1,152 research outputs found
Short term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure
No full textInitiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults, we conducted a double blind study in which seven GH-deficient patients (aged 24-74 yr) each received in random order daily sc injections of placebo, a physiological dose of GH (0.04 U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose) for 7 days, separated by 21-day washout periods. On the seventh day, measurements were made of serum insulin-like growth factor I, body weight, exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone, atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and blood pressure. GH significantly increased mean insulin-like growth factor I levels from 105 ± 11 to 304 ± 45 μg/L during low dose treatment (P = 0.006) and 400 ± 76 μg/L during high dose treatment (P = 0.004). High dose GH caused a 1.2 ± 0.3 kg increase in body weight (P = 0.01) and a 193 ± 65 mmol increase in exchangeable sodium (P = 0.008). Low dose GH had a lesser effect, with no significant increase in body weight, but an increase in exchangeable sodium of 113 ± 37 mmol (P = 0.02). Plasma volume was not significantly affected by GH treatment. Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine pRA levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were not significantly affected by GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h heart rate was significantly higher during low dose (82 ± 2 beats/min; P = 0.0001) and high dose (88 ± 3 beats/min; P = 0.0001) GH treatment than during placebo (67 ± 3 beats/min). However, no significant change in mean 24-h systolic or diastolic blood pressure was observed. In summary, acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium, but no associated increase in blood pressure. We conclude that 1) sodium retention is a physiological effect of GH, but does not cause an acute rise in blood pressure; and 2) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect
RNAseq analysis of fast skeletal muscle in restriction-fed transgenic coho salmon (Oncorhynchus kisutch) : an experimental model uncoupling the growth hormone and nutritional signals regulating growth
No full textBackground Coho salmon (Oncorhynchus kisutch) transgenic for growth hormone (Gh) express Gh in multiple tissues which results in increased appetite and continuous high growth with satiation feeding. Restricting Gh-transgenics to the same lower ration (TR) as wild-type fish (WT) results in similar growth, but with the recruitment of fewer, larger diameter, muscle skeletal fibres to reach a given body size. In order to better understand the genetic mechanisms behind these different patterns of muscle growth and to investigate how the decoupling of Gh and nutritional signals affects gene regulation we used RNA-seq to compare the fast skeletal muscle transcriptome in TR and WT coho salmon. Results Illumina sequencing of individually barcoded libraries from 6 WT and 6 TR coho salmon yielded 704,550,985 paired end reads which were used to construct 323,115 contigs containing 19,093 unique genes of which >10,000 contained >90 % of the coding sequence. Transcripts coding for 31 genes required for myoblast fusion were identified with 22 significantly downregulated in TR relative to WT fish, including 10 (vaspa, cdh15, graf1, crk, crkl, dock1, trio, plekho1a, cdc42a and dock5) associated with signaling through the cell surface protein cadherin. Nineteen out of 44 (43 %) translation initiation factors and 14 of 47 (30 %) protein chaperones were upregulated in TR relative to WT fish. Conclusions TR coho salmon showed increased growth hormone transcripts and gene expression associated with protein synthesis and folding than WT fish even though net rates of protein accretion were similar. The uncoupling of Gh and amino acid signals likely results in additional costs of transcription associated with protein turnover in TR fish. The predicted reduction in the ionic costs of homeostasis in TR fish associated with increased fibre size were shown to involve multiple pathways regulating myotube fusion, particularly cadherin signaling.Peer reviewe
GH and the cardiovascular system: an update on a topic at heart
No full textIn this review, the importance of growth hormone (GH) for the maintenance of normal cardiac function in adult life is discussed. Physiological effects of GH and underlying mechanisms for interactions between GH and insulin-like growth factor I (IGF-I) and the cardiovascular system are covered as well as the cardiac dysfunction caused both by GH excess (acromegaly) and by GH deficiency in adult hypopituitary patients. In both acromegaly and adult GH deficiency, there is also increased cardiovascular morbidity and mortality possibly linked to aberrations in GH status. Finally, the status of the GH/IGF-I system in relation to heart failure and the potential of GH as a therapeutic tool in the treatment of heart failure are reviewed in this article. © 2014 The Author(s)
Book Review: Comrades Betrayed: Jewish World War I Veterans Under Hitler
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in [German History] following peer review. The version of record [Grady, T. (2021). [Review of the book Comrades Betrayed: Jewish World War I Veterans Under Hitler by M. Geheran]. German History, 39(3), 478–479] is available online at: https://academic.oup.com/gh/article/39/3/478/6308748Book review of Comrades Betrayed: Jewish World War I Veterans Under HitlerUnfundedAAM out of embargo 24/06/2023, output uploaded to CR 30/01/202
Espressione genica indotta dall'ormone somatotropo nei monociti di bambini sani e con deficit di GH
No full text2018 - 2019Somatotropic hormone (GH) has transcriptional effects on the cells of many organs, directly by activating its receptor (GHR) or indirectly through induction of IGF-1 or other mediators. The presence of GHR in almost all cellular tissues makes GH action systemic even if, to date, still not well characterized. The immune system is among the districts where the effect of the somatotropic hormone is documented by mechanisms that are still poorly understood.The primary objective of this study is to determine the transcriptional effect of GH on peripheral blood monocytes. These cells were chosen for the significant expression of GHR on their surface and because they are easily accessible. Although the transcriptional response to somatotropic hormone is specific tissue, the study of the effects of GH on monocytes can serve as a model for other cell types and highlight differences between healthy subjects and those with GH deficiency (GHD).The diagnosis of GHD, during the developmental age, is classically based on the clinical evaluation associated with radiological and laboratory investigations (GH-IGF-1 axis stimulus test). Although provocation tests represent diagnostic gold standard, they have poor reproducibility and accuracy and are characterized by a considerable number of false positives and sometimes negatives.The secondary objective of this study is to identify differential transcriptional profiles between healthy subjects and with GHD.For this purpose, the gene expression of monocytes from healthy children and with GHD was compared in culture, under basal conditions and after stimulation with recombinant GH (rh-GH).Two groups of 12 subjects were selected, group S: healthy male children with normal height and growth rate and group D: children of the same sex and age and suffering from GHD, not yet in replacement therapy. Peripheral blood monocytes were purified by subtraction with monoclonal antibodies and the purity level was determined by laminar flow cytofluorimetry with monoclonal antibodies. Monocytes were grown for 24 hours with and without rh-GH. Total RNA was extracted and frozen until the analysis was performed simultaneously for all the experimental points using the Next Generation Sequencing methodology on Illumina platform. Differential expression of mRNA was analyzed by comparing the monocytes of healthy children and with GHD, stimulated in culture with rh-GH or not stimulated: GHD not stimulated (D-CNTR) vs healthy not stimulated (S-CNTR); healthy non-stimulated (S-CNTR) vs healthy stimulated (S-GH); non-stimulated GHD (D-CNTR) vs stimulated GHD (D-GH); GHD stimulated (D-GH) vs healthy stimulated (S-GH).The analysis between D-CNTR vs S-CNTR groups identified 58 genes with differential expression. Furthermore, 23 genes were modulated by GH in healthy children and 4 genes in children with GHD. Differential analysis between D-GH vs S-GH groups, on the other hand, identified 150 genes with differential expression.Finally, analysis performed by Ingenuity Pathway Analysis software showed a significant increase in NFAT immune pathways and dendritic cell maturation and a consistent increase in the expression of dendritic markers (HLA-A, HLA-C, CCR7) in monocytes of children with GHD compared to healthy children, after stimulation in culture with recombinant GH.In conclusion, the results of this study have demonstrated a clear transcriptional effect of GH on monocytes, direct and indirect through intermediate mediators, suggesting to evaluate the pro-inflammatory status of children with growth hormone deficiency more in depth.Furthermore, this study identified a gene expression profile of monocytes in children with GHD which, once verified in a larger number of patients, could represent an alternative to stimulus tests and guide the diagnosis of GH deficiency.Finally, our study opens future perspectives in order to identify a transcriptional profile or specific genes specific to GHD condition. [edited by Author]XXXII cicl
Comparison of Two Methods for In Vivo Estimation of the Glenohumeral Joint Rotation Center (GH-JRC) of the Patients with Shoulder Hemiarthroplasty
No full textDetermination of an accurate glenohumeral-joint rotation center (GH-JRC) from marker data is essential for kinematic and dynamic analysis of shoulder motions. Previous studies have focused on the evaluation of the different functional methods for the estimation of the GH-JRC for healthy subjects. The goal of this paper is to compare two widely used functional methods, namely the instantaneous helical axis (IHA) and symmetrical center of rotation (SCoRE) methods, for estimating the GH-JRC in vivo for patients with implanted shoulder hemiarthroplasty. The motion data of five patients were recorded while performing three different dynamic motions (circumduction, abduction, and forward flexion). The GH-JRC was determined using the CT-images of the subjects (geometric GH-JRC) and was also estimated using the two IHA and SCoRE methods. The rotation centers determined using the IHA and SCoRE methods were on average 1.4760.62 cm and 2.0760.55 cm away from geometric GH-JRC, respectively. The two methods differed significantly (two-tailed p-value from paired t-Test ,0.02, post-hoc power ,0.30). The SCoRE method showed a significant lower (two-tailed p-value from paired t-Test ,0.03, post-hoc power ,0.68) repeatability error calculated between the different trials of each motion and each subject and averaged across all measured subjects (0.6260.10 cm for IHA vs. 0.4360.12 cm for SCoRE). It is concluded that the SCoRE appeared to be a more repeatable method whereas the IHA method resulted in a more accurate estimation of the GH-JRC for patients with endoprostheses.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin
Hemicellulases and auxiliary enzymes for improved conversion of lignocellulosic biomass to monosaccharides
No full textBackground
High enzyme loading is a major economic bottleneck for the commercial processing of pretreated lignocellulosic biomass to produce fermentable sugars. Optimizing the enzyme cocktail for specific types of pretreated biomass allows for a significant reduction in enzyme loading without sacrificing hydrolysis yield. This is especially important for alkaline pretreatments such as Ammonia fiber expansion (AFEX) pretreated corn stover. Hence, a diverse set of hemicellulases supplemented along with cellulases is necessary for high recovery of monosaccharides.
Results
The core fungal cellulases in the optimal cocktail include cellobiohydrolase I [CBH I; glycoside hydrolase (GH) family 7A], cellobiohydrolase II (CBH II; GH family 6A), endoglucanase I (EG I; GH family 7B) and β-glucosidase (βG; GH family 3). Hemicellulases tested along with the core cellulases include xylanases (LX1, GH family 10; LX2, GH family 10; LX3, GH family 10; LX4, GH family 11; LX5, GH family 10; LX6, GH family 10), β-xylosidase (LβX; GH family 52), α-arabinofuranosidase (LArb, GH family 51) and α-glucuronidase (LαGl, GH family 67) that were cloned, expressed and/or purified from different bacterial sources. Different combinations of these enzymes were tested using a high-throughput microplate based 24 h hydrolysis assay. Both family 10 (LX3) and family 11 (LX4) xylanases were found to most efficiently hydrolyze AFEX pretreated corn stover in a synergistic manner. The optimal mass ratio of xylanases (LX3 and LX4) to cellulases (CBH I, CBH II and EG I) is 25:75. LβX (0.6 mg/g glucan) is crucial to obtaining monomeric xylose (54% xylose yield), while LArb (0.6 mg/g glucan) and LαGl (0.8 mg/g glucan) can both further increase xylose yield by an additional 20%. Compared with Accellerase 1000, a purified cocktail of cellulases supplemented with accessory hemicellulases will not only increase both glucose and xylose yields but will also decrease the total enzyme loading needed for equivalent yields.
Conclusions
A diverse set of accessory hemicellulases was found necessary to enhance the synergistic action of cellulases hydrolysing AFEX pretreated corn stover. High glucose (around 80%) and xylose (around 70%) yields were achieved with a moderate enzyme loading (~20 mg protein/g glucan) using an in-house developed cocktail compared to commercial enzymes.Peer reviewed
BIOLOGICAL SIGNIFICANCE OF THE GROWTH HORMONE (GH) / INSULIN-LIKE GROWTH FACTOR AXIS (IGF)
No full textLa hormona del crecimiento (GH) y los factores de crecimiento similares a la insulina (IGF-I, IGF-II) regulan el crecimiento, la diferenciación, el metabolismo y la expresión génica en múltiples tipos de células a través de mecanismos autocrinos y/o paracrinos, además de la vía endocrina clásica. Este resumen presenta los resultados más significativos obtenidos por el autor y su grupo de investigación en relación con los mecanismos moleculares del eje GH/IGF y sus implicaciones en dos aspectos particulares. En primer lugar, su función como inmunomodulador del estrés nutricional en células linfoides y, en segundo lugar, su papel en el desarrollo de la enfermedad trofoblástica gestacional.The growth hormone (GH) and insulin-like growth factors (IGF-I, IGF-II) regulate growth, differentiation, metabolism, and gene expression in multiple cell types through autocrine and/or paracrine mechanisms, in addition to the classic endocrine pathway. This summary presents the most significant results obtained by the author and their research group regarding the molecular mechanisms of the GH/IGF axis with implications in two specific aspects. First, its function as an immunomodulator of nutritional stress in lymphoid cells, and second, its role in the development of gestational trophoblastic disease
Strategy for identification of novel fungal and bacterial glycosyl hydrolase hybrid mixtures that can efficiently saccharify pretreated lignocellulosic biomass
No full textWe have applied a rational four-step strategy to identify novel bacterial glycosyl hydrolases (GH), in combination with various fungal enzymes, in order to define an efficient enzyme cocktail to hydrolyze pretreated lignocellulosic biomass. The fungal cellulases include cellobiohydrolase I (CBH I; GH family 7A), cellobiohydrolase II (CBH II; GH family 6A), endoglucanase I (EG I; GH family 7B) and ß-glucosidase (ßG; GH family 3). Bacterial endocellulases (LC1 and LC2; GH family 5), ß-glucosidase (LßG; GH family 1), endoxylanases (LX1 and LX2; GH family 10) and ß-xylosidase (LßX; GH family 52) from multiple sources were cloned, expressed and purified as well. Enzymatic hydrolysis for various enzyme combinations was performed on Ammonia Fiber Expansion (AFEX) treated corn stover at various total protein loadings (30, 15 and 10 mg enzyme/g glucan). The optimal mass ratio of enzymes necessary for obtaining high glucan and xylan yields was determined using a suitable mixture design of experiments. The optimal hybrid enzyme mixtures contain fungal cellulases (78% of total protein loading), which include CBH I (loading ranging between 9-51% of total enzyme load), CBH II (9-51%), EG I (10-50%), and bacterial hemicellulases (22% of total protein loading) comprising of LXl (13%) and LßX (9%). The hybrid mixture works effectively at 50 °C and pH 4.5 to efficiently saccharify AFEX treated corn stover giving as high as 95% glucan and 65% xylan conversion, respectively. This strategy of screening enzyme mixtures on pretreated lignocellulose will ultimately help develop enzyme cocktails that can hydrolyze plant cell walls efficiently and economically to produce cellulosic ethanol.The final publication (Version of Record) is available at Springer via http://dx.doi.org/10.1007/s12155-009-9066-
THE MUSICAL-DRAMATURGIC CONCEPT OF THE MONOOPERA ATEH BY GH. CIOBANU IN CORRELATION WITH THE LITERARY SOURCE
No full textThe article is devoted to the peculiarities of the musical embodiment of the literary source in the mono-opera-ballet „Ateh or the revelations of the Khazar princess” by Gh. Ciobanu, based on three fragments from the lexicon-novel „Dictionary of the Khazars” by M. Pavic, a reference work of art of the end of the 20th century. Following from the genre characteristics of modern mono-operas, on the one hand, and on the exceptional qualities of Ateh’s image in the novel, on the other hand, the author reveals the basic principles of the composer’s approach to the literary text — selectivity, economy of verbal means, simplification of the content plan by eliminating the text with symbolic and mystical components and increasing the role of musical-dramatic means. The author considers various types of semantic relation between the text and music in the mono-opera — convergence (illustration, parallelism, association and others) and divergence of meanings. The author comes to the conclusion that the semantic concepts of the monoopera by Gh. Ciobanu occur at the intersection of the self-reflection principle, on the one hand, on the other hand — of the idea of transformations that moves the musical-dramaturgical process
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