Iowa State Daily (April 25, 2012)

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Growth after Hypophyseal Stalk Transection and Hypophysectomy in Beef Calves

Growth hormone (GH) is a metabolic hormone that plays an important role in long-bone growth and muscle accretion in mammals. The anterior pituitary gland at the base of the brain is the primary site of GH production and release into the general circulation. Neurons in the arcuate nucleus of the hypothalamus in the lower part of the brain secrete GH-releasing hormone ([GHRH] or factor [GRF]) and GH-release-inhibiting hormone ([GHRIH] or somatostatin [SRIH]) that acutely modulate GH secretion by the pituitary gland. The pituitary gland is connected to the median eminence of the hypothalamus by a stalk (hypophyseal stalk). Complete surgical removal of the pituitary gland (hypophysectomy) arrests growth and greatly impairs metabolism in laboratory and farm animal species. Daily subcutaneous injection of bovine GH (bGH) in immature hypophysectomized rats significantly increased body growth and epiphyseal plate width of the long-bone (tibia) compared with diluent-treated hypophysectomized controls. Growth rate was less, however, in the bGH-treated animals compared with intact controls. In beef calves, hypophysectomy completely arrested body weight gain and long-bone growth. GH is secreted in an episodic pattern in young growing intact calves. Episodic GH secretion was abolished immediately following hypophyseal stalk transection, and basal GH blood concentration was less than in shamoperated controls. Regardless, growth continued in these stalk-transected calves during a 1,008-day period, but at a lower growth rate than seen in the sham-operated controls. At autopsy, pituitary gland weight was greatly decreased in hypophyseal stalktransected compared with sham-operated calves. Thus, in spite of obliterated episodic GH release and decreased basal secretion of GH, the isolated pituitary gland of hypophyseal stalk transected calves continues to secrete sufficient amounts of GH for significant growth and development throughout a long period.

Effects of Initial Fat Thickness, Hip Height, and Concentration of Dietary Energy on Growth of Area of the Longissimus dorsi Muscle and Subcutaneous Fat of Yearling Steers

Steers were sorted into four groups based on hip height and fat cover at the start of the finishing period. Each group of sorted steers was fed diets containing 0.59 or 0.64 Mcal NEg per lb. of diet dry matter. Steers with less initial fat cover (0.08 in.) compared with those with more (0.17) had less carcass fat cover 103 days later. The steers with less fat cover accumulated fat at a faster rate, but this was not apparent prior to 80 days. Accretion of fat was best predicted by an exponential growth equation, and was not affected by the two concentrations of energy fed in this study. Steers with greater initial height accumulated fat cover at a slower rate than shorter steers. This difference was interpreted to mean that large-frame steers accumulate subcutaneous fat at a slower rate than medium-frame steers. Increase in area of the ribeye was best described by a linear equation. Initial fat cover, hip height, and concentrations of energy in the diet did not affect rate of growth of this muscle. Predicting carcass fat cover from the initial ultrasound measurement of fat thickness found 46 of the 51 carcasses with less than 0.4 in. of fat cover. Twelve carcasses predicted to have less than 0.4 in. of fat cover had more than 0.4 in. Five carcasses predicted to have more than 0.4 in. actually had less than that. Accurate initial measurements of initial fat thickness with ultrasound might be a useful measurement to sort cattle for specific marketing grids.

Brain Regulation of Growth in Beef Calves

Small peptide hormones produced in the lower part of the brain (hypothalamus) regulate episodic and basal secretion of hormones from the anterior pituitary gland that affect metabolism and growth in cattle. This study focused on long-term growth in young calves subjected to hypophysectomy (HYPOX), hypophyseal stalk transection (HST), and sham operation control (SOC). Crossbred (Hereford x Aberdeen Angus) and Hereford, and Aberdeen Angus calves were HYPOX (n = 5), HST (n = 5), or SOC (n = 8) at 146 days of age, whereas another group was HST (n = 5) or SOC (n = 7) at 273 days of age. Body weight was determined every 21 days from birth to 1008 days of age. From day 146-1008, growth was arrested (P < 0.001) in HYPOX (0.06 kg/day) compared with SOC (0.50 kg/day) calves. Growth continued but at a significantly lower rate (P < 0.05) in calves HST at 146 days (0.32 kg/day) and 273 days (0.32 kg/day) compared with SOC (0.50 kg/day). Although episodic growth hormone (GH) secretion was abolished and peripheral blood serum GH concentration remained consistently lower in HST calves (2.4 ng/ml) than in the SOC (5.5 ng/ml; P < 0.01), the calves continued to grow throughout 1008 days. Peripheral serum thyroid stimulating hormone (TSH) concentration was less (P < 0.05) in HST compared with SOC calves. There was an abrupt decrease (P < 0.001) in serum thyroxine (T4) (4-fold) and triiodothyronine (T3) (3-fold) concentration after surgery that remained to 360 days in HST compared with SOC calves. At sacrifice, pituitary gland weight was markedly reduced (P < 0.001) in HST (0.18 g/100 kg body weight) compared with SOC (0.55 g/100 kg body weight) calves. Histological examination of pituitary glands from HST calves indicated the persistence of secretory GH and TSH cells in the same areas of the anterior pituitary gland as SOC calves. Coronal sections of the gland revealed GH and TSH secreting cells in HST calves that were similar to the controls. These results indicate that long-term growth continues, but at a slower rate, after hypophyseal stalk transection of immature calves in spite of complete abolition of episodic GH secretion and consistently decreased basal secretion of GH, TSH, T4, and T3 compared with sham-operated animals. Growth was abolished after hypophysectomy of immature calves in which circulating GH and TSH was undetectable.

Effects of Novel Growth Hormone Secretagogues on Growth Hormone Secretion in Farm Animals

The requirement for growth hormone (GH) secretion by the anterior pituitary gland in beef calves is demonstrated by a complete lack of long bone-growth and muscle accretion after hypophysectomy (surgical removal of the pituitary gland). When the connecting link (hypophyseal stalk) to the basal region (hypothalamus) of the brain is surgically severed, long bone growth and body weight gain are greatly limited compared with sham-operated controls. This limited growth results from obliteration of episodic GH secretion and reduced basal blood concentration of the hormone compared with sham-operated controls. Thus, the hypophyseal stalk-transected (HST) calf provides an appropriate model to determine mechanisms by which hypothalamic neuropeptides from the brain regulate GH secretion, and thereby growth in the young calf. Neuropeptides have been isolated and characterized in bovine hypothalamus that stimulate GH secretion (GH-releasing hormone [GHRH]) or factor [GHRF] and inhibit GH secretion (GH release-inhibiting hormone [GHRIH] or somatostatin [SRIH]). A dose of .067 micrograms of GHRF per kilogram of body weight injected intravenously in HST calves abruptly increased plasma GH concentration to 55 nanograms per milliliter from the control period mean of 5 nanograms per milliliter. HST calves then were infused intravenously with .033 and .067 microgram somatostatin per kilogram of body weight, during which a pulse injection of .067 microgram of GHRF was administered. GH increase was limited to 9 and 5 micrograms per kilogram body weight during the .033- and .067 microgram SRIH infusions after GHRF; no GH rebound was observed after the SRIH was discontinued. GHRF from humans contains 40 to 44 amino acids. Rat hypothalamic GHRF analogs containing 29 to 32 amino acids elicited dose-dependent GH peak release in these HST calves. In 1977, Bowers and Monomy isolated novel GH releasing peptides consisting of only six amino acids; they caused GH release by isolated pituitary cells in culture and acute GH release when administered intravenously. We recently have utilized a novel nonpeptidyl GH secretagogue of low molecular weight in the pig to determine its mechanisms of action within the central nervous system.

Effects of Bovine Somatotropin and Revalor-S® on Growth Performance and Carcass Leanness in Beef Cattle

Twenty crossbred steers were used to evaluate bovine somatotropin (bST) and an anabolic steroid implant, Revalor-S® (REV), to improve growth and increase carcass leanness. During the first 70 days on feed, bST-treated steers tended to improve live weight gains, consume more feed, and numerically improve feed utilization for growth. The implanted steers grew faster and utilized feed better than steers not implanted with REV. The improvement in gain and feed utilization for growth was maintained throughout the feeding period for REV-implanted steers. At slaughter, REV steers had heavier carcasses which resulted in more pounds of muscle, bone, and fat. When adjusted for hot carcass weight, bST increased leanness of the carcass as evident by the increased weight of the semitendinosus muscle, more pounds of dissected lean, and fewer pounds of dissected fat. Thus, REV and bST can be used to improve growth performance and increase carcass leanness.

Progress Report on Iowa State University Burroughs Endowment Activities

Faculty in the Department of Animal Science initiated soliciting of funds in 1987 to establish a permanent endowment to recognize the distinguished career and major contributions of Dr. Wise Burroughs, a distinguished professor in animal science at Iowa State University. The endowment was established in the Iowa State University Foundation in 1991. The purpose of the fund is to support research and graduate education in the areas of fundamental factors regulating growth in food-producing animals, with emphasis on ruminants; to enhance growth of animals with the goal of improving the competitive position of ruminants as food-producing animals; and to develop innovative approaches to ruminant nutrition and/or growth enhancement as a means to improve desirability of meat produced by food animals. Dr. Burroughs’ research resulted in important and significant developments in technology for modern production systems for beef cattle. He was widely known for his ability to communicate complex ideas and research results for use by those involved in the animal industry. The current Burroughs Team has established three research projects: 1) Ghrelin--How does ghrelin affect blood and body composition in rats?; 2) Use of 25- hydroxyvitamin D3 to improve tenderness of beef; 3) Redesigning beef cattle to have a more healthful fatty acid composition.

A Historical Review of the 4-H Beef of Merit Carcass Contest at the Iowa State Fair

A total of 1,033 head of steers competing in the Iowa State Fair Beef of Merit class from 1975 through 2000 were summarized. Those grading low Choice and higher averaged 55.4 percent, and the average yield grade was 2.44. Due to rule changes over time the quality grade and cutability shifted. In recent years with the emphasis placed on acceptable quality grade and carcass weight, the BOM cattle have improved dramatically in the percent grading Prime and upper Choice. However, with this change has been a reduction in the percent of cattle making yield grade 1 and 2. Growth rate increased through the late 1980s, but has remained static since that time.

Growth Response and Carcass Characteristics of Yearling Steers Subjected to Differing Implant Strategies

A 106-day demonstration utilizing yearling steers to measure feedlot performance and carcass response to implant strategies was conducted at the ISU Allee Demonstration Farm. Treatments were: 100 mg progesterone + 10 mg estradiol benzoate (ComponentÒ EC) on day 0 followed by 120 mg trenbolone acetate + 24 mg estradiol (ComponentÒ TES) implant 57 days later, or 120 mg trenbolone acetate + 24 mg estradiol (ComponentÒ TES) only on day 0. The control group received no implant. The steers were weighed every 28 days and ultrasound data were collected from demonstration initiation until slaughter. The cattle were marketed as one group on d 106 of the demonstration. Implanted cattle had higher average daily gains, heavier carcass weights, larger rib eye areas, and tended to have improved feed efficiency over control steers. Additionally, the reimplanted steers had higher marbling scores than controls, but no differences existed between once and twice-implanted steers.

Short stature caused by a biologically inactive mutant growth hormone (GH-C53S).

Human GH has two disulfide bridges linking Cys-53 to Cys-165 and Cys-182 to Cys-189. Although absence of the first disulfide bridge has been shown to affect the bioactivity of GH in transgenic mice, little is known of the importance of this bridge in mediating the GH/GH-receptor (GHR) interaction in humans. However, we have identified a missense mutation (G705C) in the GH1 gene of a Serbian patient. This mutation was found in the homozygous state and leads to the absence of the disulfide bridge Cys-53 to Cys-165. To study the impact of this mutation in vitro, GHR binding and Janus kinase (Jak)2/signal transducer and activator of transcription (Stat)5 activation experiments were performed, in which it was observed that at physiological concentrations (3-50 ng/ml) both GHR binding and Jak2/Stat5 signaling pathway activation were significantly reduced in the mutant GH-C53S, compared with wild-type (wt)-GH. Higher concentrations (400 ng/ml) were required for this mutant to elicit responses similar to wt-GH. These results demonstrate that the absence of the disulfide bridge Cys-53 to Cys-165 affects the binding affinity of GH for the GHR and subsequently the potency of GH to activate the Jak2/Stat5 signaling pathway. In conclusion, we have demonstrated that GH-C53S is a bioinactive GH at the physiological range and that the disulfide bridge Cys-53 to Cys-163 is required for mediating the biological effects of GH.

Pyroelectric and piezoelectric scanning microscopy applied to reveal the bipolar state of 4-iodo-4′-nitrobiphenyl (INBP)

Two recent scanning probe techniques were applied to investigate the bipolar twin state of 4-iodo-4′-nitrobiphenyl (INBP) crystals. Solution grown crystals of INBP show typically a morphology which does not express that of a mono-domain polar structure (Fdd2, mm2). From previous X-ray diffraction a twinning volume ratio of [similar]70 : 30 is now explained by two unipolar domains (Flack parameter: 0.075(29)) of opposite orientation of the molecular dipoles, joined by a transition zone showing a width of [similar]140 μm. Scanning pyroelectric microscopy (SPEM) demonstrates a continuous transition of the polarization P from +P into −P across the zone. Application of piezoelectric force microscopy (PFM) confirms unipolar alignment of INBP molecules down to a resolution of [similar]20 nm. A previously proposed real structure for INBP crystals built from lamellae with antiparallel alignment is thus rejected. Anomalous X-ray scattering was used to determine the absolute molecular orientation in the two domains. End faces of the polar axis 2 are thus made up by NO2 groups. Using a previously determined negative pyroelectric coefficient pc leads to a confirmation also by a SPEM analysis. Calculated values for functional group interactions (DA), (AA), (DD) and the stochastic theory of polarity formation allow us to predict that NO2 groups should terminate corresponding faces. Following the present analysis, INBP may represent a first example undergoing dipole reversal upon growth to end up in a bipolar state.

Gene Therapy for Pediatric Cancer: State of the Art and Future Perspectives.

While modern treatments have led to a dramatic improvement in survival for pediatric malignancy, toxicities are high and a significant proportion of patients remain resistant. Gene transfer offers the prospect of highly specific therapies for childhood cancer. "Corrective" genes may be transferred to overcome the genetic abnormalities present in the precancerous cell. Alternatively, genes can be introduced to render the malignant cell sensitive to therapeutic drugs. The tumor can also be attacked by decreasing its blood supply with genes that inhibit vascular growth. Another possible approach is to modify normal tissues with genes that make them more resistant to conventional drugs and/or radiation, thereby increasing the therapeutic index. Finally, it may be possible to attack the tumor indirectly by using genes that modify the behavior of the immune system, either by making the tumor more immunogenic, or by rendering host effector cells more efficient. Several gene therapy applications have already been reported for pediatric cancer patients in preliminary Phase 1 studies. Although no major clinical success has yet been achieved, improvements in gene delivery technologies and a better understanding of mechanisms of tumor progression and immune escape have opened new perspectives for the cure of pediatric cancer by combining gene therapy with standard therapeutic available treatments.

Site- and species-specific responses of forest growth to climate across the European continent

Aim To evaluate the climate sensitivity of model-based forest productivity estimates using a continental-scale tree-ring network. Location Europe and North Africa (30–70° N, 10° W–40° E). Methods We compiled close to 1000 annually resolved records of radial tree growth for all major European tree species and quantified changes in growth as a function of historical climatic variation. Sites were grouped using a neural network clustering technique to isolate spatiotemporal and species-specific climate response patterns. The resulting empirical climate sensitivities were compared with the sensitivities of net primary production (NPP) estimates derived from the ORCHIDEE-FM and LPJ-wsl dynamic global vegetation models (DGVMs). Results We found coherent biogeographic patterns in climate response that depend upon (1) phylogenetic controls and (2) ambient environmental conditions delineated by latitudinal/elevational location. Temperature controls dominate forest productivity in high-elevation and high-latitude areas whereas moisture sensitive sites are widespread at low elevation in central and southern Europe. DGVM simulations broadly reproduce the empirical patterns, but show less temperature sensitivity in the boreal zone and stronger precipitation sensitivity towards the mid-latitudes. Main conclusions Large-scale forest productivity is driven by monthly to seasonal climate controls, but our results emphasize species-specific growth patterns under comparable environmental conditions. Furthermore, we demonstrate that carry-over effects from the previous growing season can significantly influence tree growth, particularly in areas with harsh climatic conditions – an element not considered in most current-state DGVMs. Model–data discrepancies suggest that the simulated climate sensitivity of NPP will need refinement before carbon-cycle climate feedbacks can be accurately quantified.

Reproducibility of effects of homeopathically potentised gibberellic acid on the growth of Lemna gibba L. in a randomised and blinded bioassay

BACKGROUND: Reproducibility of basic research investigations in homeopathy is challenging. This study investigated if formerly observed effects of homeopathically potentised gibberellic acid (GA3) on growth of duckweed (Lemna gibba L.) were reproducible. METHODS: Duckweed was grown in potencies (14x-30x) of GA3 and one time succussed and unsuccussed water controls. Outcome parameter area-related growth rate was determined by a computerised image analysis system. Three series including five independent blinded and randomised potency experiments (PE) each were carried out. System stability was controlled by three series of five systematic negative control (SNC) experiments. Gibbosity (a specific growth state of L. gibba) was investigated as possibly essential factor for reactivity of L. gibba towards potentised GA3 in one series of potency and SNC experiments, respectively. RESULTS: Only in the third series with gibbous L. gibba L. we observed a significant effect (p = 0.009, F-test) of the homeopathic treatment. However, growth rate increased in contrast to the former study, and most biologically active potency levels differed. Variability in PE was lower than in SNC experiments. The stability of the experimental system was verified by the SNC experiments. CONCLUSIONS: Gibbosity seems to be a necessary condition for reactivity of L. gibba to potentised GA3. Further still unknown conditions seem to govern effect direction and the pattern of active and inactive potency levels. When designing new reproducibility studies, the physiological state of the test organism must be considered. Variability might be an interesting parameter to investigate effects of homeopathic remedies in basic research.

Germania: l’indomabile trading state

Basato su interviste con i principali attori tedeschi e su un’analisi della letteratura, l’articolo analizza lo sviluppo recente dell’economia tedesca e la strategia tedesca nell’affrontare la crisi dell’eurozona. La Germania è uno stato commerciale (trading state), la cui crescita è fortemente trainata dalle esportazioni. Fino agli anni novanta, rigidità istituzionali forti, nel sistema di relazioni industriali e nel sistema di protezione sociale, contribuivano a conciliare lo sviluppo delle esportazioni con una crescita armonica dei consumi interni, contribuendo cosi a ingabbiare la «tigre» tedesca. A partire dagli anni novanta, sia le relazioni industriali sia la protezione sociale sono state fortemente liberalizzate, stimolando ulteriormente la competitività estera e indebolendo i consumi interni. Il modello economico tedesco, cosi come è venuto profilandosi negli ultimi dieci anni, è alla base delle politiche di austerità che la Germania impone all’Europa. Tali politiche sono fortemente condivise dai partiti politici, dagli attori sociali e dall’opinione pubblica, e le probabilità che la strategia tedesca cambi sono minime.