A Small-Molecule Inhibitor of Factor Inhibiting HIF Binding to a Tyrosine-flip Pocket for the Treatment of Obesity.

In animals limiting oxygen upregulates hypoxia-inducible factor (HIF) promoting a metabolic shift towards glycolysis. Factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that regulates HIF function by reducing its interaction with histone acetyl transferases. HIF levels are negatively regulated by the HIF prolyl hydroxylases (PHDs), which like FIH, are 2-oxoglutarate(2OG) oxygenases. Genetic loss of FIH promotes both glycolysis and aerobic metabolism. FIH has multiple non-HIF substrates making it challenging to connect its biochemistry with physiology. A structure-mechanism guided approach identified a highly potent in vivo active FIH inhibitor, ZG-2291, binding of which promotes a conformational flip of a catalytically important tyrosine, enabling selective inhibition of FIH over other JmjC subfamily 2OG oxygenases. Consistent with genetic studies, ZG-2291 promotes thermogenesis and ameliorates symptoms of obesity and metabolic dysfunction in ob/ob mice. The results reveal ZG-2291 as a useful probe for the physiological functions of FIH and identify FIH inhibition as a promising strategy for obesity treatment.

The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a largely incurable disease, for which new treatments are urgently needed. While leukemogenesis occurs in the hypoxic bone marrow, the therapeutic tractability of the hypoxia-inducible factor (HIF) system remains undefined. Given that inactivation of HIF-1α/HIF-2α promotes AML, a possible clinical strategy is to target the HIF-prolyl hydroxylases (PHDs), which promote HIF-1α/HIF-2α degradation. Here, we reveal that genetic inactivation of Phd1/Phd2 hinders AML initiation and progression, without impacting normal hematopoiesis. We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to disable pro-leukemogenic pathways, re-program metabolism and induce apoptosis, in part via upregulation of BNIP3. Notably, concurrent inhibition of BCL-2 by venetoclax potentiates the anti-leukemic effect of PHD inhibition. Thus, PHD inhibition, with consequent HIF-1α stabilization, is a promising nontoxic strategy for AML, including in combination with venetoclax.

How Lazy Are Pet Cats Really? Using Machine Learning and Accelerometry to Get a Glimpse into the Behaviour of Privately Owned Cats in Different Households.

Surprisingly little is known about how the home environment influences the behaviour of pet cats. This study aimed to determine how factors in the home environment (e.g., with or without outdoor access, urban vs. rural, presence of a child) and the season influences the daily behaviour of cats. Using accelerometer data and a validated machine learning model, behaviours including being active, eating, grooming, littering, lying, scratching, sitting, and standing were quantified for 28 pet cats. Generalized estimating equation models were used to determine the effects of different environmental conditions. Increasing cat age was negatively correlated with time spent active (p < 0.05). Cats with outdoor access (n = 18) were less active in winter than in summer (p < 0.05), but no differences were observed between seasons for indoor-only (n = 10) cats. Cats living in rural areas (n = 7) spent more time eating than cats in urban areas (n = 21; p < 0.05). Cats living in single-cat households (n = 12) spent more time lying but less time sitting than cats living in multi-cat households (n = 16; p < 0.05). Cats in households with at least one child (n = 20) spent more time standing in winter (p < 0.05), and more time lying but less time sitting in summer compared to cats in households with no children (n = 8; p < 0.05). This study clearly shows that the home environment has a major impact on cat behaviour.

Selective targeting of human TET1 by cyclic peptide inhibitors: Insights from biochemical profiling.

Ten-Eleven Translocation (TET) enzymes are Fe(II)/2OG-dependent oxygenases that play important roles in epigenetic regulation, but selective inhibition of the TETs is an unmet challenge. We describe the profiling of previously identified TET1-binding macrocyclic peptides. TiP1 is established as a potent TET1 inhibitor (IC50 = 0.26 µM) with excellent selectivity over other TETs and 2OG oxygenases. TiP1 alanine scanning reveals the critical roles of Trp10 and Glu11 residues for inhibition of TET isoenzymes. The results highlight the utility of the RaPID method to identify potent enzyme inhibitors with selectivity over closely related paralogues. The structure-activity relationship data generated herein may find utility in the development of chemical probes for the TETs.

Structure-guided optimisation of N-hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-α.

The human 2-oxoglutarate (2OG)- and Fe(ii)-dependent oxygenases factor inhibiting hypoxia-inducible factor-α (FIH) and HIF-α prolyl residue hydroxylases 1-3 (PHD1-3) regulate the response to hypoxia in humans via catalysing hydroxylation of the α-subunits of the hypoxia-inducible factors (HIFs). Small-molecule PHD inhibitors are used for anaemia treatment; by contrast, few selective inhibitors of FIH have been reported, despite their potential to regulate the hypoxic response, either alone or in combination with PHD inhibition. We report molecular, biophysical, and cellular evidence that the N-hydroxythiazole scaffold, reported to inhibit PHD2, is a useful broad spectrum 2OG oxygenase inhibitor scaffold, the inhibition potential of which can be tuned to achieve selective FIH inhibition. Structure-guided optimisation resulted in the discovery of N-hydroxythiazole derivatives that manifest substantially improved selectivity for FIH inhibition over PHD2 and other 2OG oxygenases, including Jumonji-C domain-containing protein 5 (∼25-fold), aspartate/asparagine-ß-hydroxylase (>100-fold) and histone Nε-lysine demethylase 4A (>300-fold). The optimised N-hydroxythiazole-based FIH inhibitors modulate the expression of FIH-dependent HIF target genes and, consistent with reports that FIH regulates cellular metabolism, suppressed lipid accumulation in adipocytes. Crystallographic studies reveal that the N-hydroxythiazole derivatives compete with both 2OG and the substrate for binding to the FIH active site. Derivatisation of the N-hydroxythiazole scaffold has the potential to afford selective inhibitors for 2OG oxygenases other than FIH.

Worms and welfare: Behavioural and physiological changes associated with gastrointestinal nematode parasitism in lambs.

Parasitism with gastrointestinal nematodes (GIN) is a worldwide issue impacting negatively on animal production, health, and welfare. Therefore, early diagnostic signs of parasitism are required to allow for timely interventions. The objective of this study was to evaluate the behavioural and physiological changes in lambs associated with GIN infection. We used 30, 8-month-old Romney-cross wethers, that were administered anthelmintics until faecal egg counts (FEC) were zero and housed in an indoor facility. The study lasted 9 weeks, which comprised a 3-week pre-treatment, and a 6-week treatment phase. Lambs were randomly assigned to one of two treatments (n = 15/treatment) trickle-dosed with: 1) 1500 infective third stage larvae (L3) three days/week for 6 weeks (27,000 total L3; challenged), or 2) water 3 days/week for 6 weeks (control). Within each pen there were 5 pairs of lambs (balanced for liveweight), with each pair comprising a challenged and control lamb. Blood, faecal, and saliva samples were collected 1 week pre-treatment and weekly for 6 weeks of treatment. Behaviour was observed (e.g., feeding, lying, standing) from video-camera recordings using scan sampling every 5 min for 8 h, 1 day pre-treatment and on the day immediately prior to physiological sampling across the 6-week treatment phase (7 days in total). Accelerometers were attached to each lamb to continuously monitor behaviour from 3 weeks pre-treatment and for the remainder of the study. Liveweight, body condition, faecal soiling and faecal consistency scoring were performed weekly as was lipidomic analysis of plasma samples. From week 2 of treatment, challenged lambs spent less time feeding and more time lying than control lambs until week 5 of treatment (P ≤ 0.01). At week 3 of treatment, elevated lipids (mainly triglycerides and phospholipids), loose faeces and faecal soiling around the anus were observed in challenged lambs compared with controls (P ≤ 0.05). From week 4 of treatment, FEC were elevated in the challenged compared to control lambs (P ≤ 0.05). There was also lower liveweight gain at 4 and 5 weeks of treatment in the challenged lambs compared with control lambs (P ≤ 0.05). These results show a clear timeline of changes in behaviour (e.g., feeding and lying), lipids such as triglycerides, and digestive function (e.g., faecal soiling) suggestive of GIN subclinical disease, which show promise for use in future studies on early identification of subclinical GIN parasitism in lambs.

The Use of Triaxial Accelerometers and Machine Learning Algorithms for Behavioural Identification in Domestic Cats (Felis catus): A Validation Study.

Animal behaviour can be an indicator of health and welfare. Monitoring behaviour through visual observation is labour-intensive and there is a risk of missing infrequent behaviours. Twelve healthy domestic shorthair cats were fitted with triaxial accelerometers mounted on a collar and harness. Over seven days, accelerometer and video footage were collected simultaneously. Identifier variables (n = 32) were calculated from the accelerometer data and summarized into 1 s epochs. Twenty-four behaviours were annotated from the video recordings and aligned with the summarised accelerometer data. Models were created using random forest (RF) and supervised self-organizing map (SOM) machine learning techniques for each mounting location. Multiple modelling rounds were run to select and merge behaviours based on performance values. All models were then tested on a validation accelerometer dataset from the same twelve cats to identify behaviours. The frequency of behaviours was calculated and compared using Dirichlet regression. Despite the SOM models having higher Kappa (>95%) and overall accuracy (>95%) compared with the RF models (64-76% and 70-86%, respectively), the RF models predicted behaviours more consistently between mounting locations. These results indicate that triaxial accelerometers can identify cat specific behaviours.

5-Substituted Pyridine-2,4-dicarboxylate Derivatives Have Potential for Selective Inhibition of Human Jumonji-C Domain-Containing Protein 5.

Jumonji-C domain-containing protein 5 (JMJD5) is a 2-oxoglutarate (2OG)-dependent oxygenase that plays important roles in development, circadian rhythm, and cancer through unclear mechanisms. JMJD5 has been reported to have activity as a histone protease, as an Nε-methyl lysine demethylase, and as an arginine residue hydroxylase. Small-molecule JMJD5-selective inhibitors will be useful for investigating its (patho)physiological roles. Following the observation that the broad-spectrum 2OG oxygenase inhibitor pyridine-2,4-dicarboxylic acid (2,4-PDCA) is a 2OG-competing JMJD5 inhibitor, we report that 5-aminoalkyl-substituted 2,4-PDCA derivatives are potent JMJD5 inhibitors manifesting selectivity for JMJD5 over other human 2OG oxygenases. Crystallographic analyses with five inhibitors imply induced fit binding and reveal that the 2,4-PDCA C5 substituent orients into the JMJD5 substrate-binding pocket. Cellular studies indicate that the lead compounds display similar phenotypes as reported for clinically observed JMJD5 variants, which have a reduced catalytic activity compared to wild-type JMJD5.

Kinetic and inhibition studies on human Jumonji-C (JmjC) domain-containing protein 5.

Jumonji-C (JmjC) domain-containing protein 5 (JMJD5) is a human 2-oxoglutarate (2OG) and Fe(ii)-dependent oxygenase which catalyses the post-translational C3 hydroxylation of arginyl-residues and which is linked to the circadian rhythm and to cancer biology through as yet unidentified mechanisms. We report robust solid phase extraction coupled to mass spectrometry (SPE-MS)-based JMJD5 assays which enable kinetic and high-throughput inhibition studies. The kinetic studies reveal that some synthetic 2OG derivatives, notably including a 2OG derivative with a cyclic carbon backbone (i.e. (1R)-3-(carboxycarbonyl)cyclopentane-1-carboxylic acid), are efficient alternative cosubstrates of JMJD5 and of factor inhibiting hypoxia-inducible transcription factor HIF-α (FIH), but not of the Jumonji-C (JmjC) histone Nε-methyl lysine demethylase KDM4E, apparently reflecting the closer structural similarity of JMJD5 and FIH. The JMJD5 inhibition assays were validated by investigating the effect of reported 2OG oxygenase inhibitors on JMJD5 catalysis; the results reveal that broad-spectrum 2OG oxygenase inhibitors are also efficient JMJD5 inhibitors (e.g. N-oxalylglycine, pyridine-2,4-dicarboxylic acid, ebselen) whereas most 2OG oxygenase inhibitors that are in clinical use (e.g. roxadustat) do not inhibit JMJD5. The SPE-MS assays will help enable the development of efficient and selective JMJD5 inhibitors for investigating the biochemical functions of JMJD5 in cellular studies.

The Behaviour of Sheep around a Natural Waterway and Impact on Water Quality during Winter in New Zealand.

Access of livestock, such as cattle, to waterways has been shown to be a cause of poor water quality due to pugging damage and excretion entering the water. In New Zealand, regulations require that cattle, deer, and pigs are excluded from accessing waterways, but there are no such requirements for sheep. The current study utilised 24 h video cameras, global positioning system units, and triaxial accelerometers to observe the interaction of Romney ewes (n = 40) with a natural waterway. Ewes were either restricted (week 1) or given access to a reticulated water trough (week 2). Proximity data showed that ewes spent more time within 3 m of the waterway when the trough was unrestricted than when restricted (14.1 ± 5.7 and 10.8 ± 5.1 min/ewe/day, respectively; p < 0.05). Ewes travelled shorter distances on the steeper areas of paddock than flatter areas. Similarly, ewes showed a spatial preference for the flat and low sloped areas of the paddock. Concentrations of suspended sediment and total phosphorus were higher during access to a reticulated water trough which coincided with the week with more rainy days. Phosphorus and E. coli concentrations in the stream water samples were the above recommended Australian and New Zealand Environment and Conservation Council water quality guidelines, especially after rainy days, but did not appear to be directly related to sheep activity. Overall, the results suggest that during winter, ewes interacted very little with the waterway and were thus unlikely to influence the levels of nutrient and pathogens in the waterway.

Practices and opinions of New Zealand sheep farmers towards pain management in lambs during castration and/or tail docking.

AIMS: To collect baseline data from New Zealand sheep farmers on techniques for docking and castrating lambs, their perceptions of the level of pain lambs experience following these procedures, and their opinions about the use of pain relief. METHODS: From a voluntary cross-sectional survey of New Zealand sheep farmers, descriptive statistics were provided for quantitative study variables. Thematic analysis was performed on the free-text comments. Univariable logistic regression was used to assess factors associated with farmers indicating they would consider using a device allowing administration of pain relief simultaneously with castration and tail docking. RESULTS: There were 432 survey responses containing sufficiently complete data for analysis. Of the 340 individuals (77.5%) always or sometimes performing castration of ram lambs, 242 (72.2%) used rubber rings for complete castration, 23 (6.9%) used the short scrotum method for cryptorchid castration, and 75 (22.4%) used a combination of both methods. Of the 423 individuals (97.9%) who indicated that they always or sometimes performed tail docking, 245 (57.9%) used a hot iron only, 148 (35.0%) used a rubber ring only, 26 (5.8%) used both methods, 3 (0.7%) used a surgical knife, and 1 (0.2%) provided no response. Less than 2% of respondents always or sometimes used pain relief for these procedures. Of the 432 respondents, 139 (32.2%) and 180 (41.7%) strongly agreed that castration and tail docking do not cause sufficient pain to warrant using pain relief, respectively. Time and cost were identified as major barriers to providing pain relief. In the unadjusted logistic regression analyses, respondents who were female, had high levels of education, had been farming < 20 years, who believed lambs experienced high levels of pain following the procedures, and who believed pain lasted longer than 6 hours, were more likely to indicate willingness to use pain control devices. CONCLUSION AND CLINICAL RELEVANCE: Our results suggest very few New Zealand sheep farmers currently provide lambs with pain relief following tail docking or castration. This is likely due to the perception that the procedures are not painful enough to warrant pain relief, and concern over time and cost. This highlights the need to educate farmers about lamb pain and distress following tail docking and castration, and its negative impact on animal welfare. Farmers also need pain relief techniques and tools that can be administered simultaneously with these procedures to save time and labour cost.

Breeding Ewe Lambs: An Australasian Perspective.

A number of potential advantages have been identified for breeding ewe lambs at 7 to 9 months of age, including increased lifetime productivity and profitability. However, breeding at this young age in extensive pastoral systems, such as in Australasia, can be associated with a number of disadvantages resulting in uptake of this management procedure being relatively low. This review highlights the known differences between ewe lamb and mature ewe reproductive performance, thus differing in their management. The review then summaries the scientific literature of factors that affect ewe lamb reproductive success, with a focus on recent studies conducted under extensive pasture-based conditions in Australasia. In particular, this review outlines the importance of ewe lamb live weight and body condition score on their productivity. The potential long-term consequences of breeding a ewe lamb at a young age in terms of her future success and that of her offspring to weaning are briefly outlined. In addition, the potential impacts of selecting progeny born to ewe lambs as future replacement ewes are discussed. Throughout this review, optimal management guidelines from prior to breeding the ewe lambs until rebreeding at 2 years of age are provided. Lastly, areas requiring future research are identified and discussed.

Factors Associated with Mortality of Lambs Born to Ewe Hoggets.

The reproductive performance of ewe hoggets is poorer than that of mature-age ewes due to production of fewer lambs with poorer survival. Scant data are available on the risk factors for, and causes of, the mortality for lambs born to ewe hoggets, the impact of ewe deaths on lamb loss, and the causes of death for lambs born to ewe hoggets vs. mature-age ewes lambing in the same circumstances. In this study, 297 lambs born to 1142 ewe hoggets were necropsied along with 273 lambs born to 1050 mature-age ewes. Low lamb birthweight, multiple litter size, and increasing ewe hogget average daily gain from breeding to late pregnancy were risk factors for lamb mortality. The most common cause of mortality for lambs born to ewe hoggets was stillbirth and the risk factors for stillbirth were similar to those for lamb mortality generally. Approximately 11% of ewe hoggets' lamb deaths were due to the death of the dam. Causes of mortality differed between lambs born to ewe hoggets vs. those born to mature-age ewes. Management practices to increase ewe hogget lambs' birthweights (particularly those from multiple litters) and supervision of ewe hoggets at lambing time are recommended.

Ewe wastage in commercial sheep flocks: a review of current knowledge.

Ewe wastage encompasses ewes that do not reach the end of their potential productive lives and is the combination of premature culling and on-farm mortality. Increased ewe wastage results in reduced flock productivity and profitability, primarily driven by the need for increased replacement ewe lambs to maintain flock numbers and the costs associated with these additional replacements (e.g. reduced sale lambs, reduced flock age resulting in lower lamb production, and reduced ability to utilise terminal sires). Annual ewe mortality rates are reported to range from 2.8 to 40.2% in New Zealand commercial flocks, while wastage over a ewe's productive lifespan (i.e. mortality and premature culling combined to 6-7 years-of-age) is reported to be up to 90%. To date, ewe wastage has received relatively little attention in the published literature. This article reviews published studies describing wastage in non-dairy ewes, focusing on New Zealand commercial flocks, although overseas pasture-based data is also considered. The relevance of, and challenges associated with, investigating ewe wastage are discussed. Ewe culling and mortality data is outlined, and causes are described. Known key risk factors for wastage, namely, reproductive performance, udder health, dental health, body condition score and breeding of ewe lambs, are reviewed. Finally, current knowledge gaps and future areas of research are identified and evaluated.

Effect of Breeding Heavier Romney Ewe Lambs at Seven Months of Age on Lamb Production and Efficiency over Their First Three Breeding Seasons.

This experiment examined the effect of breeding heavier ewe lambs on lamb production and their efficiency over their first three breeding seasons. Two groups of ewe lambs were bred at seven months of age at an average pre-breeding live weight of either 47.9 ± 0.36 kg (heavy; n = 135) or 44.9 ± 0.49 kg (control; n = 135). Ewe live weight, number of lambs born and weaned, and lamb live weight were recorded until 39 months of age, and efficiency was calculated for each ewe. Although the number and lamb weaning weight did not differ between treatments over three years, when data were pooled, heavier ewe lambs at breeding weaned a greater number of lambs over the three-year period. The total lamb weaning weight over the three-year period increased by 2% for each additional kilogram at ewe lamb breeding. Breeding heavier ewe lambs had no effect on efficiency. These results suggest that although breeding heavier ewe lambs had a positive effect on lamb production over the three-year period, it had no effect on efficiency. Before final recommendations can be made, lifetime performance and longevity to five years of age of heavier ewe lambs at breeding are required.

Predicting ewe body condition score using adjusted liveweight for conceptus and fleece weight, height at withers, and previous body condition score record.

The relationship between ewe body condition score (BCS) and liveweight (LW) has been exploited previously to predict the former from LW, LW-change, and previous BCS records. It was hypothesized that if fleece weight and conceptus-free liveweight and LW-change, and in addition, height at withers were used, the accuracy of current approaches to predicting BCS would be enhanced. Ewes born in 2017 (n = 429) were followed from 8 mo to approximately 42 mo of age in New Zealand. Individual ewe data were collected on LW and BCS at different stages of the annual production cycle (i.e., prebreeding, at pregnancy diagnosis, prelambing, and weaning). Additionally, individual lambing dates, ewe fleece weight, and height at withers data were collected. Linear regression models were fitted to predict current BCS at each ewe age and stage of the annual production cycle using two LW-based models, namely, unadjusted for conceptus weight and fleece weight (LW alone1) and adjusted (LW alone2) models. Furthermore, another two models based on a combination of LW, LW-change, previous BCS, and height at withers (combined models), namely, unadjusted (combined1) and adjusted for conceptus and fleece weight (combined2), were fitted. Combined models gave more accurate (with lower root mean square error: RMSE) BCS predictions than models based on LW records alone. However, applying adjusted models did not improve BCS prediction accuracy (or reduce RMSE) or improve model goodness of fit (R 2) (P > 0.05). Furthermore, in all models, both LW-alone and combined models, a great proportion of variability in BCS, could not be accounted for (0.25 ≥ R 2 ≥ 0.83) and there was substantial prediction error (0.33 BCS ≥ RMSE ≥ 0.49 BCS) across age groups and stages of the annual production cycle and over time (years). Therefore, using additional ewe data which allowed for the correction of LW for fleece and conceptus weight and using height at withers as an additional predictor did not improve model accuracy. In fact, the findings suggest that adjusting LW data for conceptus and fleece weight offer no additional value to the BCS prediction models based on LW. Therefore, additional research to identify alternative methodologies to account for individual animal variability is still needed.

What Are Sheep Doing? Tri-Axial Accelerometer Sensor Data Identify the Diel Activity Pattern of Ewe Lambs on Pasture.

Monitoring activity patterns of animals offers the opportunity to assess individual health and welfare in support of precision livestock farming. The purpose of this study was to use a triaxial accelerometer sensor to determine the diel activity of sheep on pasture. Six Perendale ewe lambs, each fitted with a neck collar mounting a triaxial accelerometer, were filmed during targeted periods of sheep activities: grazing, lying, walking, and standing. The corresponding acceleration data were fitted using a Random Forest algorithm to classify activity (=classifier). This classifier was then applied to accelerometer data from an additional 10 ewe lambs to determine their activity budgets. Each of these was fitted with a neck collar mounting an accelerometer as well as two additional accelerometers placed on a head halter and a body harness over the shoulders of the animal. These were monitored continuously for three days. A classification accuracy of 89.6% was achieved for the grazing, walking and resting activities (i.e., a new class combining lying and standing activity). Triaxial accelerometer data showed that sheep spent 64% (95% CI 55% to 74%) of daylight time grazing, with grazing at night reduced to 14% (95% CI 8% to 20%). Similar activity budgets were achieved from the halter mounted sensors, but not those on a body harness. These results are consistent with previous studies directly observing daily activity of pasture-based sheep and can be applied in a variety of contexts to investigate animal health and welfare metrics e.g., to better understand the impact that young sheep can suffer when carrying even modest burdens of parasitic nematodes.

Associations among Mammary Ultrasound Measurements, Milk Yield of Non-Dairy Ewe Lambs and the Growth of Their Single Lambs.

Mammary cistern size was positively correlated with milk yield of mature dairy ewes, but the association in ewe lambs is unknown. This experiment aimed to examine the associations between mammary ultrasound measurements and the milk yield of ewe lambs at one year of age and to determine the accuracy of using maternal mammary ultrasound to predict single lamb growth rates. Single-bearing ewe lambs (n = 45) were randomly selected and 30 were milked once at weeks three (W3), five (W5), and seven (W7) of lactation. Mammary ultrasound scans were performed at day 110 of pregnancy, W3, W5, W7, and weaning (L69). Single lambs (n = 30) were weighed at birth and at each mammary scanning event. Udder measurements explained 26.8%, 21.4%, and 38.4% of the variation in milk yield at W3, W5 and W7, respectively, and 63.5% and 36.4% of the variation in single lamb growth to W3 and to L69. This ultrasound technique was more accurate in predicting single lamb growth to W3 than milk yield and may enable the identification of pregnant ewe lambs whose progeny would have greater growth rates. More research is needed to identify accurate indicators of superior milk yield and determine whether ultrasound could be used to select ewe lambs.

The Effect of Age of Dam and Birth Rank on the Reproductive Performance of Ewes as One- and Two-Year-Olds.

Currently, 30-43% of New Zealand sheep farmers breed their ewe lambs, but few retain the offspring as replacements for their flock. No difference in lamb production as a yearling among singletons and twins born to ewe lambs and twins born to mature ewes has been reported, provided the ewe lambs had reached the 60-65% of their likely mature weight prior to breeding at seven to eight months of age. The aim of this experiment was to determine the lamb production from singletons and twins born to ewe lambs and twins born to mature ewes during their first two years of lambing. The experiment included 8-month-old ewes born as twins to mature ewes (M2, n = 135), singletons born to ewe lambs (L1, n = 135), and twins born to ewe lambs (L2, n = 88), bred during the same period to the same rams, over two years. The efficiency of lamb production (total litter weight at weaning divided by the pre-breeding weight of the ewe, for all ewes presented for breeding) after two years of production was not significantly different (p > 0.05) among the groups (0.40 ± 0.02, 0.39 ± 0.02, and 0.39 ± 0.03, for M2, L1, and L2, respectively).

Mammary Gland Structures Are Not Affected by an Increased Growth Rate of Yearling Ewes Post-Weaning but Are Associated with Growth Rates of Singletons.

The experiment aimed to examine the impacts of an increased growth rate of ewes between three and seven months of age on udder development using ultrasound and to establish whether ultrasonography could be used to identify ewe mammary structures that may be indirect indicators of singleton growth to weaning. Udder dimensions, depths of gland cistern (GC), parenchyma (PAR) and fat pad (FP) were measured in late pregnancy (P107), early lactation (L29), and at weaning (L100) in 59 single-bearing yearling ewes selected from two treatments. The 'heavy' group (n = 31) was preferentially fed prior to breeding achieving an average breeding live-weight of 47.9 ± 0.38 kg at seven months of age. The 'control' group (n = 28) had an average breeding live-weight of 44.9 ± 0.49 kg. Udder dimensions, GC, PAR and FP did not differ between treatments. Lamb growth to L100 was positively associated (p < 0.05) with PAR at P107 and GC at L29. There was no evidence of negative effects of the live-weight gain treatments on udder development of yearling ewes as measured by ultrasonography. The results suggest that this ultrasound method has the potential to identify pregnant yearling ewes which would wean heavier singletons.