Consumer perception of plant-based yoghurt: Sensory drivers of liking and emotional, holistic and conceptual associations.

Plant-based (PB) yoghurts is a rapidly expanding food category with the potential to reduce many of the negative environmental impacts associated with the farming of dairy cattle and related greenhouse gas emissions. Within the context of growing consumer demand for PB products, this research aimed to identify the main drivers of consumer acceptance of PB yoghurts through data drawn from a consumer study of 113 adult New Zealand participants who tasted a representative range of commercially available vanilla-flavoured PB yoghurts, and provided sample evaluations using a multi-variable measurement approach comprised of liking ratings, emotional responses, sensory characterisations, and holistic / conceptual perceptions. The primary finding of this study was that the overall acceptability of currently available PB yoghurts is low, leading to poor attitudes and low willingness to consume PB yoghurts. The examined products were characterised by the presence of several sensory attributes that negatively impacted consumer liking, either because they were unexpected or because their intensity level was too high. Among the main sensory issues identified were perceived sourness (acidity), lumpy appearance and non-white colour. In contrast, vanilla flavour and a creamy/smooth texture were identified as the main drivers of liking. The multi-response approach used in this study enabled a comprehensive characterisation of the products. One of the key insights gained was that negative emotional activation, caused by the presence of unexpected sensory attributes in the samples, was the main driver of product rejection. This was likely due to the disparity between consumers' sensory expectations, formed primarily based on their experience with dairy yoghurts, and the actual experience upon tasting the PB yoghurts. Overall, the findings indicate that the sensory properties of currently available PB yoghurts are a significant barrier to their adoption by most consumers and that addressing these sensory deficiencies is essential to achieving mainstream market acceptance of these products.

Consumer Preference Segments for Plant-Based Foods: The Role of Product Category.

A survey of willingness to consume (WTC) 5 types of plant-based (PB) food was conducted in USA, Australia, Singapore and India (n = 2494). In addition to WTC, emotional, conceptual and situational use characterizations were obtained. Results showed a number of distinct clusters of consumers with different patterns of WTC for PB foods within different food categories. A large group of consumers did not discriminate among PB foods across the various food categories. Six smaller, but distinct clusters of consumers had specific patterns of WTC across the examined food categories. In general, PB Milk and, to a much lesser extent, PB Cheese had highest WTC ratings. PB Fish had the lowest WTC, and two PB meat products had intermediate WTC. Emotional, conceptual and situational use characterizations exerted significant lifts/penalties on WTC. No penalty or lifts were imparted on WTC by the situational use of 'moving my diet in a sustainable direction', whereas uses related to 'when I want something I like' and 'when I want something healthy' generally imparted WTC lifts across clusters and food categories. The importance of this research for the study of PB foods is its demonstration that consumers are not monolithic in their willingness to consume these foods and that WTC is often a function of the food category of the PB food.

Pioneering BRCA1/2 Point-Of-Care Testing for Integration of Germline and Tumor Genetics in Breast Cancer Risk Management: A Vision for the Future of Translational Pharmacogenomics.

Research performed in South African (SA) breast, ovarian and prostate cancer patients resulted in the development of a rapid BRCA point-of-care (POC) assay designed as a time- and cost-effective alternative to laboratory-based technologies currently used for first-tier germline DNA testing. In this study the performance of the new assay was evaluated for use on a portable screening device (ParaDNA), with the long-term goal to enable rollout at POC as an inventive step to meet the World Health Organization's sustainable development goals for Africa. DNA samples for germline testing were obtained retrospectively from 50 patients with early-stage hormone receptor-positive breast cancer referred for genomic tumor profiling (MammaPrint). Currently, SA patients with the luminal-type breast cancer are not routinely selected for BRCA1/2 testing as is the case for triple-negative disease. An initial evaluation involved the use of multiple control samples representing each of the pathogenic founder/recurrent variants included in the BRCA 1.0 POC Research Assay. Comparison with a validated laboratory-based first-tier real-time polymerase chain reaction (PCR) assay demonstrated 100% concordance. Clinical utility was evident in five patients with the founder BRCA2 c.7934delG variant, identified at the 10% (5/50) threshold considered cost-effective for BRCA1/2 testing. BRCA2 c.7934delG carrier status was associated with a significantly younger age (p=0.03) at diagnosis of breast cancer compared to non-carriers. In three of the BRCA2 c.7934delG carriers a high-risk MammaPrint 70-gene profile was noted, indicating a significantly increased risk for both secondary cancers and breast cancer recurrence. Initiating germline DNA testing at the POC for clinical interpretation early in the treatment planning process, will increase access to the most common pathogenic BRCA1/2 variants identified in SA and reduce loss to follow-up for timely gene-targeted risk reduction intervention. The ease of using cheek swabs/saliva in future for result generation within approximately one hour assay time, coupled with low cost and a high BRCA1/2 founder variant detection rate, will improve access to genomic medicine in Africa. Application of translational pharmacogenomics across ethnic groups, irrespective of age, family history, tumor subtype or recurrence risk profile, is imperative to sustainably implement preventative healthcare and improve clinical outcome in resource-constrained clinical settings.

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases.

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases. Case 1, after following the PSGT program for 15 years, had an expanded disability status scale (EDSS) of 2.0 (no neurological sequelae) together with preserved brain volume on magnetic resonance imaging (MRI). A novel form of iron deficiency was identified in Case 1, as biochemical testing at each hospital submission due to MS symptoms showed low serum iron, ferritin and transferrin saturation, while hematological status and erythrocyte sedimentation rate measurement of systemic inflammation remained normal. Case 2 was unable to walk unaided until her EDSS improved from 6.5 to 4.0 over 12 months after implementation of the PSGT program, with amelioration of her suboptimal biochemical markers and changes to her diet and lifestyle, allowing her to regain independence. Genotype-phenotype correlation using a pathway panel of functional single nucleotide variants (SNVs) to facilitate clinical interpretation of whole exome sequencing (WES), elucidated the underlying metabolic pathways related to the biochemical deficits. A cure for MS will remain an elusive goal if separated from nutritional support required for production and maintenance of myelin, which can only be achieved by a lifelong investment in wellness.

Human whole genome sequencing in South Africa.

The advent and evolution of next generation sequencing has considerably impacted genomic research. Until recently, South African researchers were unable to access affordable platforms capable of human whole genome sequencing locally and DNA samples had to be exported. Here we report the whole genome sequences of the first six human DNA samples sequenced and analysed at the South African Medical Research Council's Genomics Centre. We demonstrate that the data obtained is of high quality, with an average sequencing depth of 36.41, and that the output is comparable to data generated internationally on a similar platform. The Genomics Centre creates an environment where African researchers are able to access world class facilities, increasing local capacity to sequence whole genomes as well as store and analyse the data.

Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing.

BACKGROUND: Multiple sclerosis is a disorder related to demyelination of axons. Iron is an essential cofactor in myelin synthesis. Previously, we described two children (males of mixed ancestry) with relapsing-remitting multiple sclerosis (RRMS) where long-term remission was achieved by regular iron supplementation. A genetic defect in iron metabolism was postulated, suggesting that more advanced genetic studies could shed new light on disease pathophysiology related to iron. METHODS: Whole exome sequencing (WES) was performed to identify causal pathways. Blood tests were performed over a 10 year period to monitor the long-term effect of a supplementation regimen. Clinical wellbeing was assessed quarterly by a pediatric neurologist and regular feedback was obtained from the schoolteachers. RESULTS: WES revealed gene variants involved in iron absorption and transport, in the transmembrane protease, serine 6 (TMPRSS6) and transferrin (TF) genes; multiple genetic variants in CUBN, which encodes cubilin (a receptor involved in the absorption of vitamin B12 as well as the reabsorption of transferrin-bound iron and vitamin D in the kidneys); SLC25A37 (involved in iron transport into mitochondria) and CD163 (a scavenger receptor involved in hemorrhage resolution). Variants were also found in COQ3, involved with synthesis of Coenzyme Q10 in mitochondria. Neither of the children had the HLA-DRB1*1501 allele associated with increased genetic risk for MS, suggesting that the genetic contribution of iron-related genetic variants may be instrumental in childhood MS. In both children the RRMS has remained stable without activity over the last 10 years since initiation of nutritional supplementation and maintenance of normal iron levels, confirming the role of iron deficiency in disease pathogenesis in these patients. CONCLUSION: Our findings highlight the potential value of WES to identify heritable risk factors that could affect the reabsorption of transferrin-bound iron in the kidneys causing sustained iron loss, together with inhibition of vitamin B12 absorption and vitamin D reabsorption (CUBN) and iron transport into mitochondria (SLC25A37) as the sole site of heme synthesis. This supports a model for RRMS in children with an apparent iron-deficient biochemical subtype of MS, with oligodendrocyte cell death and impaired myelination possibly caused by deficits of energy- and antioxidant capacity in mitochondria.

Holistic and consumer-centric assessment of beer: A multi-measurement approach.

Despite occupying a cornerstone position in consumer research and innovation, product liking/disliking provides only partial insight into consumer behaviour. By adopting a consumer-centric perspective and drawing on additional factors that underpin food-related consumer behaviour, a more complete product understanding is gained. The present research showcases this approach in a study with New Zealand beer (incl. pilsner, lager and ale categories). Implementation of a multi-variate approach with 128 regular beer drinkers provided assessments pertaining to liking and sensory novelty/complexity, situational appropriateness of consumption, as well as attitudes/perceptions and emotional associations. The 9 samples grouped into two clusters, where 4 of the beers were similar in being perceived as having less complex flavours, being appropriate for many uses and evoking stronger emotional associations of "relaxed/calm." The 4 beers were perceived as "easy to drink", and were, on average, most liked. One of the samples in this cluster was lighter in alcohol (2.5% ABV), but not inferior to beers with 4-5% ABV. The 5 beers in the second cluster were, on average, less liked and were associated with more negative emotions, e.g. "unhappy, "jittery", and "tense". Additional insights were gained from segmentation which identified two groups of consumers, named 'Lager Lovers' and 'Ale Aficionados'. Beers 1-4 were positively perceived by 'Lager Lovers' but less so by 'Ale Aficionados', and vice versa. The study was conducted under central location test conditions compatible with testing protocols often used in product research. The study protocol can be amended to include few/many consumer-centric measures and extended to product testing where packaging, brand, and other extrinsic information is available to consumers.

Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway.

Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two BRCA1/2 mutation-negative breast cancer patients from the same family for WES. Homozygosity for the MTHFR 677 C>T mutation detected during this PSGT pre-screen step was considered insufficient to cause bilateral breast cancer in the index case and her daughter diagnosed with early-onset breast cancer (<30 years). Extended genetic testing using WES identified the RAD50 R385C missense mutation in both cases. This rare variant with a minor allele frequency (MAF) of <0.001 was classified as a VUS after exclusion in an affected cousin and extended genotyping in 164 unrelated breast cancer patients and 160 controls. Detection of functional polymorphisms (MAF > 5%) in the folate pathway in all three affected family members is consistent with inheritance of the luminal-type breast cancer in the family. PSGT assisted with the decision to pursue extended genetic testing and facilitated clinical interpretation of WES aimed at reduction of recurrence risk.

An emotional approach to beef evaluation.

The emotions associated with beef consumption, the influence of breeding system information on emotions ("Conventional" - C vs "Only from the Italian Simmental" - OIS label) and their relationship with liking were evaluated by 93 meat consumers. Respondents were asked to evaluate the same samples of Italian Simmental meat provided with the two different labels. Liking scores were obtained using a 9-point scale and the emotions from the EsSense25 list were scored on 5-point scale (1="not at all", 5="extremely"). A positive and significant effect of OIS information was highlighted on liking scores. Moreover, the breeding system information significantly affected 22 out of the 25 emotions. OIS label elicited higher positive and lower negative feelings about the meat than did the C label. Providing the same beef with different breeding information led to different emotions being evoked in consumers, and these differences in emotions were associated with different levels of liking for beef.

Multiple sclerosis-like diagnosis as a complication of previously treated malaria in an iron and vitamin D deficient Nigerian patient.

In contrast to malaria, multiple sclerosis (MS) is infrequently found in Black Africans. We describe a 29 year old Nigerian female who developed an MS-like condition with symptoms similar to relapsing-remitting MS following malaria infection, leading to a diagnosis of MS. However, absence of hyperintense lesions in the brain and spinal cord presented a conundrum since not all the diagnostic criteria for MS were met. Pathology supported genetic testing (PSGT) was applied to combine family and personal medical history, lifestyle factors, and biochemical test results for interpretation of genetic findings. This approach provides a means of identifying risk factors for different subtypes of demyelinating disease. The patient was subsequently treated according to an individualised intervention program including nutritional supplementation as well as a change in diet and lifestyle. Deficiencies of vitamin B12, iron and vitamin D were addressed. Genetic analysis revealed absence of the HLA DRB1*1501 allele, considered to be the most prominent genetic risk factor for MS. Extended mutation analysis identified variations in three genes in the folate-vitamin B12 metabolic pathway, which could have increased the patient's sensitivity to the antifolate drugs used to treat the malaria. A glutathione-S-transferase GSTM1 null allele, previously associated with neurological complications of malaria, was also detected. Furthermore, a heterozygous variation in the iron-related transmembrane protease serine 6 (TMPRSS6) gene, rs855791 was found, which could have impacted the patient's iron status following two successive blood donations and exposure to malaria preceding the MS diagnosis. PSGT identifies relevant risk factors for demyelinating disorders resembling MS and uses the data for individualised treatment programs, and to systematically build a database that can provide evidence in large patient cohorts. Follow-up investigations may be suggested, such as whole exome sequencing in selected cases, to ensure that remyelination and restoration of function are achieved.

GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper.

Endoplasmic reticulum (ER) release and cell-surface export of many G protein-coupled receptors (GPCRs) are tightly regulated. For gamma-aminobutyric acid (GABA)B receptors of GABA, the major mammalian inhibitory neurotransmitter, the ligand-binding GB1 subunit is maintained in the ER by unknown mechanisms in the absence of hetero-dimerization with the GB2 subunit. We report that GB1 retention is regulated by a specific gatekeeper, PRAF2. This ER resident transmembrane protein binds to GB1, preventing its progression in the biosynthetic pathway. GB1 release occurs upon competitive displacement from PRAF2 by GB2. PRAF2 concentration, relative to that of GB1 and GB2, tightly controls cell-surface receptor density and controls GABAB function in neurons. Experimental perturbation of PRAF2 levels in vivo caused marked hyperactivity disorders in mice. These data reveal an unanticipated major impact of specific ER gatekeepers on GPCR function and identify PRAF2 as a new molecular target with therapeutic potential for psychiatric and neurological diseases involving GABAB function.

Genomic medicine and risk prediction across the disease spectrum.

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures. Regarding the small subset of highly penetrant monogenic disorders, a positive family history and early disease onset are mostly sufficient to determine the appropriateness of genetic testing in the index case and to inform pre-symptomatic diagnosis in at-risk family members. In more prevalent polygenic non-communicable diseases (NCDs), the use of appropriate eligibility criteria is required to ensure a balance between benefit and risk. An additional screening step may therefore be necessary to identify individuals most likely to benefit from genetic testing. This need provided the stimulus for the development of a pathology-supported genetic testing (PSGT) service as a new model for the translational implementation of genomic medicine in clinical practice. PSGT is linked to the establishment of a research database proven to be an invaluable resource for the validation of novel and previously described gene-disease associations replicated in the South African population for a broad range of NCDs associated with increased cardio-metabolic risk. The clinical importance of inquiry concerning family history in determining eligibility for personalized genotyping was supported beyond its current limited role in diagnosing or screening for monogenic subtypes of NCDs. With the recent introduction of advanced microarray-based breast cancer subtyping, genetic testing has extended beyond the genome of the host to also include tumor gene expression profiling for chemotherapy selection. The decreasing cost of next generation sequencing over recent years, together with improvement of both laboratory and computational protocols, enables the mapping of rare genetic disorders and discovery of shared genetic risk factors as novel therapeutic targets across diagnostic boundaries. This article reviews the challenges, successes, increasing inter-disciplinary integration and evolving strategies for extending PSGT towards exome and whole genome sequencing (WGS) within a dynamic framework. Specific points of overlap are highlighted between the application of PSGT and exome or WGS, as the next logical step in genetically uncharacterized patients for whom a particular disease pattern and/or therapeutic failure are not adequately accounted for during the PSGT pre-screen. Discrepancies between different next generation sequencing platforms and low concordance among variant-calling pipelines caution against offering exome or WGS as a stand-alone diagnostic approach. The public reference human genome sequence (hg19) contains minor alleles at more than 1 million loci and variant calling using an advanced major allele reference genome sequence is crucial to ensure data integrity. Understanding that genomic risk prediction is not deterministic but rather probabilistic provides the opportunity for disease prevention and targeted treatment in a way that is unique to each individual patient.

Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance.

OBJECTIVE: In this study, we hypothesized that mutations in the resistin encoding gene, RETN, may cause a monogenic form of obesity. DESIGN/METHODS: We screened the coding region of RETN in 81 morbidly obese adults, 263 overweight and obese children/adolescents, and 116 healthy lean subjects. In vitro experiments include qPCR, ELISA, and western blot for WT and mutant resistin transfected into 3T3-L1 adipocytes. RESULTS: Mutation analysis identified five sequence variants in our patient populations: 3'-UTR +87 G/A, 3'-UTR +100 A/G, T73T, IV3-61 C/A, and C78S. In our control population, we only found the 3'-UTR +87 G/A variant. We started functional experiments for the C78S mutation that was found in a 20-year-old obese male (body mass index (BMI)=39.7 kg/m(2)) and his obese mother (BMI=31.9 kg/m(2)). In vitro testing demonstrated that the mutation does not impair mRNA expression. We identified a 100-fold lower extracellular protein concentration for mutant resistin compared with WT levels using a resistin ELISA on cell culture medium (P=4.87×10(-6)). We also detected a decreased intracellular concentration for the mutant protein (tenfold lower relative levels, P=0.007). The plasma resistin levels of the proband and his mother, however, did not differ significantly from lean control individuals. CONCLUSIONS: In conclusion, we identified the first missense mutation in resistin in a morbidly obese proband and his obese mother. Functional testing of the mutant protein suggests that the C78S mutant protein is degraded, possibly resulting in a decreased extracellular concentration, which may predispose to obesity.

Identification of three novel genetic variants in the melanocortin-3 receptor of obese children.

The melanocortin-3 receptor (MC3R), a G-protein-coupled receptor expressed in the hypothalamus, is a key component of the leptin-melanocortin pathway that regulates energy homeostasis. It is suggested that an MC3R defect leads to an increased feed efficiency, by which nutrients are partitioned preferentially into fat. In this study, we hypothesized that early-onset obesity could be induced by mutations in MC3R. To investigate this hypothesis, we screened the entire coding region of the MC3R gene for mutations in obese subjects. A total of 404 overweight and obese children and adolescents, 86 severely obese adults (BMI ≥40 kg/m²), and 150 normal-weight control adults were included. Besides three synonymous coding variations in the MC3R gene (S69S, L95L, I226I), we were able to identify three novel heterozygous, nonsynonymous, coding mutations (N128S, V211I, L299V) in three unrelated obese children. None of these mutations were found in any of the control subjects. Functional studies assessing localization and signaling properties of the mutant receptors provided proof for impaired function of the L299V mutated receptor, whereas no conclusive evidence for functional impairment of the N128S and V211I mutated receptors could be established. First, these results provide supporting evidence for a role of the MC3R gene in the pathogenesis of obesity in a small subset of patients. Second, they show that caution is called for the interpretation of newly discovered mutations in MC3R.

Core biopsies of the breast: diagnostic pitfalls.

The incidence of breast cancer is increasing worldwide. In this review article, the authors compare and contrast the incidence of breast cancer, and the inherent differences in the United States (US) and India in screening techniques used for diagnosing breast cancer. In spite of these differences, core biopsies of the breast are common for diagnosis of breast cancer in both countries. The authors describe "Best Practices" in the reporting and processing of core biopsies and in the analysis of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor Receptor 2 (Her2/neu). The pitfalls in the diagnosis of fibroepithelial lesions of the breast on core biopsy are discussed, as also the significance of pseudoangiomatous stromal hyperplasia of the breast (PASH) is discussed in core biopsy. In this review, the management and diagnosis of flat epithelial atypia and radiation atypia are elaborated and the use of immunohistochemistry (IHC) in papillary lesions, phyllodes tumor, and complex sclerosing lesions (radial scars) is illustrated. Rarer lesions such as mucinous and histiocytoid carcinoma are also discussed.

Identification and functional characterization of novel mutations in the melanocortin-4 receptor.

OBJECTIVE: Melanocortin-4 receptor (MC4R) deficiency is the most common cause of monogenic obesity. In the present study, we screened the MC4R gene for mutations in a population of overweight and obese children and adolescents. METHOD: Cross-sectional mutation analysis of 112 overweight/obese children and adolescents and 121 lean individuals. RESULTS: We identified 11 sequence variations, 5 of which were present in our control population or had been previously reported as polymorphisms. The remaining 6 variations are disease-causing mutations including 2 novel ones: a I186V mutation and a F280L mutation. The 4 previously described mutations (D90N, M200V, P260Q, Q307X) were identified in single probands. Using confocal imaging, we demonstrated that F280L and P260Q cause intracellular retention of the mutant receptor. No difference in cell surface expression could be detected for the I186V mutation. Using a cAMP responsive luciferase vector, we demonstrated that the receptor with I186V is unable to activate its intracellular signaling pathway while the P260Q mutation causes reduced activation of the receptor. CONCLUSION: We detected MC4R deficiency in 6 patients from our cohort, amounting to a prevalence of 5.3%. Two novel mutations were identified. We also confirmed that intracellular retention is a common pathogenic effect of MC4R mutations.

Protein malnutrition during pregnancy in C57BL/6J mice results in offspring with altered circadian physiology before obesity.

The mechanisms linking intrauterine growth retardation (IUGR) with adulthood obesity and diabetes are unclear. These studies investigated energy homeostasis in 8- and 20-wk-old male and female mice subjected to protein deficiency in utero. Pregnant C57BL/6J female mice were fed a protein-deficient diet (6% protein). Undernourished offspring (UO) and controls (CO) were cross-fostered to lactating dams fed a 20% control diet. The 24-h profiles of energy expenditure, feeding behavior, physical activity, and whole-body substrate preference was assessed using 8-wk UO and CO weaned onto control diet. Blood chemistries, glucose tolerance, and expression of genes involved in hepatic lipid and glucose metabolism were analyzed in 8- and 20-wk-old CO and UO fed control or a high-fat diet. UO exhibited IUGR with catch-up growth at 8 wk of age and increased severity of diet-induced obesity and insulin resistance by 20 wk of age. Therefore, fetal malnutrition in the C57BL/6J mouse increases sensitivity to diet-induced obesity. Abnormal daily rhythms in food intake and metabolism, increased lipogenesis, and inflammation preceded obesity in the UO group. Arrhythmic expression of circadian oscillator genes was evident in brain, liver, and muscle of UO at 8 and 20 wk of age. Expression of the clock-associated nuclear receptor and transcription repressor Rev-erbalpha was reduced in liver and muscle of UO. Altered circadian physiology may be symptomatic of the metabolic dysregulation associated with IUGR, and altered feeding behavior and substrate metabolism may contribute to the obese phenotype.