Academic literature on the topic 'Metabolic maturity'

Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growth-constrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.

Maturity and sensory evaluation of peach (cv. Suncrest) fruits were evaluated in response to three leaf:fruit ratios, 6, 18 and 30, respectively. Fruit growth rates increased with increasing leaf:fruit ratios so that, at maturity, fruit weights of 75, 140 and 180 g were obtained from the three treatments, respectively. Metabolic activity (oxygen consumption) although indifferent between treatments when fruits were immature, segregated according to leaf:fruit ratios as fruits matured. Autocatalytic production of ethylene was delayed in fruits suffering from nutritional stress and the intensity of ethylene production was also dependent on assimilate supply. Sugars, especially sucrose, accumulated at slower rates when assimilate supply was lowest, i.e. six leaves per fruit. Malic and citric acids metabolisms were influenced by the leaves:fruit ratios. Quinic and shikimic acid levels were reduced according to the treatments. Key words: Peach, ripening, quality, assimilates, metabolic activity, sugars, acids

Urbanization has impacted the knowledge and use of traditional leafy vegetables. The present investigation is conducted to understand the importance of edible leaves and the variation in their nutritional content at different stages of maturity. Hygrophila spinosa and Chenopodium album leaves have been selected owing to their economic cost, accessibility, and utilization within the population. A leaf undergoes several physiological and metabolic changes during maturity, which may affect its biochemical content. Hence, the samples have been analyzed for their nutritional composition at distinct stages (I to IV) of maturity based on the length of the leaf post-germination. Results revealed that both samples possessed the highest content of nutrients, including carbohydrates, proteins, minerals, β carotene, and vitamin C at stage 1 compared to the older stages. Alteration in metabolic patterns and environmental influences during various phases may be responsible for this effect. Stage I manifested the notable existence of essential phytonutrients and the diminished presence of potent anti-nutrients. Moreover, a significant percentage of micronutrients are found to be available post in vitro gastrointestinal digestion. The study highlights the importance of consuming young edible leaves. Regular dietary incorporation of the same may lead to alleviation of nutrient deficiency disorders and food insecurity.

Unlike other Canadian Pacific salmon (Oncorhynchus spp.), long-term declines in the size at maturity of Fraser River sockeye salmon (O. nerka) have not been reported in past studies. Using data specific for 10 Fraser River sockeye stocks, we demonstrate that size at maturity has generally declined over the past 42 yr for females in all stocks and for males from eight stocks. Independent of this temporal trend, we found that size at maturity of both sexes in all stocks was smaller in years when sea surface temperatures were relatively warm. Slower growth in warmer years may be caused directly by increased metabolic demand, or indirectly by oceanic changes that influence food acquisition. We speculate that fitness of Fraser River sockeye will be reduced in the future if sea surface temperature increases and salmon abundance remains near present levels.

The decline in dairy cow fertility over the past 30 years has major economic, welfare, genetic and environmental consequences. A significant number of potential replacement heifers either never calve or else complete only a single lactation. The relationships between metabolic status and fertility may change with age as cows reach physical maturity. To determine the reasons behind the high loss rates attributable to infertility, this study tracked a group of animals until the end of their second lactation to compare fertility and metabolic hormone profiles in the same cows at different ages.

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A avaliação clinica, hematológica e bioquimica de potros nascidos de eguas com placentite auxilia na identificação dos animais de maior risco. O primeiro estudo teve objetivo avaliar a maturidade neonatal de potros nascidos de éguas com placentite. Foram avaliados seis potros, divididos de acordo com o grau de viabilidade e sobrevivência até 60 horas: grupo não sobreviventes (GNS, n=2); grupo debilitados (GD, n=2); grupo saudáveis (GS, n=2). O GS apresentou maior tempo de gestação (320±2 dias) e maior intervalo inoculação-parto (20,5±2,5 dias). Os potros do GNS e GD apresentaram atraso para decúbito esternal e reflexo de sucção. O GNS apresentou bradicardia e hipotermia com 48hs de vida. Conclui-se que a manutenção da gestação após a injúria placentária, influencia na maturação fetal e na capacidade de resposta neonatal. O segundo estudo teve objetivo descrever a resposta hematológica e bioquímica de potros nascidos de éguas com placentite. Foram avaliados 58 potros, divididos em grupo controle (GC, n=22) e grupo placentite (GP, n=36). O GP foi subdividido em três grupos, de acordo com o diagnostico de placentite: grupo saudáveis (GS, n=12), hiperlactatemia (GH, n=14) e Dismaturos (GD, n=10). Fibrinogênio plasmático e creatinina ao nascimento foi maior (p<0,05) no GD. Os potros do GH e GD apresentaram elevação (p=0,01) nas concentrações de lactato ao nascimento, sem redução em 24 horas. Conclui-se que potros neonatos provenientes de gestações com placentite apresentam condições clínicas variadas e grau de resposta neonatal distintos, necessitando avaliação e acompanhamento neonatal na busca de possíveis alterações metabólicas imediatas e tardia.
Biochemistry, hematologic and clinic evaluation of foals newborn to mares with placentitis assist in identification high risk animals. The first study aimed to evaluate neonatal maturity foals newborn of mares with placentitis. Were evaluated six foals, dividing according to degree of viability and survival were evaluated up to 60 hours: No survivors group (NSG, n=2), Debilitated group (DG, n=2), and Healthy group (HG, n=2). The HG showed longer gestation length (320±2 days) and longer inoculationdelivery interval (20,5±2,5 days). NSG and DG showed delay to sternal recumbency and sucking reflex. The NSG had bradycardia and hypothermia to48 hours of life.. It is concluded that the longer maintenance of gestation after placental injury, better is the fetal maturation, which reflect in better viability and ability to neonatal response. The second study aimed to describe hematologic and biochemistry response of foals newborn of mares with placentitis. Was evaluated 58 neonatal foals, which was divided in Control group (CG, n=22) and Placentitis group (PG, n=36). The placentitis group was subdivided into 3 groups: healthy group (HG, n=12), higher blood concentration of plasmatic lactate group (HLG, n=14), and dysmmature group (DG, n=10). Plasma fibrinogen and creatinine on birth was higher (p<0.05) in DG. In HLG and DG presented elevation (p=0.01) in birth concentration lactate with no reduce in 24hs. It is concluded neonatal foals from gestation with placentitis present several clinic conditions, with different adaptation and neonatal response requiring neonatal evaluation and monitoring to order find metabolic changes immediately and delayed metabolic changes.

Lamb mortality in Australia averages approximately 20%, representing a major constraint to the profitability of sheep enterprises and compromised animal welfare. Most postpartum lamb loss occurs within the first three days of life and is largely caused by starvation, exposure to cold conditions and mismothering from the ewe. In this thesis we developed an over-arching hypothesis that differences in metabolic or physiological maturity exist between lambs, and that these differences relate to early postnatal vigour and survival, particularly during exposure to cold conditions. To test this hypothesis, behaviour associated with initial vigour was quantified in breeds of sheep which differ widely in neonatal survival and more specifically, risk of hypothermia. Pre-suckling blood samples were collected from these animals in order to identify potential markers of maturity chosen to represent the hypothalamic- pituitary- adrenal (HPA) axis, renal function and energy metabolism. A number of metabolite and endocrine shifts were identified in those that were quicker to reach the udder of the ewe and begin sucking. Namely, creatine, non-esterified fatty acids, leptin and ghrelin concentrations were elevated, implying these individuals may be better able to regulate energy mobilisation soon after birth. Lamb vigour was also strongly associated with rectal temperature at birth, indicating an association between maturity, post-natal behaviour and thermogenesis. A controlled water bath testing system was then used to experimentally induce mild hypothermia in the lambs, and metrics of thermoregulation included time taken for core body temperature to reach 35°C (cold resistance), and time to restore core temperature to 39°C (cold recovery). Lambs that were slow to stand and reach the udder had impaired cold resistance. None of the physiological measures (circulating metabolite and hormone concentrations at birth) were related to performance in the water bath. Somewhat surprisingly, those lambs identified as being more mature, as assessed by speed to perform peri-natal behaviours and physiological blood measures, experienced a delay in cold recovery when compared to those with lower vigour and maturity. We proposed that this may be due to a reduced ability to perform non-shivering thermogenesis in more mature individuals (as is observed to occur with age), but this need further exploration. Given these strong relationships between maturity, peri-natal vigour and thermogenesis, an attempt to alter the metabolic maturity of newborn lambs was made. Peri-conception nutrition was shown previously to influence fetal HPA axis activation (responsible for the maturation of a suite of fetal systems) hence differing nutritional treatments (0.7, 1.0 and 1.5 maintenance energy requirement) were applied to the ewes at this time. No effect of peri-conception nutritional manipulation on lamb survival was observed, but lambs from ewes fed a restricted diet around conception exhibited a decreased crown-rump length when compared to those from the high energy treatment. Whilst this had no effect on survival, under more inclement conditions this finding may increase risk of hypothermia through effects on surface area dependent heat loss. In summary, the findings presented in this thesis provide strong evidence that the metabolic maturity of lambs at birth is related to initial vigour and thermoregulatory ability, two traits that are closely linked with survivability. The attempt to reduce lamb mortality through altering HPA axis activation by nutritional means had limited effects on lamb phenotype. Consequently, peri-conception nutrition failed to influence lamb survival. Future investigations should target other means by which metabolic maturity at birth can be enhanced in order to improve lamb survival.
Thesis (Ph.D.) -- University of Adelaide, School of Animal and Veterinary Sciences, 2014

Peak oxygen uptake (V̇O2) is the criterion measure of young people's aerobic fitness, and blood lactate accumulation (BLA) is a useful indicator of aerobic fitness with reference to the ability to sustain submaximal exercise. In sport and in everyday life it is the pulmonary (p)V̇O2 kinetics of the non-steady state which best assess the integrated responses of the oxygen delivery system and the metabolic demands of the exercising muscle. Data analysis using sophisticated modelling techniques has enhanced understanding of sexual dimorphism and the independent effects of chronological age, body size, and biological maturity on peak V̇O2 and BLA. The extant data on young people's pV̇O2 kinetic responses to step changes in exercise intensity are sparse, but describe intriguing chronological age and sex differences across exercise domains. However, independent effects of biological maturation are yet to be revealed.

Metabolism consists of the sum of anabolism (construction) and catabolism (destruction) with the release of energy, and achieving a fairly constant internal environment (homeostasis). The aquatic external environment favours differences from mammalian pathways of excretion and requires osmoregulatory adjustments for fresh water and seawater though some taxa, notably marine elasmobranchs, avoid osmoregulatory problems by retaining osmotically active substances such as urea, and molecules protecting tissues from urea damage. Ion regulation may occur through chloride cells of the gills. Most fish are not temperature regulators but a few are regional heterotherms, conserving heat internally. The liver has many roles in metabolism, including in some fish the synthesis of antifreeze seasonally. Maturing females synthesize yolk proteins in the liver. Energy storage may include the liver and, surprisingly, white muscle. Fish growth can be indeterminate and highly variable, with very short (annual) life cycles or extremely long cycles with late and/or intermittent reproduction.

Success in youth sport is underpinned by a range of chronological age- and biological maturity status-related factors which affect performance in a sex- and sport-specific manner. Pubertal changes in body size, shape, composition, muscle metabolism, muscle strength, aerobic fitness, and anaerobic fitness strongly influence sport performance but biological clocks run at different rates. As selection and retention in youth sport is based on chronological age, competition is not always on a level playing field. Young athletes benefit from exercise training but there is no convincing evidence of the existence of a ‘maturation threshold’ below which the effects of training will be minimal or will not occur, or of ‘windows of opportunity’ during which training effects are enhanced. Participation in sport provides a positive environment for the promotion of personal development but evidence is accumulating that elite youth sport also presents risks to current and future health and well-being.

Bones are multifunctional passive organs of movement that supports soft tissue and directly attached muscles. They also protect internal organs and are a reserve of calcium, phosphorus and magnesium. Each bone is covered with periosteum, and the adjacent bone surfaces are covered by articular cartilage. Histologically, the bone is an organ composed of many different tissues. The main component is bone tissue (cortical and spongy) composed of a set of bone cells and intercellular substance (mineral and organic), it also contains fat, hematopoietic (bone marrow) and cartilaginous tissue. Bones are a tissue that even in adult life retains the ability to change shape and structure depending on changes in their mechanical and hormonal environment, as well as self-renewal and repair capabilities. This process is called bone turnover. The basic processes of bone turnover are: • bone modeling (incessantly changes in bone shape during individual growth) following resorption and tissue formation at various locations (e.g. bone marrow formation) to increase mass and skeletal morphology. This process occurs in the bones of growing individuals and stops after reaching puberty • bone remodeling (processes involve in maintaining bone tissue by resorbing and replacing old bone tissue with new tissue in the same place, e.g. repairing micro fractures). It is a process involving the removal and internal remodeling of existing bone and is responsible for maintaining tissue mass and architecture of mature bones. Bone turnover is regulated by two types of transformation: • osteoclastogenesis, i.e. formation of cells responsible for bone resorption • osteoblastogenesis, i.e. formation of cells responsible for bone formation (bone matrix synthesis and mineralization) Bone maturity can be defined as the completion of basic structural development and mineralization leading to maximum mass and optimal mechanical strength. The highest rate of increase in pig bone mass is observed in the first twelve weeks after birth. This period of growth is considered crucial for optimizing the growth of the skeleton of pigs, because the degree of bone mineralization in later life stages (adulthood) depends largely on the amount of bone minerals accumulated in the early stages of their growth. The development of the technique allows to determine the condition of the skeletal system (or individual bones) in living animals by methods used in human medicine, or after their slaughter. For in vivo determination of bone properties, Abstract 10 double energy X-ray absorptiometry or computed tomography scanning techniques are used. Both methods allow the quantification of mineral content and bone mineral density. The most important property from a practical point of view is the bone’s bending strength, which is directly determined by the maximum bending force. The most important factors affecting bone strength are: • age (growth period), • gender and the associated hormonal balance, • genotype and modification of genes responsible for bone growth • chemical composition of the body (protein and fat content, and the proportion between these components), • physical activity and related bone load, • nutritional factors: – protein intake influencing synthesis of organic matrix of bone, – content of minerals in the feed (CA, P, Zn, Ca/P, Mg, Mn, Na, Cl, K, Cu ratio) influencing synthesis of the inorganic matrix of bone, – mineral/protein ratio in the diet (Ca/protein, P/protein, Zn/protein) – feed energy concentration, – energy source (content of saturated fatty acids - SFA, content of polyun saturated fatty acids - PUFA, in particular ALA, EPA, DPA, DHA), – feed additives, in particular: enzymes (e.g. phytase releasing of minerals bounded in phytin complexes), probiotics and prebiotics (e.g. inulin improving the function of the digestive tract by increasing absorption of nutrients), – vitamin content that regulate metabolism and biochemical changes occurring in bone tissue (e.g. vitamin D3, B6, C and K). This study was based on the results of research experiments from available literature, and studies on growing pigs carried out at the Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences. The tests were performed in total on 300 pigs of Duroc, Pietrain, Puławska breeds, line 990 and hybrids (Great White × Duroc, Great White × Landrace), PIC pigs, slaughtered at different body weight during the growth period from 15 to 130 kg. Bones for biomechanical tests were collected after slaughter from each pig. Their length, mass and volume were determined. Based on these measurements, the specific weight (density, g/cm3) was calculated. Then each bone was cut in the middle of the shaft and the outer and inner diameters were measured both horizontally and vertically. Based on these measurements, the following indicators were calculated: • cortical thickness, • cortical surface, • cortical index. Abstract 11 Bone strength was tested by a three-point bending test. The obtained data enabled the determination of: • bending force (the magnitude of the maximum force at which disintegration and disruption of bone structure occurs), • strength (the amount of maximum force needed to break/crack of bone), • stiffness (quotient of the force acting on the bone and the amount of displacement occurring under the influence of this force). Investigation of changes in physical and biomechanical features of bones during growth was performed on pigs of the synthetic 990 line growing from 15 to 130 kg body weight. The animals were slaughtered successively at a body weight of 15, 30, 40, 50, 70, 90, 110 and 130 kg. After slaughter, the following bones were separated from the right half-carcass: humerus, 3rd and 4th metatarsal bone, femur, tibia and fibula as well as 3rd and 4th metatarsal bone. The features of bones were determined using methods described in the methodology. Describing bone growth with the Gompertz equation, it was found that the earliest slowdown of bone growth curve was observed for metacarpal and metatarsal bones. This means that these bones matured the most quickly. The established data also indicate that the rib is the slowest maturing bone. The femur, humerus, tibia and fibula were between the values of these features for the metatarsal, metacarpal and rib bones. The rate of increase in bone mass and length differed significantly between the examined bones, but in all cases it was lower (coefficient b <1) than the growth rate of the whole body of the animal. The fastest growth rate was estimated for the rib mass (coefficient b = 0.93). Among the long bones, the humerus (coefficient b = 0.81) was characterized by the fastest rate of weight gain, however femur the smallest (coefficient b = 0.71). The lowest rate of bone mass increase was observed in the foot bones, with the metacarpal bones having a slightly higher value of coefficient b than the metatarsal bones (0.67 vs 0.62). The third bone had a lower growth rate than the fourth bone, regardless of whether they were metatarsal or metacarpal. The value of the bending force increased as the animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. The rate of change in the value of this indicator increased at a similar rate as the body weight changes of the animals in the case of the fibula and the fourth metacarpal bone (b value = 0.98), and more slowly in the case of the metatarsal bone, the third metacarpal bone, and the tibia bone (values of the b ratio 0.81–0.85), and the slowest femur, humerus and rib (value of b = 0.60–0.66). Bone stiffness increased as animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. Abstract 12 The rate of change in the value of this indicator changed at a faster rate than the increase in weight of pigs in the case of metacarpal and metatarsal bones (coefficient b = 1.01–1.22), slightly slower in the case of fibula (coefficient b = 0.92), definitely slower in the case of the tibia (b = 0.73), ribs (b = 0.66), femur (b = 0.59) and humerus (b = 0.50). Bone strength increased as animals grew. Regardless of the growth point tested, bone strength was as follows femur > tibia > humerus > 4 metacarpal> 3 metacarpal> 3 metatarsal > 4 metatarsal > rib> fibula. The rate of increase in strength of all examined bones was greater than the rate of weight gain of pigs (value of the coefficient b = 2.04–3.26). As the animals grew, the bone density increased. However, the growth rate of this indicator for the majority of bones was slower than the rate of weight gain (the value of the coefficient b ranged from 0.37 – humerus to 0.84 – fibula). The exception was the rib, whose density increased at a similar pace increasing the body weight of animals (value of the coefficient b = 0.97). The study on the influence of the breed and the feeding intensity on bone characteristics (physical and biomechanical) was performed on pigs of the breeds Duroc, Pietrain, and synthetic 990 during a growth period of 15 to 70 kg body weight. Animals were fed ad libitum or dosed system. After slaughter at a body weight of 70 kg, three bones were taken from the right half-carcass: femur, three metatarsal, and three metacarpal and subjected to the determinations described in the methodology. The weight of bones of animals fed aa libitum was significantly lower than in pigs fed restrictively All bones of Duroc breed were significantly heavier and longer than Pietrain and 990 pig bones. The average values of bending force for the examined bones took the following order: III metatarsal bone (63.5 kg) <III metacarpal bone (77.9 kg) <femur (271.5 kg). The feeding system and breed of pigs had no significant effect on the value of this indicator. The average values of the bones strength took the following order: III metatarsal bone (92.6 kg) <III metacarpal (107.2 kg) <femur (353.1 kg). Feeding intensity and breed of animals had no significant effect on the value of this feature of the bones tested. The average bone density took the following order: femur (1.23 g/cm3) <III metatarsal bone (1.26 g/cm3) <III metacarpal bone (1.34 g / cm3). The density of bones of animals fed aa libitum was higher (P<0.01) than in animals fed with a dosing system. The density of examined bones within the breeds took the following order: Pietrain race> line 990> Duroc race. The differences between the “extreme” breeds were: 7.2% (III metatarsal bone), 8.3% (III metacarpal bone), 8.4% (femur). Abstract 13 The average bone stiffness took the following order: III metatarsal bone (35.1 kg/mm) <III metacarpus (41.5 kg/mm) <femur (60.5 kg/mm). This indicator did not differ between the groups of pigs fed at different intensity, except for the metacarpal bone, which was more stiffer in pigs fed aa libitum (P<0.05). The femur of animals fed ad libitum showed a tendency (P<0.09) to be more stiffer and a force of 4.5 kg required for its displacement by 1 mm. Breed differences in stiffness were found for the femur (P <0.05) and III metacarpal bone (P <0.05). For femur, the highest value of this indicator was found in Pietrain pigs (64.5 kg/mm), lower in pigs of 990 line (61.6 kg/mm) and the lowest in Duroc pigs (55.3 kg/mm). In turn, the 3rd metacarpal bone of Duroc and Pietrain pigs had similar stiffness (39.0 and 40.0 kg/mm respectively) and was smaller than that of line 990 pigs (45.4 kg/mm). The thickness of the cortical bone layer took the following order: III metatarsal bone (2.25 mm) <III metacarpal bone (2.41 mm) <femur (5.12 mm). The feeding system did not affect this indicator. Breed differences (P <0.05) for this trait were found only for the femur bone: Duroc (5.42 mm)> line 990 (5.13 mm)> Pietrain (4.81 mm). The cross sectional area of the examined bones was arranged in the following order: III metatarsal bone (84 mm2) <III metacarpal bone (90 mm2) <femur (286 mm2). The feeding system had no effect on the value of this bone trait, with the exception of the femur, which in animals fed the dosing system was 4.7% higher (P<0.05) than in pigs fed ad libitum. Breed differences (P<0.01) in the coross sectional area were found only in femur and III metatarsal bone. The value of this indicator was the highest in Duroc pigs, lower in 990 animals and the lowest in Pietrain pigs. The cortical index of individual bones was in the following order: III metatarsal bone (31.86) <III metacarpal bone (33.86) <femur (44.75). However, its value did not significantly depend on the intensity of feeding or the breed of pigs.

Yoga is an ancient mind-body practice originated in India more than 2.000 years ago and is described systematically early on. The research on the psychophysiological benefits of yoga in children has been found to improve concentration, attention, memory, resilience, mood, self-control, academic performance, psychomotor and cardiac functions, as well as metabolic parameters. Consequently, yoga seems to help children with attention problems such as ADHD, and with special needs or during physical rehabilitation. Therefore, yoga might represent an important life skill tool for all children to deal with health issues, cognitive challenges and emotinal self-regulation. In this chapter, the supporting evidence of yoga for children will be discussed, as well as the effectiveness of frequency, duration and the issue of age appropriateness. Among many reasons, but specially due to their brain maturity, children's yoga is not a version of yoga for adults, it is a unique practice where children should allow to have fun while they experience the well known health benefits of yoga.

The synthesis of seed storage reserves occurs during seed filling, and many seeds contain large and characteristic levels of polymeric reserves. Storage reserves are found in the endosperm of cereal seeds and in the endosperm and/or cotyledons of dicot seeds depending of the plant crop species. Recently progress has been made in understanding the complex network of genetic regulation associated with seed filling. These advances in storage reserve quantity and nutrient quality contribute to a comprehensive understanding of reserve composition, synthesis, and regulation. Phytohormones such as abscisic acid (ABA), cytokinin, gibberellic acid, Indole-3-acetic acid (IAA), ethylene and their interactions play critical roles in seed filling and development. At different stages of seed development, the levels of different hormones such as ABA, IAA zeatin and zeatin riboside changes gradually from the beginning of the process to maturity. In addition, the quality and yield of seed storage reserves are significantly affected by the environmental conditions before and during the synthesis of the reserves. Given the fateful importance of seed storage reserves for food and feed and their use as sustainable industrial feedstock to replace dwindling fossil reserves, understanding the metabolic and developmental control of seed filling will be an important focus of plant research.

• Diabetes mellitus is a chronic hyperglycaemia state, caused by defects in: ◦ insulin secretion ◦ insulin action ◦ both. • Type 1 diabetes accounts for ~95% of cases. ◦ Rising incidence in UK (25/100,000 children/year) now appears to be stabilizing. ◦ Peaks at younger age (4–6 years of age) and also puberty. • Therapy: ■ With subcutaneous insulin (multiple daily injections, continuous subcutaneous insulin infusion (CSII) (less used now, twice- and thrice-daily mixtures)) to mimic physiological secretion, maintain euglycaemia, minimize hypoglycaemic episodes and diabetic ketoacidosis. ◦ Monitoring: ■ Minimum of five self-monitored blood glucose measurements a day recommended. Continuous glucose monitoring increasingly utilized, especially with CSII. ■ Overall control assessed using glycated haemoglobin. • Outcome: ■ Clear evidence that good diabetic control associated with reduction in complications (micro- and macrovascular). ■ Screening recommended at an early stage to detect complications and prevent progression. • Type 2 diabetes: ◦ Increasingly recognized in children/adolescents. ◦ Increased incidence in: ■ females ■ ethnic minorities ■ overweight/obese ■ those with family history. ◦ Part of metabolic syndrome: T2DM/insulin resistance, hypertension, hyperlipidaemia, cardiovascular disease, adrenarche/polycystic ovarian syndrome. ◦ A combination of insulin resistance and (relative) insulin deficiency; oral hypoglycaemics may be appropriate (at least initially). • Other forms of diabetes (uncommon): ◦ Maturity-onset diabetes of the young (MODY): ■ autosomal dominant inheritance; dependent on type, variable ■ response to oral hypoglycaemics ■ development of microvascular complications. ◦ Association with syndromes, e.g. Wolfram, Walcott–Rallison, Prader–Willi syndrome. ◦ Cystic fibrosis-related diabetes: ■ not autoimmune in origin, due to combination of insulin deficiency/resistance ■ increasing incidence with age ■ treatment is with insulin.

The thyroid gland, which is the largest endocrine organ, secretes primarily thyroid hormones that play a critical role in the normal growth and development of the maturing human. In the adult, thyroid hormones maintain metabolic stability by regulating oxygen requirements, body weight, and intermediary metabolism. Thyroid function is under hypothalamic-pituitary control, and thus, like the gonads and adrenal cortex, it serves as a classical model of endocrine physiology. In addition, the physiological effects of thyroid hormones are regulated by complex extrathyroidal mechanisms resulting from the peripheral metabolism of the hormones, mechanisms that are not under hypothalamic-pituitary regulation. Thyroid function abnormalities are very prevalent, especially in females and in certain geographic areas, and are often a result of autoimmunity or iodine deficiency. The thyroid originates from two distinct parts of the embryonic endoderm: • The follicular structures arise from a midline thickening of the anterior pharyngeal floor (the base of the tongue), adjacent to the differentiating heart. This thyroid diverticulum first expands ventrally while still attached to the pharyngeal floor by its stalk (thyroglossal duct), and then expands laterally, leading to the characteristic bilobed structure. As the developing heart descends, the thyroid gets pulled into its final position, a process that leads to the rapid stretch and degeneration of the thyroglossal duct. • The parafollicular cells are derived from the ultimobranchial bodies (originating from the neural crest) but ultimately are surrounded by the medial thyroid. The parafollicular cells represents <10 % of the adult thyroid gland. The thyroid completes its structural development by 9 weeks of gestation, the first endocrine organ to assume its definitive form during organogenesis; yet full functional maturation and integration with the hypothalamic-pituitary axis continues throughout gestation. Abnormal thyroid development can lead to persistence of the thyroglossal duct, presence of ectopic thyroid tissue (lingual thyroid, lateral aberrant thyroid), and malposition (thoracic goiter), all of which can remain clinically silent or present later in life as diagnostic challenges. The shape of the human thyroid resembles that of a butterfly.

Plants have a P concentration between 0.03 and 0.70%, but the usual amount is between 0.1 and 0.4%. Phosphorus is found in every living cell of a plant and is involved in genetic transfer and energy relationships. The actively growing parts, that is, stem tips, new leaves, and new roots, need much P. Seeds, especially at maturity, also have a rich supply of P acting as reserve food. Phosphorus is used in plants for (a) root development—especially the lateral and fibrous roots; (b) cell division—energy for metabolism; (c) reproduction—flowering, fruiting, seed formation all controlled by nucleic acids; (d) maturation—counteracts the ill effects of excessive N fertilization; arid (e) disease resistance— especially important in root rots of seedlings. Plant P is a major constituent of chromosomes present as DNA (deoxyribonucleic acid) used in reproduction and RNA (ribonucleic acid) used in growth processes. Plant P is also a constituent of adenosine triphosphate (ATP) that stores energy for plant use, along with many other phosphate compounds, such as phytin (inositol hexaphosphate) stored in seeds, phospholipids in the chloroplasts, and complexes of sugars, sugar amines, aldehydes, amides, and acids—all involved in plant metabolism. Deficiency of P is not striking or characteristic and is difficult to diagnose. The older leaves may be dark bluish-green, bronze, or purple. The stalks are thin, leaves small, limited lateral growth, delayed maturity, and defoliate prematurely. Probably the most obvious symptom would be the purple coloration, but this is exhibited by only a limited number of plants. The best way to determine if a plant is deficient in P would be to conduct a plant tissue test. If the P level is lower than 0.2% P, then P probably is deficient and the soil in which the plant is growing would benefit from P fertilization. . . . Phosphorus Toxicity? . . . Phosphorus toxicity has not been observed in the field and has only been evident in greenhouse culture solutions when P was present at extremely high concentrations.

This chapter studies intake and growth targets. For clarity, earlier chapters have treated intake and growth targets as static points integrated across a particular period in the life of an animal. In reality they are, of course, not static but rather trajectories that move in time. In the short term, the requirements of the animal change as environmental circumstances impose differing demands for nutrients and energy. At a somewhat longer timescale, targets move as the animal passes through the various stages of its life, from early growth and development to maturity, reproduction, and senescence. On an even longer timescale, nutritional traits are subject to natural selection and move as species evolve to exploit new or changing nutritional environments and to adopt differing life-history strategies. Presaging such evolutionary change in gene frequencies within populations are epigenetic effects, whereby the nutritional experiences of parents influence the behavior and metabolism of their offspring without requiring changes in gene frequencies.

Scavenging free radical potency of cordycepin is the major bioactive segment extricated from Cordyceps species. In some new years, Cordyceps has gotten growing thought inferable from its distinctive restorative/pharmacological tests. This assessment reviews continuous explores on the counter oxidant impacts and the associated analyses of Cordyceps species. The results from our review show that Cordyceps of the cordycepin applies protective effects against hostile to oxidant injury for certain, afflictions including constant obstructive pneumonic infection (COPD), hepatitis, asthma, cerebral paralysis, Parkinson’s illness (PD), coronary course sickness (CAD), Alzheimer illness, respiratory failure, malignancy infection, maturing, waterfalls, and mind brokenness. Cordyceps coordinates the NF-κB, RIP2/Caspase-1, Akt/GSK-3β/p70S6K, TGF-β/Smads, and Nrf2/HO-1 hailing pathways among others of cordycepin. A couple of assessments focusing in on Cordyceps auxiliaries were surveyed and found to down metabolic speed of Cordyceps and augmentation its bioavailability. In addition, cordycepin further developed opposition, prevented the duplication of viral RNA, and covered cytokine storms, therefore proposing its capacity to treat COVID-19 and other viral defilements. From the accumulated and assessed information, this article gives the speculative reason to the clinical usages of cordycepin and inspects the way for future assessments focusing in on expanding the restorative use of Cordyceps species. Cordycepin and its analogs show unfathomable potential as the accompanying new class of against oxidant specialists.

<i>Abstract</i>.—In the past decade, advances in our understanding of Paddlefish <i>Polyodon spathula</i> life history have provided additional insight into the information needed for sustainable harvest management of this long-lived species. Recovery of known-age fish in some stocks has enabled stock assessment biologists and managers to not only validate ages of individual fish, but to begin to validate the life histories. A framework for potentially recruited Paddlefish life history can be broken into five stages: 1) immature, 2) maturing, 3) somatic growth and reproduction, 4) prime reproduction, and 5) senescence to death. These stages involve measurable changes in growth in length and weight, gonadosomatic index (GSI), gonadal fat storage (GFBs), reproductive periodicity, natural mortality rates, and, in some cases, fish migrations. Stages 2–5 are typically initiated at younger ages for males than for females. Metabolic demands on Paddlefish result in them progressing through these life history stages more rapidly in southern stocks, inhabiting warmer waters, than in northern ones, inhabiting colder waters. Lifespans in most northerly stocks tend to be 2–3 times longer than for southern stocks. Natural mortality is also typically lower in northern stocks. These differences necessitate fundamentally different harvest management strategies among stocks. Regardless of the stock, however, in the prime reproduction stage, somatic growth is slow or negative, as energy is routed more strongly into reproduction, GSI is at a maximum, the period of gonadal recrudescence (i.e., spawning interval) is minimized, and GFBs are largely or completely depleted in females. Consistent with recommendations for other long-lived freshwater and marine species, harvest management strategies should be specifically planned to retain some older, prime spawning females in the population. In addition, sporadic or episodic recruitment in many stocks makes steady-state harvest models unrealistic, necessitating that harvest be appropriately matched to recruitment rates or events.

Heavy metals represent a very important group of environmental pollutants because they are potential metabolic inhibitors. A study was conducted to investigate the content of heavy metals (Pb) in the soil and their accumulation in the wheat tree - Triticum sp., in the phase of full maturity in four wheat varieties, to obtain information on the health of cultivated genotypes, and to determine which variety wheat is the least susceptible to lead accumulation. The concentration of lead was highest in the cultivars Renaissance and Apache.

The presented study identifies the existing dependencies between the time course of phenological phenomena in the oak stands, from three sample surfaces, and the factors with a major impact on their evolution. The usefulness of the oak tree research is necessary both for scientific and practical reasons, knowing that the issue of ensuring the production of high quality forest seeds and the necessary quantity is an actual one. The researches show that the formation and development of the oak inflorescences, the amount of acorns reached maturity and the degree of its viability (in the region under study) were in direct correlation with the climatic parameters, during the vegetation period, the presence of defoliating and seminophage species , factors that can induce tree metabolic imbalances, low fructification, and premature fall of fruit. The most intense fructification was certified for the Ivancea research area, followed by the Codrii and Mereşeni areas.

In human walking, the ankle plays an important role of supplying power needed for the forward motion [1]. However, traditional transtibial (TT, a.k.a. below-knee, BK) prostheses are passive, lacking the ability of generating power output in the prosthetic ankle. Consequently, amputees fitted with such prostheses suffer from multiple issues (asymmetric gait, greater metabolic energy expenditure, etc.). To address such issues, researchers have explored various technical approaches to develop powered TT prostheses. Hydraulics and pneumatics have been attempted, leveraging the high power density with these actuators (e.g. [2]). Electromagnetic actuators were used more extensively with its technological maturity and convenience in packaging. Typical examples include the multiple prototypes developed by the MIT Biomechatronics Group (e.g., [3]), the SPARKy project, and the Vanderbilt Transtibial Prosthesis. The TT prostheses mentioned above all include powered ankle joints to provide power for the users’ locomotion. However, cost and complexity are often given lower priority than performance in the development of such devices. Powered TT prosthesis is a typical low-volume product from a commercial perspective, and the resulting high cost is a major hurdle for the large-scale adoption among amputee users. General robotic components (motors, gearsets, etc.), in contrary, are produced in large quantities with relatively low prices. Such contrast is the major inspiration for this work: the goal is to develop a modular powered TT prosthesis based on low-cost commercial robotic components while minimizing the complexity in manufacturing and assembly.

The report considers the approach to the mechanism of interpretation of the oneiric content from the position of authentic psychotherapy: the basic elements of a dream, principles of the analysis of images, sources of psychogenesis of images. 174 "Authentic counseling is intended for any individual who is aware of being part of life, as this type of counseling belongs exclusively to the sphere of the individual. Counseling of this type is oriented to those people who feel a transcendent need, who in the face of a problem do not panic but transform it in a moment of growth" [A. Meneghetti]. The main goal of authentication psychotherapy is the identification, authentication and development of the client's personal ethics, which leads him/her to a recovery of responsibility in an existential sense and the need to realize their creative potential. Authentication means that the subject's logical-historical self has reached the necessary level of maturity to realize its ontic uniqueness. Authentic psychotherapy relies on six languages of the unconscious (linguistic anamnesis and historical biography, symptom or problem analysis, physiognomic-kinetic-proxemic analysis, oneiric analysis, semantic field and outcome), among which the oneiric language is one of the most important. From the point of view of ontopsychology, a dream is a set of figurative projections identifying the subject's real state in biological, psychological and ontic terms. The main elements (principles) on which the psychotherapist relies are: the causal cause of the symbol, the functionality of the action for the subject and the semantic criterion, which is one of the tools of ontopsychology. In the course of therapy, complete dreams are analyzed, in which it is possible to see both the current situation and the cause of it and the solution – a positive way out for the client's existential situation. The results of research of dynamics of changes of symbols in oneiric activity accompanying process of historical evolution of subjects during authentication psychotherapy have shown, that functional changes in a historical situation of the client undergoing authentication psychotherapy lead to functional changes of symbols of a dream. Conventionally they can be designated as images of: life, opportunity, freedom and natural metabolism. When a person is in a situation of historical non-functionality, symbols of moral and ideological order will prevail: authority, subordination, super-self, honors. In this way the oneiric analysis allows identifying and verbalizing the most important intention for the client, leading to sustainable success and health. В докладе рассматривается подход к механизму интерпретации онейрического содержания с позиции психотерапии аутентификации: основные элементы сновидения, принципы анализа образов, источники психогенеза образов. «Аутентифицирующее консультирование предназначено для любого индивида, который осознает себя частью жизни, так как этот вид консультирования относится исключительно к сфере личности. Консультирование такого типа ориентировано на тех людей, кто чувствует трансцендентную потребность, кто перед лицом проблемы не пасует, а преобразует ее в момент роста» [А. Менегетти]. Основная цель психотерапии аутентификации состоит в идентификации, аутентификации и развитии личной этики клиента, что приводит его к восстановлению ответственности в экзистенциальном смысле и необходимости реализации творческого потенциала. Аутентификация означает, что логико-историческое «Я» субъекта достигло необходимого уровня зрелости для реализации своей онтической уникальности. Психотерапия аутентификации опирается на шесть языков бессознательного (лингвистический анамнез и историческая биография, анализ симптома или проблемы, физиогномико-кинетико-проксемический анализ, онейрический анализ, семантическое поле и результат), среди которых онейрический язык является одним из важнейших. С точки зрения онтопсихологии, сновидение представляет собой совокупность образных проекций, идентифицирующих реальное состояние субъекта в биологическом, психологическом и онтическом плане. Основными элементами (принципами), на которые опирается психотерапевт, являются: каузальная причина символа, функциональность действия для субъекта и семантический критерий, являющийся одним из инструментов онтопсихологии. В процессе терапии анализируются полные сновидения, в которых можно увидеть как текущую ситуацию и причину ее вызывающую, так и решение – позитивный для экзистенциальной ситуации клиента выход. Результаты исследования динамики измененийсимволов онейрическойдеятельности, сопровождающих процесс историческойэволюции субъектов в ходе психотерапии аутентификации, показали, что функциональные изменения в исторической ситуации проходящего психотерапию аутентификации клиента приводят к функциональным изменениям символов сновидения. Условно они могут быть обозначены, как образы: жизни, возможностей, свободы, природосообразного метаболизма. Когда человек находится в ситуации исторической нефункциональности будут превалировать символы морально-идеологического порядка: авторитет, подчинение, сверх-Я, почести. Таким образом, онейрический анализ позволяет определять и вербализовывать наиболее важную для клиента интенцию, приводящую к устойчивому успеху и здоровью.

The cucurbit family, including melon, translocates the galactosyl-sucrose oligosaccharides, raffinose and stachyose, in addition to sucrose, from the source leaves to the fruit sink. The metabolism of these photoassimilates in the fruit sink controls fruit growth and development, including the horticulturally important phenomenon of sucrose accumulation, which determines melon fruit sweetness. During this research project we have characterized the complete pathway of galactosyl sucrose metabolism in developing fruit, from before anthesis until maturity. We have also compared the metabolic pathway in scurose accumulating genotypes, as compared to non-accumulating genotypes. Furthermore, we studied the pathway in different fruit tissues, in response to pollination, and also analyzed the response of the individual steps of the pathway to perturbations such as low temperature and leaf removal. The results of our studies have led to the conclusion that generally galactosyl-sucrose metabolism functions as a coordinately controlled pathway. In one case, as an immediate response to the absence of pollination, the activity of a single enzyme, UDPglu pyrophosphorylase, was drastically reduced. However, during young fruit development, sucrose accumulation, and in response to perturbations of the system, groups of enzymes, rather than single enzymes, respond in a concerted manner. Our research has characterized in detail the initial enzymes of galactosyl-sucrose metabolism, including the galactosidases, galactokinase and the UDPgal- and UDPglu pyrophosphorylases. We have discovered a novel alkaline a-galactoside which hydrolyzes both stachyose and reaffinose and thereby may have solved the dilemma of cytosolic-sucrose metabolism, since prior to this research there was no known alkaline a-galactosidase capable of hydrolyzing raffinose.

Accumulation of citric acid is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate citric acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Citrate is accumulated in the vacuole of the juice sac cell, a process that requires both metabolic changes and transport across cellular membranes, in particular, the mitochondrial and the vacuolar (tonoplast) membranes. Although the accumulation of citrate in the vacuoles of juice cells has been clearly demonstrated, the mechanisms for vacuolar citrate homeostasis and the components controlling citrate metabolism and transport are still unknown. Previous results in the PIs’ laboratories have indicated that the expression of a large number of a large number of proteins is enhanced during fruit development, and that the regulation of sugar and acid content in fruits is correlated with the differential expression of a large number of proteins that could play significant roles in fruit acid accumulation and/or regulation of acid content. The objectives of this proposal are: i) the characterization of transporters that mediate the transport of citrate and determine their role in uptake/retrieval in juice sac cells; ii) the study of citric acid metabolism, in particular the effect of arsenical compounds affecting citric acid levels and mobilization; and iii) the development of a citrus fruit proteomics platform to identify and characterize key processes associated with fruit development in general and sugar and acid accumulation in particular. The understanding of the cellular processes that determine the citrate content in citrus fruits will contribute to the development of tools aimed at the enhancement of citrus fruit quality. Our efforts resulted in the identification, cloning and characterization of CsCit1 (Citrus sinensis citrate transporter 1) from Navel oranges (Citrus sinesins cv Washington). Higher levels of CsCit1 transcripts were detected at later stages of fruit development that coincided with the decrease in the juice cell citrate concentrations (Shimada et al., 2006). Our functional analysis revealed that CsCit1 mediates the vacuolar efflux of citrate and that the CsCit1 operates as an electroneutral 1CitrateH2-/2H+ symporter. Our results supported the notion that it is the low permeable citrateH2 - the anion that establishes the buffer capacity of the fruit and determines its overall acidity. On the other hand, it is the more permeable form, CitrateH2-, which is being exported into the cytosol during maturation and controls the citrate catabolism in the juice cells. Our Mass-Spectrometry-based proteomics efforts (using MALDI-TOF-TOF and LC2- MS-MS) identified a large number of fruit juice sac cell proteins and established comparisons of protein synthesis patterns during fruit development. So far, we have identified over 1,500 fruit specific proteins that play roles in sugar metabolism, citric acid cycle, signaling, transport, processing, etc., and organized these proteins into 84 known biosynthetic pathways (Katz et al. 2007). This data is now being integrated in a public database and will serve as a valuable tool for the scientific community in general and fruit scientists in particular. Using molecular, biochemical and physiological approaches we have identified factors affecting the activity of aconitase, which catalyze the first step of citrate catabolism (Shlizerman et al., 2007). Iron limitation specifically reduced the activity of the cytosolic, but not the mitochondrial, aconitase, increasing the acid level in the fruit. Citramalate (a natural compound in the juice) also inhibits the activity of aconitase, and it plays a major role in acid accumulation during the first half of fruit development. On the other hand, arsenite induced increased levels of aconitase, decreasing fruit acidity. We have initiated studies aimed at the identification of the citramalate biosynthetic pathway and the role(s) of isopropylmalate synthase in this pathway. These studies, especially those involved aconitase inhibition by citramalate, are aimed at the development of tools to control fruit acidity, particularly in those cases where acid level declines below the desired threshold. Our work has significant implications both scientifically and practically and is directly aimed at the improvement of fruit quality through the improvement of existing pre- and post-harvest fruit treatments.

The acid content of the juice sac cells is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Pulp acidity is thought to be dependent on two mechanisms: the accumulation of citric acid in the vacuoles of the juice sac cells, and acidification of the vacuole. The major aim of the project was to direct effort toward understanding the mechanism of citric acid accumulation in the fruit. The following objectives were suggested: Measure the activity of enzymes likely to be involved in acid accumulation and follow their pattern of expression in developing fruit (Sadka, Erner). Identify and clone genes which are associated with high and low acid phenotypes and with elevated acid level (Roose, Sadka, Erner). Convert RAPD markers that map near a gene that causes low acid phenotype to specific co dominant markers (Roose). Use genetic co segregation to test whether specific gene products are responsible for low acid phenotype (Roose and Sadka). Objective 1 was fully achieved. Most of the enzymes of organic acid metabolism were cloned from lemon pulp. Their expression was studied during fruit development in low and high acid varieties. The activity and expression of citrate synthase, aconitase and NADP-isocitrate dehydrogenase (IDH) were studied in detail. The role that each enzyme plays in acid accumulation and decline was evaluated. As a result, a better understanding of the metabolic changes that contribute to acid accumulation was achieved. It was found that the activity of the mitochondrial aconitase is greatly reduced early in high-acid fruits, but not in acidless ones, suggesting that this enzyme plays an important role in acid accumulation. In addition, it was demonstrated that increases in the cytosolic forms of aconitase and NADP-IDH towards fruit maturation play probably a major role in acid decline. Our studies also demonstrated that the two mechanisms that contribute to fruit acidity, vacuolar acidification and citric acid accumulation, are independent, although they are tightly co-regulated. Additional, we demonstrated that sodium arsenite, which reduce fruit acidity, causes a transient inhibition in the activity of citrate synthase, but an induction in the gene expression. This part of the work has resulted in 4 papers. Objective 3 was also fully achieved. Using bulked segregant analysis, three random amplified polymorphic DNA (RAPD) markers were identified as linked to acitric, a gene controlling the acidless phenotype of pummelo 2240. One of them, which mapped 1.2 cM from acitric was converted into sequence characterized amplified region (SCAR marker, and into co dominant restriction length polymorphism (RFLP) marker. These markers were highly polymorphic among 59 citrus accessions, and therefore, they should be useful for selecting seedling progeny heterozygous for acitric in nearly all crosses between pummelo 2240 and other citrus genotypes. This part of the project resulted in one paper. Objective 4 was also fully achieved. Clones isolated by the Israeli group were sent to the American laboratory for co segregation analysis. However, none of them seemed to co segregate with the low acid phenotype. Both laboratories invested much effort in achieving the goals of Objective 2, namely the isolation of genes that are elevated in expression in low and high acid phenotypes, and in tissue cultures treated with arsenite (a treatment which reduces fruit acidity). However, conventional differential display and restriction fragment differential display analyses could not identify any differentially expressed genes. The isolation of such genes was the major aim of a continuation project, which was recently submitted.

: The necessity to improve broiler thermotolerance and performance led to the following hypothesis: (a) thethermoregulatory-response threshold for heat production can be altered by thermal manipulation (TM) during incubation so as to improve the acquisition of thermotolerance in the post-hatch broiler;and (b) TM during embryogenesis will improve myoblast proliferation during the embryonic and post-hatch periods with subsequent enhanced muscle growth and meat production. The original objectives of this study were as follow: 1. to assess the timing, temperature, duration, and turning frequency required for optimal TM during embryogenesis; 2. to evaluate the effect of TM during embryogenesis on thermoregulation (heat production and heat dissipation) during four phases: (1) embryogenesis, (2) at hatch, (3) during growth, and (4) during heat challenge near marketing age; 3. to investigate the stimulatory effect of thermotolerance on hormones that regulate thermogenesis and stress (T₄, T₃, corticosterone, glucagon); 4. to determine the effect of TM on performance (BW gain, feed intake, feed efficiency, carcass yield, breast muscle yield) of broiler chickens; and 5. to study the effect of TM during embryogenesis on skeletal muscle growth, including myoblast proliferation and fiber development, in the embryo and post-hatch chicks.This study has achieved all the original objectives. Only the plasma glucagon concentration (objective 3) was not measured as a result of technical obstacles. Background to the topic: Rapid growth rate has presented broiler chickens with seriousdifficulties when called upon to efficiently thermoregulate in hot environmental conditions. Being homeotherms, birds are able to maintain their body temperature (Tb) within a narrow range. An increase in Tb above the regulated range, as a result of exposure to environmental conditions and/or excessive metabolic heat production that often characterize broiler chickens, may lead to a potentially lethal cascade of irreversible thermoregulatory events. Exposure to temperature fluctuations during the perinatal period has been shown to lead to epigenetic temperature adaptation. The mechanism for this adaptation was based on the assumption that environmental factors, especially ambient temperature, have a strong influence on the determination of the “set-point” for physiological control systems during “critical developmental phases.” In order to sustain or even improve broiler performance, TM during the period of embryogenesis when satellite cell population normally expand should increase absolute pectoralis muscle weight in broilers post-hatch. Major conclusions: Intermittent TM (39.5°C for 12 h/day) during embryogenesis when the thyroid and adrenal axis was developing and maturing (E7 to E16 inclusive) had a long lasting thermoregulatory effect that improved thermotolerance of broiler chickens exposed to acute thermal stress at market age by lowering their functional Tb set point, thus lowering metabolic rate at hatch, improving sensible heat loss, and significantly decreasing the level of stress. Increased machine ventilation rate was required during TM so as to supply the oxygen required for the periods of increased embryonic development. Enhancing embryonic development was found to be accomplished by a combination of pre-incubation heating of embryos for 12 h at 30°C, followed by increasing incubation temperature to 38°C during the first 3 days of incubation. It was further facilitated by increasing turning frequency of the eggs to 48 or 96 times daily. TM during critical phases of muscle development in the late-term chick embryo (E16 to E18) for 3 or 6 hours (39.5°C) had an immediate stimulatory effect on myoblast proliferation that lasted for up to two weeks post-hatch; this was followed by increased hypertrophy at later ages. The various incubation temperatures and TM durations focused on the fine-tuning of muscle development and growth processes during late-term embryogenesis as well as in post-hatch chickens.

The hypothalamic melanocortin system plays a central role in the regulation of food consumption and energy homeostasis in mammals. Accordingly, our working hypothesis in this project was that genetic editing of the mc4r gene, encoding Melanocortin Receptor 4 (MC4R), will enhance food consumption, feed efficiency and growth in fish. To test this hypothesis and to assess the utility of mc4r editing for the enhancement of feed efficiency and growth in fish, the following objectives were set: Test the effect of the mc4r-null allele on feeding behavior, growth, metabolism and survival in zebrafish. Generate mc4r-null alleles in tilapia and examine the consequences for growth and survival, feed efficiency and body composition. Generate and examine the effect of naturally-occurring mc4r alleles found in swordfish on feeding behavior, growth and survival in zebrafish. Define the MC4R-mediated and MC4R-independent effects of AgRP by crossing mc4r- null strains with fish lacking AgRP neurons or the agrpgene. Our results in zebrafish did not support our hypothesis. While knockout of the agrpgene or genetic ablation of hypothalamic AgRP neurons led to reduced food intake in zebrafish larvae, knockout (KO) of the mc4r gene not only did not increase the rate of food intake but even reduced it. Since Melanocortin Receptor 3 (MC3R) has also been proposed to be involved in hypothalamic control of food intake, we also tested the effectofmc3r gene KO. Again, contrary to our hypothesis, the rate of food intake decreased. The next step was to generate a double mutant lucking both functional MC3R and MC4R. Again, the double KO exhibited reduced food intake. Thus, the only manipulation within the melanocortin system that affected food intake in consistent with the expected role of the system was seen in zebrafish larvae upon agrpKO. Interestingly, despite the apparent reduced food intake in the larval stage, these fish grow to be of the same size as wildtype fish at the adult stage. Altogether, it seems that there is a compensatory mechanism that overrides the effect of genetic manipulations of the melanocortin system in zebrafish. Under Aim 3, we introduced the Xna1, XnB1l, and XnB2A mutations from the Xiphophorus MC4R alleles into the zebrafish MC4R gene. We hypothesized that these MC4R mutations would act as dominant negative alleles to increase growth by suppressing endogenous MC4R activity. When we examined the activity of the three mutant alleles, we were unable to document any inhibition of a co-transfected wild type MC4R allele, hence we did not introduce these alleles into zebrafish. Since teleost fish possess two agrpgenes we also tested the effect of KO of the agrp2 gene and ablation of the AgRP2 cells. We found that the AgRP2 system does not affect food consumption but may rather be involved in modulating the stress response. To try to apply genetic editing in farmed fish species we turned to tilapia. Injection of exogenous AgRP in adult tilapia induced significant changes in the expression of pituitary hormones. Genetic editing in tilapia is far more complicated than in zebrafish. Nevertheless, we managed to generate one mutant fish carrying a mutation in mc4r. That individual died before reaching sexual maturity. Thus, our attempt to generate an mc4r-mutant tilapia line was almost successful and indicate out non-obvious capability to generate mutant tilapia.