bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Necrosis Factor-α Attenuates Thyroid Hormone-Induced Apoptosis in Vascular Endothelial Cell Line XLgoo Established from Xenopus Tadpole Tails
Authors: Mawaribuchi Shuuji , Tamura Kei , Okano Saori , Takayama Shutaro , Yaoita Yoshio , Shiba Tadayoshi , Takamatsu Nobuhiko , Ito Michihiko
Published: April 2008

Amphibian metamorphosis induced by T3 involves programmed cell death and the differentiation of various types of cells in degenerated and reconstructed tissues. However, the signaling pathway that directs the T3-dependent cell-fate determinations remains unclear. TNF-α is a pleiotropic cytokine that affects diverse cellular responses. Engagement of TNF-α with its receptor (TNFR1) causes intracellular apoptotic and/or survival signaling. To investigate TNF signaling functions during anuran metamorphosis, we first identified Xenopus laevis orthologs of TNF (xTNF)-α and its receptor. We found that xTNF-α activated nuclear factor-κB in X. laevis A6 cells through the Fas-associated death domain and receptor-interacting protein 1. Interestingly, xTNF-α mRNA in blood cells showed prominent expression at prometamorphosis during metamorphosis. Next, to elucidate the apoptotic and/or survival signaling induced by xTNF-α in an in vitro model of metamorphosis, we established a vascular endothelial cell line, XLgoo, from X. laevis tadpole tail. XLgoo cells formed actin stress fibers and elongated in response to xTNF-α. T3 induced apoptosis in these cells, but the addition of xTNF-α blocked the T3-induced apoptosis. In addition, treatment of the cells with T3 for 2 d induced the expression of thyroid hormone receptor-β and caspase-3, and this thyroid hormone receptor-β induction was drastically repressed by xTNF-α. Furthermore, in organ culture of the tail, xTNF-α significantly attenuated the tail degeneration induced by T3. These findings suggested that xTNF-α could protect vascular endothelial cells from apoptotic cell death induced by T3 during metamorphosis and thereby participate in the regulation of cell fate.
Corticotropin-Releasing Hormone Deficiency Is Associated with Reduced Local Inflammation in a Mouse Model of Experimental Colitis
Authors: Gay Jérôme , Kokkotou Efi , O’Brien Michael , Pothoulakis Charalabos , Karalis Katia P.
Published: April 2008

CRH, the hypothalamic component of the hypothalamic-pituitary adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. CRH is expressed in the intestine and up-regulated in patients with ulcerative colitis. However, its pathophysiological significance in intestinal inflammatory diseases has just started to emerge. In a mouse model of acute, trinitrobenzene sulfonic acid-induced experimental colitis, we demonstrate that, despite low glucocorticoid levels, CRH-deficient mice develop substantially reduced local inflammatory responses. These effects were shown by histological scoring of tissue damage and neutrophil infiltration. At the same time, CRH deficiency was found to be associated with higher serum leptin and IL-6 levels along with sustained anorexia and weight loss, although central CRH has been reported to be a strong appetite suppressor. Taken together, our results support an important proinflammatory role for CRH during mouse experimental colitis and possibly in inflammatory bowel disease in humans. Moreover, the results suggest that CRH is involved in homeostatic pathways that link inflammation and metabolism.
Spermatogenesis and Sertoli Cell Activity in Mice Lacking Sertoli Cell Receptors for Follicle-Stimulating Hormone and Androgen
Authors: Abel M. H. , Baker P. J. , Charlton H. M. , Monteiro A. , Verhoeven G. , De Gendt K. , Guillou F. , O’Shaughnessy P. J.
Published: April 2008

Spermatogenesis in the adult male depends on the action of FSH and androgen. Ablation of either hormone has deleterious effects on Sertoli cell function and the progression of germ cells through spermatogenesis. In this study we generated mice lacking both FSH receptors (FSHRKO) and androgen receptors on the Sertoli cell (SCARKO) to examine how FSH and androgen combine to regulate Sertoli cell function and spermatogenesis. Sertoli cell number in FSHRKO-SCARKO mice was reduced by about 50% but was not significantly different from FSHRKO mice. In contrast, total germ cell number in FSHRKO-SCARKO mice was reduced to 2% of control mice (and 20% of SCARKO mice) due to a failure to progress beyond early meiosis. Measurement of Sertoli cell-specific transcript levels showed that about a third were independent of hormonal action on the Sertoli cell, whereas others were predominantly androgen dependent or showed redundant control by FSH and androgen. Results show that FSH and androgen act through redundant, additive, and synergistic regulation of spermatogenesis and Sertoli cell activity. In addition, the Sertoli cell retains a significant capacity for activity, which is independent of direct hormonal regulation.
Coordinated Synchronization in the Electrically Coupled Network of Terminal Nerve Gonadotropin-Releasing Hormone Neurons as Demonstrated by Double Patch-Clamp Study
Authors: Haneda Kosuke , Oka Yoshitaka
Published: April 2008

The peptidergic neurons play important roles such as neuromodulatory and neuroendocrine functions in the central nervous system. However, our knowledge about the organization and the function of the peptidergic neuromodulator systems is still very poor. The terminal nerve GnRH peptidergic neurons of a teleost, the dwarf gourami (Colisa lalia), serve as an excellent model system for such study. The cell bodies are large and make up a tight cell cluster, and the easy access to the cell bodies on the ventral surface of the brain makes the electrophysiological measurements in a precisely controlled manner. Here we show direct evidence to demonstrate the electrical coupling and the synchronization of the neural firing activity among the terminal nerve GnRH neurons by using the double patch-clamp recording technique. The electrical coupling coefficient was strong enough (ranged from 0.083 to 0.370) to synchronize spontaneous firings of GnRH neurons in the cluster. A model, in which the firings in the cluster occur within a small time window (dozens of milliseconds), was verified by using the serial loose-seal extracellular patch-clamp recordings and the cross-correlogram analysis. The present findings provide several insights for understanding the physiological mechanisms and functional significance of synchronized activities in the peptidergic and/or aminergic neuromodulator system as well as in the peptidergic neuroendocrine cells.
Imaging Mass Spectrometry Reveals Unique Protein Profiles during Embryo Implantation
Authors: Burnum Kristin E. , Tranguch Susanne , Mi Deming , Daikoku Takiko , Dey S. K. , Caprioli Richard M.
Published: April 2008

A reciprocal interaction between the implantation-competent blastocyst and receptive uterus is an absolute requirement for implantation, a process crucial for pregnancy success. A comprehensive understanding of this interaction has yet to be realized. One major difficulty in clearly defining this discourse is the complexity of the implantation process involving heterogeneous cell types of both the uterus and blastocyst, each endowed with unique molecular signatures that show dynamic changes during the course of pregnancy. Whereas gene expression studies by in situ hybridization or immunohistochemistry have shown differential expression patterns of specific genes during implantation, there is no report how numerous signaling proteins are spatially displayed at specific times and stages of implantation in the context of blastocyst-uterine juxtaposition. Using in situ imaging (matrix assisted laser desorption/ionization) mass spectrometry directly on uterine sections, here we provide molecular composition, relative abundance, and spatial distribution of a large number of proteins during the periimplantation period. This approach has allowed us for the first time to generate in situ proteome profiles of implantation and interimplantation sites in mice in a region- and stage-specific manner with the progression of implantation. This application is reliable because patterns of expression of several proteins displayed by in situ imaging mass spectrometry correlate well with in situ hybridization results. More interestingly, the use of this approach has provided new insights regarding uterine biology of cytosolic phospholipase A2α null females that show implantation defects.
Bargaining for Absolutism: A Spanish Path to Nation-State and Empire Building
Authors: Irigoin Alejandra , Grafe Regina
Published: April 2008

Social scientists use the history of Spain and her empire as a standard against which they establish the relatively superior efficiency of Anglo-Saxon institutions. This historical “experiment” underpins the core argument of new institutional economic history. This essay argues that such comparisons are based on a misleading characterization of Spanish rule in the metropolis and overseas. For some time, historians of Spain and colonial Spanish America have emphasized that the Spanish system of governance was highly negotiated rather than absolutist. This essay confirms this view by analyzing the workings of the peninsular and colonial fiscal systems. Revenues were not extracted to Madrid but instead were widely redistributed across regions. Contrary to received wisdom, there was a great degree of local autonomy in managing and allocating these intraregional transfers of revenues. The crown barely controlled the system; yet it acted as the ultimate arbiter of a very flexible arrangement that effected the distribution of the fiscal burden across colonial regions and economic sectors. This setup explains the lack of serious challenges from within during three hundred years of imperial rule. Napoleon’s invasion of Spain in 1808 and the abduction of the king caused a major shock to this system of redistribution. The implosion of Spanish rule led to conflict over revenues and resources among constituent parts of the empire. The ensuing search for a legitimate replacement ruler consumed the following century in postcolonial Spanish America. A comparable pattern of constitutional failure, political instability, and poor economic performance was replicated in Spain throughout the nineteenth century.
Rethinking Negotiation and Coercion in an Imperial State
Authors: Marichal Carlos
Published: April 2008

By reinterpreting the recent literature on the fiscal history of Spain and Spanish America during the long span of the sixteenth and eighteenth centuries, Irigoin and Grafe have written a major revisionist essay that will probably change the way historians think about intra-imperial fiscal relations and that raises many important issues regarding the strategies of local elites within the imperial structure. They also demonstrate that the analysis of the internal dynamics of the Spanish empire can contribute forcefully to contemporary debates on the comparative study of eighteenth-century empires.

Nonetheless, numerous facets of the essay run counter to the findings of many historians who have laboriously reconstructed the Bourbon tax system in Spanish America. A reading of the historical literature produced over the last two decades suggests that while political negotiations between the Spanish monarchy and privileged corporations and urban governments were of great importance, it would be a mistake to discount the importance of coercion and censorship as essential and frequently used instruments of the crown and the powerful to maintain the status quo. These were common instruments in the metropolis but were not infrequently applied with singular severity in the colonies. In the case of Spanish America in the second half of the eighteenth century, the nature of coercion and the brutal response to popular protests (particularly tax revolts) have been analyzed by numerous historians but are downplayed in the essay under discussion. Similarly, it is important to note that most recent historical studies demonstrate that the fiscal reforms carried out by the Bourbon regime throughout Spanish America were much more homogeneous and successful in extracting a rapidly rising level of tax resources from the colonial population than the authors would appear to suggest.
National Narratives and the Politics of Inclusion: Historicizing American Literature Anthologies
Authors: Lockard Joe , Sandell Jillian
Published: April 2008

This essay discusses the history of American literature anthologies from the early nineteenth century to the late twentieth century; examines their racial and gender inclusions and exclusions; and argues that literary anthologies have played an important role in the production of the American, and more recently multicultural, national narrative.
Vectoring Genre and Character: A Pedagogical Model for Chaucer'sTroilus and Criseydeand Other Multigeneric Texts
Authors: Pugh Tison
Published: April 2008

Troilus and Criseyde is a work of magnificent scope and intimidating breadth. A strategy that I have found effective for addressing the potentially overwhelming pedagogical task of teaching this masterpiece is to ask students to analyze the relationships between genre and character. Through this process, I encourage students to engage in vectored analysis, which I describe as the examination of a text from at least two converging yet separate perspectives. Encouraging students to examine literature from complementary and vectoring perspectives enables them to make the cognitive leap from a static analysis of one issue to a more vibrant exploration of textual interplay. Vectored analysis provides a pedagogical foundation for students of all abilities to approach multigeneric texts and to reach deeper insights about them. In this essay, I demonstrate this approach with Chaucer's Troilus and Criseyde, but it could be readily reformulated for a range of multigeneric texts.
Controlling morpholino experiments: don't stop making antisense
Authors: Eisen Judith S. , Smith James C.
Published: April 2008

One of the most significant problems facing developmental biologists who do not work on an organism with well-developed genetics - and even for some who do - is how to inhibit the action of a gene of interest during development so as to learn about its normal biological function. A widely adopted approach is to use antisense technologies, and especially morpholino antisense oligonucleotides. In this article, we review the use of such reagents and present examples of how they have provided insights into developmental mechanisms. We also discuss how the use of morpholinos can lead to misleading results, including off-target effects, and we suggest controls that will allow researchers to interpret morpholino experiments correctly.
TheArabidopsis OBERON1andOBERON2genes encode plant homeodomain finger proteins and are required for apical meristem maintenance
Authors: Saiga Shunsuke , Furumizu Chihiro , Yokoyama Ryusuke , Kurata Tetsuya , Sato Shusei , Kato Tomohiko , Tabata Satoshi , Suzuki Mitsuhiro , Komeda Yoshibumi
Published: April 2008

Maintenance of the stem cell population located at the apical meristems is essential for repetitive organ initiation during the development of higher plants. Here, we have characterized the roles of OBERON1(OBE1) and its paralog OBERON2 (OBE2), which encode plant homeodomain finger proteins, in the maintenance and/or establishment of the meristems in Arabidopsis. Although the obe1 and obe2 single mutants were indistinguishable from wild-type plants, the obe1 obe2 double mutant displayed premature termination of the shoot meristem, suggesting that OBE1 and OBE2 function redundantly. Further analyses revealed that OBE1 and OBE2allow the plant cells to acquire meristematic activity via the WUSCHEL-CLAVATA pathway, which is required for the maintenance of the stem cell population, and they function parallel to the SHOOT MERISTEMLESS gene, which is required for preventing cell differentiation in the shoot meristem. In addition, obe1 obe2 mutants failed to establish the root apical meristem, lacking both the initial cells and the quiescent center. In situ hybridization revealed that expression of PLETHORA and SCARECROW, which are required for stem cell specification and maintenance in the root meristem, was lost from obe1 obe2 mutant embryos. Taken together, these data suggest that the OBE1 and OBE2 genes are functionally redundant and crucial for the maintenance and/or establishment of both the shoot and root meristems.
Dkk1andWnt3interact to control head morphogenesis in the mouse
Authors: Lewis Samara L. , Khoo Poh-Lynn , De Young R. Andrea , Steiner Kirsten , Wilcock Chris , Mukhopadhyay Mahua , Westphal Heiner , Jamieson Robyn V. , Robb Lorraine , Tam Patrick P. L.
Published: April 2008

Loss of Dkk1 results in ectopic WNT/β-catenin signalling activity in the anterior germ layer tissues and impairs cell movement in the endoderm of the mouse gastrula. The juxtaposition of the expression domains of Dkk1 and Wnt3 is suggestive of an antagonist-agonist interaction. The downregulation of Dkk1 when Wnt3 activity is reduced reveals a feedback mechanism for regulating WNT signalling. Compound Dkk1;Wnt3 heterozygous mutant embryos display head truncation and trunk malformation, which are not found in either Dkk1+/- or Wnt3+/- embryos. Reducing the dose of Wnt3 gene in Dkk1-/- embryos partially rescues the truncated head phenotype. These findings highlight that head development is sensitive to the level of WNT3 signalling and that DKK1 is the key antagonist that modulates WNT3 activity during anterior morphogenesis.
Single-Step Scalable-Throughput Molecular Screening for Huntington Disease
Authors: Teo Clara R L , Wang Wen , Yang Law Hai , Lee Caroline G , Chong Samuel S
Published: April 2008

Background: Huntington disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by an unstable expansion of the CAG trinucleotide repeat in exon 1 of the HTT (huntingtin) gene and typically has an adult onset. Molecular diagnosis and screening for HD currently involve separate amplification and detection steps.

Methods: We evaluated a novel, rapid microplate-based screening method for HD that combines the amplification and detection procedures in a single-step, closed-tube format. We carried out both the PCR for the HTT CAG-repeat region and the subsequent automated melting-curve analysis of the amplicon in the same wells on the plate. To establish cutoff melting temperatures (Tms) for each allelic class, we used a panel of reference DNA samples of known CAG-repeat sizes that represent a range of HTT alleles [normal (≤26 repeats), intermediate (27–35 repeats), reduced penetrance expanded (36–39 repeats), and fully penetrant expanded (≥40 repeats)]. We also measured well-to-well variation in Tm across the thermal block and validated cutoff Tms with DNA samples from 5 different populations. We also conducted a blinded validation analysis of clinical samples from an additional 40 HD-affected and 30 unaffected individuals.

Results: We observed a strong correlation between CAG-repeat size and amplicon Tm among the reference DNA samples. Use of the Tm cutoffs we established revealed that 5 samples from unaffected individuals had been misclassified as affected (1.1% false-positive rate). All samples from HD-affected and unaffected individuals were correctly identified in the blinded analysis.

Conclusions: This simple and scalable homogeneous assay may serve as a convenient, rapid, and accurate screen to detect the presence of pathologic expanded HD alleles in symptomatic patients.
Modified HPLC-Electrospray Ionization/Mass Spectrometry Method for HbA1c Based on IFCC Reference Measurement Procedure
Authors: Kaiser Patricia , Akerboom Theodorus , Molnar Petra , Reinauer Hans
Published: April 2008

Background: Monitoring of hemoglobin A1c (HbA1c) is important in the management of diabetes. The IFCC reference measurement procedure for HbA1c is based on the ratio of glycated to nonglycated N-terminal hexapeptides of the β-chains of hemoglobin after digestion with Glu-C endoproteinase. We developed a modification of the original reference measurement procedure with HPLC-electrospray ionization/mass spectrometry (ESI/MS).

Method: We performed chromatographic separation of the hexapeptides using a C12 reversed-phase column and a binary gradient system consisting of a mixture of H2O/acetonitrile/formic acid.

Results: Using this method, we obtained higher signal intensities and improved system stability compared with the reference measurement procedure. In the range of 3% to 14% HbA1c, intralaboratory CVs were 0.71% to 1.86%. Deviations from IFCC target values were −0.87 to 1.00 relative %. These values fulfill acceptability criteria for HbA1c determination set by the IFCC Working Group on HbA1c Standardization.

Conclusions: This procedure for the determination of HbA1c improves the existing reference measurement procedure.
Medium Term Production Scheduling of a Hydro-thermal System under Uncertainty using Nested Benders Decomposition (Produktionsplanung eines hydro-thermischen Kraftwerkssystems unter Unsicherheit für mittlere Planungshorizonte unter Anwendung der Nested Benders Decomposition)
Authors: Nolde Kristian , Uhr Markus , Morari Manfred
Published: April 2008

We present a multistage stochastic programming formulation for monthly production planning of a hydro-thermal system. The formulation explicitly considers the stochasticity from variations in water reservoir inflows and electric energy demand. The problem is solved efficiently applying Nested Benders Decomposition. The solution is implemented in a model predictive control scheme. Closed loop simulation results are shown to illustrate performance of the controller. The solutions of the medium term scheduling problem can then be used as reference inputs for short term planning and lower level controllers to avoid greedy usage of reservoir water.

Die Veröffentlichung stellt eine Multistage-Stochastic-Programming Formulierung zur Lösung eines monatlichen Produktionsplanungsproblems für ein hydro-thermisches Kraftwerkssystem vor. Diese Modellierung beinhaltet explizit die stochastischen Variationen der Zuflüsse zu den Wasserspeichern, sowie die Schwankungen des elektrischen Energiebedarfs. Das Problem wird unter Anwendung der Nested Benders Decomposition effizient gelöst. Simulationen des geschlossenen Regelkreises werden vorgestellt, um die Funktionsweise des Reglers zu zeigen. Die Lösungen des Problems für mittlere Zeithorizonte können als Eingangssignale für Regler mit kurzen Zeithorizonten genutzt werden. Somit wird ein Aufbrauchen des gespeichertenWassers durch zu kurze Planungshorizonte vermieden.
Ein neues Werkzeug zur Produktionsplanung (A New Tool for Production Planning)
Authors: Metz Rudolf
Published: April 2008

Für Mehrproduktanlagen in der Prozessindustrie hat Bayer Technology Services das optimierende Planungswerkzeug BayAPS®-PP entwickelt. Kernstück der Software BayAPS®-PP ist ein neuer und schneller Algorithmus. Dieser verteilt die verfügbare Produktionskapazität einer Mehrproduktanlage auf die verschiedenen Produkte so, dass - je nach Blickwinkel - der gesamte Service-Level bzw. der gesamte erwartete Absatz maximiert wird. Dabei werden die für die Prozessindustrie typischen Nebenbedingungen beachtet.

For multi-product lines in the process industry Bayer Technology Services developed the optimization planning tool BayAPS®-PP. The core of the software BayAPS®-PP is a new and fast algorithm that distributes the production capacity of a multi-product line to the several products such that - depending on the perspective - the total service level or the totally expected sales are maximized. The algorithm obeys constraints, which are typical for the process industry.
Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.
Authors: Aksglaede Lise , Jensen Rikke Beck , Carlsen Elisabeth , Kok Petra , Keenan Daniel M , Veldhuis Johannes , Skakkebæk Niels E , Juul Anders
Published: April 2008

Objective

The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary–gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes.

Design

Cross-sectional study.

Methods

In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined.

Results

Basal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibullλanalysis. There was no difference between approximate entropy ratios or Weibullγanalyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution.

Conclusion

In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic–pituitary–gonadal axis has undergone functional changes.
Mifepristone for ectopic ACTH secretion in metastatic endocrine carcinomas: report of two cases.
Authors: Cassier Philippe A , Abou-Amara-Olivieri Sawsan , Artru Pascal , Lapalus Marie-George , Riou Jean-Paul , Lombard-Bohas Catherine
Published: April 2008

Ectopic adrenocorticotropin secretion (EAS) remains a therapeutic challenge whenever the tumor responsible for the syndrome is not amenable to curative resection. Two cases of EAS related to metastatic foregut-derived endocrine carcinomas led us to use mifepristone, an antagonist of both progesterone and glucocorticoids. Mifepristone clearly improved skin lesions and diabetes associated with hypercorticism. The beneficial effect lasted for about 10 months. In both cases, recurrent hypertension and hypokalemia eventually required adrenalectomy.
A novel missense mutation in GALNT3 causing hyperostosis–hyperphosphataemia syndrome.
Authors: Olauson Hannes , Krajisnik Tijana , Larsson Charlotta , Lindberg Bengt , Larsson Tobias E
Published: April 2008

Objective

Hyperostosis–hyperphosphataemia syndrome (HHS) is a rare hereditary disorder characterized by hyperphosphataemia, inappropriately normal or elevated 1,25-dihydroxyvitamin D3 and localized painful cortical hyperostosis. HHS was shown to be caused by inactivating mutations in GALNT3, encoding UDP-N-acetyl-α-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3). Herein, we sought to identify the genetic cause of hyperphosphataemia and tibial hyperostosis in a 19-year-old girl of Colombian origin.

Methods

Genomic DNA was extracted and sequencing analysis of the GALNT3 and fibroblast growth factor 23 (FGF23) genes performed. Serum levels of intact and C-terminal FGF23 were measured using two different ELISA methods.

Results

Mutational analysis identified a novel homozygous missense mutation in exon 6 of GALNT3 (1584 G>A), leading to an amino acid shift from Arg to His at residue 438 (R438H). The mutation was not found in over 200 control alleles or in any single nucleotide polymorphism databases. The R438 residue is highly conserved throughout species and in all known GalNAc-transferase family members. Modelling predicted the substitution deleterious for protein structure. Importantly, the phosphaturic factor FGF23 was differentially processed, as reflected by low intact (15 pg/ml) but high C-terminal (839 RU/ml) serum FGF23 levels.

Conclusions

We report on the first missense mutation in GALNT3 giving rise to HHS, since previous GALNT3 mutations in HHS caused aberrant splicing or premature truncation of the protein. The R438H substitution likely abrogates GALNT3 activity, in turn causing enhanced FGF23 degradation and subsequent hyperostosis/hyperphosphataemia.
Decreased insulin sensitivity in small for gestational age males treated with GH and preterm untreated males: a study in young adults.
Authors: Rotteveel J , van Weissenbruch M M , Delemarre-Van de Waal H A
Published: April 2008

Background

Low birth weight and preterm birth are associated with growth delay as well as the development of insulin resistance. Insulin resistance is especially seen in subjects with catch-up growth. GH therapy induces growth in short subjects with low birth weight at term, but little is known about the long-term effects on insulin sensitivity. GH therapy is now also proposed for preterms that remain short.

Methods

We investigated insulin sensitivity using the gold standard hyperinsulinemic-euglycemic clamp technique in 10 young adult males born small for gestational age (SGA) who had been treated with GH during childhood (GH) in comparison with 15 males born preterm AGA (premAGA), 13 males born preterm SGA (premSGA), and 15 males born at term with normal birth weight (CON). Furthermore, we investigated the presence of the metabolic syndrome.

Results

Insulin sensitivity was decreased in premAGA, premSGA, and GH subjects compared with CON males. The metabolic syndrome was not present in any of the groups.

Conclusion

Insulin sensitivity is decreased in GH-treated SGA born males as well as in preterm born males. With respect to the SGA subjects, whether the difference results from perinatal-, postnatal-, or GH therapy-related factors are not known. With respect to the preterm born subjects, close surveillance is needed when commencing GH therapy.
Effects of maternal cold exposure and nutrient restriction on the ghrelin receptor, the GH–IGF axis, and metabolic regulation in the postnatal ovine liver
Authors: Hyatt M A , Butt E A , Budge H , Stephenson T , Symonds M E
Published: April 2008

Maternal cold exposure of pregnant sheep promotes fetal growth, whereas nutrient restriction (NR) can reverse this effect. The present study was designed to establish whether cold exposure induced by winter shearing of the mother at 70 days gestation (term=147 days), with or without NR (induced by a 50% reduction in maternal food intake from 110 days gestation), has specific effects on mRNA abundance of hepatic genes related to growth and liver energy metabolism that could regulate postnatal body and liver growth. Measurements of hepatic gene expression for the GH secretagog receptor-1a (GHSR-1A), peroxisome proliferator-activated receptor (PPAR)α, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase activity together with glycogen content were made in the livers of offspring at 1 and 30 days of age. Maternal NR reduced liver mass at day 1, whereas offspring of cold-exposed mothers had larger livers at day 30 irrespective of maternal diet. Cold exposure resulted in the up-regulation of GHSR-1A mRNA abundance and reduced glucose-6-phosphatase activity at 1, but not 30 days of age, whereas IGF-II mRNA was decreased at 1 and 30 days. PPARα mRNA abundance was enhanced, while PEPCK was reduced in 30-day old offspring of cold-exposed mothers. NR caused reductions in IGF-I mRNA and, at 1-day postnatal age, down-regulated GHR, while, at 30 days, reduced GHSR-1A gene expression and hepatic glycogen content. In conclusion, we have shown that maternal cold exposure and NR have different effects on the hepatic GH–IGF and metabolic axis that may contribute to changes in liver growth over the first month of life.
S-adenosylhomocysteine treatment of adult female fibroblasts alters X-chromosome inactivation and improves in vitro embryo development after somatic cell nuclear transfer
Authors: Jeon Byeong-Gyun , Coppola Gianfranco , Perrault Steven D , Rho Gyu-Jin , Betts Dean H , King W Allan
Published: April 2008

The poor outcome of somatic cell nuclear transfer (SCNT) is thought to be a consequence of incomplete reprogramming of the donor cell. The objective of this study was to investigate the effects of treatment withS-adenosylhomocysteine (SAH) a DNA demethylation agent, on DNA methylation levels and X-chromosome inactivation status of bovine female fibroblast donor cells and the subsequent impact on developmental potential after SCNT. Compared with non-treated controls, the cells treated with SAH revealed (i) significantly (P<0.05) reduced global DNA methylation, (ii) significantly (∼1.5-fold) increased telomerase activity, (iii) diminished distribution signals of methylated histones H3-3mK9 and H3-3mK27 on the presumptive inactive X-chromosome (Xi), (iv) alteration in the replication pattern of the Xi, and (v) elevation of transcript levels for X-chromosome linked genes,ANT3,MECP2,XIAP,XIST, andHPRT. SCNT embryos produced with SAH-treated donor cells compared with those derived from untreated donor cells revealed (i) similar cleavage frequencies, (ii) significant elevation in the frequencies of development of cleaved embryos to hatched blastocyst stage, and (iii) 1.5-fold increase in telomerase activity. We concluded that SAH induces global DNA demethylation that partially reactivates the Xi, and that a hypomethylated genome may facilitate the nuclear reprogramming process.
Expression of NANOG, but not POU5F1, points to the stem cell potential of primitive germ cells in neonatal pig testis
Authors: Goel Sandeep , Fujihara Mayako , Minami Naojiro , Yamada Masayasu , Imai Hiroshi
Published: April 2008

Gonocytes are primitive germ cells that are present in the neonatal testis and are committed to male germline development. Gonocytes differentiate to spermatogonia, which establish and maintain spermatogenesis in the postnatal testis. However, it is unknown whether large animal species have pluripotency-specific proteins in the testis.NanogandPou5f1(Oct3/4) have been identified as transcription factors essential for maintaining pluripotency of embryonic stem cells in mice. Here, we show that NANOG protein was expressed in the germ cells of neonatal pig testes, but was progressively lost with age. NANOG was expressed in most of the lectinDolichos biflorusagglutinin- and ZBTB16-positive gonocytes, which are known gonocyte-specific markers in pigs. NANOG was also expressed in Sertoli and interstitial cells of neonatal testes. Interestingly, POU5F1 expression was not detected at either the transcript or the protein level in neonatal pig testis. In the prepubertal testis, NANOG and POU5F1 proteins were primarily detected in differentiated germ cells, such as spermatocytes and spermatids, and rarely in undifferentiated spermatogonia. By using a testis transplantation assay, we found that germ cells from 2- to 4-day-old pigs could colonize and proliferate in the testes of the recipient mice, suggesting that primitive germ cells from neonatal pig testes have stem cell potential.
Changes in LH secretion in response to an estradiol challenge in male- and female-oriented rams and in ewes
Authors: Stormshak F , Estill C T , Resko J A , Roselli C E
Published: April 2008

Two experiments were conducted to determine whether an estradiol challenge could cause a female-type LH surge in castrated male- and female-oriented rams (MORs and FORs). Administration of 17β-estradiol to castrated MORs and FORs and ovariectomized ewes caused an initial reduction in LH secretion followed for 12–20 h by a surge release of LH in the ewes. No surge release of LH occurred in the MORs and FORs. The pattern of changes in LH secretion within rams and ewes did not differ between the breeding and nonbreeding seasons. Treatment failed to elicit female-typical receptive sexual behaviors in the rams but did stimulate increased sexual receptivity in the ewes as determined by the measures of responsiveness to the teaser ram. Overall, no differences were found in hypothalamic–hypophyseal function in response to exogenous estradiol between MORs and FORs. These data are interpreted to suggest that in contrast to sexual attraction, the neural mechanisms controlling the LH surge and female receptivity are defeminized in MORs.
Glucogenic supply increases ovulation rate by modifying follicle recruitment and subsequent development of preovulatory follicles without effects on ghrelin secretion
Authors: Letelier C , Mallo F , Encinas T , Ros J M , Gonzalez-Bulnes A
Published: April 2008

This study determined the effects of short-term energy inputs on ghrelin secretion and possible links with changes in the follicle population or the ovulation rate. Oestrous cycle was synchronized in 16 Manchega sheep using progestagen sponges and cloprostenol. Half of the animals were treated from days 0 to 4 by the oral administration, twice daily, of 200 ml of a glucogenic mixture containing 70% of glycerol, 20% of 1,2-propanediol and 10% of water; the control group received 200 ml water. The mean (±s.e.m.) plasma glucose increased immediately after the first administration (3.9±0.3 vs 3.0±0.1 mmol/l in control group, P<0.05), remaining statistically different during the treatment. However, plasma ghrelin levels were similar in both groups. On the other hand, the results indicated that short-term energy inputs modify ovulation rate (1.9±0.1 vs 1.3±0.2 in control group, P<0.05) by increasing the number of follicles able to be selected to ovulate during the period of treatment (≥4 mm in size; 5.9±0.6 vs 4.3±0.4 at day 2, P<0.05). After sponge withdrawal, the number of these follicles decreased throughout follicular phase (5.8±0.8 to 1.5±0.4, P<0.0005) while the number of large follicles increased (≥6 mm in size; 0.8±0.4 to 2.0±0.3, P<0.05); this would indicate an active growth of preovulatory follicles that were not found in the control group. Thus, the increases of ovulation rate by high-energy inputs would be caused by an enhancement in the developmental competence of preovulatory follicles.
Efficient Serum-Free Derivation of Oligodendrocyte Precursors from Neural Stem Cell-Enriched Cultures
Authors: Rao Rajesh C. , Boyd Justin , Padmanabhan Raji , Chenoweth Josh G. , McKay Ronald D.
Published: April 2008

Oligodendrocytes derived in the laboratory from stem cells have been proposed as a treatment for acute and chronic injury to the central nervous system. Platelet-derived growth factor (PDGF) receptor α (PDGFRα) signaling is known to regulate oligodendrocyte precursor cell numbers both during development and adulthood. Here, we analyze the effects of PDGFRα signaling on central nervous system (CNS) stem cell-enriched cultures. We find that AC133 selection for CNS progenitors acutely isolated from the fetal cortex enriches for PDGF-AA-responsive cells. PDGF-AA treatment of fibroblast growth factor 2-expanded CNS stem cell-enriched cultures increases nestin+ cell number, viability, proliferation, and glycolytic rate. We show that a brief exposure to PDGF-AA rapidly and efficiently permits the derivation of O4+ oligodendrocyte-lineage cells from CNS stem cell-enriched cultures. The derivation of oligodendrocyte-lineage cells demonstrated here may support the effective use of stem cells in understanding fate choice mechanisms and the development of new therapies targeting this cell type.
Platelet-Derived Growth Factor-D Overexpression Contributes to Epithelial-Mesenchymal Transition of PC3 Prostate Cancer Cells
Authors: Kong Dejuan , Wang Zhiwei , Sarkar Sarah H. , Li Yiwei , Banerjee Sanjeev , Saliganan Allen , Kim Hyeong-Reh Choi , Cher Michael L. , Sarkar Fazlul H.
Published: April 2008

The majority of human malignancies are believed to have epithelial origin, and the progression of cancer is often associated with a transient process named epithelial-mesenchymal transition (EMT). EMT is characterized by the loss of epithelial markers and the gain of mesenchymal markers that are typical of “cancer stem-like cells,” which results in increased cell invasion and metastasis in vivo. Therefore, it is important to uncover the mechanistic role of factors that may induce EMT in cancer progression. Studies have shown that platelet-derived growth factor (PDGF) signaling contributes to EMT, and more recently, PDGF-D has been shown to regulate cancer cell invasion and angiogenesis. However, the mechanism by which PDGF-D promotes invasion and metastases and whether it is due to the acquisition of EMT phenotype remain elusive. For this study, we established stably transfected PC3 cells expressing high levels of PDGF-D, which resulted in the significant induction of EMT as shown by changes in cellular morphology concomitant with the loss of E-cadherin and zonula occludens-1 and gain of vimentin. We also found activation of mammalian target of rapamycin and nuclear factor-κB, as well as Bcl-2 overexpression, in PDGF-D PC3 cells, which was associated with enhanced adhesive and invasive behaviors. More importantly, PDGF-D-overexpressing PC3 cells showed tumor growth in SCID mice much more rapidly than PC3 cells. These results provided a novel mechanism by which PDGF-D promotes EMT, which in turn increases tumor growth, and these results further suggest that PDGF-D could be a novel therapeutic target for the prevention and/or treatment of prostate cancer.

Disclosure of potential conflicts of interest is found at the end of this article.
Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Mediate Human Stem Cell Tropism to Malignant Solid Tumors
Authors: Gutova Margarita , Najbauer Joseph , Frank Richard T. , Kendall Stephen Edward , Gevorgyan Anna , Metz Marianne Z. , Guevorkian Mark , Edmiston Marissa , Zhao Donghong , Glackin Carlotta A. , Kim Seung U. , Aboody Karen S.
Published: April 2008

Human neural and mesenchymal stem cells have been identified for cell-based therapies in regenerative medicine and as vehicles for delivering therapeutic agents to areas of injury and tumors. However, the signals required for homing and recruitment of stem cells to these sites are not well understood. Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) are involved in chemotaxis and cell guidance during normal development and are upregulated in invasive tumors. Here we provided evidence that activation of uPA and uPAR in malignant solid tumors (brain, lung, prostate, and breast) augments neural and mesenchymal stem cell tropism. Expression levels of uPAR on human solid tumor cell lines correlated with levels of uPA and soluble uPAR in tumor cell-conditioned media. Cytokine expression profiles of these tumor-conditioned media were determined by protein arrays. Among 79 cytokines investigated, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 were the most highly expressed cytokines in uPAR-positive tumors. We provided evidence that human recombinant uPA induced stem cell migration, whereas depletion of uPA from PC-3 prostate cancer cell-conditioned medium blocked stem cell migration. Furthermore, retrovirus-mediated overexpression of uPA and uPAR in neuroblastoma (NB1691) cells induced robust migration of stem cells toward NB1691 cell-conditioned media, compared with media derived from wild-type NB1691 cells. We conclude that expression of uPA and uPAR in cancer cells underlies a novel mechanism of stem cell tropism to malignant solid tumors, which may be important for development of optimal stem cell-based therapies.

Disclosure of potential conflicts of interest is found at the end of this article.
Totipotency/Pluripotency and Patentability
Authors: Denker Hans-Werner
Published: April 2008

In their article entitled “Commentary: Is totipotency of a human cell a sufficient reason to exclude its patentability under the European law” (Stem Cells 2007;25:3026–3028), K.T. Vrtovec and B. Vrtovec conclude that arguments based on differentiation potential should not be an obstacle to patenting human embryonic stem cells (and related cells referred to as totipotent or pluripotent). While concentrating on formal legal aspects, however, these authors fail to consider a major biological and ethical argument already found in the literature, namely that an obstacle to patenting is to be seen in the potential of cells (e.g., of embryonic stem cell lines), if this potential allows (re)constitution of an embryo when tetraploid complementation is performed.

Disclosure of potential conflicts of interest is found at the end of this article.
Social structure of Alouatta guariba clamitans: a group with a dominant female
Authors: Miranda João M. D. , Bernardi Itiberê P. , Moro-Rios Rodrigo F. , Aguiar Lucas M. , Ludwig Gabriela , Passos Fernando C.
Published: April 2008

No abstract
Further information on Neotropical monkeys reported in the XVI century
Authors: Urbani Bernardo
Published: April 2008

No abstract
The meanings of Cacajao and Uacari: folk etymology in Neotropical primate taxonomy
Authors: Barnett Adrian A.
Published: April 2008

No abstract
The parasite behavior hypothesis and the use of sleeping sites by black howler monkeys (Alouatta caraya) in a discontinuous forest
Authors: Kowalewski Martin , Zunino Gabriel E.
Published: April 2008

No abstract
Discriminative feeding on legumes by mantled howler monkeys (Alouatta palliata) may select for persistence
Authors: Jones Clara B.
Published: April 2008

No abstract
Predation of a bearded saki (Chiropotes utahicki) by a harpy eagle (Harpia harpyja)
Authors: Martins Simone Souza , Lima Eldianne Moreira , Silva Jr José Sousa
Published: April 2008

No abstract
Cytochrome b sequences show subdivision between populations of the brown howler monkey (Alouatta guariba) from Rio de Janeiro and Santa Catarina, Brazil
Authors: Harris Eugene E. , Gifalli-Iughetti Cristiani , Braga Zelinda Hirano , Koiffmann Célia P.
Published: April 2008

No abstract
Formas não usuais para a obtenção de água por Alouatta guariba clamitans em ambiente de floresta com araucária no sul do Brasil
Authors: Miranda João M. D. , Moro-Rios Rodrigo F. , Bernardi Itiberê P. , Passos Fernando C.
Published: April 2008

No abstract
An update on the distribution of primates of the Tapajós-Xingu interfluvium, central Amazonia
Authors: Pimenta Flávio Eduardo , Silva Jr José Souza
Published: April 2008

No abstract
Novos registros de primatas no Parque Nacional do Itatiaia, com ênfase em Brachyteles arachnoides (Primates, Atelidae)
Authors: Loretto Diogo , Rajão Henrique
Published: April 2008

No abstract
Dieta, forrajeo y presupuesto de tiempo en cotoncillos (Callicebus discolor) del Parque Nacional Yasuní en la Amazonia Ecuatoriana
Authors: Carrillo-Bilbao Gabriel , Di Fiore Anthony , Fernández-Duque Eduardo
Published: April 2008

No abstract
Male tenure and reproductive success in single-male vs. multi-male groups of free-ranging howling monkeys in Costa Rica
Authors: Clarke Margaret R. , Glander Kenneth E.
Published: April 2008

No abstract
Estudos preliminares da presença de sagüis no município de Bauru, São Paulo, Brasil
Authors: De Paula Hugo Medeiros Garrido , Távora Renata Souza , Almeida Marcos Vinícius , Pelegrini Larissa Sbeghen , Silva Graziela Valença , Zaganini Rosângela Lopes , Lucindo Anderson
Published: April 2008

No abstract
Making sustainable water and sanitation in the Peruvian Andes: an intervention model
Authors: Campos Marco
Published: April 2008

Sustainability of water supplies in remote rural communities is problematic and resource consuming. CARE has a long history of working hand in hand with remote rural communities and devising programs tailored to their needs. We present here an intervention that integrates development of water supplies and sanitation, with operation and maintenance skills development and training of health promoters that can educate from within the community that ensures the sustainability of drinking water supply systems in rural communities. The training used is innovative in that it uses a series of video-workshops which are found to be particularly useful in communities with high illiteracy rates.