Heterozygous GHR gene mutation in a child with idiopathic short stature.

Abstract Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subjects.

Radiometrical, hormonal and biological correlates of skeletal growth in the female rat from birth to senescence

OBJECTIVE We investigated the skeletal growth profile of female rats from birth to senescence (100weeks) on the basis of sequential radiometrical, hormonal and biochemical parameters. DESIGN Weaning rats entered the study which was divided into two sections: a) sequential measurements of vertebral and tibial growths and bone mineral density (BMD), estimation of mineral content of the entire skeleton (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp) throughout the experimental period. RESULTS Vertebral and tibial growths ceased at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak bone mass at week 40. rGH pulsatile profiles were significantly higher in younger animals coinciding with the period of active growth and IGF-I peaked at 7weeks, slowly declining thereafter and stabilizing after week 60. OC and dp closely paralleled IGF-I coinciding with the period of enhanced skeletal growth, remaining thereafter in the low range indicative of reduced bone turnover. E2 increased during reproductive life but the lower values subsequently recorded were still in the physiological range, strongly suggesting a protective role of this steroid on bone remodeling. PTH followed a similar profile to E2, but the significance of this after completion of growth remains unclear. CONCLUSIONS Mechanisms governing skeletal growth in the female rat appear similar to those in humans. Bone progression and attainment of peak bone mass are under simultaneous control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This steroid seems to protect the skeleton from resorption before senescence whereas the role of PTH in this context remains uncertain.

Invited review: Growth-promoting effects of colostrum in calves based on interaction with intestinal cell surface receptors and receptor-like transporters

The postnatal development and maturation of the gastrointestinal (GI) tract of neonatal calves is crucial for their survival. Major morphological and functional changes in the calf's GI tract initiated by colostrum bioactive substances promote the establishment of intestinal digestion and absorption of food. It is generally accepted that colostrum intake provokes the maturation of organs and systems in young calves, illustrating the significance of the cow-to-calf connection at birth. These postnatal adaptive changes of the GI tissues in neonatal calves are especially induced by the action of bioactive substances such as insulin-like growth factors, hormones, or cholesterol carriers abundantly present in colostrum. These substances interact with specific cell-surface receptors or receptor-like transporters expressed in the GI wall of neonatal calves to elicit their biological effects. Therefore, the abundance and activity of cell surface receptors and receptor-like transporters binding colostral bioactive substances are a key aspect determining the effects of the cow-to-calf connection at birth. The present review compiles the information describing the effects of colostrum feeding on selected serum metabolic and endocrine traits in neonatal calves. In this context, the current paper discusses specifically the consequences of colostrum feeding on the GI expression and activity of cell-receptors and receptor-like transporters binding growth hormone, insulin-like growth factors, insulin, or cholesterol acceptors in neonatal calves.

Total Factor Productivity, Human Capital and Outward Orientation: Differences by Stage of Ddevelopment and Geographic Regions

Do openness and human capital accumulation promote economic growth? While intuition argues yes, the existing empirical evidence provides mixed support for such assertions. We examine Cobb-Douglas production function specifications for a 30-year panel of 83 countries representing all regions of the world and all income groups. We estimate and compare labor and capital elasticities of output per worker across each of several income and geographic groups, finding significant differences in production technology. Then we estimate the total factor productivity series for each classification. Using determinants of total factor productivity that include, among many others, human capital, openness, and distortion of domestic prices relative to world prices, we find significant differences in results between the overall sample and sub-samples of countries. In particular, a policy of outward orientation may or may not promote growth in specific country groups. even if geared to reducing price distortion and increasing openness. Human capital plays a smaller role in enhancing growth through total factor productivity.

Influencia de la castración y la línea genética paterna sobre el rendimiento productivo y la calidad de la canal y de la carne en cerdos sacrificados a pesos elevados

El objetivo general de esta Tesis Doctoral fue estudiar la influencia del sexo, el método de castración de los machos y la línea genética paterna sobre la productividad y la calidad de la canal y de la carne en cerdos blancos sacrificados a pesos elevados con destino a la industria de los productos curados de calidad. En el experimento 1, se utilizaron 360 cerdos sacrificados a 125 kg de peso vivo (PV) para estudiar la influencia del sexo y la castración [machos inmunocastrados (MI), machos castrados quirúrgicamente (MC) y hembras enteras (HE)] de dos líneas genéticas paternas Large White (Top York y Tempo) sobre los rendimientos productivos y la calidad de la canal y de la carne. La línea materna utilizada fue Large White × Landrace en todos los casos. Los MI se inmunizaron contra el factor de liberación de gonadotropina (GnRF) mediante la utilización de Improvac a los 78 (16 d en prueba) y 126 (64 d en prueba y 48 d antes del sacrificio) d de edad. Cada uno de los 6 tratamientos experimentales fue replicado 6 veces (cuadra con 10 cerdos). Desde el inicio de la prueba hasta el día de la primera inyección con Improvac (62 a 78 d de edad) los MI y las HE crecieron menos (P < 0,001) que los MC sin que se observaran diferencias en el consumo medio diario de pienso (CMD). Los MC tuvieron peor eficiencia alimenticia que las HE con los MI mostrando valores intermedios (P < 0,01). Entre las dos inyecciones de Improvac (78 a 126 d de edad), los MI crecieron y comieron menos que los MC, mostrando las HE valores intermedios (P < 0,001). Los MI fueron más eficientes que las HE y ambos más eficientes que los MC (P < 0,001). Sin embargo, desde la segunda inyección de Improvac hasta el sacrificio (126 a 174 d de edad) los MI crecieron más y fueron más eficientes (P < 0,001) que las HE y los MC. Al final de la prueba, MI y MC crecieron más (P < 0,01) que HE. Asimismo, los MI fueron más eficientes (P < 0,001) pero presentaron menor rendimiento de canal (P < 0,001) que los MC y las HE. Por otro lado, los MI y las HE depositaron menos grasa dorsal que los MC (P < 0,001). Las hembras tuvieron mayor rendimiento de lomo y menos grasa intramuscular que MI y MC (P < 0,01). Asimismo, las HE tuvieron mayor rendimiento de jamón en fresco y perfilado que los MC con los MI mostrando valores intermedios (P < 0,05). Los cerdos híbridos procedentes de machos Tempo crecieron más (P < 0,001) que los procedentes de machos Top York, sin que se encontraran diferencias para el CMD o para la eficiencia alimenticia. Los híbridos de los cruces con Top York tuvieron mejores rendimientos de jamones frescos y perfilados (P < 0,05) pero menor rendimiento de lomo y menos grasa intramuscular que los cruces con Tempo (P < 0,01). En conclusión, los MI presentaron mejor eficiencia alimenticia, pero menor rendimiento de canal que los MC y las HE. El contenido en grasa intramuscular fue similar entre MC y MI y superior para ambos que para las HE. Los cruces procedentes de la línea paterna Tempo crecieron más y tuvieron mayor contenido en grasa intramuscular, pero un rendimiento en jamón perfilado ligeramente inferior al de los cruces procedentes de la línea paterna Top York. Se concluye que la inmunocastración de los machos es una alternativa viable a la castración quirúrgica para la producción de cerdos pesados destinados a la industria de los productos curados. Debido a su mayor potencial de crecimiento y mayor contenido en grasa intramuscular, los híbridos procedentes de la línea paterna Tempo presentan ventajas frente a los híbridos procedentes de la línea paterna Top York cuando se destinan a la industria de productos curados de calidad. En el experimento 2, se utilizaron 240 cerdos para comparar los rendimientos productivos y los parámetros de calidad de la canal de MI, MC y HE destinados a la industria de productos cárnicos curados procedentes del cruce de la línea materna Large White × Landrace con la línea genética paterna Duroc o Pietrain. Entre las 2 inyecciones de Improvac (87 a 137 d de edad), los MI y las HE crecieron menos que los MC (P < 0,01). Asimismo, los MI comieron menos pienso que las HE y ambos menos que los MC (2,33, 2,55 y 2,77 kg/d; respectivamente; P < 0,001). Como resultado, los MI fueron más eficientes que los MC y las HE (P < 0,001). Desde la segunda inyección de Improvac hasta el momento del sacrificio (137 a 164 d de edad), los MI fueron más eficientes que las HE y ambos más que los MC (0,346, 0,323 y 0,300, respectivamente; P < 0,001). Las diferencias observadas en este periodo entre los sexos en cuanto a rendimientos productivos fueron más pronunciadas en los cerdos procedentes de la línea paterna Pietrain que los de la línea Duroc (P < 0,05 para la interacción). En el global de la prueba (87 a 164 d de edad) el sexo no afectó al crecimiento en los cerdos procedentes de la línea paterna Duroc pero en los cerdos procedentes de la línea paterna Pietrain, los MI y los MC crecieron más que las HE (P < 0,05 para la interacción). Asimismo, los MI tuvieron mejor eficiencia alimenticia (0,406, 0,364 y 0,380, P < 0,001) y menor rendimiento de la canal (76,6, 78,1 y 78,8%; P < 0,001) que los MC y las HE. Las canales de las HE fueron más magras que las canales de los MC, con las canales de los MI mostrando valores intermedios (P < 0,01). El rendimiento en jamones y lomos fue mayor para las HE que para los MI y los MC (P < 0,001). El contenido en grasa intramuscular fue menor en las HE que en los MC, con los MI mostrando valores intermedios (3,5 vs. 3,9 y 3,7%; P < 0,05). Por otra parte, los híbridos procedentes de machos Duroc crecieron más rápido (1,167 vs. 0,986 kg/d; P < 0,001), consumieron más pienso (3,07 vs. 2,56 kg/d; P < 0,001) y tuvieron más grasa intramuscular (P < 0,001), pero menor rendimiento en jamones y lomos (P < 0,01) que los híbridos procedentes de machos Pietrain. Se concluye que los MI presentaron mejores productividades pero menores rendimientos de canal que MC y HE. El contenido en grasa intramuscular en el músculo longissimus dorsi fue menor para las HE que para los MC con valores intermedios para los MI. Los cruces procedentes de la genética paterna Duroc crecieron más y tuvieron más grasa intramuscular pero menos rendimiento de jamón que los cerdos procedentes de machos Pietrain. Por tanto, los MI deben ser preferidos a los MC y los cruces con la línea paterna Duroc deben ser preferidos a los cruces con Pietrain para producir canales cuando sus partes nobles están destinadas a la industria de productos cárnicos curados. En base a estos resultados, se concluye que la inmunocastración es una alternativa factible a la castración quirúrgica y que líneas genéticas paternas Tempo y Duroc son mejores para la producción de cerdo blanco pesado que las líneas Top York y Pietrain. Las interacciones entre el sexo y las líneas genéticas paternas estudiadas, sugieren que el resultado final depende en parte de la línea genética paterna utilizada. En cualquier caso, la inmunocastración es una alternativa factible a la castración quirúrgica para la producción de canales destinadas a la industria de los productos cárnicos curados. ABSTRACT The general aim of this PhD Thesis was to study the influence of sex, method of castration, and genetic background of the sire line on growth performance and carcass and meat quality merits of heavy white pigs destined to the dry-cured industry. In experiment 1, 360 pigs slaughtered at 125 kg of body weight were used to study the influence of sex and castration methodology [immunocastrated males (ICM), surgically castrated males (SCM), and intact females (IF)] of 2 terminal Large White sire lines (Top York and Tempo) on growth performance and carcass and meat quality. The female line was Large White × Landrace in all cases. The ICM pigs were immunized against gonadotropin-releasing factor with Improvac at 78 (16 d on trial) and 126 (64 d on trial and 48 d before slaughter) d of age. Each of the 6 treatments was replicated 6 times (10 pigs/pen). From the start of the experiment to the day of the first Improvac injection (62 to 78 d of age), ICM and IF grew slowlier (P < 0.001) than SCM but no differences in feed intake were detected. The SCM pigs had greater gain to feed ratio (G:F) than the IF with the ICM pigs being intermediate (P < 0.01). Between the 2 Improvac injections (78 to 126 d of age), the ICM pigs ate less feed (P < 0.001) and grew slowlier rate than the SCM pigs, with the growth of IF being intermediate. The ICM pigs were more efficient than the IF, and both were more efficient than the SCM pigs (P < 0.001). However, from the second Improvac injection to slaughter (126 to 174 d of age), the ICM pigs grew at a faster rate (P < 0.001) and were more efficient (P < 0.001) than the IF and the SCM pigs. Cumulatively, ICM and SCM pigs grew faster (P < 0.01) than IF and the ICM pigs were more efficient than the other two sexes (P < 0.001). However, the ICM pigs had reduced (P < 0.001) carcass yield compared with SCM and IF. The ICM and IF pigs also had less (P < 0.001) backfat depth than the SCM pigs. Intact females had higher (P < 0.01) loin yield but less intramuscular fat (P < 0.01) than ICM and SCM pigs and higher (P < 0.05) fresh and trimmed ham yields than SCM pigs, with ICM pigs being intermediate. Crossbreds from the Tempo sires grew faster (P < 0.001) than crossbreds from the Top York sires but no differences (P > 0.10) were detected for feed intake or feed efficiency. Crossbreds from the Top York sires had higher (P < 0.05) fresh and trimmed ham yields but less (P < 0.01) loin yield and intramuscular fat content than crossbreds from the Tempo sires. In conclusion, ICM pigs are more efficient, but have less carcass yield than SCM and IF pigs. The intramuscular fat content was lowest for the IF and similar for ICM and SCM pigs. Crossbreds from Tempo sires were heavier and had greater intramuscular fat content, but had less trimmed ham yield as compared with crossbreds from the Top York sires. Immunocastrated pigs can replace SCM pigs for the production of heavy pigs destined for the dry-cured industry. Because of increased carcass weight and the higher intramuscular content, crossbreds from Tempo sires may have an advantage over crossbreds from Top York sires for the dry-cured industry. In experiment 2, a total of 240 pigs were used to compare growth performance and carcass quality traits of immunocastrated males, surgically castrated males, and intact females of crossbreds from Large White × Landrace females and Duroc or Pietrain sires destined to the dry-cured industry. Between the 2 Improvac injections (87 and 137 d of age), ICM and IF pigs had lower average daily gain (ADG) than SCM pigs (P < 0.01). Also, ICM pigs ate less feed than IF and both type of pigs ate less than SCM pigs (2.33, 2.55, and 2.77 kg/d; P < 0.001). Consequently, ICM pigs had better G:F than SCM and IF (P < 0.001). From the second Improvac injection to slaughter (137 to 164 d of age), ICM pigs were more efficient than IF and both were more efficient than SCM pigs (0.346, 0.323, and 0.300 g/g; P < 0.001). The differences in growth performance among genders observed in this period were more pronounced for the Pietrain than for the Duroc crossbreds (P < 0.05 for the interaction). For the entire experimental period (87 to 164 d of age), gender did not affect ADG for Duroc crossbreds but for Pietrain crossbreds ICM and SCM had higher ADG than IF (P < 0.05 for the interaction). The ICM pigs had better feed efficiency (0.406, 0.364, and 0.380; g/g; P < 0.001) and lower carcass yield (76.6, 78.1, and 78.8%; P < 0.001) than SCM or IF. Carcasses from IF were leaner than carcasses from SCM with carcasses from ICM being intermediate (P < 0.01). Ham and loin (P < 0.001) yields were higher for IF than for ICM or SCM pigs. Intramuscular fat content was lower for IF than for SCM pigs with that of ICM pigs being intermediate (3.5 vs. 3.9 and 3.7%; P < 0.05). Cumulatively, crossbreds from Duroc sires had higher ADG (1.167 vs. 0.986 kg/d; P < 0.001) and average daily feed intake (3.07 vs. 2.56 kg/d; P < 0.001) and more intramuscular fat (P < 0.001) but less ham and loin yields (P < 0.01) than crossbreds from Pietrain sires. It is concluded that growth performance was better, but carcass yield lower, for ICM pigs than for SCM and IF. Intramuscular fat content in longissimus dorsi muscle was lower for IF than for SCM pigs with ICM pigs being intermediate. Crossbreds from Duroc sires grew faster and had more intramuscular fat but less ham yield than crossbreds from Pietrain sires. Therefore, ICM pigs should be preferred to SCM pigs, and Duroc crossbreds should be preferred to Pietrain crossbreds to produce carcasses destined to the production of primal cuts for the dry-cured industry. We conclude that immunocastration might be a sound alternative to surgical castration in pigs and that Tempo and Duroc might be better for the production of heavy pigs than Top York and Pietrain. The interactions reported between sex and genetic sire line, suggested that the benefits of immunocastration as an alternative to surgical castration might depend at least part on the sire line used. In any case, immunocastration is a good alternative to surgical castration for the production of carcasses destined to the dry-cured industry.

Exogenous Administration of Gangliosides Displaces GPI-anchored Proteins from Lipid Microdomains in Living Cells

Exogenous application of gangliosides to cells affects many cellular functions. We asked whether these effects could be attributed to the influence of gangliosides on the properties of sphingolipid–cholesterol microdomains on the plasma membrane, also termed rafts. The latter are envisaged as lateral assemblies of sphingolipids (including gangliosides), cholesterol, and a specific set of proteins. Rafts have been implicated in processes such as membrane trafficking, signal transduction, and cell adhesion. Recently, using a chemical cross-linking approach with Madin-Darby canine kidney (MDCK) cells permanently expressing a GPI-anchored form of growth hormone decay accelerating factor (GH-DAF) as a model system, we could show that GPI-anchored proteins are clustered in rafts in living cells. Moreover, this clustering was dependent on the level of cholesterol in the cell. Here we show that incubation of MDCK cells with gangliosides abolished subsequent chemical cross-linking of GH-DAF. Furthermore, insertion of gangliosides into the plasma membrane of MDCK GH-DAF cells renders GH-DAF soluble when subjected to extraction with Triton X-114 at 4°C. Our data suggest that exogenous application of gangliosides displaces GPI-anchored proteins from sphingolipid–cholesterol microdomains in living cells.

Mode matches and their locations in the hydrophobic free energy sequences of peptide ligands and their receptor eigenfunctions

Patterns in sequences of amino acid hydrophobic free energies predict secondary structures in proteins. In protein folding, matches in hydrophobic free energy statistical wavelengths appear to contribute to selective aggregation of secondary structures in “hydrophobic zippers.” In a similar setting, the use of Fourier analysis to characterize the dominant statistical wavelengths of peptide ligands’ and receptor proteins’ hydrophobic modes to predict such matches has been limited by the aliasing and end effects of short peptide lengths, as well as the broad-band, mode multiplicity of many of their frequency (power) spectra. In addition, the sequence locations of the matching modes are lost in this transformation. We make new use of three techniques to address these difficulties: (i) eigenfunction construction from the linear decomposition of the lagged covariance matrices of the ligands and receptors as hydrophobic free energy sequences; (ii) maximum entropy, complex poles power spectra, which select the dominant modes of the hydrophobic free energy sequences or their eigenfunctions; and (iii) discrete, best bases, trigonometric wavelet transformations, which confirm the dominant spectral frequencies of the eigenfunctions and locate them as (absolute valued) moduli in the peptide or receptor sequence. The leading eigenfunction of the covariance matrix of a transmembrane receptor sequence locates the same transmembrane segments seen in n-block-averaged hydropathy plots while leaving the remaining hydrophobic modes unsmoothed and available for further analyses as secondary eigenfunctions. In these receptor eigenfunctions, we find a set of statistical wavelength matches between peptide ligands and their G-protein and tyrosine kinase coupled receptors, ranging across examples from 13.10 amino acids in acid fibroblast growth factor to 2.18 residues in corticotropin releasing factor. We find that the wavelet-located receptor modes in the extracellular loops are compatible with studies of receptor chimeric exchanges and point mutations. A nonbinding corticotropin-releasing factor receptor mutant is shown to have lost the signatory mode common to the normal receptor and its ligand. Hydrophobic free energy eigenfunctions and their transformations offer new quantitative physical homologies in database searches for peptide-receptor matches.

A new endogenous natriuretic factor: LLU-alpha.

For over three decades, renal physiology has sought a putative natriuretic hormone (third factor) that might control the body's pool of extracellular fluid, an important determinant in hypertension, congestive heart failure, and cirrhosis. In our search for this hormone, we have isolated several pure natriuretic factors from human uremic urine that would appear, alone or in combination, to mark a cluster of phenomena previously presumed to be that of a single "natriuretic hormone." This paper reports the purification, chemical structure, and total synthesis of the first of these compounds, LLU-alpha, which proved to be 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman, presumably a metabolite of gamma-tocopherol. Both natural LLU-alpha and synthetic material are identical (except for optical activity) with respect to structure and biological activity. It appears that the natriuretic activity of LLU-alpha is mediated by inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the kidney.

Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions.

Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these studies, we demonstrate that 291 bp of the proximal scavenger receptor promoter, in concert with a 400-bp upstream enhancer element, is sufficient to direct macrophage-specific expression of a human growth hormone reporter in transgenic mice. These regulatory elements, which contain binding sites for PU.1, AP-1, and cooperating ets-domain transcription factors, are also sufficient to mediate regulation of transgene expression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor. Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene. The ability of the scavenger receptor promoter and enhancer to target gene expression to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general utility in the study of macrophage differentiation and function by permitting specific modifications of macrophage gene expression.

Two auxin-responsive domains interact positively to induce expression of the early indoleacetic acid-inducible gene PS-IAA4/5.

The plant growth hormone indole-3-acetic acid (IAA) transcriptionally activates expression of several genes in plants. We have previously identified a 164-bp promoter region (-318 to -154) in the PS-IAA4/5 gene that confers IAA inducibility. Linker-scanning mutagenesis across the region has identified two positive domains: domain A (48 bp; -203 to -156) and domain B (44 bp; -299 to -256), responsible for transcriptional activation of PS-IAA4/5 by IAA. Domain A contains the highly conserved sequence 5'-TGTCCCAT-3' found among various IAA-inducible genes and behaves as the major auxin-responsive element. Domain B functions as an enhancer element which may also contain a less efficient auxin-responsive element. The two domains act cooperatively to stimulate transcription; however, tetramerization of domain A or B compensates for the loss of A or B function. The two domains can also mediate IAA-induced transcription from the heterologous cauliflower mosaic virus 35S promoter (-73 to +1). In vivo competition experiments with icosamers of domain A or B show that the domains interact specifically and with different affinities to low abundance, positive transcription factor(s). A model for transcriptional activation of PS-IAA4/5 by IAA is discussed.

Synthesis Report on the Impact of Capital Use. Factor Markets Working Document No. 57, August 2013

This paper examines the drivers of productivity in EU agriculture from a factor markets perspective. Using econometrically estimated production elasticities and shadow prices of factors for a set of eight EU member states, we focus on field crop farms represented in the FADN database for the years 2002-08. As it turned out that output reacts most elastically to materials input, we investigate this factor further and find different rationing regimes represented in different member states. Marginal return on materials is low in Denmark and West Germany, but significantly above typical market interest rates in East Germany, Italy and Spain. In the latter countries and in Denmark it also increased towards the end of the observed period. This finding is consistent with a perception of tightening funding access, possibly induced or reinforced by the unfolding financial crisis. Marginal returns to land, labour and fixed capital are generally low. We conclude that the functioning of factor markets plays a crucial role for productivity growth, but that factor market operations display considerable heterogeneity across EU member states.

Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin-1β

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.

Canine and Feline Diabetes Mellitus: Nature or Nurture?

There is evidence for the role of genetic and environmental factors in feline and canine diabetes. Type 2 diabetes is the most common form of diabetes in cats. Evidence for genetic factors in feline diabetes includes the overrepresentation of Burmese cats with diabetes. Environmental risk factors in domestic or Burmese cats include advancing age, obesity, male gender, neutering, drug treatment, physical inactivity, and indoor confinement. High-carbohydrate diets increase blood glucose and insulin levels and may predispose cats to obesity and diabetes. Low-carbohydrate, high-protein diets may help prevent diabetes in cats at risk such as obese cats or lean cats with underlying low insulin sensitivity. Evidence exists for a genetic basis and altered immune response in the pathogenesis of canine diabetes. Seasonal effects on the incidence of diagnosis indicate that there are environmental influences on disease progression. At least 50% of diabetic dogs have type 1 diabetes based on present evidence of immune destruction of P-cells. Epidemiological factors closely match those of the latent autoimmune diabetes of adults form of human type 1 diabetes. Extensive pancreatic damage, likely from chronic pancreatitis, causes similar to28% of canine diabetes cases. Environmental factors such as feeding of high-fat diets are potentially associated with pancreatitis and likely play a role in the development of pancreatitis in diabetic dogs. There are no published data showing that overt type 2 diabetes occurs in dogs or that obesity is a risk factor for canine diabetes. Diabetes diagnosed in a bitch during either pregnancy or diestrus is comparable to human gestational diabetes.

Benign intracranial hypertension associated with acromegaly

This is the first reported case of benign intracranial hypertension (BIH) occurring with acromegaly and resolving after successful treatment of a growth hormone-secreting pituitary adenoma. BIH has been reported with recombinant human growth hormone (rhGH) therapy of GH deficient patients and insulin-like growth factor I (IGF-I) treatment of growth hormone (GH) insensitivity (Laron syndrome) in children. We postulate that the proposed mechanism causing BIH in rhGH-treated children and in acromegaly results from increased cerebrospinal fluid production from the choroid plexi secondary to elevated cerebrospinal fluid growth hormone concentrations that trigger local IGF-I secretion and activation of IGF-I receptors.

The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention

Hormone replacement therapy (HRT) has been reported to exert a positive effect on preserving muscle strength following the menopause, however, the mechanism of action remains unclear. We examined whether the mechanism involved preservation of muscle composition as determined by skeletal muscle attenuation. Eighty women aged 50-57 years were randomly assigned to either: HRT, exercise (Ex), HRT + exercise (ExHRT), and control (Co) for 1 year. The study was double-blinded with subjects receiving oestradiol and norethisterone acetate (Kliogest) or placebo. Exercise included progressive high-impact training for the lower limbs. Skeletal muscle attenuation in Hounsfield units (HU) was determined by computed tomography of the mid-thigh. Areas examined were the quadriceps compartment (includes intermuscular adipose tissue), quadriceps muscles, the posterior compartment and posterior muscles. Muscle performance was determined by knee extensor strength, vertical jump height, and running speed over 20 m. Fifty-one women completed the intervention. Vertical jump height and running speed improved in the HRT and ExHRT groups compared with Co (interaction, P < 0.01). For both the quadriceps compartment and quadriceps muscles, HU significantly increased (interaction, P <= 0.005) for HRT, Ex, and ExHRT compared with Co. For the posterior compartment, HU for the HRT and ExHRT were significantly increased compared with Co, while for posterior muscles, ExHRT was significantly greater than Co. Although the effects were modest, the results indicate that HRT, either alone or combined with exercise, may play a role in preserving/improving skeletal muscle attenuation in early postmenopausal women and thereby exert a positive effect on muscle performance.