bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the TGF-beta1 system in human testicular pathologies
Authors: Gonzalez Candela R , Matzkin María E , Frungieri Mónica B , Terradas Claudio , Ponzio Roberto , Puigdomenech Elisa , Levalle Oscar , Calandra Ricardo S , Gonzalez-Calvar Silvia I 
Published: December 2010

Abstract

Background
In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertility.

Methods
Specific immunostaining of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-β1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR.

Results
Immunohistochemical studies revealed that TGF-β1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-β1 signaling, are also detected in both their phosphorylated (activated) and dephosphorylated form in all samples TGF-β1, ALK-1 and endoglin gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither TGFBRII nor ALK-5 gene expression showed significant differences between pathologies. A significant correlation between ALK-1 and endoglin expression was observed.

Conclusions
In conclusion, the high levels of mRNA and protein expression of the TGF-β1 system in patients with LCH, particularly ALK1 and its correlation with endoglin, suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia.
Fibrillin assemblies: extracellular determinants of tissue formation and fibrosis
Authors: Olivieri Jacopo , Smaldone Silvia , Ramirez Francesco 
Published: December 2010

AbstractThe extracellular matrix (ECM) plays a key role in tissue formation, homeostasis and repair, mutations in ECM components have catastrophic consequences for organ function and therefore, for the fitness and survival of the organism. Collagen, fibrillin and elastin polymers represent the architectural scaffolds that impart specific mechanic properties to tissues and organs. Fibrillin assemblies (microfibrils) have the additional function of distributing, concentrating and modulating local transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signals that regulate a plethora of cellular activities, including ECM formation and remodeling. Fibrillins also contain binding sites for integrin receptors, which induce adaptive responses to changes in the extracellular microenvironment by reorganizing the cytoskeleton, controlling gene expression, and releasing and activating matrix-bound latent TGF-β complexes. Genetic evidence has indicated that fibrillin-1 and fibrillin-2 contribute differently to the organization and structural properties of non-collagenous architectural scaffolds, which in turn translate into discrete regulatory outcomes of locally released TGF-β and BMP signals. Additionally, the study of congenital dysfunctions of fibrillin-1 has yielded insights into the pathogenesis of acquired connective tissue disorders of the connective tissue, such as scleroderma. On the one hand, mutations that affect the structure or expression of fibrillin-1 perturb microfibril biogenesis, stimulate improper latent TGF-β activation, and give rise to the pleiotropic manifestations in Marfan syndrome (MFS). On the other hand, mutations located around the integrin-binding site of fibrillin-1 perturb cell matrix interactions, architectural matrix assembly and extracellular distribution of latent TGF-β complexes, and lead to the highly restricted fibrotic phenotype of Stiff Skin syndrome. Understanding the molecular similarities and differences between congenital and acquired forms of skin fibrosis may therefore provide new therapeutic tools to mitigate or even prevent disease progression in scleroderma and perhaps other fibrotic conditions.
GnRH Receptor Gene Expression in the Developing Rat Hippocampus: Transcriptional Regulation and Potential Roles in Neuronal Plasticity
Authors: Schang Anne-Laure , Ngô-Muller Valérie , Bleux Christian , Granger Anne , Chenut Marie-Claude , Loudes Catherine , Magre Solange , Counis Raymond , Cohen-Tannoudji Joëlle , Laverrière Jean-Noël 
Published: December 2010

AbstractIn the pituitary of mammals, the GnRH receptor (GnRHR) plays a primary role in the control of reproductive function. It is further expressed in the hippocampus, where its function, however, is not well defined. By quantitative RT-PCR analyses, we demonstrate herein that the onset of GnRHR gene (Gnrhr) expression in the rat hippocampus was unexpectedly delayed as compared to the pituitary and only occurred after birth. Using a previously described transgenic mouse model bearing the human placental alkaline phosphatase reporter gene under the control of the rat Gnrhr promoter, we established a positive correlation between the temporal pattern of Gnrhr mRNA levels and promoter activity in the hippocampal formation. The gradual appearance of human placental alkaline phosphatase transgene expression occurred simultaneously in the hippocampus and interconnected structures such as the lateral septum and the amygdala, coinciding with the establishment of hippocampo-septal projections. Analysis of transcription factors together with transient transfection assays in hippocampal neurons indicated that the combinatorial code governing the hippocampus-specific expression of the Gnrhr is distinct from the pituitary, likely involving transactivating factors such as NUR77, cyclic AMP response element binding protein, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene homolog. A silencing transcription factor acting via the -3255/-1135 promoter region of the Gnrhr may be responsible for the transcriptional repression observed around birth. Finally, GnRH directly stimulated via activation of its receptor the expression of several marker genes of neuronal plasticity such as Egr1, synaptophysin, and spinophilin in hippocampal primary cultures, suggesting a role for GnRHR in neuronal plasticity. Further characterization of these mechanisms may help unravel important functions of GnRH/GnRHR signaling in the brain.
Activation of Type 1 CRH Receptor Isoforms Induces Serotonin Release from Human Carcinoid BON-1N Cells: An Enterochromaffin Cell Model
Authors: Wu S. Vincent , Yuan Pu-Qing , Lai Jim , Wong Kelvin , Chen Monica C. , Ohning Gordon V. , Taché Yvette 
Published: December 2010

AbstractCRH and 5-hydroxytryptamine (5-HT) are expressed in human colonic enterochromaffin (EC) cells, but their interactions at the cellular level remain largely unknown. The mechanistic and functional relationship between CRH and 5-HT systems in EC cells was investigated in a human carcinoid cloned BON cell line (BON-1N), widely used as an in vitro model of EC cell function. First, we identified multiple CRH1 splice variants, including CRH1a, CRH1c, CRH1f, and a novel form lacking exon 4, designated here as CRH1i, in the BON-1N cells. The expression of CRH1i was also confirmed in human brain cortex, pituitary gland, and ileum. Immunocytochemistry and immunoblot analysis confirmed that BON-1N cells were CRH1 and 5-HT positive. CRH, urocortin (Ucn)-1, and cortagine, a selective CRH1 agonist, all increased intracellular cAMP, and this concentration-dependent response was inhibited by CRH1-selective antagonist NBI-35965. CRH and Ucn-1, but not Ucn-2, stimulated significant ERK1/2 phosphorylation. In transfected human embryonic kidney-293 cells, CRH1i isoforms produced a significant increase in pERK1/2 in response to CRH1 agonists that was sensitive to NBI-35965. CRH and Ucn-1 stimulated 5-HT release that reached a maximal increase of 3.3- and 4-fold at 10−8m over the basal level, respectively. In addition, exposure to CRH for 24-h up-regulated tryptophan hydroxylase-1 mRNA levels in the BON-1N cells. These findings define the expression of EC cell-specific CRH1 isoforms and activation of CRH1-dependent pathways leading to 5-HT release and synthesis; thus, providing functional evidence of a link exists between CRH and 5-HT systems, which have implications in stress-induced CRH1 and 5-HT-mediated stimulation of lower intestinal function.
Effect of Caloric Restriction with and without Exercise on Metabolic Intermediates in Nonobese Men and Women
Authors: Redman Leanne M. , Huffman Kim M. , Landerman Lawrence R. , Pieper Carl F. , Bain James R. , Muehlbauer Michael J. , Stevens Robert D. , Wenner Brett R. , Kraus Virginia B. , Newgard Christopher B. , Kraus William E. , Ravussin Eric 
Published: December 2010

abstract

Objectives:
The objective of the study was to evaluate whether serum concentrations of metabolic intermediates are related to adiposity and insulin sensitivity (Si) in overweight healthy subjects and compare changes in metabolic intermediates with similar weight loss achieved by diet only or diet plus exercise.

Design:
This was a randomized controlled trial.

Participants and Intervention:
The cross-sectional study included 46 (aged 36.8 ± 1.0 yr) overweight (body mass index 27.8 ± 0.7 kg/m2) subjects enrolled in a 6-month study of calorie restriction. To determine the effect of diet only or diet plus exercise on metabolic intermediates, 35 subjects were randomized to control (energy intake at 100% of energy requirements); CR (25% calorie restriction), or CR+EX: (12.5% CR plus 12.5% increase in energy expenditure by exercise).

Main Outcome Measures:
Serum concentrations of eight fatty acids, 15 amino acids, and 45 acylcarnitines (ACs) measured by targeted mass spectrometry.

Results:
In overweight subjects, the concentrations of C2 AC and long-chain ACs were positively associated with percent fat (R2 = 0.75, P = 0.0001) and Si (R2 = 0.12, P = 0.05). The percent fat (R2 = 0.77, P &lt; 0.0001), abdominal visceral fat (R2 = 0.64, P &lt; 0.0001), and intrahepatic fat (R2 = 0.30, P = 0.0002) were positively associated with fatty acid concentrations. There was a significant increase in an AC factor (comprised of C2 and several medium chain ACs) in the CR group (P = 0.01).

Conclusion:
In nonobese subjects, fasted serum ACs are associated with Si and fat mass. Despite similar weight loss, serum ACs increase with CR alone but not CR+EX. A greater improvement in Si with weight loss during CR+EX interventions may be related to improved coupling of β-oxidation and tricarboxylic acid cycle flux induced by exercise.
Vitamin D Toxicity due to a Commonly Available “Over the Counter” Remedy from the Dominican Republic
Authors: Lowe Hyesoo , Cusano Natalie E. , Binkley Neil , Blaner William S. , Bilezikian John P. 
Published: December 2010

abstractContext:Hypercalcemia in ambulatory patients is occasionally caused by vitamin D toxicity.Objective:We report nine patients presenting to Columbia University Medical Center with hypercalcemia due to a supplement from the Dominican Republic containing massive amounts of vitamin D.Methods:Case histories and laboratory evaluation (calcium, PTH, vitamin D metabolites) are discussed in the context of other published cases of vitamin D toxicity. The supplement was analyzed by HPLC to quantitate vitamin D and A content.Results:Nine patients presented with hypercalcemia (range, 10.8–17.2 mg/dl; normal, 8.4–9.8 mg/dl), suppressed PTH (range, &lt;3 to 11 pg/ml), and elevated 25-hydroxyvitamin D (range, 94–525 ng/ml; normal, 30–80 ng/ml) levels. All reported recently taking an over-the-counter vitamin supplement called Soladek readily available in the Dominican Republic and in Upper Manhattan. Although serum calcium values before the ingestion of Soladek were not elevated (baseline serum calcium range, 8.7–9.2 mg/dl), most had a disorder that can be associated with hypercalcemia [squamous cell cancer (n = 1), Pneumocystis or mycobacterial infection (n = 3), lymphoma (n = 1), granulomatous disease (n = 1), hyperthyroidism (n = 2)]. According to the manufacturer's label, each 5-ml vial of Soladek contains vitamin D (600,000 IU), vitamin A (120,000 IU), and vitamin E (5 mg). Laboratory analysis by HPLC revealed that the supplement actually contained vitamin D3 (864,000 IU) and vitamin A (predominantly retinyl palmitate 123,500 IU) per vial.Conclusion:Although hypercalcemia due to exogenous use of vitamin D is unusual, it is important to consider it in the differential diagnosis, particularly among individuals with access to Soladek.
Ionicity Phase Diagram of Trifluoromethyl-TCNQ (CF3TCNQ) Charge-Transfer Solids
Authors: Saito Gunzi , Ikegami Hideo , Yoshida Yukihiro , Drozdova Olga O , Nishimura Kazukuni , Horiuchi Sachio , Yamochi Hideki , Otsuka Akihiro , Hiramatsu Takaaki , Maesato Mitsuhiko , Nakamura Takayoshi , Akutagawa Tomoyuki , Yumoto Toru 
Published: December 2010

Abstract
A series of charge-transfer (CT) solids of trifluoromethyl-7,7,8,8-tetracyanoquinodimethane (CF3TCNQ) with various electron donor molecules were prepared and their IR and UV–vis–near-IR spectra and electrical conductivity were measured. The information was applied to produce an ionicity phase diagram of CF3TCNQ CT solids. A boundary for ionicity of CF3TCNQ was found in combination with donor molecules of dibenzo[c,d]phenothiazine, diaminodurene, or dibenzotetrathiafulvalene (DBTTF). With stronger donors than DBTTF, the CF3TCNQ molecules were fully ionized and acted as a counter anion. No conductors with partially charged CF3TCNQ species were obtained. Besides the conventional 1:1 fully ionic insulators with segregated stacks, tetramethyl-TTF·CF3TCNQ·CH3CN and bis(methylthio)ethylenedithio-TTF·CF3TCNQ had fully ionic alternating stacks of DDAA units and showed Frenkel triplet excitons. (BEDO-TTF)2(CF3TCNQ) [BEDO-TTF: bis(ethylenedioxy)-TTF] consisted of a mixed-valence segregated stack of donor molecules and completely ionized acceptor molecules, and showed metallic behavior down to 1.8 K even in a compressed pellet sample. Langmuir–Blodgett films composed of (BEDO-TTF)2(CF3TCNQ) and matrix (arachidic acid) showed a conductivity of 3–6 S cm−1 at room temperature and a nearly temperature-independent conductivity down to 80 K. Semiconducting (TMTSF)2(CF3TCNQ) (TMTSF: tetramethyltetraselenafulvalene) had one-dimensional segregated stacks of dimerized TMTSF molecules separated by completely ionized CF3TCNQ, the molecular plane of which was arranged parallel to the TMTSF column. The ionicity phase diagram of the CF3TCNQ CT solids, i.e., a plot of the first CT transition energy vs. donor strength, clearly discriminated these different kinds of CT solids and will be utilized for the prediction and design of the functional CT solids.
Uranyl(VI)–Acetylacetonate Coordination Compounds with Various N-Heterocyclic Ligands
Authors: Kawasaki Takeshi , Nishimura Tatsuru , Kitazawa Takafumi 
Published: December 2010

Abstract
Seven uranyl(VI) complexes, [UO2(acac)2(L)] [L = 4-methylpyridine (1), 4-ethylpyridine (2), 2,4-dimethylpyridine (3), (−)-nicotine (4), and imidazole (5)], [{UO2(acac)2}2(4,4′-bipyridine)] (6), and [(2,2′-bipyridine)2H][UO2(acac)(NO3)2] (7) have been synthesized and characterized crystallographically. The coordination geometry of U has a UNO6 pentagonal-bipyramidal coordination in 1–6, and a UO8 hexagonal-bipyramidal coordination in 7.
Diastereoselective Michael Addition of Magnesium Amide to O-(2-Alkenoyl)TEMPOs and Comparison of Reactivity with Acyl Substituent-Modified Carboxylic Analogues
Authors: Ma Li-Jian , Mei Zhen-Wu , Toyohara Keisuke , Kawafuchi Hiroyuki , Nokami Junzo , Inokuchi Tsutomu 
Published: December 2010

Abstract
O-(2-Alkenoyl)TEMPOs bearing an O–N bond in the acyl substituent are highly reactive in Michael addition of magnesium amide compared with their acyl substituent-modified analogs. Highly diastereoselective addition is achieved to the AlMe3-treated O-(2-alkenoyl)TEMPO as an acceptor with the Mg amide generated from optically active secondary amine.
Pyrazolato- and 3,5-Dimethylpyrazolato-Bridged Dinuclear Platinum(II), Palladium(II), and Their Mixed-Metal Complexes of 2,2′-Bipyrimidine. Syntheses, Structures, and Luminescent Properties
Authors: Umakoshi Keisuke , Kimura Kazutoyo , Kim Yong Hun , Tsukimoto Yuya , Arikawa Yasuhiro , Onishi Masayoshi , Ishizaka Shoji , Kitamura Noboru 
Published: December 2010

Abstract
The pyrazolato (pz)- and 3,5-dimethylpyrazolato (Me2pz)-bridged dinuclear platinum(II) and palladium(II) complexes of 2,2′-bipyrimidine (bpym), [Pt2(bpym)2(μ-pz′)2](PF6)2 (pz′ = pz (1a) and Me2pz (1b)) and [Pd2(bpym)2(μ-pz′)2](PF6)2 (pz′ = pz (2a) and Me2pz (2b)), have been synthesized and structurally characterized. The Pd–Pt complex, [PdPt(bpym)2(μ-Me2pz)2](PF6)2 (4b), has also been synthesized and characterized by 1H NMR spectroscopy. Among these Pt2, Pd2, and PdPt complexes, only 1a and 1b exhibit greenish blue and yellow-green luminescence, respectively, in the solid state at ambient temperature. The emissions of 1a and 1b in the solid state are tentatively assigned as the emission from the 3LC/MLCT and 3MMLCT excited states, respectively.
Establishment of a paediatric age-related reference interval for the measurement of urinary total fractionated metanephrines
Authors: Griffin Alison , O'Shea Paula , FitzGerald Roland , O'Connor Gerard , Tormey William 
Published: December 2010

Introduction Normetanephrine and metanephrine are intermediate metabolites of noradrenaline and adrenaline metabolism. To assess whether normetanephrine and metanephrine analysis may aid in the diagnosis of Neuroblastoma, a reference interval for these metabolites must first be established. Aim The overall aim of this study was to establish a paediatric age-related reference interval for the measurement of total fractionated metanephrines. Methods A total of 267 urine samples were analysed following acid hydrolysis. This releases the metanephrines from their sulphate-bound metabolites. The samples were analysed using reverse phase high-performance liquid chromatography with electro-chemical detection on a Gilson automated sequential trace enrichment of dialysate sample system. Results Data were analysed using Minitab Release version 14. Outliers were removed using the Dixon/Reed one-third rule. Partitioning of the age groups was achieved using Harris and Boyd's standard normal deviate test. Non-parametric analysis of the data was performed, followed by the establishment of the 2.5th and the 97.5th reference limits. Conclusions The established reference intervals are described in Table 2.
Interpretation of increments in serial tumour biomarker concentrations depends on the distance of the baseline concentration from the cut-off
Authors: Petersen Per Hyltoft , Sölétormos György , Pedersen Merete Frejstrup , Lund Flemming 
Published: December 2010

Abstract

Background: In the management of breast cancer, several algorithms for interpretation of measured concentrations during monitoring have been introduced, without objective evaluation of their performance regarding the distance of the starting concentration from the cut-off concentration.

Methods: A computer simulation model has developed using parameters for the tumour biomarker CA 15-3 regarding biological variation and different rates of increase during progressive disease. Seven different algorithms, which include the cut-off point in the calculations, are applied to the simulated data corresponding to 1000 surrogate patients. Steady-state variation (CV-within-subject=14.9%) is based on Gaussian random numbers and an exponential increase in tumour growth (λ=0.009, 0.021, and 0.090 kU/day).

Results: The main outcome of the simulations was that low starting concentrations (baseline concentrations) delay the detection of progressive disease (true-positive), whereas, baseline concentrations just below the cut-off value results in false-positive results of progression during steady-state situations. The algorithms investigated show varying susceptibility for baseline concentrations approaching the cut-off. Thus, three of the algorithms show >90% false-positives and three algorithms <5% false-positives when baseline concentrations were just below the cut-off point.

Conclusions: Based on the simulations, it is possible to select the optimal algorithms for early detection of progressive disease and a low percentage of false-positives.
Longitudinal mechanical properties of cell wall of Masson pine (Pinus massoniana Lamb) as related to moisture content: A nanoindentation study
Authors: Yu Yan , Fei Benhua , Wang Hankun , Tian Genlin 
Published: December 2010

Abstract
The in situ imaging nanoindentation technique was used to investigate how the moisture content (MC) affects the longitudinal mechanical properties of Masson pine cell wall. Furthermore, nanoindentation tests in liquid water were performed. The results indicate that elastic modulus, hardness, and compression yield stress of wood wall are all linearly correlated to the selected MC region in the range from 4.5% to 13.1%. Remarkable differences were found between the experimental values measured in water and the extrapolated values based on regression equations below fiber saturation point.
What Is Bioethics: Notes toward a New Approach?
Authors: Tomasini Floris J. W. 
Published: December 2010

The question what is bioethics is a controversial area of debate amongst practitioners of bioethics, not least because it sets out disciplinary boundaries to practise the subject, which involve deeper assumptions about how one should approach and practise the subject. There are at least four ways of answering the question what is bioethics? that raise the controversy aforementioned. These can be identified in the following ways: (1) what has the word bioethics come to mean? What limits of scope should we place on an answer to what is bioethics?; (2)	what discipline does bioethics involve? Does it involve a single disciplinary perspective or does it involve many disciplines?; (3) are there different cultural principles or values to be contested in bioethics?; and (4) conclusions - what methodological approach should we adopt in answering the question what is bioethics?