Association of glucose metabolism and insulin resistance with feed efficiency and production traits of finishing beef steers.

Increasing nutrient utilization efficiency is an important component of enhancing the sustainability of beef cattle production. The objective of this experiment was to determine the association of glucose metabolism and insulin resistance with dry matter intake (DMI), average daily gain (ADG), gain:feed ratio (G:F), and residual feed intake (RFI). Steers (n = 54; initial body weight = 518 ±â€…27.0 kg) were subjected to an intravenous glucose tolerance test (IVGTT) where glucose was dosed through a jugular catheter and serial blood samples were collected. Three days after the last group's IVGTT, steers began a 63-d DMI and ADG test. Body weight was measured on days 0, 1, 21, 42, 62, and 63, and DMI was measured using an Insentec Roughage Intake Control system (Hokofarm Group, Emmeloord, the Netherlands). To examine relationships between DMI, ADG, G:F, and RFI with IVGTT measurements, Pearson correlations were calculated using Proc Corr of SAS 9.4 (SAS Inst. Inc., Cary, NC). Additionally, cattle were classified based on DMI, ADG, RFI, and G:F, where the medium classification was set as mean ±â€…0.5 SD, the low classification was < 0.5 SD from the mean, and the high classification was > 0.5 SD from the mean. No associations between DMI and IVGTT parameters were observed, and no differences were detected when classifying cattle as having low, medium, or high DMI. Peak insulin concentration in response to the IVGTT tended to be correlated with ADG (r = 0.28; P = 0.07), indicating cattle with greater ADG tend to have a greater insulin release in response to glucose. Glucose nadir concentrations tended to be positively correlated with ADG (r = 0.26; P = 0.10). Additionally, the glucose nadir was greater in high-ADG steers (P = 0.003). The association of greater glucose nadir with high-ADG could indicate that high-ADG steers do not clear glucose as efficiently as low-ADG steers, potentially indicating increased insulin resistance. Further, RFI was not correlated with IVGTT measurements, but low RFI steers had a greater peak glucose concentration (P = 0.040) and tended to have a greater glucose area under the curve (P = 0.09). G:F was correlated with glucose area under the curve (r = 0.33; P = 0.050), glucose nadir (r = 0.35; P = 0.011), and insulin time to peak (r = 0.39; P = 0.010). These results indicate that glucose metabolism and insulin signaling are associated with growth and efficiency, but the molecular mechanisms that drive these effects need to be elucidated.

Feed efficiency is an important component of improving the sustainability of beef production. There is a need to understand how metabolism influences feed efficiency. This experiment aimed to explore the association of glucose metabolism and insulin resistance with feed intake, growth, and efficiency of finishing beef cattle. The results indicate that there is a relationship between insulin resistance and improved efficiency measured as the ratio of growth to feed intake. The findings of this experiment are novel as they show a relationship between insulin resistance and feed efficiency and indicate further research is needed to determine the mechanisms of insulin resistance in ruminants that contribute to improved feed efficiency.

Late gestational nutrient restriction in primiparous beef females: Performance and metabolic status of lactating dams and pre-weaning calves.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation in Calan gates until day 149 of lactation, which limited calves to milk only. From day 150 of lactation until weaning at day 243, dams and calves were group-fed in drylots. Dam BW and metabolic status were determined every 21 d, and BCS and backfat (BF) were determined every 42 d of lactation until weaning. Pre-weaning calf BW, size, and metabolic status were determined every 21 d. Data were analyzed with nutritional plane, calving date, and calf sex (when P < 0.25) as fixed effects. Circulating metabolites included day and nutritional plane × day as repeated measures. We previously reported that post-calving, NR dams were 64 kg and 2.0 BCS less than CON, but calf BW and size at birth were not affected. During the first 147 d of lactation, NR dams gained more (P < 0.01) BW than CON and increased (P < 0.01) BCS, while CON decreased (P ≤ 0.01) BCS and BF. Previously, NR dams had lower (P < 0.01) circulating triglycerides on day 1 of lactation, tended to have lower (P = 0.08) triglycerides on day 21, and had lower (P ≤ 0.04) non-esterified fatty acids (NEFA) on days 21 and 243 than CON. Maternal glucose and urea N were not affected (P ≥ 0.73). At weaning, NR dams weighed 17 kg less (P = 0.15), were 0.67 BCS lower (P < 0.01), and tended to have less (P = 0.06) BF. Calves born to NR dams weighed less (P = 0.02) than CON by day 42 of age and were 13% smaller (P < 0.01) at weaning. Calf girth measures diverged (P ≤ 0.05) by day 21 of age, and skeletal size measures were less (P ≤ 0.08) for calves born to NR dams at most timepoints after day 63 of age. Calves born to NR dams tended to have lower (P = 0.09) circulating urea N pre-weaning than CON, but glucose, triglycerides, and NEFA were not affected (P ≥ 0.16). In summary, first-parity beef females that were nutrient restricted during late gestation experienced compensatory growth and gained body condition during lactation but were still thinner at weaning. Nutrient restriction reduced pre-weaning calf growth, likely due to decreased milk production.

Nutrient requirements increase substantially during late gestation in the beef female; however, poor forage nutrient availability can result in undernutrition. For heifers, the added nutrient requirements needed to continue growing during their first pregnancy and lactation pose an even greater challenge. It is plausible that lingering effects of late gestational nutrient restriction may exist for the dam and calf pre-weaning. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation recovered quickly metabolically and experienced compensatory growth, but still had less body condition at weaning than controls. Late gestational nutrient restriction did not affect calf size at birth but resulted in calf body weight and size measures diverging early in life. Ultimately, nutrient restriction resulted in a 13% decrease in weaning weight, which was likely due to decreased milk production (in a companion paper). Despite this, metabolic status of calves born to nutrient restricted dams was not greatly altered. In summary, first-parity beef females that were nutrient restricted during late gestation prioritized partitioning nutrients to maternal growth and energy reserves over milk production during lactation, but dams were thinner at weaning, and pre-weaning calf growth was slowed.

Nutrient restriction during late gestation reduces milk yield and mammary blood flow in lactating primiparous beef females.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation until day 149 of lactation. Four-hour milk yields were collected on days 21, 42, 63, 84, 105, and 147 of lactation, and milk nutrient composition was determined. Doppler ultrasonography of both pudendoepigastric arterial trunks was conducted every 21 d from days 24 to 108 of lactation. Total mammary blood flow was calculated, and hemodynamics from both sides were averaged. Data were analyzed as repeated measures with nutritional plane, day of lactation, their interaction, calving date, and calf sex (if P < 0.25) as fixed effects. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Milk weight and volume were 15% less (P = 0.04) for NR dams than CON. Milk protein concentration was lower (P = 0.008) for NR dams than CON, but triglyceride and lactose concentrations were not affected (P ≥ 0.20) by nutritional plane. Milk urea N concentration of NR dams tended to be greater (P = 0.07) on day 42 but was lower (P = 0.01) on day 147 of lactation than CON. Total milk protein, triglyceride, and lactose yields were less (P ≤ 0.05) for NR dams than CON. Total milk urea N yield was less (P ≤ 0.03) for NR dams than CON on days 21, 63, and 147 of lactation. Maternal heart rate was greater (P = 0.008), but pudendoepigastric arterial trunk peak systolic velocity, resistance index, and cross-sectional area were less (P ≤ 0.04) and pulsatility index tended to be less (P = 0.06) for NR dams than CON. Mammary blood flow was 19% less (P = 0.004) for NR dams than CON, but mammary blood flow relative to milk weight or dam BW was not affected (P ≥ 0.14) by nutritional plane. Most milk yield, milk nutrient composition, and mammary blood flow variables were affected (P ≤ 0.04) by day of lactation. In summary, first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had decreased milk nutrient yield and a similar reduction in mammary blood flow.

Mammary development in preparation for lactation is largely complete at the time of calving, and final prepartum mammary growth and differentiation are occurring for the first time in heifers. Nutrient requirements increase substantially during late gestation, resulting in competition for nutrient use among maternal growth, fetal growth, and mammary growth in primiparous beef females. Undernutrition during late gestation can occur due to poor forage nutrient availability or drought, potentially impacting mammary gland development and subsequent milk production. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had 15% lower milk yield, reduced milk protein concentration, and less total milk protein, triglycerides, lactose, and urea N available for their calves than controls. Additionally, previously nutrient restricted dams had 19% less total mammary blood flow, and the major arteries supplying the mammary gland were smaller.

Effects of copper, zinc, and manganese source and inclusion during late gestation on beef cow-calf performance, mineral transfer, and metabolism.

To determine effects of Cu, Zn, and Mn source and inclusion during late gestation, multiparous beef cows [n = 48; 649 ±â€…80 kg body weight (BW); 5.3 ±â€…0.5 body condition score (BCS)] were individually-fed hay and supplement to meet or exceed all nutrient recommendations except Cu, Zn, and Mn. From 91.2 ±â€…6.2 d pre-calving to 11.0 ±â€…3.2 d post-calving, cows received: no additional Cu, Zn, or Mn (control, CON), sulfate-based Cu, Zn, and Mn (inorganic, ITM) or metal methionine hydroxy analogue chelates (MMHAC) of Cu, Zn, and Mn at 133% recommendations, or a combination of inorganic and chelated Cu, Zn, and Mn (reduce and replace, RR) to meet 100% of recommendations. Data were analyzed with treatment and breeding group (and calf sex if P < 0.25 for offspring measures) as fixed effects, animal as experimental unit, and sampling time as a repeated effect for serum, plasma, and milk measures over time. Post-calving cow liver Cu was greater (P ≤ 0.07) in MMHAC compared with all other treatments. Calves born to RR had greater (P ≤ 0.05) liver Cu than ITM and CON, and MMHAC had greater (P = 0.06) liver Cu than CON. Liver Mn was less (P ≤ 0.08) for RR calves than all other treatments. Calf plasma Zn was maintained (P ≥ 0.15) from 0 to 48 h of age in ITM and MMHAC but decreased (P ≤ 0.03) in CON and RR. Gestational cow BW, BCS, and metabolites were not affected (P ≥ 0.13) by treatment, but gestational serum thiobarbituric acid reactive substances (TBARS) were greater (P = 0.01) for CON than MMHAC. Treatment did not affect (P ≥ 0.13) calf birth size, vigor, placental size and minerals, or transfer of passive immunity. Neonatal calf serum Ca was greater (P ≤ 0.05) for MMHAC than all other treatments; other calf serum chemistry and plasma cortisol were not affected (P ≥ 0.12). Pre-suckling colostrum yield, and lactose concentration and content, were greater (P ≤ 0.06) for MMHAC compared with ITM and RR. Colostral triglyceride and protein concentrations were greater (P ≤ 0.08) for RR than MMHAC and CON. Cow lactational BW and BCS, milk yield and composition, and pre-weaning calf BW and metabolism were not affected (P ≥ 0.13) by treatment. Lactational serum TBARS were greater (P = 0.04) for RR than CON at day 35 and greater (P ≤ 0.09) for MMHAC at day 60 than all other treatments. Source and inclusion of Cu, Zn, and Mn altered maternal and neonatal calf mineral status, but calf size and vigor at birth, passive transfer, and pre-weaning growth were not affected in this study.

Visceral adipose microbial and inflammatory signatures in metabolically healthy and unhealthy nonhuman primates.

OBJECTIVE: Obesity is a key risk factor for metabolic syndrome (MetS); however, >10% of lean individuals meet MetS criteria. Visceral adipose tissue (VAT) disproportionately contributes to inflammation and insulin resistance compared with subcutaneous fat depots. The primary aim of this study was to profile tissue microbiome components in VAT over a wide range of metabolic statuses in a highly clinically relevant model. METHODS: VAT was profiled from nonhuman primates that naturally demonstrate four distinct health phenotypes despite consuming a healthy diet, namely metabolically healthy lean and obese and metabolically unhealthy lean and obese. RESULTS: VAT biopsied from unhealthy lean and obese nonhuman primates demonstrated upregulation of immune signaling pathways, a tissue microbiome enriched in gram-negative bacteria including Pseudomonas, and deficiencies in anti-inflammatory adipose tissue M2 macrophages. VAT microbiomes were distinct from fecal microbiomes, and fecal microbiomes did not differ by metabolic health group, which was in contrast to the VAT bacterial communities. CONCLUSIONS: Immune activation with gram-negative VAT microbial communities is a consistent feature in elevated MetS risk in both lean and obesity states.

Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design.

Cellular senescence increases with aging and results in secretion of pro-inflammatory factors that induce local and systemic tissue dysfunction. We conducted the first preclinical trial in a relevant middle-aged nonhuman primate (NHP) model to allow estimation of the main translatable effects of the senolytic combination dasatinib (D) and quercetin (Q), with and without caloric restriction (CR). A multi-systemic survey of age-related changes, including those on immune cells, adipose tissue, the microbiome, and biomarkers of systemic organ and metabolic health are reported. Age-, weight-, sex-, and glycemic control-matched NHPs (D + Q, n = 9; vehicle [VEH] n = 7) received two consecutive days of D + Q (5 mg/kg + 50 mg/kg) monthly for 6 months, where in month six, a 10% CR was implemented in both D + Q and VEH NHPs to induce equal weight reductions. D + Q reduced senescence marker gene expressions in adipose tissue and circulating PAI-1 and MMP-9. Improvements were observed in immune cell types with significant anti-inflammatory shifts and reductions in microbial translocation biomarkers, despite stable microbiomes. Blood urea nitrogen showed robust improvements with D + Q. CR resulted in significant positive body composition changes in both groups with further improvement in immune cell profiles and decreased GDF15 (p = 0.05), and the interaction of D + Q and CR dramatically reduced glycosylated hemoglobin A1c (p = 0.03). This work indicates that 6 months of intermittent D + Q exposure is safe and may combat inflammaging via immune benefits and improved intestinal barrier function. We also saw renal benefits, and with CR, improved metabolic health. These data are intended to provide direction for the design of larger controlled intervention trials in older patients.

Late gestational nutrient restriction in primiparous beef females: nutrient partitioning among the dam, fetus, and colostrum during gestation.

Fall-calving primiparous crossbred beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were allocated by fetal sex and expected calving date to receive either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to calving. Heifers were individually-fed chopped poor quality hay and supplemented to meet targeted nutritional planes based on estimated hay intakes. Dam BW, BCS, backfat, and metabolic status were determined pre-treatment, every 21 d (BW and metabolic status) or 42 d (BCS and backfat) during gestation, and post-calving. At birth, calf BW and size were measured, and total colostrum from the most full rear quarter was collected pre-suckling. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Gestational metabolites included day and nutritional plane × day as repeated measures. During late gestation, CON dams gained (P < 0.01) maternal (non-gravid) BW and maintained (P ≥ 0.17) BCS and backfat, while NR dams lost (P < 0.01) maternal BW, BCS, and backfat. Circulating glucose, urea N, and triglycerides were less (P ≤ 0.05) in NR dams than CON at most late gestational timepoints after treatment initiation. Circulating non-esterified fatty acids were greater (P < 0.01) in NR dams than CON. Post-calving, NR dams weighed 63.6 kg less (P < 0.01) and were 2.0 BCS less (P < 0.01) than CON. At 1 h post-calving, NR dams had less (P = 0.01) plasma glucose and tended to have less (P = 0.08) plasma triglycerides than CON. Nutrient restriction did not affect (P ≥ 0.27) gestation length, calf birth weight, or calf size at birth. Colostrum yield was 40% less (P = 0.04) in NR dams than CON. Protein and immunoglobulin concentrations were greater (P ≤ 0.04), but free glucose and urea N concentrations were less (P ≤ 0.03), in colostrum of NR dams than CON. Colostrum total lactose, free glucose, and urea N were less (P ≤ 0.03) in NR dams than CON, but total protein, triglycerides, and immunoglobulins were not affected (P ≥ 0.55). In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth. During undernutrition, fetal and colostral nutrient demands were largely compensated for by catabolism of maternal tissue stores.

Nutrient requirements increase substantially during late gestation in the beef female. Even in well-managed herds, it is possible for females to be nutrient restricted during this time due to challenges of poor forage quality or availability and environmental stress. For heifers, the added nutrient requirements needed to continue growing pose an even greater challenge during their first pregnancy. However, little is known about how late gestational undernutrition impacts nutrient partitioning between maternal growth, the developing offspring, and colostrum production in beef heifers. Our data show that late gestational nutrient restriction in heifers slowed the expected maternal growth and instead maternal tissue stores were catabolized. Less nutrients were available in the maternal circulation, yet calf weight and size at birth were not affected. Late gestational nutrient restriction resulted in less colostrum produced by the dam and less lactose available to the offspring, but the total protein, fat, and immunoglobulins available in colostrum were not altered. In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth and maintenance of body condition.

Impaired Response to Polysaccharide Vaccine in Selective IgE Deficiency.

PURPOSE: Immunoglobulin E deficiency (IgED) (defined as IgE < 2 IU/mL) is enriched in patients with primary antibody deficiency (PAD). We hypothesized that selective IgED (sIgED) is a more sensitive predictor of the development of PAD than declining IgG, as IgE production typically requires two class switch recombination (CSR) events in contrast to IgG. Thus, the inability of patients with sIgED to mount an appropriate antibody response to a T-cell independent antigen or evidence of aberrant induction of ɛ germ line (ɛGL) or IgE heavy chain (IgEHC) transcripts in vitro would support the concept that sIgED is a biomarker for emerging PAD. METHODS: We compared pre- and post-polysaccharide vaccination titers in healthy patients with sIgED without a history of recurrent infections or autoimmunity (n = 20) and in healthy controls (HCs) (n = 17). Subsequently, we assessed in vitro induction of εGL and IgEHC transcripts in patients with sIgED and HC (n = 6) in response to IL-4 + CD40L stimulation. RESULTS: Thirty percent of patients with sIgED did not have a robust vaccine response compared to 0% of HCs (p = 0.017). Individuals with sIgED with an abnormal vaccine response demonstrated persistent germline mRNA expression in their B-cells at day 5, with lower levels of IgEHC, compared to both HCs and sIgED participants with a normal vaccine response. CONCLUSION: Patients with sIgED are more likely to have abnormal antibody responses to a T cell-independent antigen and may have dysregulated CSR machinery. Following individuals with sIgED longitudinally may be beneficial in the early identification of PAD.

Effects of adding ruminal propionate on dry matter intake and glucose metabolism in steers fed a finishing ration.

The objective of this experiment was to determine if supplying additional propionate to the rumen alters dry matter intake (DMI), feeding behavior, glucose metabolism, and rumen fluid metabolites in steers fed a finishing diet. Ruminally cannulated steers (n = 6) were fed a finishing diet ad libitum. Steers were randomly assigned to one of three treatments in a 3 × 6 Latin rectangle design with three 15 d periods. Treatments of no Ca propionate (Control), 100 g/d (Low), or 300 g/d (High) were ruminally dosed twice daily. Individual intake was measured using an Insentec feeding system. Pre-feeding blood samples were collected on day 7 and rumen fluid samples were collected on day 13. An intravenous glucose tolerance test (IVGTT) was conducted on day 14 and liver biopsies were collected on day 15. Liver samples were analyzed for expression of genes involved in gluconeogenesis. Data were analyzed using a mixed model with period, treatment, day, and their interaction included, with day and minute within period as a repeated measure and steer as a random effect. Meal size (P = 0.049), meal frequency (P = 0.046), and DMI (P < 0.001) were decreased in High steers. Day 7 plasma glucose (P = 0.23) and lactate (P = 0.47) were not affected by treatment, but insulin was decreased (P = 0.008) and non-esterified fatty acids were increased (P = 0.044) in the High treatment compared with the Control. Rumen fluid lactate was decreased (P = 0.015) in the High treatment compared with the Low treatment. Total VFA concentrations did not differ (P = 0.88) between treatments. There was treatment × time interaction for proportions of acetate and propionate (P < 0.001) and the acetate:propionate ratio (P = 0.005). The effect on acetate was due to a decrease in the High treatment 2 h after dosing the treatment. Propionate proportions were greater in the High treatment than the Control at all time points and differed from the Low except at 0 h. Propionate treatments had no major effects on the glucose and insulin parameters observed in the IVGTT other than a tendency (P = 0.09) for an increased insulin time to peak. These data indicate that exogenous propionate decreases DMI but the decrease in propionate from fermentation due to reduced DMI might negate the supply of exogenous propionate in VFA supply to the animal. Mechanisms other than hepatic oxidation of propionate might be responsible for DMI regulation.

Propionate metabolism by the liver is thought to be a key regulator of appetite and feed intake of animals, including cattle. Previous research has shown that providing propionate to the rumen of cattle decreases feed intake. Propionate is also a major contributor to glucose for cattle to use as an energy source for growth and maintenance. In this experiment, it was hypothesized that increasing ruminal propionate would depress feed intake and decrease insulin sensitivity. Supplying 300 g of propionate a day to the rumen decreased feed intake and increased the proportion of propionate in the rumen fluid of steers. However, when propionate production was calculated based on feed intake, there was likely no difference in propionate supply to the animal. The lack of increase in propionate supply to the animal could explain the lack of effect on glucose metabolism, insulin sensitivity, and liver gene expression. The lack of an increase in propionate also indicates that the effect of propionate on feed intake could be due to alternative mechanisms than liver metabolism of propionate.

Technical note: colorimetric methods for accurate determination of nutrient composition in beef cow colostrum and milk.

Our objectives were to develop colorimetric methods to accurately measure nutrient concentrations of beef cow colostrum and milk, to determine if the yield of colostrum from a single rear quarter is representative of complete collection of colostrum in beef cows, and to compare data from our developed colorimetric methods with Fourier transform infrared spectroscopy (FTIR) analysis to determine the accuracy of FTIR for beef cow colostrum and milk. In Exp. 1, colostral weight and volume of the most full rear quarter were compared with complete collection of colostrum from post-calving, unsuckled beef heifers. Both volume and weight had r2 = 0.85 (P < 0.001) between single-quarter and 4 quarter yields. In Exp. 2, colostrum (n = 35) and milk at d 35 (n = 42) and d 60 (n = 38) of lactation were collected from multiparous, fall-calving, crossbred beef cows. Subsamples were submitted for FTIR analysis and frozen for colorimetric analysis. Colorimetric analyses were developed for lactose, triglycerides (measure of fat), protein, and urea N. To validate method accuracy, spike recoveries were determined for lactose (96.8% average) and milk protein (100.1% average), triglyceride concentration was compared with fat concentration determined by the Mojonnier method (r2 ≥ 0.91, P < 0.001), and colostral or milk urea N was compared with serum urea N from the same sampling day (r2 ≥ 0.72, P < 0.001). Coefficients of determination between colorimetric methods and FTIR were determined for colostrum, d 35 milk, and d 60 milk. Colostral lactose concentration from FTIR was positively associated (r2 = 0.24, P = 0.01) with colorimetric analysis, but there was no relationship (r2 ≤ 0.09, P ≥ 0.14) between methods for colostral fat, protein, or urea N. Milk nutrient composition was positively associated for all nutrients measured at d 35 (r2 = 0.28 to 0.58, P < 0.001), and coefficients of determination strengthened for all nutrients measured at d 60 (r2 = 0.38 to 0.82, P < 0.001). In conclusion, colostrum yield of a single rear quarter can be used to indicate complete collection of colostrum for beef cows, and colorimetric methods developed have adequate accuracy for beef cow colostral and milk nutrient analysis. Based on our analyses, nutrient composition of beef cow colostrum was not accurately analyzed by FTIR. Accuracy of FTIR for beef cow milk varies with component and may be affected by the day of lactation.

The purpose was to develop laboratory methods to measure lactose, fat, protein, and urea nitrogen in beef cow colostrum (first milk) and milk and to validate single-quarter colostrum yield as a predictor of total colostrum yield. Additionally, new methods were compared with Fourier transform infrared spectroscopy (FTIR), which is the primary method of dairy cow milk nutrient analysis. New laboratory methods were determined to be accurate for beef cow colostrum and milk analysis, and single-quarter colostrum yield was successful in predicting total colostrum yield. Overall, our data suggest that beef cow colostrum cannot be accurately analyzed by FTIR instruments, and accuracy of FTIR for beef cow milk analysis varies with nutrients and may be affected by the day of lactation.

Brief Communication: Histological Assessment of Nonhuman Primate Brown Adipose Tissue Highlights the Importance of Sympathetic Innervation.

Objective: The objective of this study was to functionally analyze the correlation of key histological features in brown adipose tissue (BAT) with clinical metabolic traits in nonhuman primates. Methods: Axillary adipose tissue biopsies were collected from a metabolically diverse nonhuman primate cohort with clinical metabolism-related data. Expression of tyrosine hydroxylase (TH), uncoupling protein 1 (UCP1), cluster of differentiation 31 (CD31), cytochrome c oxidase subunit 4 (COX IV), beta-3 adrenergic receptor (ß3-AR), and adipose cell size were quantified by immunohistochemical analysis. Computed tomography scans were performed to assess body composition. Results: Tyrosine hydroxylase was negatively correlated with whole body fat mass as a percentage of body weight (p = 0.004) and was positively correlated with the density of UCP1 (p = 0.02), COX IV (p = 0.006), CD31 (p = 0.007), and cell density (p = 0.02) of the BAT samples. Beta-3 adrenergic receptor abundance had a weak positive correlation with COX IV (p = 0.04) in BAT but did not significantly correlate to UCP1 or TH expression in BAT. Conclusions: Our findings highlight that there is a disparity in innervation provided to BAT based on body composition, as seen with the negative association between TH, a marker for innervation, and adiposity. These findings also support the importance of innervation in the functionality of BAT, as TH abundance not only supports leaner body composition but is also positively correlated with known structural elements in BAT (UCP1, COX IV, CD31, and cell density). Based on our observations, ß3-AR abundance does not strongly drive these structural elements or TH, all of which are known to be important in the function of brown adipose tissue. In effect, while the role of other receptors, such as ß2-AR, should be reviewed in BAT function, these results support the development of safe sympathetic nervous system stimulants to activate brown adipose tissue for obesity treatment.

Delayed effects of radiation in adipose tissue reflect progenitor damage and not cellular senescence.

The pathogenesis of many age-related diseases is linked to cellular senescence, a state of inflammation-inducing, irreversible cell cycle arrest. The consequences and mechanisms of age-associated cellular senescence are often studied using in vivo models of radiation exposure. However, it is unknown whether radiation induces persistent senescence, like that observed in ageing. We performed analogous studies in mice and monkeys, where young mice and rhesus macaques received sub-lethal doses of ionizing radiation and were observed for ~ 15% of their expected lifespan. Assessments of 8-hydroxy-2' -deoxyguanosine (8-OHdG), senescence-associated beta-galactosidase (SAß-gal), and p16Ink4a and p21 were performed on mitotic and post-mitotic tissues - liver and adipose tissue - 6 months and 3 years post-exposure for the mice and monkeys, respectively. No elevations in 8-OHdG, SA-ßgal staining, or p16 Ink4a or p21 gene or protein expression were found in mouse and monkey liver or adipose tissue compared to control animals. Despite no evidence of senescence, progenitor cell dysfunction persisted after radiation exposure, as indicated by lower in situ CD34+ adipose cells (p = 0.03), and deficient adipose stromal vascular cell proliferation (p < 0.05) and differentiation (p = 0.04) ex vivo. Our investigation cautions that employing radiation to study senescence-related processes should be limited to the acute post-exposure period and that stem cell damage likely underpins the dysfunction associated with delayed effects of radiation.

Effects of spring- versus fall-calving on perinatal nutrient availability and neonatal vigor in beef cattle.

To determine the effect of calving season on perinatal nutrient availability and neonatal beef calf vigor, data were collected from 4 spring- (average calving date: February 14; n = 203 total) and 4 fall- (average calving date: September 20; n = 179 total) calving experiments. Time to stand was determined as minutes from birth to standing for 5 s. After birth, calf weight and size (length, heart and abdominal girth, and cannon circumference) were recorded. Jugular blood samples and rectal temperatures were obtained at 0, 6, 12, and 24 h postnatally in 6 experiments and at 48 h postnatally in Exp. 2 to 8. Data were analyzed with fixed effects of season (single point) or season, hour, and their interaction (over time, using repeated measures). Experiment was a random effect; calf sex was included when P ≤ 0.25. Within calving season, correlations were determined between calf size, vigor, and 48-h serum total protein. Fall-born calves tended to have lighter (P = 0.09) birth weight and faster (P = 0.05) time to stand than spring-born calves. Season did not affect (P ≥ 0.18) gestation length, other calf size measures, or 48-h serum total protein. Fall-born calves had greater (P ≤ 0.003) rectal temperature at 0, 24, and 48 h postnatal. Spring-born calves had greater (P ≤ 0.009) circulating glucose at 0 h, serum non-esterified fatty acids at 0 and 6 h, and plasma triglycerides at 0, 6, 12, and 48 h. Fall-born calves had greater (P ≤ 0.03) sodium from 6 to 48 h and magnesium from 0 to 24 h of age. Phosphorus was greater (P ≤ 0.02) at 6 and 12 h of age in spring-born calves. Spring-born calves had greater (P ≤ 0.04) aspartate aminotransferase at 12 and 24 h and creatine kinase at 0 and 12 h of age. Fall-born calves had greater (P ≤ 0.03) albumin, calcium, and chloride, had lower (P ≤ 0.03) bicarbonate and direct bilirubin, and tended to have greater (P = 0.10) anion gap (all main effects of calving season). Calf birth weight had a weak positive relationship (P ≤ 0.03) with 48-h serum total protein and time to stand in fall-born, but not spring-born, calves. Overall, fetal growth was restricted and neonatal dehydration was increased by warm conditions for fall-born calves, but vigor and metabolism were negatively affected by cold conditions in spring-born calves. These data suggest that calving season influences perinatal nutrient availability, which may impact the transition of beef calves to postnatal life.

Macrophage Phenotypes and Gene Expression Patterns Are Unique in Naturally Occurring Metabolically Healthy Obesity.

Obesity impacts 650 million individuals globally, often co-occurring with metabolic syndrome. Though many obese individuals experience metabolic abnormalities (metabolically unhealthy obese [MUO]), ~30% do not (metabolically healthy obese [MHO]). Conversely, >10% of lean individuals are metabolically unhealthy (MUL). To evaluate the physiologic drivers of these phenotypes, a 44-animal African green monkey cohort was selected using metabolic syndrome risk criteria to represent these four clinically defined health groups. Body composition imaging and subcutaneous adipose tissue (SQ AT) biopsies were collected. Differences in adipocyte size, macrophage subtype distribution, gene expression, vascularity and fibrosis were analyzed using digital immunohistopathology, unbiased RNA-seq, endothelial CD31, and Masson's trichrome staining, respectively. MHO AT demonstrated significant increases in M2 macrophages (p = 0.02) and upregulation of fatty acid oxidation-related terms and transcripts, including FABP7 (p = 0.01). MUO AT demonstrated downregulation of these factors and co-occurring upregulation of immune responses. These changes occurred without differences in AT distributions, adipocyte size, AT endothelial cells, collagen I deposition, or circulating cytokine levels. Without unhealthy diet consumption, healthy obesity is defined by an increased SQ AT M2/M1 macrophage ratio and lipid handling gene expression. We highlight M2 macrophages and fatty acid oxidation as targets for improving metabolic health with obesity.

Xenon-enhanced computed tomography assessment of brown adipose tissue distribution and perfusion in lean, obese, and diabetic primates.

OBJECTIVE: This study aimed to validate xenon-enhanced computed tomography (XECT) for the detection of brown adipose tissue (BAT) and to use XECT to assess differences in BAT distribution and perfusion between lean, obese, and diabetic nonhuman primates (NHPs). METHODS: Whole-body XECT imaging was performed in anesthetized rhesus and vervet monkeys during adrenergic stimulation of BAT thermogenesis. In XECT images, BAT was identified as fat tissue that, during xenon inhalation, underwent significant radiodensity enhancement compared with subcutaneous fat. To measure BAT blood flow, BAT radiodensity enhancement was measured over time on the six computed tomography scans acquired during xenon inhalation. Postmortem immunohistochemical staining was used to confirm imaging findings. RESULTS: XECT was able to correctly identify all BAT depots that were confirmed at necropsy, enabling construction of the first comprehensive anatomical map of BAT in NHPs. A significant decrease in BAT perfusion was found in diabetic animals compared with obese animals and healthy animals, as well as absence of axillary BAT and significant reduction of supraclavicular BAT in diabetic animals compared with obese and lean animals. CONCLUSIONS: The use of XECT in NHP models of obesity and diabetes allows the analysis of the impact of metabolic status on BAT mass and perfusion.

Blood chemistry and rectal temperature changes in a population of healthy, fall-born, suckling beef calves from birth to 72 h of age.

To determine changes in suckling neonatal beef calf blood chemistry and body temperature during the first 72 h of life, jugular blood samples and rectal temperatures were obtained from 24 healthy, fall-born Angus-cross and Hereford calves (average calving date = September 11) at 0 (after standing, but pre-suckling), 6, 12, 24, 48, and 72 h postnatally. Serum chemistry panels were conducted, and plasma triglycerides and serum non-esterified fatty acids (NEFA) were also determined. Data were analyzed using sampling hour as a repeated effect, and individual data points were compared to adult bovine reference intervals. All serum chemistry measures were affected by hour of age except bicarbonate (P = 0.48). Serum glucose, total protein, and globulin concentrations increased (P < 0.001) from 0 to 24 h. Plasma triglycerides increased (P < 0.001) from 0 to 6 h and 24 to 72 h. Serum urea nitrogen increased (P < 0.001) from 0 to 6 h and decreased (P = 0.01) from 48 to 72 h. Serum NEFA and creatine kinase (CK) increased (P < 0.001) from 0 to 6 h, but decreased (P ≤ 0.02) from 12 to 72 h. Serum magnesium, aspartate aminotransferase (AST), and total and direct bilirubin increased (P < 0.001) during the first 12 h, then decreased (P < 0.001) from 24 to 72 h. Gamma-glutamyl transpeptidase (GGT) increased (P < 0.001) from 0 to 12, and then decreased (P < 0.003) from 12 to 48 h. Serum creatinine decreased (P < 0.001) from 0 to 72 h, and albumin decreased (P < 0.01) from 0 to 12 h but increased (P < 0.001) from 24 to 48 h. Anion gap decreased (P ≤ 0.05) from 6 to 24 h. No serum components measured were within adult bovine reference intervals for all calves at all sampling times. All serum albumin concentrations were outside of reference intervals, and the majority of serum glucose, calcium, phosphorus, potassium, CK, GGT, and total bilirubin were outside of reference intervals. More serum chemistry measures diverged from reference intervals in the first 24 h of neonatal life. Rectal temperature decreased (P = 0.003) from 0 to 6 h of age, then increased (P ≤ 0.02) from 12 to 48 h. In summary, blood chemistry profiles of healthy, suckling neonatal beef calves change over the first 72 h of life, indicating rapid changes in metabolism and physiology. Bovine reference intervals based on adults do not appear to represent neonatal calves; thus, neonatal status and animal age should be taken into consideration when interpreting serum chemistry in a clinical or research setting.

Effects of supplementation rate of an extruded dried distillers' grains cube fed to growing heifers on voluntary intake and digestibility of bermudagrass hay.

Our objectives were to 1) investigate the difference in chemical composition and disappearance kinetics between loose dried distillers' grains (DDG) and extruded DDG cubes and 2) evaluate the effects of supplementation rate of extruded DDG cubes on voluntary dry matter intake (DMI), rate and extent of digestibility, and blood parameters of growing beef heifers offered ad libitum bermudagrass (Cynodon dactylon) hay. To characterize the changes in chemical composition during the extrusion process, loose and extruded DDG were evaluated via near-infrared reflectance spectroscopy, and dry matter (DM) disappearance kinetics were evaluated via time point in situ incubations. Extruded DDG cubes had greater (P ≤ 0.01) contents of fat, neutral detergent insoluble crude protein, and total digestible nutrients, but lower (P ≤ 0.01) neutral and acid detergent fiber than loose DDG. Additionally, the DM of extruded DDG cubes was more immediately soluble (P < 0.01), had greater (P < 0.01) effective degradability and lag time, and tended (P = 0.07) to have a greater disappearance rate than loose DDG. In the 29-d supplementation rate study, 23 Charolais-cross heifers were randomly assigned to one of four supplemental treatments: 1) control, no supplement; 2) low, 0.90 kg DDG cubes per d; 3) intermediate, 1.81 kg DDG cubes per d; or 4) high, 3.62 kg DDG cubes per d. Titanium dioxide was used as an external marker to estimate fecal output and particulate passage rate (Kp). Blood was collected from each animal to determine supplementation effects on blood metabolites. Indigestible neutral detergent fiber was used as an internal marker to assess the rate and extent of hay and diet DM digestibility (DMD). Increasing supplementation rate increased Kp and total diet DMI linearly (P < 0.01), yet linearly decreased (P < 0.01) hay DMI. Hay DMD decreased quadratically (P < 0.01), while total diet DMD increased linearly (P < 0.01) with increased DDG cube inclusion. Supplemented heifers had greater (P = 0.07) blood urea nitrogen concentrations than control animals 4 h post-supplementation. Intermediate and high rates of supplementation resulted in lower (P < 0.01) serum nonesterified fatty acid concentrations post-supplementation than control heifers. Concentrations of serum glucose and lactate were greatest (P ≤ 0.06) 8 h post-supplementation. Our results suggest that extruded DDG cubes may be an adequate supplement for cattle consuming moderate-quality forage, and further research is warranted.

Growing cattle are oftentimes provided supplemental concentrate as a source of protein and energy in order to meet performance goals when consuming low-quality forages. The effects of supplemental concentrate on forage intake vary, which may be related to the quality of forage and the characteristics of the supplement being evaluated. Dried distillers' grains (DDG) are a by-product of ethanol production and have become a common supplement for growing cattle due to the increased energy and rumen undegradable protein content. A stable DDG cube made via a novel extrusion process may be advantageous for pasture supplementation due to the reduced risk of loss of product from wind and soil mixing that is common with loose DDG. The effects of supplementation rate of traditional concentrate sources on forage intake are abundant, but research regarding extruded DDG cubes is almost nonexistent. Thus, our objective was to evaluate extruded DDG cube supplementation rate (0, 0.90, 1.81, or 3.62 kg DDG cubes per d) for growing cattle on voluntary intake and digestibility of moderate-quality forage. Although increasing supplementation rate reduced forage intake and digestibility, total diet intake and digestibility were increased. Our results suggested that extruded DDG cubes have potential as a supplement for cattle consuming moderate-quality forage.

Effects of increasing calcium propionate in a finishing diet on dry matter intake and glucose metabolism in steers.

The objective of this study was to determine whether increasing propionate alters dry matter intake (DMI), glucose clearance rate, blood metabolites, insulin concentrations, and hepatic gene expression in steers fed a finishing diet. Holstein steers (n = 15; BW = 243 ± 3.6 kg) were individually fed a finishing diet ad libitum. Steers were allocated by body weight (BW) to receive: no Ca propionate (Control), 100 g/d Ca propionate (Low), or 300 g/d Ca propionate (High) in the diet. Orts were collected and weighed daily to determine DMI. Blood samples were collected on days 0, 7, and 21, and BW recorded on days 0, 14, and 28. An intravenous glucose tolerance test (IVGTT) was conducted on days 14 and 28 of the trial. Liver biopsies were collected on day 33 for gene expression analysis. Blood samples were analyzed for whole blood glucose and lactate, plasma non-esterified fatty acids (NEFAs), and insulin concentrations. Data were analyzed using a mixed model with treatment, day and their interaction included, with day and minute as a repeated measure. The control treatment had greater (P < 0.01) DMI than low and high steers. Body weight was increased in control steers on days 14 and 28 compared with the steers receiving the High treatment (P = 0.03 for the interaction). Blood glucose concentrations tended (P = 0.09) to be higher on day 21 than days 0 and 7 but was not affected by treatment (P = 0.58). Plasma NEFA concentrations were lower (P = 0.05) for control steers than other treatments, and greater (P = 0.002) on day 0 than days 7 and 21. Blood lactate concentrations were greater (P = 0.05) on day 7, than days 0 and 21, but not affected by treatment (P = 0.13). High steers had greater plasma insulin concentrations in response to the IVGTT than steers on the other treatments (P = 0.001). There was no treatment (P ≥ 0.16) or day effect (P ≥ 0.36) on glucose peak, plateau, or clearance rate. High steers had greater expression of solute carrier family 16 member 1 (SLC16A1; P = 0.05) and tended to have greater hepatic expression of solute carrier family 2 member 2 (SLC2A2; P = 0.07). These data indicate that increased propionate may decrease DMI and insulin sensitivity.

TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study.

Biallelic loss-of-function variants in the thrombospondin-type laminin G domain and epilepsy-associated repeats (TSPEAR) gene have recently been associated with ectodermal dysplasia and hearing loss. The first reports describing a TSPEAR disease association identified this gene is a cause of nonsyndromic hearing loss, but subsequent reports involving additional affected families have questioned this evidence and suggested a stronger association with ectodermal dysplasia. To clarify genotype-phenotype associations for TSPEAR variants, we characterized 13 individuals with biallelic TSPEAR variants. Individuals underwent either exome sequencing or panel-based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia, while three newly reported individuals have hearing loss. Of the individuals displaying hearing loss, all have additional variants in other hearing-loss-associated genes, specifically TMPRSS3, GJB2, and GJB6, that present competing candidates for their hearing loss phenotype. When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features but creates significant doubt as to whether TSPEAR variants are a monogenic cause of hearing loss. Further functional evidence is needed to evaluate this phenotypic association.

Potential regional declines in species richness of tomato pollinators in North America under climate change.

About 70% of the world's main crops depend on insect pollination. Climate change is already affecting the abundance and distribution of insects, which could cause geographical mismatches between crops and their pollinators. Crops that rely primarily on wild pollinators (e.g., crops that cannot be effectively pollinated by commercial colonies of honey bees) could be particularly in jeopardy. However, limited information on plant-pollinator associations and pollinator distributions complicate the assessment of climate change impacts on specific crops. To study the potential impacts of climate change on pollination of a specific crop in North America, we use the case of open-field tomato crops, which rely on buzz pollinators (species that use vibration to release pollen, such as bumble bees) to increase their production. We aimed to (1) assess potential changes in buzz pollinator distribution and richness, and (2) evaluate the overlap between areas with high densities of tomato crops and high potential decrease in richness. We used baseline (1961-1990) climate and future (2050s and 2080s) climatic projections in ecological niche models fitted with occurrences of wild bees, documented in the literature as pollinators of tomatoes, to estimate the baseline and future potential distribution of suitable climatic conditions of targeted species and to create maps of richness change across North America. We obtained reliable models for 15 species and found important potential decreases in the distribution of some pollinators (e.g., Lasioglossum pectorale and Augochlorella aurata). We observed geographical discrepancies in the projected change in species richness across North America, detecting important declines in the eastern United States (up to 11 species decrease for 2050s). After overlapping the maps of species richness change with a tomato crop map for the United States, we found spatial correspondence between richness declines and areas with high concentration of tomato crops. Disparities in the effects of climate change on the potential future distribution of different wild pollinators and geographical variation in richness highlight the importance of crop-specific studies. Our study also emphasizes the challenges of compiling and modeling crop-specific pollinator data and the need to improve our understanding of current distribution of pollinators and their community dynamics under climate change.