4 + CX had lower TNSALP activity those for P4 + CX and P4 + IFNT ewes. Immunoreactive TNSALP protein appeared greater in the mid- and deep-glandular epithelia in RU486 + P4 + CX treated ewes as compared to the other treatment groups. Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486 + P4 + CX compared to the other treatment groups. Conclusions: These results suggest that P4, but not IFNT, regulates the expression and activity of TNSALP in utero-placental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy. [ABSTRACT FROM AUTHOR]

Simple Summary: L-Glutamate (Glu) and L-glutamine (Gln) are abundant amino acids in feedstuffs and ruminants. Dietary Gln is extensively utilized by ruminal microbes, but dietary Glu undergoes little catabolism by these microbes because they do not take up extracellular Glu due to the lack of the necessary transporters. Microbial proteins and dietary Glu exit the rumen into the abomasum and then the small intestine, where proteins undergo hydrolysis to release amino acids (including Glu and Gln) and small peptides for transport into enterocytes. Most dietary Gln escapes the underdeveloped rumen of preruminants, instead entering the abomasum and the small intestine. Within the enterocytes, Glu and Gln are extensively oxidized to provide ATP and are actively used to synthesize glutathione and other amino acids (alanine, ornithine, citrulline, arginine, proline, and aspartate), whereas Gln and aspartate are essential for purine and pyrimidine syntheses. Under normal feeding conditions, all diet- and rumen-derived Glu and Gln are extracted by the small intestine and, therefore, do not enter the portal circulation. De novo synthesis plays a crucial role in maintaining the homeostasis of Glu and Gln in the whole body but may be insufficient for maximal growth performance, production (e.g., lactation and pregnancy), and optimal health in ruminants. Dietary supplementation with Glu or Gln can safely improve the digestive, endocrine, and reproduction functions of ruminants and thus augment health and production parameters. Although both L-glutamate (Glu) and L-glutamine (Gln) have long been considered nutritionally nonessential in ruminants, these two amino acids have enormous nutritional and physiological importance. Results of recent studies revealed that extracellular Gln is extensively degraded by ruminal microbes, but extracellular Glu undergoes little catabolism by these cells due to the near absence of its uptake. Ruminal bacteria hydrolyze Gln to Glu plus ammonia and, intracellularly, use both amino acids for protein synthesis. Microbial proteins and dietary Glu enter the small intestine in ruminants. Both Glu and Gln are the major metabolic fuels and building blocks of proteins, as well as substrates for the syntheses of glutathione and amino acids (alanine, ornithine, citrulline, arginine, proline, and aspartate) in the intestinal mucosa. In addition, Gln and aspartate are essential for purine and pyrimidine syntheses, whereas arginine and proline are necessary for the production of nitric oxide (a major vasodilator) and collagen (the most abundant protein in the body), respectively. Under normal feeding conditions, all diet- and rumen-derived Glu and Gln are extensively utilized by the small intestine and do not enter the portal circulation. Thus, de novo synthesis (e.g., from branched-chain amino acids and α-ketoglutarate) plays a crucial role in the homeostasis of Glu and Gln in the whole body but may be insufficient for maximal growth performance, production (e.g., lactation and pregnancy), and optimal health (particularly intestinal health) in ruminants. This applies to all types of feeding systems used around the world (e.g., rearing on a milk replacer before weaning, pasture-based production, and total mixed rations). Dietary supplementation with the appropriate doses of Glu or Gln [e.g., 0.5 or 1 g/kg body weight (BW)/day, respectively] can safely improve the digestive, endocrine, and reproduction functions of ruminants to enhance their productivity. Both Glu and Gln are truly functional amino acids in the nutrition of ruminants and hold great promise for improving their health and productivity. [ABSTRACT FROM AUTHOR]

Coastal and ocean management in the United States is a complex issue requiring an equally complex management policy. Federal policy has historically been carried out in a siloed (sector-by-sector) fashion causing inefficient and bureaucratic management by federal agencies. The Obama administration took a novel approach to coastal and ocean management by signing an executive order that brought together federal agencies and empowered regional stakeholders, creating a first of its kind comprehensive National Ocean Policy. In 2018, former President Donald Trump rescinded the Obamaera policy and enacted his own version of National Ocean Policy that shifted authority to the states and focused on the economic potential of American waters. This research addresses a significant challenge in federal management of a complex natural resource. Here we identify common management strategies between different administrations to provide insights for future attempts at National Ocean Policy. We collect policy documents, press releases, and congressional testimony from high-level stakeholders and identified the most common themes over a 12-year period from 2009-2021. We find three common themes between the administrations even though their policies varied in strategy and scope: 1) the importance of a strong and enduring marine economy, 2) creating a strategic and efficient ocean policy, and 3) devolving authority from the federal government to state and regional decision-makers. We argue that coastal and ocean management via executive order is too easily rescinded to have a lasting impact. These novel findings highlight potential strategies for bipartisan cooperation in future attempts at National Ocean Policy. [ABSTRACT FROM AUTHOR]

Background: Propofol‐based total intravenous anesthesia is gaining popularity in pediatric anesthesia. Electroencephalogram can be used to guide propofol dosing to the individual patient to mitigate against overdosing and adverse events. However, electroencephalogram interpretation and propofol pharmacokinetics are not sufficiently taught in training programs to confidently deploy electroencephalogram‐guided total intravenous anesthesia. Aims: We conducted a quality improvement project with the smart aim of increasing the percentage of electroencephalogram‐guided total intravenous anesthesia cases in our main operating room from 0% to 80% over 18 months. Balancing measures were number of total intravenous anesthesia cases, emergence times, and perioperative emergency activations. Methods: The project key drivers were education, equipment, and electronic health record modifications. Plan‐Do‐Study‐Act cycles included: (1) providing journal articles, didactic lectures, intraoperative training, and teaching documents; (2) scheduling electroencephalogram‐guided total intravenous anesthesia teachers to train faculty, staff, and fellows for specific cases and to assess case‐based knowledge; (3) adding age‐based propofol dosing tables and electroencephalogram parameters to the electronic health record (EPIC co, Verona, WI); (4) procuring electroencephalogram monitors (Sedline, Masimo Inc). Electroencephalogram‐guided total intravenous anesthesia cases and balancing measures were identified from the electronic health record. The smart aim was evaluated by statistical process control chart. Results: After the four Plan‐Do‐Study‐Act cycles, electroencephalogram‐guided total intravenous anesthesia increased from 5% to 75% and was sustained at 72% 9 months after project completion. Total intravenous anesthesia cases/mo and number of perioperative emergency activations did not change significantly from start to end of the project, while emergence time for electroencephalogram‐guided total intravenous anesthesia was greater statistically but not clinically (total intravenous anesthesia without electroencephalogram [16 ± 10 min], total intravenous anesthesia with electroencephalogram [18 ± 9 min], sevoflurane [17 ± 9 min] p <.001). Conclusion: Quality improvement methods may be deployed to adopt electroencephalogram‐guided total intravenous anesthesia in a large academic pediatric anesthesia practice. Keys to success include education, in operating room case training, scheduling teachers with learners, electronic health record modifications, and electroencephalogram devices and supplies. [ABSTRACT FROM AUTHOR]

Mammals differ regarding their placentae, but in all species placental trophoblasts interact intimately with the uterine endometrium to mediate the transfer of nutrients from the mother to the embryo/fetus through the closely juxtaposed microcirculatory systems of the uterus and placenta. Placentation in ruminants is intermediate between the non-invasive type, as observed in the epitheliochorial placenta of pigs, and the invasive type, as observed in the haemochorial placentae of mice and humans. In ruminants, placental trophoblast cells invade uterine endometrial tissue, but invasion is believed to be limited to the endometrial luminal epithelium (LE). In the LE there are varying degrees of syncytialisation among species, with syncytialisation being more extensive in sheep than cows. The hallmarks of placentation in ruminants include: (1) an extended period in which conceptuses (embryos and associated placental membranes) elongate and must be supported by secretions (histotroph) from the uterus; (2) a cascade involving an array of adhesion molecules that includes integrin-mediated attachment of the conceptus trophoblast to the endometrial LE for implantation; (3) syncytialisation of the developing early placenta, a process for which there is currently limited understanding; and (4) development of placentomes that define the cotyledonary placentae of cows and sheep, and provide haemotrophic support of fetal development. The United States cattle industry is burdened by losses of pregnancies of up to 45% of cows bred. Many of these losses in ruminant species are the result of errors in the development of the placenta. This review describes and discusses what is currently known about some of the complex molecular and physiological events that underlie successful placentation in cows and sheep. Increased understanding of placentation is critical for developing advances to improve reproductive efficiency in animal agriculture enterprises that provide high-quality animal protein for human consumption. Photograph by Dr Robert C. Burghardt. [ABSTRACT FROM AUTHOR]

This study determined the effects of dietary supplementation with creatine to gestating gilts (n = 6) on their ability to form guanidinoacetate (GA) and creatine in placentae and maternal tissues. Gilts were assigned randomly to one of two dietary groups: control and creatine supplementation (Cr; n = 12 gilts/ diet). Once estrus was detected (d 0), gilts were artificially inseminated 12 h and 24 h later. All gilts were individually housed and fed 0.9 kg of a corn- and soybean-based diet containing 14% crude protein (but no creatine or GA) twice daily. Gilts in the control and Cr groups received daily top dressing of 0 or 2 × 15 g Cr either between d 10 and 60 or between d 10 and 90 of gestation. There were 6 gilts per dietary treatment per gestational stage. On either d 60 or 90 of gestation, gilts were euthanized to collect maternal tissues and placentae. Each tissue (~150 mg) was incubated at 37 ℃ for 2 h in 2 mL of oxygenated (95% O2 /5% CO2 ) Krebs bicarbonate buffer with or without a) 2 mM glycine plus 2 mM L-arginine or b) 0.2 mM GA plus 0.5 mM L-methionine (the source of S-adenosylmethionine). After the 2-h period of incubation, 0.2 mL of 1.5 M HClO4 was added to the medium. The acidified medium plus tissue was homogenized and the homogenizer rinsed with 1 mL water, followed by the addition of 0.1 mLl of 2 M K2CO3. The extract was analyzed for GA, creatine, and amino acids using HPLC. Results indicated that on both d 60 and 90 of gestation, a) GA was formed from glycine plus L-arginine by maternal kidneys and pancreas of all gilts, but not maternal liver, placentae, or endometria; b) GA was converted into Cr by both maternal liver and pancreas, but not maternal kidneys, endometria, or placentae; c) dietary supplementation with Cr did not affect (P > 0.05) either the formation of GA from glycine plus L-arginine in maternal kidneys and pancreas or the conversion of GA into creatine in maternal liver and pancreas (Tables 1 and 2). Collectively, these results indicate interorgan cooperation to form creatine in pregnant gilts to support fetal growth and development, as well as the lack of inhibition of this metabolic pathway by dietary supplementation with creatine. [ABSTRACT FROM AUTHOR]

4-hydroxy-L-proline (Hyp) is an abundant amino acid in the collagen of pigs. The turnover of this protein releases a large amount of Hyp, traditionally considered a metabolic waste. However, results of recent studies documented the conversion of Hyp into glycine in young pigs. Because pregnant gilts are typically fed a soybean meal-based diet that contains insufficient glycine and provides only 35% of the total glycine needed by pregnant gilts, it is possible that the conceptus can form glycine from Hyp. This hypothesis was tested in the present study. Gilts were fed a 1.8-kg corn- and soybean meal-based diet containing 14% crude protein. On d 90 of gestation, gilts (n = 5) were hysterectomized after euthanasia. Slices (~ 100 mg) of placentae or endometria were incubated at 37 °C for 2 h in oxygenated (95% O2/5% CO2) Krebs-Henseleit bicarbonate buffer (pH 7.4, with 5 mM D-glucose) containing 0 or 2 mM Hyp. After a period of 2 h incubation, 200 μL of 1.5 M HClO4 was added into the incubation medium to stop the reaction. The tissues were homogenized and rinsed with 1 mL water, followed by the addition of 100 μL of 2 M K²CO³. The neutralized extract was analyzed for amino acids using HPLC involving derivatization with o-phthaldialdehyde. Tissues that received no incubation time were determined as well. Data were analyzed by the paired t-test. Results indicated that glycine was produced from 2 mM Hyp by the placenta (Table 1). Glycine was subsequently converted into serine by the placenta. The formation of glycine and serine from Hyp was not due to protein breakdown because there were no differences (P > 0.05) in concentrations of tyrosine (an amino acid that is neither synthesized nor degraded by porcine placentae) in the incubation medium plus tissue at the end of a 2-h incubation period. In contrast to placentae, endometria did not form glycine or serine from Hyp. These findings indicate an important role for Hyp in the provision of both glycine and serine in the conceptus, which may be nutritionally and physiologically significant to compensate for a deficiency of glycine in maternal diets for gestating gilts. (Supported by a USDA/NIFA grant # 2022-67015-36376 and USDA multistate Hatch project #7752: S1081) [ABSTRACT FROM AUTHOR]

In pigs, the majority of embryonic mortality occurs when free-floating conceptuses (embryos/fetuses and associated placental membranes) elongate, and the uterine-placental interface undergoes folding and develops areolae. Both periods involve proliferation, migration, and changes in morphology of cells that require adenosine triphosphate (ATP). We hypothesize that insufficient ATP in conceptus and uterine tissues contributes to conceptus loss in pigs. Creatine is stored in cells as phosphocreatine for ATP regeneration through the creatine-creatine kinase- phosphocreatine pathway. However, the expression of components of this pathway in pigs has not been examined throughout gestation. Results of qPCR analyses indicated increases in AGAT, GAMT, CKM, CKB, and SLC6A8 mRNAs in elongating porcine conceptuses, and immunofluorescence microscopy localized guanidinoacetate N-methyltransferase, creatine kinase M, and creatine kinase B proteins to the trophectoderm of elongating conceptuses, to the columnar chorionic epithelial cells at the bottom of chorioallantoic troughs, and to endometrial luminal epithelium at the tops of the endometrial ridges of uterine-placental folds on Days 40, 60, and 90 of gestation. Guanidinoacetate N-methyltransferase protein is expressed in endometrial luminal epithelium at the uterine-placental interface, but immunostaining is more intense in luminal epithelium at the bottoms of the endometrial ridges. Results of this study indicate that key elements of the pathway for creatine metabolism are expressed in cells of the conceptus, placenta, and uterus for potential production of ATP during two timepoints in pregnancy with a high demand for energy; elongation of the conceptus for implantation and development of uterine-placental folding during placentation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The fertilization of oocytes ovulated by pigs, sheep, cows, and horses is not considered a limiting factor in successful establishment of pregnancy. Pig, sheep, and cow embryos undergo cleavage to the blastocyst stage, hatch from the zona pellucida, and undergo central-type implantation. Hatched blastocysts of pigs, sheep, and cows transition from tubular to long filamentous forms to establish surface area for exchange of nutrients and gases with the uterus. The equine blastocyst, surrounded by external membranes, does not elongate but migrates throughout the uterine lumen before attaching to the uterine luminal epithelium (LE) to begin implantation. Pregnancy recognition signaling in pigs requires the trophectoderm to express interleukin 1 beta, estrogens, prostaglandin E2, and interferon gamma. Sheep and cow conceptus trophectoderm expresses interferon tau that induces interferon regulatory factor 2 that inhibits transcription of estrogen and oxytocin receptors by uterine epithelia. This prevents oxytocin-induced luteolytic pulses of prostaglandin F2-alpha from regressing the corpora lutea, as well as ensuring the secretion of progesterone required for maintenance of pregnancy. The pregnancy recognition signal produced by equine blastocysts is not known. Implantation in these species requires interactions between extracellular matrix (ECM) proteins and integrins as the conceptus undergoes apposition and firm attachment to the uterine LE. This review provides details with respect to early embryonic development and the transition from spherical to filamentous conceptuses in pigs, sheep, and cows, as well as pre-implantation development of equine blastocysts and implantation of the conceptuses.

Although both L-glutamate (Glu) and L-glutamine (Gln) have long been considered nutritionally nonessential in ruminants, these two amino acids have enormous nutritional and physiological importance. Results of recent studies revealed that extracellular Gln is extensively degraded by ruminal microbes, but extracellular Glu undergoes little catabolism by these cells due to the near absence of its uptake. Ruminal bacteria hydrolyze Gln to Glu plus ammonia and, intracellularly, use both amino acids for protein synthesis. Microbial proteins and dietary Glu enter the small intestine in ruminants. Both Glu and Gln are the major metabolic fuels and building blocks of proteins, as well as substrates for the syntheses of glutathione and amino acids (alanine, ornithine, citrulline, arginine, proline, and aspartate) in the intestinal mucosa. In addition, Gln and aspartate are essential for purine and pyrimidine syntheses, whereas arginine and proline are necessary for the production of nitric oxide (a major vasodilator) and collagen (the most abundant protein in the body), respectively. Under normal feeding conditions, all diet- and rumen-derived Glu and Gln are extensively utilized by the small intestine and do not enter the portal circulation. Thus, de novo synthesis (e.g., from branched-chain amino acids and α-ketoglutarate) plays a crucial role in the homeostasis of Glu and Gln in the whole body but may be insufficient for maximal growth performance, production (e.g., lactation and pregnancy), and optimal health (particularly intestinal health) in ruminants. This applies to all types of feeding systems used around the world (e.g., rearing on a milk replacer before weaning, pasture-based production, and total mixed rations). Dietary supplementation with the appropriate doses of Glu or Gln [e.g., 0.5 or 1 g/kg body weight (BW)/day, respectively] can safely improve the digestive, endocrine, and reproduction functions of ruminants to enhance their productivity. Both Glu and Gln are truly functional amino acids in the nutrition of ruminants and hold great promise for improving their health and productivity.