bluuebunny/crossref_metadata_2025 huggingface dataset:
CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines that are relatively chemoresistant but sensitive to mutant HSV
Authors: Pressey Joseph G. , Haas Marilyn C. , Pressey Christine S. , Kelly Virginia M. , Parker Jacqueline N. , Gillespie G. Yancey , Friedman Gregory K.
Published: March 2012

Background

Rhabdomyosarcoma (RMS) is characterized by features of skeletal muscle and is comprised of two major histological subtypes, embryonal (E‐RMS), and alveolar (A‐RMS). Subsets of each RMS subtype demonstrate resistance to multimodal therapy leading to treatment failure. Cancer stem cells or cancer‐initiating cells (CIC) represent a theorized population of cells that give rise to tumors and are responsible for treatment resistance.

Procedure

We investigated the ability of CD133, a putative CIC marker, to distinguish a chemoresistant, myogenically primitive population in alveolar (RH30), and embryonal (RD) RMS cell lines. We tested CD133+/− cells for sensitivity to engineered herpes simplex virus (oHSV).

Results

Relative to CD133− cells, CD133+ A‐RMS, and E‐RMS cells demonstrate an enhanced colony‐forming ability, are less differentiated myogenically, and are more resistant to cytotoxic chemotherapy but equally sensitive to oHSV oncolysis. Compared to CD133− RD cells, CD133+ cells express relatively high levels of genes typically expressed in skeletal muscle progenitor satellite cells including PAX7, c‐MET, and the GLI effectors of the hedgehog signaling pathway. In contrast, CD133+ RH30 cells were not associated with enhanced expression of satellite cell markers or Hh targets.

Conclusions

Our findings demonstrate that CD133+ cells from A‐RMS and E‐RMS cell lines are characterized by a myogenically primitive phenotype. These cells have the capacity to form colonies in vitro and are more resistant to chemotherapy than CD133− cells. CD133 expression may denote a subset of RMS cells with an important role in tumorigenesis and treatment failure. These resistant cells may be effectively targeted by oHSV therapy. Pediatr Blood Cancer 2013; 60: 45–52. © 2012 Wiley Periodicals, Inc.
A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis
Authors: Chandran Binu , Goel Ajay
Published: March 2012

Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty‐five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large‐scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.
High throughput discovery of thermo‐responsive materials using water contact angle measurements and time‐of‐flight secondary ion mass spectrometry
Authors: Hook Andrew L. , Scurr David J. , Anderson Daniel G. , Langer Robert , Williams Paul , Davies Martyn , Alexander Morgan
Published: March 2012

Switchable materials that alter their chemical or physical properties in response to external stimuli allow for temporal control of material‐biological interactions, thus, are of interest for many biomaterial applications. Our interest is the discovery of new materials suitable to the specific requirements of certain biological systems. A high throughput methodology has been developed to screen a library of polymers for thermo‐responsiveness, which has resulted in the identification of novel switchable materials. To elucidate the mechanism by which the materials switch, time‐of‐flight secondary ion mass spectrometry has been employed to analyse the top 2 nm of the polymer samples at different temperatures. The surface enrichment of certain molecular fragments has been identified by time‐of‐flight secondary ion mass spectrometry analysis at different temperatures, suggesting an altered molecular conformation. In one example, a switch between an extended and collapsed conformation is inferred. Copyright © 2012 John Wiley & Sons, Ltd.
Studies on wetting behavior of hot‐dip galvanizing process by use of model specimens with tailored surface oxides
Authors: Kawano Takashi , Renner Frank U.
Published: March 2012

The hot‐dip galvanizing process is widely used in steel production for automotive applications. The wetting behavior of molten zinc containing a small amount of aluminum and a steel surface is one of the most important issues concerning this process. Especially, studies on the degradation of wettability caused by surface oxides of steels have been focused on in recent years. This present work focused on the wetting of MnO which is a typical oxide appearing on steel surfaces. The reaction between the aluminum in the molten zinc and the MnO has been expected to improve wettability in the galvanizing process. However, no direct evidence has been reported on this, likely due to the difficulty of observation during the process. For this observation, a simple MnO layer was prepared, and wetting experiments by the sessile drop method were conducted in a laboratory‐made apparatus. The apparatus included a unique spin‐off technique that allowed us to stop a reaction during wetting and make an interface analysis at an early stage of the wetting. It was revealed that aluminum precipitated at the interface during wetting, which is assumed to be due to the aluminothermic reaction. However, the contact angle of the wetting was large and did not change during the wetting. The decrement of the MnO by the reaction was estimated as small as a few nanometers in 7 seconds. This indicated that the effect of the reaction on wettability in the real process condition can be seen to be minor. Copyright © 2012 John Wiley & Sons, Ltd.
Imaging in gynecological disease (7): clinical and ultrasound features of Brenner tumors of the ovary
Authors: Dierickx I. , Valentin L. , Van Holsbeke C. , Jacomen G. , Lissoni A. A. , Licameli A. , Testa A. , Bourne T. , Timmerman D.
Published: March 2012

Objectives

To describe clinical and ultrasound features of Brenner tumors of the ovary.

Methods

In this retrospective study, the databases of the International Ovarian Tumor Analysis (IOTA) studies and one tertiary center were searched to identify patients who had undergone an ultrasound scan before surgery for an adnexal mass that proved to be a Brenner tumor. Twenty‐eight patients with 29 Brenner tumors were included, most of which had been collected within the framework of the IOTA studies. An experienced ultrasound examiner reviewed available ultrasound images (available for 14 tumors), searching for a pattern specific to Brenner tumors.

Results

Most patients were postmenopausal and asymptomatic. Twenty‐four (83%) tumors were benign, two (7%) were borderline and three (10%) were malignant. Most benign tumors (17/24, 71%) contained solid components and manifested no or minimal blood flow on Doppler examination (19/24, 79%). Information about calcifications was available for 15 benign tumors, and in 13 (87%) calcifications were present. The five borderline and invasively malignant tumors contained solid components less often than did the benign ones (3/5, 60%) and were more richly vascularized on Doppler examination. Information about calcifications was available for four borderline or invasively malignant tumors, and in three (75%) calcifications were present.

Conclusion

We failed to demonstrate ultrasound features specific to Brenner tumors. A prospective study is needed to determine if ultrasound features of calcifications can discriminate between Brenner tumors and other types of ovarian tumor. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Integration of proteomics into systems biology of cancer
Authors: Hanash S. , Schliekelman M. , Zhang Q. , Taguchi A.
Published: March 2012

Deciphering the complexity and heterogeneity of cancer, benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date, and the challenges involved in integrating diverse datasets are addressed in this review. WIREs Syst Biol Med 2012 doi: 10.1002/wsbm.1169

This article is categorized under:

Translational, Genomic, and Systems Medicine > Diagnostic Methods

Laboratory Methods and Technologies > Proteomics Methods

Translational, Genomic, and Systems Medicine > Translational Medicine
Cassette series designed for live‐cell imaging of proteins and high‐resolution techniques in yeast
Authors: Young Carissa L. , Raden David L. , Caplan Jeffrey L. , Czymmek Kirk J. , Robinson Anne S.
Published: March 2012

During the past decade, it has become clear that protein function and regulation are highly dependent upon intracellular localization. Although fluorescent protein variants are ubiquitously used to monitor protein dynamics, localization and abundance; fluorescent light microscopy techniques often lack the resolution to explore protein heterogeneity and cellular ultrastructure. Several approaches have been developed to identify, characterize and monitor the spatial localization of proteins and complexes at the suborganelle level, yet many of these techniques have not been applied to yeast. Thus, we have constructed a series of cassettes containing codon‐optimized epitope tags, fluorescent protein variants that cover the full spectrum of visible light, a TetCys motif used for fluorescein arsenical hairpin (FlAsH)‐based localization, and the first evaluation in yeast of a photoswitchable variant, mEos2, to monitor discrete subpopulations of proteins via confocal microscopy. This series of modules, complete with six different selection markers, provides the optimal flexibility during live‐cell imaging and multicolour labelling in vivo. Furthermore, high‐resolution imaging techniques include the yeast‐enhanced TetCys motif, which is compatible with diaminobenzidine photo‐oxidation used for protein localization by electron microscopy, and mEos2, which is ideal for super‐resolution microscopy. We have examined the utility of our cassettes by analysing all probes fused to the C‐terminus of Sec61, a polytopic membrane protein of the endoplasmic reticulum of moderate protein concentration, in order to directly compare fluorescent probes, their utility and technical applications. Our series of cassettes expand the repertoire of molecular tools available to advance targeted spatiotemporal investigations using multiple live‐cell, super‐resolution or electron microscopy imaging techniques. Copyright © 2012 John Wiley & Sons, Ltd.
Incorporating Rare Earth Metal Complexes and Conjugated Organic Cations into Polymeric Iodoargentate: Structures and Properties of Two Hybrid Iodoargentates
Authors: Li Hao‐Hong , Huang Shu‐Wei , Lian Zhao‐Xun , Liu Ji‐Bo , Wang Min , Chen Zhi‐Rong
Published: March 2012

Two new polymeric iodoargentate hybrids induced by rare earth metal complexes and conjugated organic cations, {[Er(DMF)8][Ag6I9]}n (1) and [(MMP)(AgI2)]n (2) (MMP = 1‐methyl‐4‐methylpyridinium) were obtained by the routine synthetic reaction and structurally determined. In compound 1, a (Ag6I9)n3n– chain is defined by edge‐sharing Ag6I12 units, and in 2, the (Ag2I4)n2– chains are constructed by edge‐sharing AgI4 tetrahedra. C–H···I hydrogen bonds between cations and iodoargentate polyanions contribute to their structural extension from 1D to a 2D layer (for 1) and a 3D network (for 2). The UV/Vis spectra indicate that compared with 2, compound 1 exhibits a narrower adsorption scope with an onset at about 360 nm, and it has a much wider bandgap of about 3.50 eV.
Pr5F[SiO4]2[SeO3]3: Another Complex Fluoride Oxosilicate Oxoselenate(IV)
Authors: Lipp Christian , Burns Peter C. , Schleid Thomas
Published: March 2012

During attempts to synthesize lanthanoid(III) fluoride oxoselenates(IV) with the simple composition MF[SeO3], not only Pr3F[SeO3]4, but also Pr5F[SiO4]2[SeO3]3 appeared as pale green crystalline by‐products in the case of praseodymium. Pr5F[SiO4]2[SeO3]3 crystallizes triclinically in space group P$\bar{1}$ (no. 2) with a = 701.14(5), b = 982.68(7), c = 1286.79(9) pm, α = 70.552(3), β = 76.904(3), γ = 69.417(3)° and Z = 2. The five crystallographically different Pr3+ cations on the general positions 2i show coordination numbers of eight and nine. [(Pr1)O8]13– and [(Pr2)O8]13– polyhedra are connected to$\bar{1}${[(Pr1, 2)2O12]18–} chains along the [100] direction. [(Pr3)O7F]12–, [(Pr4)O8F]14– and [(Pr4)O8F]14– polyhedra generate [F(Pr3, 4, 5)3O19]30– units about their central F– anion in triangular Pr3+ coordination. These units form $\bar{1}${[F(Pr3, 4, 5)3O16]24–} strands, again running parallel to [100]. Their alternating connection with the $\bar{1}${[(Pr1, 2)2O12]18–} chains results in $\bar{1}${[Pr5O20F]26–} sheets parallel to the (001) plane. Like in the already known related compound Er3F[SiO4][SeO3]2, a three‐dimensional network $\bar{1}${[Pr5O17F]20–} is achieved without the contribution of both the tetravalent silicon and selenium components. However, two Si4+ and three Se4+ cations forming tetrahedral [SiO4]4– and ψ1‐tetrahedral [SeO3]2– units with all O2– anions guarantee the charge balance. The formation of Pr5F[SiO4]2[SeO3]3 was observed when praseodymium sesquioxide (Pr2O3: in‐situ produced from Pr and Pr6O11 in a molar ratio of 3/11:4/11),praseodymium trifluoride (PrF3) and selenium dioxide (SeO2) in 1:1:3 molar ratios were reacted with CsBr as fluxing agent for five days at 750 °C in evacuated fused silica (SiO2) ampoules.
Synthesis, Structure, and Solution Study of a Mercury(II) Complex with the Ligand [1‐(2‐Methoxyphenyl)‐3‐(4‐chlorophenyl)]triazene
Authors: Rofouei Mohammad Kazem , Ghalami Zahra , Attar Gharamaleki Jafar , Ghoulipour Vanik , Bruno Giuseppe , Rudbari Hadi Amiri
Published: March 2012

The title ligand, [1‐(2‐methoxyphenyl)‐3‐(4‐chlorophenyl)]triazene, HL (1), was prepared. In a reaction with Hg(NO3)2 it forms the complex [Hg(C26H22Cl2N6O2)], [HgL2] (2). Both compounds were characterized by means of X‐ray crystallography, CHN analysis, FT‐IR, 1H NMR, and 13C NMR spectroscopy. In the structure of compound 1, two independent fragments are present in the unit cell. They exhibit trans arrangement about the –N=N– double bond. The dihedral angles between two benzene rings in both fragments are 4.36 and 18.79 Å, respectively. Non‐classic C–H···N hydrogen bonding and C–H···π interactions form a layer structure along the crystallographic ab plane [110]. In compound 2, the HgII atom is hexacoordinated by two tridentate [1‐(2‐methoxyphenyl)‐3‐(4‐chlorophenyl)]triazenide ligands through a N2O2 set. In addition, in the structure of 2, monomeric complexes are connected to each other by C–H···π stacking interactions, resulting in a 2D architecture. These C–H···π edge‐to‐face interactions are present with H···π distances of 3.156 and 3.027 Å. The results of studies of the stoichiometry and formation of complex 2 in methanol solution were found to support its solid state stoichiometry.
Synthesis and Reaction Chemistry of Sb(ECH2CH2NMe2)3 (E = O, S)
Authors: Horley Graeme A. , Kociok‐Köhn Gabriele , Molloy Kieran C. , Rodriguez Castro Jorge , Morreale Sergio
Published: March 2012

The antimony aminoalkoxide and aminothiolates Sb(ECH2CH2NMe2)3 [E = O (1), S (2)] were synthesized and their ability to form adducts with other metal moieties investigated. Compound 1 forms 1:1 adducts with NiI2 (3) and M(acac)2 [M = Cd (4), Ni (5)], while 2 undergoes ligand exchange with AlMe3 to afford Me2AlSCH2CH2NMe2 (6). The structures of 2–4 and 6 were determined. Compound 2 incorporates three S, N‐chelating ligands though the interaction with nitrogen is weaker than in analogous alkoxide complexes. Product 3 reveals one iodine has migrated from nickel to antimony, and all three alkoxide ligands bridge the two metals through μ2‐O atoms. In contrast, in 4, only one alkoxide links the antimony and cadmium. Compound 6 adopts the same structure, a chelating S,N ligand generating a tetrahedral center at aluminum, as known tBu2AlSCH2CH2NR2 species (R = Me, Et).
Lewis Acid Base Reactions between Boron Trifluoride and Complex Oxoanions as a Versatile Access to Fluorooxoanions: Synthesis of Sodium (Trifluoroborato)sulfate
Authors: Pilz Thomas , Jansen Martin
Published: March 2012

Na2SO4BF3, synthesized in a closed vessel from BF3 and Na2SO4 at 603 K, crystallizes in the triclinic space group P$\bar{1}$ (a = 6.6033(2), b = 6.6328(2), c = 6.6349 (1) Å, α = 84.542(2), β = 84.458(1) and γ = 65.762(1)°). The novel fluorooxo anion [SO4BF3]2– displays a structure similar to the disulfate anion S2O72–. Heating the title compound in the absence of BF3 in the gas phase leads to decomposition even at 553 K, which is below the temperature of synthesis under BF3 pressure.
Challenges of Surgery in Developing Countries: A Survey of Surgical and Anesthesia Capacity in Uganda’s Public Hospitals
Authors: Linden Allison F. , Sekidde Francis Serufusa , Galukande Moses , Knowlton Lisa Marie , Chackungal Smita , McQueen K. A. Kelly
Published: March 2012

Background

There are large disparities in access to surgical services due to a multitude of factors, including insufficient health human resources, infrastructure, medicines, equipment, financing, logistics, and information reporting. This study aimed to assess these important factors in Uganda’s government hospitals as part of a larger study examining surgical and anesthesia capacity in low‐income countries in Africa.

Methods

A standardized survey tool was administered via interviews with Ministry of Health officials and key health practitioners at 14 public government hospitals throughout the country. Descriptive statistics were used to analyze the data.

Results

There were a total of 107 general surgeons, 97 specialty surgeons, 124 obstetricians/gynecologists (OB/GYNs), and 17 anesthesiologists in Uganda, for a rate of one surgeon per 100,000 people. There was 0.2 major operating theater per 100,000 people. Altogether, 53% of all operations were general surgery cases, and 44% were OB/GYN cases. In all, 73% of all operations were performed on an emergency basis. All hospitals reported unreliable supplies of water and electricity. Essential equipment was missing across all hospitals, with no pulse oximeters found at any facilities. A uniform reporting mechanism for outcomes did not exist.

Conclusions

There is a lack of vital human resources and infrastructure to provide adequate, safe surgery at many of the government hospitals in Uganda. A large number of surgical procedures are undertaken despite these austere conditions. Many areas that need policy development and international collaboration are evident. Surgical services need to become a greater priority in health care provision in Uganda as they could promise a significant reduction in morbidity and mortality.
Utility of the Surgical Apgar Score in a District General Hospital
Authors: Thorn Christopher C. , Chan Melanie , Sinha Nihal , Harrison Richard A.
Published: March 2012

Background

The Surgical Apgar Score (SAS) is a simple tool for intraoperative risk stratification. The aim of this prospective observational study was to assess its performance in predicting outcome after general/vascular and orthopedic surgery and its utility in a U.K. district general hospital.

Method

A prospective cohort of 223 consecutive general, vascular, and orthopedic surgical cases was studied. The SAS was calculated for all patients, and its relationship to 30 day mortality and major complication assessed with reference to the mode of surgery (elective or emergent). Statistical analysis of categorical data was performed with Fisher’s exact test and the AUC (area under the curve) on receiver operating characteristic (ROC) analysis. Selected cases were reviewed to assess the potential of the SAS to modify postoperative management.

Results

The proportion of patients who died or experienced major complications increased monotonically with Surgical Apgar Score category in general and vascular but not orthopedic cases. The relative risks of mortality or major complication between SAS categories were less marked than in previous publications. The SAS performed variably on ROC curve analysis, with an AUC of 0.62–0.73. Discrimination achieved significance in general and vascular cases (p = 0.0002) but not in orthopedic cases (p = 0.15). Subgroup analysis of high (SAS < 7) and low risk (SAS ≥ 7) groups demonstrated utility of the score in general surgery and vascular cases overall (p < 0.0001), and in the emergency (p = 0.004) but not elective (p = 0.12) subgroups. Case note review of those patients who died indicated that despite their identification by the SAS, there would have been limited scope to modify outcome.

Conclusion

This study provides further evidence that the SAS is a simple and effective predictive tool in the emergency general and vascular surgical setting. It appears to have a limited role in the management of individual patients after orthopedic surgery and elective general/vascular surgery. The SAS has been proven to reliably stratify risk in larger populations and might be applied most usefully as a marker of quality. Further studies are required to determine whether its application can influence outcome.
A Novel Definition of Extrathyroidal Invasion for Patients with Papillary Thyroid Carcinoma for Predicting Prognosis
Authors: Hotomi Muneki , Sugitani Iwao , Toda Kazuhisa , Kawabata Kazuyoshi , Fujimoto Yoshihide
Published: March 2012

Objectives

Extrathyroidal invasion is one of the most significant risk factors for patients with papillary thyroid carcinoma (PTC). The purpose of this study was to evaluate a novel definition of extrathyroidal invasion for patients with PTC as a method for predicting a patient’s prognosis.

Methods

The prospective study was conducted for consecutive 930 patients with primary PTC who received surgery during 1993–2009. We defined only patients who had preoperative recurrent laryngeal nerve palsy or patients in whom the tumor had invaded to the mucosa of the trachea and/or esophagus as Ex3. Patients with minimal invasion were classified as Ex1, and patients with massive invasion, when we could shave off the tumors, were classified as Ex2. Patients without extrathyroidal invasion were classified as Ex0.

Results

Patients classified Ex3 showed significantly shorter disease‐free survival (p = 0.03) and disease‐specific survival (p = 0.007) than patients classified Ex2. The time to recurrence at resection sites was shorter in patients classified Ex3 than in patients classified Ex2 (p = 0.02). The time to death due to distant metastasis of patients classified Ex3 was significantly shorter than that of patients classified Ex2 (p = 0.02). Within the patients classified Ex3, disease‐specific survival of patients with invasion to other nearby structures was shorter than that of patients with invasion to only recurrent laryngeal nerve (p = 0.008).

Conclusions

The degree and site of invasion is an important prognostic factor for PTC. Our novel classification of extrathyroidal invasion is valuable in predicting the prognosis of PTC.
Adenosine, dopamine and serotonin receptors imbalance in lymphocytes of Lesch‐Nyhan patients
Authors: García Marta G. , Puig Juan G. , Torres Rosa J.
Published: March 2012

Lesch‐Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine‐guanine phosphoribosyltransferase enzyme. It is characterized by overproduction of uric acid, jointly with severe motor disability and self‐injurious behaviour which physiopathology is unknown. These neurological manifestations suggest a dysfunction in the basal ganglia, and three neurotransmitters have been implicated in the pathogenesis of the disease: dopamine, adenosine and serotonin. All of them are implicated in motor function and behaviour, and act by binding to specific G‐protein coupled receptors in the synaptic membrane where they seem to be integrated through receptor–receptor interactions. In this work we have confirmed at protein level the previously reported increased expression of DRD5 and the variably aberrant expression of ADORA2A, in LND PBL respect to control PBL. We have also described, for the first time, a decreased expression and protein level of 5‐HTR1A in LND PBL respect to control PBL. If these results were confirmed in the Lesch‐Nyhan patients basal ganglia cells, this would support the hypothesis that pathogenesis of neurological manifestations of Lesch‐Nyhan patients may be related to an imbalance of neurotransmitters, rather than to the isolated disturbance of one of the neurotransmitters, and this fact should be taken into account in the design of pharmacologic treatment for their motor and behavioural disturbances.
The dengue virus M protein localises to the endoplasmic reticulum and forms oligomers
Authors: Wong Sook-San , Haqshenas Gholamreza , Gowans Eric J. , Mackenzie Jason
Published: March 2012

The dengue virus membrane (M) protein is a key component of the mature virion. Here, we characterised the cellular behaviour of M using a recombinant protein construct to understand its inherent properties. Using confocal microscopy, we showed that M and its intracellular precursor, prM, localised to the endoplasmic reticulum. M protein was also detected on the cell surface and secreted, suggesting that M can enter the secretory pathway. In addition, cross‐linking studies showed that M can form dimers and tetramers. These findings suggest that M behaves as a secretory protein analogous to the major envelope protein E.
SnoN signaling in proliferating cells and postmitotic neurons
Authors: Bonni Shirin , Bonni Azad
Published: March 2012

The transcriptional regulator SnoN plays a fundamental role as a modulator of transforming growth factor beta (TGFβ)‐induced signal transduction and biological responses. In recent years, novel functions of SnoN have been discovered in both TGFβ‐dependent and TGFβ‐independent settings in proliferating cells and postmitotic neurons. Accumulating evidence suggests that SnoN plays a dual role as a corepressor or coactivator of TGFβ‐induced transcription. Accordingly, SnoN exerts oncogenic or tumor‐suppressive effects in epithelial tissues. At the cellular level, SnoN antagonizes or mediates the ability of TGFβ to induce cell cycle arrest in a cell‐type specific manner. SnoN also exerts key effects on epithelial‐mesenchymal transition (EMT), with implications in cancer biology. Recent studies have expanded SnoN functions to postmitotic neurons, where SnoN orchestrates key aspects of neuronal development in the mammalian brain, from axon growth and branching to neuronal migration and positioning. In this review, we will highlight our understanding of SnoN biology at the crossroads of cancer biology and neurobiology.
Human apolipoprotein L1 (ApoL1) in cancer and chronic kidney disease
Authors: Hu Chien-An A. , Klopfer Edward I. , Ray Patricio E.
Published: March 2012

Human apolipoprotein L1 (ApoL1) possesses both extra‐ and intra‐cellular functions crucial in host defense and cellular homeostatic mechanisms. Alterations in ApoL1 function due to genetic, environmental, and lifestyle factors have been associated with African sleeping sickness, atherosclerosis, lipid disorders, obesity, schizophrenia, cancer, and chronic kidney disease (CKD). Importantly, two alleles of APOL1 carrying three coding‐sequence variants have been linked to CKD, particularly in Sub‐Saharan Africans and African Americans. Intracellularly, elevated ApoL1 can induce autophagy and autophagy‐associated cell death, which may be critical in the maintenance of cellular homeostasis in the kidney. Similarly, ApoL1 may protect kidney cells against renal cell carcinoma (RCC). We summarize the role of ApoL1 in RCC and CKD, highlighting the critical function of ApoL1 in autophagy.
Intraindividual cognitive decline using a brief computerized cognitive screening test
Authors: Darby David G. , Pietrzak Robert H. , Fredrickson Julia , Woodward Michael , Moore Lynette , Fredrickson Amy , Sach Jack , Maruff Paul
Published: March 2012

Background

Progressive intraindividual decline in memory and cognition is characteristic of dementia and may be useful in detecting very early Alzheimer's disease pathology.

Methods

This study evaluated the slopes of cognitive performance over a 12‐month period in 263 healthy, community‐dwelling, adult volunteers aged ≥50 years. Participants completed a brief computerized battery of cognitive tests (CogState) at baseline and during 3‐, 6‐, 9‐, and 12‐month follow‐up assessments. Linear mixed models were used to estimate age‐adjusted mean slopes and 95% confidence intervals of change for each of the cognitive measures.

Results

By defining age‐adjusted mean slopes, and 95% confidence intervals for a measure of episodic memory, individuals with greater than expected decline (equal to or lower than the fifth percentile level of decline) were identified. From these, four individuals completed a full medical, neurologic, and neuropsychological evaluation, with none of them fulfilling criteria for mild cognitive impairment, but three (75%) having positive amyloid‐positron emission tomographic scans.

Conclusions

Intraindividual decline in cognitive performance can be detected in otherwise healthy, community‐dwelling, older persons, and this may deserve further study as a potential indicator of early Alzheimer's disease pathology.
Islamic investing
Authors: Walkshäusl Christian , Lobe Sebastian
Published: March 2012

Using a large international sample of 35 developed and emerging markets, we analyze whether Islamic indices exhibit a different performance to conventional benchmarks. While there is no compelling evidence of performance differences in robust Sharpe ratio tests and after controlling for market risk, we find a significantly positive four‐factor alpha for the aggregate developed markets region. This outperformance stems, however, mainly from the U.S. and is largely attributable to the exclusion of financial stocks in Sharia‐screened portfolios. As the extensive downturn of financials is related to the recent financial crisis, we do not argue that this outperformance will continue over time. The style analysis reveals that Islamic indices invest mainly in growth stocks and positive momentum stocks. This, for a passive portfolio intriguing result can, however, be explained by the strong sector allocation towards energy firms and their strong momentum characteristic during the sample period.
Constitutional Agenda-Setting Through Discretion in Rule Interpretation: Why the European Parliament Won at Amsterdam
Authors: HIX SIMON
Published: March 2012

It is a widely accepted that the 1999 Treaty of Amsterdam significantly increased the powers of the European Parliament (EP). The critical question, however, is why the European Union (EU) governments did this. I argue, contrary to existing explanations, that these changes came about because the EP was a ‘constitutional agenda-setter’. The rules in the EU Treaty, as established at Maastricht, were incomplete contracts, and the EU governments had imperfect information about the precise operation of the Treaty. As a result, the EP was able to re-interpret these rules to its advantage and threaten not to co-operate with the governments unless they accepted the EP's interpretations. The article shows how this process of discretion, interpretation and acceptance worked in the two main areas of EP power: in the legislative process (in the reform of the co-decision procedure), and in executive appointment (in the reform of the Commission investiture procedure). The article concludes that ‘agenda-setting through discretion in rule interpretation’ is a common story in the development of the powers of parliaments, both at the domestic and EU levels.
Becoming Tolerant? Short-Term Changes in Russian Political Culture
Authors: GIBSON JAMES L.
Published: March 2012

Though ordinary Russians have embraced many aspects of democratic culture, their learning to tolerate their political enemies has been the most difficult democratic lesson for many. In this article, I analyse change in political tolerance in Russia, using panel data I collected in 1996 and 1998 in a nationally representative sample of Russians. Two bodies of theory are considered to generate hypotheses about change: the conventional cross-sectional model of the aetiology of tolerance; and experiential theory, based on perceptions of the performance of both the economic and political systems. The dynamic character of the model is provided by perceptions of the performance of the economy, of the political system and of the seriousness of the crime problem in Russia. Many of my findings are unexpected. For instance, tolerance seems to beget tolerance, in the sense that, over time, those who are tolerant tend to perceive diminishing threats from their political enemies. Yet threat perceptions are sustained by perceptions of the political and economic conditions in contemporary Russia. Perceptions of the change in crime are especially important since they seem to exacerbate perceptions of political threat, thereby eroding both political tolerance and support for democratic institutions and process. Paradoxically, threat is also sustained by democratic values – those who support democratic institutions and processes are more likely to perceive threats from their political enemies, a finding peculiar to the unsettled Russian case. Thus, this analysis goes some distance towards discovering the causes of changes in both Russian tolerance and intolerance.
Review Article: Understanding the Regulatory State
Authors: MORAN MICHAEL
Published: March 2012

misunderstanding the regulatory state?

In the last quarter of the twentieth century something transformed government across the advanced capitalist world, and a large amount of comparative political enquiry is now concerned with pinning a convincing label on that transformation. Of the many candidates the subject of this review article has proved especially popular. As I will show, a regulatory state is now commonly said to exist in a wide range of geographical and institutional settings: writers speak of a regulatory state in the United States and in Britain; of the European regulatory state; and even of refinements like ‘a regulatory state inside the state’.
“For the Hungry Have No Past nor Do They Belong to a Political Party”: Debates over German Hunger after World War II
Authors: Weinreb Alice
Published: March 2012

When World War II finally came to an end, the Allied forces were primed to face a world of hunger. Since the earliest days of the conflict, experts throughout Europe and Asia had been predicting that the unfathomable scale of the war would result in a massive and permanent restructuring of the global food economy. Military victory itself was cast as inextricably intertwined with control over foodstuffs. In 1940, the British nutritionist and future Director-General of the United Nation's Food and Agriculture Organization, Sir John Boyd-Orr, had warned that “we are only at the beginning of what looks like a long grim struggle, in which food may be, as it was in the last war, the decisive factor for victory.” Even more ominously, such experts foresaw the end of the war as ushering in a world defined less by peace and more by hunger. Australian economist and humanitarian Frank Lidgett McDougall axiomatically declared that “the exigencies of war and of the relief period will in the next few years render almost all men everywhere in the world highly food-conscious.” The recognition of the global ramifications of hunger meant that, as Nick Cullather put it in his recent article on the history of the calorie, “the construction of a postwar international order began with food.”
Safety and efficacy of high-protein diets for weight loss
Authors: Johnstone Alexandra M.
Published: March 2012

Dietary strategies that can help reduce hunger and promote fullness are beneficial for weight control, since these are major limiting factors for success. High-protein (HP) diets, specifically those that maintain the absolute number of grams ingested, while reducing energy, are a popular strategy for weight loss (WL) due to the effects of protein-induced satiety to control hunger. Nonetheless, both the safety and efficacy of HP WL diets have been questioned, particularly in combination with low-carbohydrate advice. Nonetheless, for short-to-medium-term intervention studies (over several months), increasing the energetic contribution of protein does appear effective. The effects of HP diets on appetite, bone health, renal function, blood pressure, cardiovascular bio-markers, antioxidant status, gut health and psychological function are discussed. Further research is warranted to validate the physiological effects of HP diets over longer periods of time, including studies that modify the quality of macronutrients (i.e. the type of carbohydrate, fat and protein) and the interaction with other interventions (e.g. exercise and dietary supplements).
Chilling curves for Piaractus mesopotamicus (Holmberg, 1887) embryos stored at −8°C
Authors: Lopes Taís da S. , Streit Danilo Pedro , Fornari Darci Carlos , de Oliveira Diego , Ribeiro Ricardo Pereira , Romagosa Elizabeth
Published: March 2012

The present study investigates the effect of different slow chilling curves on the storage of pacu (Piaractus mesopotamicus) embryos submitted to chilling at −8°C. Embryos at the blastopore closure stage were divided into two groups: G1 – embryos exposed to cryoprotectant solution containing methanol (10%) and sucrose (0.5 M), treated as follows: (T1) taken directly from room temperature to the refrigerator without being submitted to the curve; (T2) chilling curve of 0.5°C/min; and (T3) chilling curve of 1°C/min; and G2 – the cryoprotectant solution alone was submitted to these same temperatures, receiving the embryos only after temperature had decreased, corresponding to treatments T4, T5 and T6, respectively. Treatments were kept at −8°C for a period of 6 h. Embryo development was evaluated for each treatment, with six replicates in an entirely randomized design. Survival among embryos not submitted to refrigeration was 94.3 ± 8.05%. Percentage of total larvae (TL) and addled eggs (AE) did not differ statistically between the groups, although percentage of swimming larvae (SL) exhibited higher values in G1 for the 1°C/min curve. Furthermore, when comparing the three chilling curves, a decrease of 1°C/min resulted in the highest TL percentage (90.85%), followed by the 0.5°C/min curve (78.52%). Thus, the use of 1°C/min chilling curves is recommended for P. mesopotamicus embryos stored for 6 h at −8°C.
Effects of cryostorage on human sperm chromatin integrity
Authors: Fortunato Adriana , Leo Rita , Liguori Francesca
Published: March 2012

The integrity of sperm chromatin structure has proven to be of great importance for human fertility. In this study, we investigated whether sperm cryopreservation has an effect on nuclear DNA tertiary structure, (i.e. condensation), measured by aniline blue staining, in 103 male patients who required consultation for hypo-fertility. Sperm DNA damage was significantly higher in patients showing oligospermia and severe morphological abnormalities than in native sperm populations. Furthermore we observed that chromatin decondensation was related to the cryostorage technique and to the duration of storage. This increase in decondensation was highly significant (P< 0.01) immediately after cryopreservation and from 90 days of cryostorage onwards. The possible mechanisms involved in sperm chromatin cryoinjury and the need to incorporate new methods for testing sperm nuclear structure alteration into the routine spermiogram are discussed.
Does congenital heart disease severely jeopardise family life and pregnancies? Obstetrical history of women with congenital heart disease in a single tertiary centre
Authors: Morissens Marielle , Viart Pierre , Tecco Laura , Wauthy Pierre , Michiels Simone , Dessy Hugues , Malekzadeh Milani Sophie , Verbeet Thierry , Castro Rodriguez Jose
Published: March 2012

Aim

Women with congenital heart disease are often considered to be restricted in their obstetrical life and even their marital life. Our single-centre study aimed to determine the real-life situation of these women with regard to successful family life and any pregnancy complications they may experience.

Methods

From our database of adults with congenital heart disease, 160 of 178 women completed a questionnaire and had their files reviewed. They were classified into three groups according to their pregnancy risk – “good condition” group, no pregnancy restriction; “at-risk” group, pregnancy allowed with close follow-up at a tertiary centre; and “contraindicated” group, pregnancy inadvisable.

Results

The proportion of women in a relationship was 46% with no difference between the three groups. In the groups where pregnancy was allowed, 55% of women conceived a child. The total incidence of spontaneous abortion was 21%. The rate of caesarean section was 15%. The incidence of cardiac failure was 4.7%, arrhythmia 1.2%, endocarditis 1.2%, hypertension 2.4%, and preeclampsia 1.2%. Foetal complications included prematurity and/or low birth weight (9.5%) and one foetal malformation (0.82%).

Conclusion

Women with severe congenital heart disease are willing to start a family and are successful in this enterprise. Although the complication rate during pregnancy in congenital heart disease remains high, with good monitoring these pregnancies occur without severe complications and a low rate of medical abortion or caesarean section.
Stenting across head and neck vessels using covered stents for persisting aortic arch obstruction
Authors: Bentham James R. , Oswal Nilesh , Yates Robert
Published: March 2012

Objective

To describe endovascular stent placement using partially covered stents to preserve flow in head and neck vessels.

Background

Endovascular stent placement has become established as a first-line therapy for native coarctation of the aorta or re-coarctation in older children and adults. Increasingly covered stents are becoming the preferred option over bare-metal stents because of the perceived lower risk of aneurysm formation. Open-cell bare-metal stents are chosen when there is a high likelihood of jailing a head and neck vessel. Here we describe partial uncovering of a covered stent before implantation to allow flow through the uncovered portion of the stent to the branch vessel but preserve the covering over the majority of the remaining stent.

Methods

We describe two cases with aortic arch hypoplasia and re-coarctation, both of which required two partially uncovered stents for a satisfactory result.

Conclusions

Endovascular stent placement is becoming the preferred option in the management of coarctation of the aorta in older children and adults. Strategies to deal with transverse arch hypoplasia and multiple levels of aortic arch obstruction frequently involving branch vessels or aneurysms need to be considered before these procedures are embarked upon. Partially uncovering stents may afford more protection than using bare-metal stents in the transverse and distal arch while preserving flow in head and neck branches, and is a technically straightforward procedure.
Hemiazygos vein “steal hypoxic-syndrome” after hemi-Fontan operation: comprehensive four-dimensional flow magnetic resonance visualisation
Authors: Valverde Israel , Razishankar Aarthi , Miller Owen , Razavi Reza
Published: March 2012

A 2-year-old boy with hypoplastic left heart syndrome and previous hemi-Fontan palliation surgery was referred for cardiovascular magnetic resonance evaluation because of progressive cyanosis. This case report illustrates the advantages of non-invasive four-dimensional magnetic resonance imaging for comprehensive identification and quantification of venovenous collaterals in patients with palliated hemi-Fontan staged surgery.
Assessment of cavopulmonary connections by advanced imaging: value of flat-detector computed tomography
Authors: Glöckler Martin , Koch Andreas , Halbfaß Julia , Greim Verena , Rüffer Andrè , Cesnjevar Robert , Achenbach Stephan , Dittrich Sven
Published: March 2012

Objectives

To investigate the impact of flat-detector computed tomography on the clinical assessment of patients with cavopulmonary connections, and to evaluate the obtained diagnostic accuracy and supplementary information, as well as the value of overlaid three-dimensional reconstructions on fluoroscopic images during catheter-based interventions.

Methods

We analysed 31 consecutive patients retrospectively in whom flat-detector computed tomography was used to visualise the cavopulmonary connection. We investigated patients with cavopulmonary connections either early post-operatively (first group), before converting to a total cavopulmonary connection (second group), and patients with failing total cavopulmonary connection (third group). Flat-detector computed tomography based on a single rotational angiography was used to create a three-dimensional vascular model. The clinical value of flat-detector computed tomography was evaluated using standard categories of diagnostic utility. Used contrast volume and radiation exposure were quantified.

Results

Within 18 months, flat-detector computed tomography was performed in 31 cases with cavopulmonary connections. The median age was 1.9 years (range 0.3–43 years). In the first group, we found anomalies in 4 out of 8 cases, which led to therapeutic or prophylactic procedures; in the second and third groups, we performed interventions in 14 out of 23 cases. The overall clinical value was always rated superior to conventional biplane angiography. The median dose area product was 91.8 microgray square metres (range 33.0–679.3 microgray square metres). The required contrast medium was 2.08 millilitres per kilogram (range 0.66–4.7 millilitres per kilogram).

Conclusion

Flat-detector computed tomography improves the diagnostic accuracy in cavopulmonary connections and provides additional diagnostic information, which may lead to therapeutic or prophylactic procedures. Overlaid three-dimensional images on fluoroscopy facilitate and provide security for interventions.
Outsourcing Business and I.T. Services: the Evidence of Success, Robust Practices and Contractual Challenges
Authors: Lacity Mary , Willcocks Leslie
Published: March 2012

In this article, Mary Lacity and Leslie Willcocks review the practice of outsourcing business and information technology services. Research finds that outsourcing can deliver value to client organisations, but that it takes a tremendous amount of detailed management by clients and providers to realise expected benefits. The proven practices that contribute to positive outsourcing outcomes can be summarised as contractual governance, relational governance, client retained capabilities, and provider capabilities. Despite outsourcing's maturity, some enduring contractual challenges remain, particularly in the areas of incentive pricing and contract adaptability.
Law Libraries: SOS (Save Our Service)
Authors: Alcock Susan
Published: March 2012

In this article Susan Alcock examines the issues relating to outsourcing of legal information services. She reflects the many concerns felt within the industry and offers many points-of-view that have been collected from those working in the field as in-house law librarians and legal information professionals.