bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure
Authors: de Ru Minke H , Boelens Jaap J , Das Anibh M , Jones Simon A , van der Lee Johanna H , Mahlaoui Nizar , Mengel Eugen , Offringa Martin , O'Meara Anne , Parini Rossella , Rovelli Attilio , Sykora Karl-Walter , Valayannopoulos Vassili , Vellodi Ashok , Wynn Robert F , Wijburg Frits A 
Published: August 2011

Abstract

Background
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder that results in the accumulation of glycosaminoglycans causing progressive multi-organ dysfunction. Its clinical spectrum is very broad and varies from the severe Hurler phenotype (MPS I-H) which is characterized by early and progressive central nervous system (CNS) involvement to the attenuated Scheie phenotype (MPS I-S) with no CNS involvement. Indication, optimal timing, safety and efficacy of the two available treatment options for MPS I, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), are subject to continuing debate. A European consensus procedure was organized to reach consensus about the use of these two treatment strategies.

Methods
A panel of specialists, including 8 specialists for metabolic disorders and 7 bone marrow transplant physicians, all with acknowledged expertise in MPS I, participated in a modified Delphi process to develop consensus-based statements on MPS I treatment. Fifteen MPS I case histories were used to initiate the discussion and to anchor decisions around either treatment mode. Before and at the meeting all experts gave their opinion on the cases (YES/NO transplantation) and reasons for their decisions were collected. A set of draft statements on MPS I treatment options composed by a planning committee were discussed and revised during the meeting until full consensus.

Results
Full consensus was reached on several important issues, including the following: 1) The preferred treatment for patients with MPS I-H diagnosed before age 2.5 yrs is HSCT; 2) In individual patients with an intermediate phenotype HSCT may be considered if there is a suitable donor. However, there are no data on efficacy of HSCT in patients with this phenotype; 3) All MPS I patients including those who have not been transplanted or whose graft has failed may benefit significantly from ERT; 4) ERT should be started at diagnosis and may be of value in patients awaiting HSCT.

Conclusions
This multidisciplinary consensus procedure yielded consensus on the main issues related to therapeutic choices and research for MPS I. This is an important step towards an international, collaborative approach, the only way to obtain useful evidence in rare diseases.
Genome-scale reconstruction and in silico analysis of the Ralstonia eutropha H16 for polyhydroxyalkanoate synthesis, lithoautotrophic growth, and 2-methyl citric acid production
Authors: Park Jong Myoung , Kim Tae Yong , Lee Sang Yup 
Published: August 2011

Abstract

Background

Ralstonia eutropha H16, found in both soil and water, is a Gram-negative lithoautotrophic bacterium that can utillize CO2 and H2 as its sources of carbon and energy in the absence of organic substrates. R. eutropha H16 can reach high cell densities either under lithoautotrophic or heterotrophic conditions, which makes it suitable for a number of biotechnological applications. It is the best known and most promising producer of polyhydroxyalkanoates (PHAs) from various carbon substrates and is an environmentally important bacterium that can degrade aromatic compounds. In order to make R. eutropha H16 a more efficient and robust biofactory, system-wide metabolic engineering to improve its metabolic performance is essential. Thus, it is necessary to analyze its metabolic characteristics systematically and optimize the entire metabolic network at systems level.

Results
We present the lithoautotrophic genome-scale metabolic model of R. eutropha H16 based on the annotated genome with biochemical and physiological information. The stoichiometic model, RehMBEL1391, is composed of 1391 reactions including 229 transport reactions and 1171 metabolites. Constraints-based flux analyses were performed to refine and validate the genome-scale metabolic model under environmental and genetic perturbations. First, the lithoautotrophic growth characteristics of R. eutropha H16 were investigated under varying feeding ratios of gas mixture. Second, the genome-scale metabolic model was used to design the strategies for the production of poly[R-(-)-3hydroxybutyrate] (PHB) under different pH values and carbon/nitrogen source uptake ratios. It was also used to analyze the metabolic characteristics of R. eutropha when the phosphofructokinase gene was expressed. Finally, in silico gene knockout simulations were performed to identify targets for metabolic engineering essential for the production of 2-methylcitric acid in R. eutropha H16.

Conclusion
The genome-scale metabolic model, RehMBEL1391, successfully represented metabolic characteristics of R. eutropha H16 at systems level. The reconstructed genome-scale metabolic model can be employed as an useful tool for understanding its metabolic capabilities, predicting its physiological consequences in response to various environmental and genetic changes, and developing strategies for systems metabolic engineering to improve its metabolic performance.
Statin-induced apoptosis via the suppression of ERK1/2 and Akt activation by inhibition of the geranylgeranyl-pyrophosphate biosynthesis in glioblastoma
Authors: Yanae Masashi , Tsubaki Masanobu , Satou Takao , Itoh Tatsuki , Imano Motohiro , Yamazoe Yuzuru , Nishida Shozo 
Published: August 2011

AbstractBackgroundStatins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. The inhibition of this key enzyme in the mevalonate pathway leads to suppression of cell proliferation and induction of apoptosis. However, the molecular mechanism of apoptosis induction by statins is not well understood in glioblastoma. In the present study, we attempted to elucidate the mechanism by which statins induce apoptosis in C6 glioma cells.MethodsThe cytotoxicity of statins toward the C6 glioma cells were evaluated using a cell viability assay. The enzyme activity of caspase-3 was determined using activity assay kits. The effects of statins on signal transduction molecules were determined by western blot analyses.ResultsWe found that statins inhibited cell proliferation and induced apoptosis in these cells. We also observed an increase in caspase-3 activity. The apoptosis induced by statins was not inhibited by the addition of farnesyl pyrophosphate, squalene, ubiquinone, and isopentenyladenine, but by geranylgeranyl-pyrophosphate (GGPP). Furthermore, statins decreased the levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt.ConclusionsThese results suggest that statins induce apoptosis when GGPP biosynthesis is inhibited and consequently decreases the level of phosphorylated ERK1/2 and Akt. The results of this study also indicate that statins could be used as anticancer agents in glioblastoma.
Branchial osmoregulation in the euryhaline bull shark, Carcharhinus leucas: a molecular analysis of ion transporters
Authors: Reilly Beau D. , Cramp Rebecca L. , Wilson Jonathan M. , Campbell Hamish A. , Franklin Craig E. 
Published: August 2011

SUMMARY
Bull sharks, Carcharhinus leucas, are one of only a few species of elasmobranchs that live in both marine and freshwater environments. Osmoregulation in euryhaline elasmobranchs is achieved through the control and integration of various organs (kidney, rectal gland and liver) in response to changes in environmental salinity. However, little is known regarding the mechanisms of ion transport in the gills of euryhaline elasmobranchs and how they are affected by osmoregulatory challenges. This study was conducted to gain insight into the branchial ion and acid-base regulatory mechanisms of C. leucas by identifying putative ion transporters and determining whether their expression is influenced by environmental salinity. We hypothesised that expression levels of the Na+/K+-ATPase (NKA) pump, Na+/H+ exchanger 3 (NHE3), vacuolar-type H+-ATPase (VHA) and anion exchanger pendrin (PDN) would be upregulated in freshwater (FW) C. leucas. Immunohistochemistry was used to localise all four ion transporters in gills of bull sharks captured in both FW and estuarine/seawater (EST/SW) environments. NHE3 immunoreactivity occurred in the apical region of cells with basolateral NKA expression whereas PDN was apically expressed in cells that also exhibited basolateral VHA immunoreactivity. In accordance with our hypotheses, quantitative real-time PCR showed that the mRNA expression of NHE3 and NKA was significantly upregulated in gills of FW-captured C. leucas relative to EST/SW-captured animals. These data suggest that NHE3 and NKA together may be important in mediating branchial Na+ uptake in freshwater environments, whereas PDN and VHA might contribute to Cl-/HCO3- transport in marine and freshwater bull shark gills.
Transdifferentiation of cancer stem cells into endothelial cells
Authors: Porta Caterina 
Published: August 2011

Abstract
Vasculogenic mimicry was first described as the unique ability of aggressive melanoma cells to express an endothelial phenotype and to form vessel-like networks in three dimensional cultures, “mimicking” the pattern of embryonic vascular networks and recapitulating the patterned networks seen in patients with aggressive tumors correlated with poor prognosis. Recent work shows the occurrence of alternative vasculogenic patterns is due to the presence of stem cell population (cancer stem cells, CSC) at least in melanoma and glioblastoma. In the present review the new perspectives to target vasculogenic mimicry for an anti-vascular treatment strategy and the possible use of AQP1 as target, are discussed. Interest in AQP1 as a target arises from the pivotal role it plays in the organisation of vascular network affecting the cytoskeleton.
Synthesis of Disubstituted Phosphinates via Palladium‐Catalyzed Hydrophosphinylation of H‐Phosphinic Acids
Authors: Petit Christelle , Fécourt Fabien , Montchamp Jean‐Luc 
Published: August 2011

AbstractThe first metal‐catalyzed hydrophosphinylation of unsaturated hydrocarbons with H‐phosphinic acids is described. A strategy to activate the PH bond through control of the tautomeric equilibrium using ethylene glycol is described. The reactions also avoid chromatographic purification.
Features of basal cell carcinomas in basal cell nevus syndrome
Authors: Tom Wynnis L. , Hurley M. Yadira , Oliver Dana S. , Shah Maulik R. , Bree Alanna F. 
Published: August 2011

AbstractBasal cell nevus syndrome (BCNS) is an autosomal dominant genodermatosis that is characterized by early onset basal cell carcinomas (BCCs) that define the disease and often lead to diagnosis of the underlying syndrome. The objective of this study was to investigate the anatomic location, subtypes, and impact of BCCs on a group of 61 individuals affected with BCNS attending a research colloquium. Fifty individuals had at least one prior BCC with 22 participants having over 100 lesions. The median age of syndrome diagnosis was 11 years and median age of first BCC was 16 years. Males had more lesions on the upper back, upper extremities, and M‐zone of the face, while females had more lesions on the scalp, back, and lower extremities. Pigmented BCCs were concentrated on the neck, upper trunk, and extremities. Subjects with >100 lesions showed wider anatomic distribution. The number of BCCs did not correlate with any of the other major features of the syndrome. Eighty percent of affected individuals reported great concern related to BCCs, citing the limitations and morbidity of available treatments. Vigilant surveillance, which was found to be inconsistent for participants in this study, is warranted. Future work should include development of a consensus guideline on skin examinations and strategies to optimize therapy of BCCs in this syndrome. © 2011 Wiley‐Liss, Inc.
Clinical and genomic characterization of siblings with a distal duplication of chromosome 9q (9q34.1‐qter)
Authors: Mizuno Seiji , Fukushi Daisuke , Kimura Reiko , Yamada Kenichiro , Yamada Yasukazu , Kumagai Toshiyuki , Wakamatsu Nobuaki 
Published: August 2011

AbstractWe report herein on two female siblings exhibiting mild intellectual disability, hypotonia in infancy, postnatal growth retardation, characteristic appearance of the face, fingers, and toes. Their healthy mother had a translocation between 9q34.1 and the 13pter. FISH and array CGH analysis demonstrated that the two children had an additional 8.5 Mb segment of the 9q34.1‐qter at 13pter. The clinical features of the present cases were similar to those of previously reported 9q34 duplication cases; however, the present cases did not exhibit other abnormal behaviors, such as autistic features or attention deficit disorders, those are reportedly associated with 9q34 duplications. A 3.0 Mb region (9q34.1‐q34.3) within 9q34 duplication in our patients are overlapped with duplication region of previously reported cases and is proposed to be critical for the presentation of several phenotypes associated with 9q34 duplications. © 2011 Wiley‐Liss, Inc.
Ionic Liquids and Nanomaterials – An Interesting Symbiosis
Authors: Schubert Thomas J. S. 
Published: August 2011

AbstractDie Kombination von Nanomaterialien und ionischen Flüssigkeiten bietet eine Vielzahl von Möglichkeiten für eine Reihe von Zukunftstechnologien. Die Anwendungen reichen dabei von der Synthese von Nanomaterialien in ionischen Flüssigkeiten, über die Herstellung stabiler Dispersionen bis hin zu zahlreichen elektrochemischen Anwendungen, wie z. B. Farbstoffsolarzellen oder Batterien.
Optimisation of the Anti‐Trypanosoma brucei Activity of the Opioid Agonist U50488
Authors: Smith Victoria C. , Cleghorn Laura A. T. , Woodland Andrew , Spinks Daniel , Hallyburton Irene , Collie Iain T. , Yi Mok N. , Norval Suzanne , Brenk Ruth , Fairlamb Alan H. , Frearson Julie A. , Read Kevin D. , Gilbert Ian H. , Wyatt Paul G. 
Published: August 2011

AbstractScreening of the Sigma–Aldrich Library of Pharmacologically Active Compounds (LOPAC) against cultured Trypanosoma brucei, the causative agent of African sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. These included (+)‐(1R,2R)‐U50488, a weak opioid agonist with an EC50 value of 59 nM as determined in our T. brucei in vitro assay reported previously. This paper describes the modification of key structural elements of U50488 to investigate structure–activity relationships (SAR) and to optimise the antiproliferative activity and pharmacokinetic properties of this compound.
Synthesis and Characterization of the Azido‐Functionalized Ruthenocene Analogue [TpmRu(p‐N3C6H4)Tp]Cl and Its Attachment to Biomolecules by Copper‐Catalyzed Azide–Alkyne Cycloaddition
Authors: Zagermann Johannes , Klein Kathrin , Merz Klaus , Molon Mariusz , Metzler‐Nolte Nils 
Published: August 2011

AbstractThe mixed‐ligand tris(pyrazolyl)borate sandwich compound [TpmRuTp′]Cl (2) was prepared by microwave‐assisted synthesis from Tp′Ru(COD)Cl (1) [Tp = tris(pyrazolyl)borate; Tp′ = p‐bromophenyltris(pyrazolyl)borate; Tpm = tris(pyrazolyl)methane; COD = 1,4‐cyclooctadiene]. Subsequently, 2 was converted to the azide‐functionalized [TpmRu(p‐N3C6H4Tp)] (3), which can be readily coupled to biomolecules by Cu‐catalyzed azide–alkyne cycloaddition (Cu‐AAC) in solution, as exemplified by the covalent attachment to pentyne‐functionalized HC(CH2)2–CO–Val–OtBu (4), and an alkyne derivative of the neuropeptide enkephaline HC(CH2)2–CO–ENK–OH (ENK = enkephaline, Tyr–Gly–Gly–Phe–Leu). The resulting triazole compounds [TpmRu({p‐C2N3H–(CH2)2–CO–Val–OtBu}Tp)]Cl (5) and [TpmRu({p‐C2N3H–(CH2)2–CO–ENK–OH}Tp)]Cl (6), represent the first [3+2] cycloaddition products of azide‐functionalized Tp compounds. They were characterized by NMR spectroscopy and mass spectrometry. Furthermore, 1, 2, and 3 as well as the reaction intermediate [(κ2‐N,N′‐Tpm)RuCl(Tp′)] (2a) were characterized in the solid state by single‐crystal X‐ray diffraction.
Synthesis and Glutathione Peroxidase‐Like Activities of Isoselenazolines
Authors: Singh Vijay P. , Singh Harkesh B. , Butcher Ray J. 
Published: August 2011

AbstractThe aromatic nucleophilic substitution (SNAr) reactions ofN‐(2‐bromo‐3‐nitrobenzyl)aniline (18),N‐(2‐bromo‐3‐nitrobenzyl)‐4‐methylaniline (19) andN‐(2‐bromo‐3‐nitrobenzyl)‐4‐nitroaniline (20) with [nBuSeNa] affordN‐[2‐(butylselanyl)‐3‐nitrobenzyl]aniline (21),N‐[2‐(butylselanyl)‐3‐nitrobenzyl]‐4‐methylaniline (22) andN‐[2‐(butylselanyl)‐3‐nitrobenzyl]‐4‐nitroaniline (23), respectively. The bromination of21results in the formation of cyclic isoselenazolines 7‐nitro‐2‐phenyl‐2,3‐dihydrobenzisoselenazole (27) and 2‐(4‐bromophenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole (28). The bromination of22affords isoselenazolines 2‐(4‐methylphenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole (29) and 2‐(2‐bromo‐4‐methylphenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole (30) along with some other products. The bromination of23under identical conditions gave 2‐(2‐bromo‐4‐nitrophenyl)‐7‐nitro‐2,3‐dihydrobenzisoselenazole (31). The oxidation reaction of21–22with H2O2yielded isoselenazolineSe‐oxides 7‐nitro‐2‐phenyl‐2,3‐dihydrobenzisoselenazole 1‐oxide (33) and 2‐(4‐methylphenyl)‐7‐nitro‐2‐phenyl‐2,3‐dihydrobenzisoselenazole 1‐oxide (34), respectively. The new isoselenazolines and isoselenazolineSe‐oxides, stabilized by intramolecular secondary Se···O interactions, have been structurally characterized by single‐crystal X‐ray diffraction studies and investigated by computational studies. In addition to the synthesis and characterization, the glutathione peroxidase (GPx)‐like activities of isoselenazolines and isoselenazolineSe‐oxides have been evaluated by coupled reductase assays.
Endogenous treatment effects for count data models with endogenous participation or sample selection
Authors: Bratti Massimiliano , Miranda Alfonso 
Published: August 2011

AbstractIn this paper, we propose an estimator for models in which an endogenous dichotomous treatment affects a count outcome in the presence of either sample selection or endogenous participation using maximum simulated likelihood. We allow for the treatment to have an effect on the participation or the sample selection rule and on the main outcome. Applications of this model are frequent in–but no limited to–health economics. We show an application of the model using data from Kenkel and Terza (2001), who investigate the effect of physician advice on the amount of alcohol consumption. Our estimates suggest that in these data (i) neglecting treatment endogeneity leads to a wrongly signed effect of physician advice on drinking intensity, (ii) accounting for treatment endogeneity but neglecting endogenous participation leads to an upward biased estimate of the treatment effect and (iii) advice affects only the drinking intensive margin but not drinking prevalence. Copyright © 2011 John Wiley & Sons, Ltd.
The risk of breast cancer in women with a BRCA1 mutation from North America and Poland
Authors: Lubinski Jan , Huzarski Tomasz , Byrski Tomasz , Lynch Henry T. , Cybulski Cezary , Ghadirian Parviz , Stawicka Malgorzata , Foulkes William D. , Kilar Ewa , Kim‐Sing Charmaine , Neuhausen Susan L. , Armel Susan , Gilchrist Dawna , Sweet Kevin , Gronwald Jacek , Eisen Andrea , Gorski Bohdan , Sun Ping , Narod Steven A. ,   the Hereditary Breast Cancer Clinical Study Group
Published: August 2011

AbstractWomen with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, nongenetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34‐0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.
Physicochemical, functional and angiotensin converting enzyme inhibitory properties of amaranth (Amaranthus hypochondriacus) 7S globulin
Authors: Quiroga Alejandra V , Aphalo Paula , Ventureira Jorge L , Martínez E Nora , Añón María C 
Published: August 2011

AbstractBACKGROUND: Amaranth 7S globulin is a minor globulin component and its impact on the properties of an amaranth protein ingredient depends on its proportion in the variety of amaranth being considered. Some physicochemical, functional and angiotesin I‐converting enzyme (ACE) inhibitory properties of amaranth vicilin were studied in this work and compared with the 11S globulin.RESULTS: Fluorescence spectroscopy results indicated that 7S globulin tryptophans were more exposed to the solvent and, by calorimetry, the 7S globulin denaturation temperature (Td) was found lower than the 11S globulin Td, suggesting a more flexible structure. The 7S globulin surface hydrophobicity was higher than that of the 11S globulin, which is in agreement with the better emulsifying properties of the 7S globulin. The solubility in neutral buffer of the 7S globulin (851 ± 25 g kg−1) was also higher than that of the 11S globulin (195 ± 6 g kg−1). Bioinformatic analyses showed the presence of ACE inhibitory peptides encrypted in 7S tryptic sequences and peptides released after in vitro gastrointestinal digestion showed a high ACE‐inhibitory capacity (IC50 = 0.17 g L−1), similar to that of 11S globulin peptides.CONCLUSION: Compared with the 11S globulin, the 7S globulin presents similar ACE inhibitory activity and some functional advantages, better solubility and emulsifying activity, which suits some food requirements. The functional behavior has been related with the structural properties. Copyright © 2011 Society of Chemical Industry
Nonequilibrium carrier dynamics in bulk HPHT diamond at two‐photon carrier generation
Authors: Ščajev Patrik , Gudelis Vytautas , Ivakin Eugeny , Jarašiūnas Kęstutis 
Published: August 2011

AbstractWe demonstrate applicability of time‐resolved free‐carrier absorption and transient grating techniques for investigation of carrier recombination and diffusion features in a bulk diamond. Carrier injection into a 1 mm thick, IIa type high‐pressure high‐temperature grown layer was realized by two‐photon absorption of ∼5 ps laser pulse at 351 nm wavelength. Kinetics of differential transmission in 80–800 K range at various excess carrier densities provided carrier lifetimes of 360 ns at room temperature and their temperature dependences. A linear increase of carrier recombination rate with injection in 450–800 K range resulted in carrier lifetimes up to 1 ns and was fitted by effective coefficient B* = 2 × 10−11– 4 × 10−9 cm3/s. The latter process was attributed to a trap‐assisted Auger recombination (TAAR) with coefficient CTAAR = B*/NTrap and tentatively ascribed to nitrogen related traps. An ambipolar carrier mobility with its peak value of ∼1500 cm2/Vs at room temperature was measured by transient grating technique at ∼1.5 × 1015 cm−3 excess carrier density.