bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression, purification, and characterization of authentic mouse prolactin obtained in Escherichia coli periplasmic space
Authors: Suzuki Miriam F. , Arthuso Fernanda S. , Oliveira João E. , Oliveira Nélio A. J. , Goulart Herbert R. , Capone Marcos V. N. , Ribela Maria Teresa C. P. , Bartolini Paolo , Soares Carlos R. J.
Published: March 2012

Prolactin (PRL) is a pleiotropic hormone produced by lactotroph cells of the anterior pituitary gland and is mainly related to lactation control and reproduction. Recombinant mouse prolactin (r‐mPRL), never obtained in its authentic form, can be very useful for research and tests in animal models, in which human prolactin (hPRL) is usually employed in a heterologous mode. Synthesis of r‐mPRL was carried out here via secretion in Escherichia coli periplasmic space using a plasmid containing mPRL cDNA joined to the DsbA signal peptide sequence under the control of a constitutive major leftward promoter of the bacteriophage λ (λPL). Fermentation in a pilot bioreactor was carried out at 30°C, with 6 H of induction at 37°C, reaching an optical density of 23 A600 units, a specific yield of 0.06–0.1 µg mPRL/(mL A600), and a concentration of up to 2.2 µg/mL. Even with such a low yield and a poor mass fraction, r‐mPRL was purified via a three‐step laboratory process based on hydrophobic chromatography, reversed‐phase high‐performance liquid chromatography, and high‐performance size‐exclusion chromatography (HPSEC). The purified hormone was then characterized using SDS‐PAGE, Western blotting, and HPSEC and showed, by Nb2 rat lymphoma cell proliferation assay, a bioactivity of 39.5 IU/mg, determined against the International Standard of recombinant hPRL [World Health Organization (WHO)‐97/714].
Innovation in biological microscopy: Current status and future directions
Authors: Swedlow Jason R.
Published: March 2012

The current revolution in biological microscopy stems from the realisation that advances in optics and computational tools and automation make the modern microscope an instrument that can access all scales relevant to modern biology – from individual molecules all the way to whole tissues and organisms and from single snapshots to time‐lapse recordings sampling from milliseconds to days. As these and more new technologies appear, the challenges of delivering them to the community grows as well. I discuss some of these challenges, and the examples where openly shared technology have made an impact on the field.
Ruthenium and Rhodium‐Catalyzed Carbonylation Reactions
Authors: Wu Xiao‐Feng , Neumann Helfried
Published: March 2012

Over the last few decades, carbonylation reactions have been accepted as important chemical transformations for both academic and industrial research. Carboxylic acid derivatives are the main product of carbonylation and are widely used in organic synthesis and fine chemicals preparation. Carbonylation reactions can increase the carbon chain of parent molecules, while introducing a carbonyl group. Herein, the main developments on ruthenium‐ and rhodium‐catalyzed carbonylation are summarized. Compared with palladium catalysts, ruthenium and rhodium catalyzed reactions are a powerful method for activating CH bonds under mild and phosphine free conditions.
IGUS – 50 Years of International Collaboration to the Benefit of Safety in the Field of Unstable Substances
Authors: de Jong E. , Lightfoot P. , Mak W. , Pfeil N. , Wehrstedt K.‐D.
Published: March 2012

IGUS is the International Group of Experts on the Explosion Risks of Unstable Substances. Today, the aim of the group is to exchange information on the behavior of unstable substances and to improve safety in production, storage, transport, and use of these substances. Full members of IGUS work for governments and independent research organizations. Experts from industry can and do attend meetings by invitation. IGUS's 50th anniversary in 2012 gives reason to have a closer look at the questions of how IGUS came to be, what IGUS's aims and objectives were, and how it is organized and working today.
2D Porous Honeycomb Polymers versus Discrete Nanocubes from Trigonal Trinuclear Complexes and Ligands with Variable Topology
Authors: Dorofeeva Victoria N. , Kolotilov Sergey V. , Kiskin Mikhail A. , Polunin Ruslan A. , Dobrokhotova Zhanna V. , Cador Olivier , Golhen Stéphane , Ouahab Lahcène , Eremenko Igor L. , Novotortsev Vladimir M.
Published: March 2012

Trinuclear building block {Fe2NiO(Piv)6} (Piv=pivalate), which possessed pseudo‐D3h symmetry, was linked by two ligands, pseudo‐D3h ligand tris‐(4‐pyridyl)pyridine (L1) and C2v ligand 4‐(N,N‐dimethylamino)phenyl‐2,6‐bis(4‐pyridyl)pyridine (L2) into two products with different topologies: 2D coordination polymer [Fe2NiO(Piv)6(L1)]n (1), and discrete molecule [{Fe2NiO(Piv)6}8{L2}12], which had a nanocube structure (2). In compound 1, trinuclear {Fe2NiO(Piv)6} blocks were linked through ligand L1 into layers with honeycomb topology. In compound 2, eight trinuclear blocks were located in the vertices of the nanocube, with each L2 ligand linked to two {Fe2NiO(Piv)6} units. In the crystal structure, these nanocubes formed infinite catenated chains. Analysis of possible structures that could be assembled from these building blocks showed that compounds 1 and 2 corresponded to their respective predicted topologies. Compound [1⋅solvent] possessed a porous structure, in which the voids were filled by solvent molecules (DMF or DMSO). This structure was retained following desolvation, and compound 1 absorbed significant quantities of N2 and H2 at 78 K (SBET=730 m2 g−1, H2 sorption capacity: 0.9 % by weight at 865 Torr). Desolvation of [2⋅solvent] led to disorder of its crystal structure, and compound 2 only adsorbed negligible quantities of N2 but adsorbed 0.27 % H2 (by weight) at 855 Torr and 78 K. The magnetic properties of these complexes (temperature dependence of molar magnetic susceptibility) were governed by the magnetic properties of the trinuclear “building block”.
Circumcision and the risk of prostate cancer
Authors: Wright Jonathan L. , Lin Daniel W. , Stanford Janet L.
Published: March 2012

BACKGROUND:

Several lines of evidence support a role for infectious agents in the development of prostate cancer (PCa). In particular, sexually transmitted infections (STIs) have been implicated in PCa etiology, and studies have found that the risk of acquiring a STI can be reduced with circumcision. Therefore, circumcision may reduce PCa risk.

METHODS:

Participant data collected as part of 2 population‐based case‐control studies of PCa were analyzed. Self‐reported circumcision status, age at circumcision, and age at first sexual intercourse were recorded along with a history of STIs or prostatitis. Multivariate logistic regression was used to estimate the relative risk of PCa by circumcision status.

RESULTS:

Data from 1754 cases and 1645 controls were available. Circumcision before first sexual intercourse was associated with a 15% reduction in risk of PCa compared to that of uncircumcised men (95% confidence interval [CI], 0.73‐0.99). This risk reduction was observed for cases with both less aggressive (odds ratio, 0.88; 95% CI, 0.74‐1.04) and more aggressive (odds ratio, 0.82; 95% CI, 0.66‐1.00) PCa features.

CONCLUSIONS:

Circumcision before first sexual intercourse is associated with a reduction in the relative risk of PCa in this study population. These findings are consistent with research supporting the infectious/inflammation pathway in prostate carcinogenesis. Cancer 2012. © 2012 American Cancer Society.
Property–Performance Control of Multidimensional, Hierarchical, Single‐Crystalline ZnO Nanoarchitectures
Authors: Cheng Qijin , Ostrikov Kostya (Ken)
Published: March 2012

Diverse morphologies of multidimensional hierarchical single‐crystalline ZnO nanoarchitectures including nanoflowers, nanobelts, and nanowires are obtained by use of a simple thermal evaporation and vapour‐phase transport deposition technique by placing Au‐coated silicon substrates in different positions inside a furnace at process temperatures as low as 550 °C. The nucleation and growth of ZnO nanostructures are governed by the vapour–solid mechanism, as opposed to the commonly reported vapour–liquid–solid mechanism, when gold is used in the process. The morphological, structural, compositional and optical properties of the synthesized ZnO nanostructures can be effectively tailored by means of the experimental parameters, and these properties are closely related to the local growth temperature and gas‐phase supersaturation at the sample position. In particular, room‐temperature photoluminescence measurements reveal an intense near‐band‐edge ultraviolet emission at about 386 nm for nanobelts and nanoflowers, which suggests that these nanostructures are of sufficient quality for applications in, for example, optoelectronic devices.
B3N3 Borazine Substitution in Hexa‐peri‐Hexabenzocoronene: Computational Analysis and Scholl Reaction of Hexaphenylborazine
Authors: Tönshoff Christina , Müller Matthias , Kar Tapas , Latteyer Florian , Chassé Thomas , Eichele Klaus , Bettinger Holger F.
Published: March 2012

The doping of graphene molecules by borazine (B3N3) units may modify the electronic properties favorably. Therefore, the influence of the substitution of the central benzene ring of hexa‐peri‐hexabenzocoronene (HBC, C42H18) by an isoelectronic B3N3 ring resulting in C36B3N3H18 (B3N3HBC) is investigated by computational methods. For comparison, the isoelectronic and isosteric all‐B/N molecule B21N21H18 (termed BN) and its carbon derivative C6B18N18H18 (C6BN), obtained by substitution of a central B3N3 by a C6 ring, are also studied. The substitution of C6 in the HBC molecule by a B3N3 unit results in a significant change of the computed IR vibrational spectrum between 1400 and 1600 cm−1 due to the polarity of the borazine core. The properties of the BN molecule resemble those of hexagonal boron nitride, and substitution of the central B3N3 ring by C6 changes the computed IR vibrational spectrum only slightly. The allowed transitions to excited states associated with large oscillator strengths shift to higher energy upon going from HBC to B3N3HBC, but to lower energy upon going from BN to C6BN. The possibility of synthesis of B3N3HBC from hexaphenylborazine (HPB) using the Scholl reaction (CuCl2/AlCl3 in CS2) is investigated. Rather than the desired B3N3HBC an insoluble and X‐ray amorphous polymer P is obtained. Its analysis by IR and 11B magic angle spinning NMR spectroscopy reveals the presence of borazine units. The changes in the 11B quadrupolar coupling constant CQ, asymmetry parameter η, and isotropic chemical shift δiso(11B) with respect to HPB are in agreement with a structural model that includes B3N3HBC‐derived monomeric units in polymer P. This indicates that both intra‐ and intermolecular cyclodehydrogenation reactions take place during the Scholl reaction of HPB.
Synthesis of PbTe‐SnTe particles by thermal decomposition of salts to create nano‐structured thermoelectric materials
Authors: Leontyev V. G. , Ivanova L. D. , Bente K. , Gremenok V. F.
Published: March 2012

Micro‐ and nanocrystalline particles of Pb‐Sn‐Te mixed crystals were synthesized using thermal decomposition and chemical interaction of lead acetate, tin oxalate and tellurium powder mixture in H2 atmosphere. For the process parameter optimization data of thermal gravimetry (TG), X‐ray diffraction (XRD), electronic microscopy (TEM, SEM) and measurements of the specific surface of particles were used. Additionally the influence of gas phases on the decomposition kinetics, crystal structure, size, specific surface of the particles, gains composition and the physical properties were analyzed. Seebeck coefficient values increased and conductivity decreased with decreasing tin concentration. The presented method for preparing PbTe‐SnTe polydisperse particles is developed to create nano‐structured thermoelectric materials with high figure of merit. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crystal growth and luminescent properties of Eu activated strontium iodide crystals
Authors: Zhang Ye , Shi Hongsheng , Shu Kangying , Qin Laishun , Ren Guohao
Published: March 2012

SrI2:Eu crystals with 1.5 inch diameter were grown by the vertical Bridgman method. The melting point of SrI2 doped with 5 at % Eu grown feedstock was determined to be 526 °C by differential scanning calorimetry (DSC). XRD proved Pbca structure of SrI2 when the SrI2:Eu sample was packaged with polyethylene film in air. The luminescent properties of SrI2:Eu crystals are presented. Under the excitation of UV light or X‐ray, the crystals exhibit a single luminescent peak centered at 435 nm. The decay time of SrI2:5%Eu crystal excited by UV were fitted to be 1.9 μs. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Enabling user‐guided segmentation and tracking of surface‐labeled cells in time‐lapse image sets of living tissues
Authors: Mashburn David N. , Lynch Holley E. , Ma Xiaoyan , Hutson M. Shane
Published: March 2012

To study the process of morphogenesis, one often needs to collect and segment time‐lapse images of living tissues to accurately track changing cellular morphology. This task typically involves segmenting and tracking tens to hundreds of individual cells over hundreds of image frames, a scale that would certainly benefit from automated routines; however, any automated routine would need to reliably handle a large number of sporadic, and yet typical problems (e.g., illumination inconsistency, photobleaching, rapid cell motions, and drift of focus or of cells moving through the imaging plane). Here, we present a segmentation and cell tracking approach based on the premise that users know their data best–interpreting and using image features that are not accounted for in any a priori algorithm design. We have developed a program, SeedWater Segmenter, that combines a parameter‐less and fast automated watershed algorithm with a suite of manual intervention tools that enables users with little to no specialized knowledge of image processing to efficiently segment images with near‐perfect accuracy based on simple user interactions. © 2012 International Society for Advancement of Cytometry
Cell–cell adhesion defects in Mrj mutant trophoblast cells are associated with failure to pattern the chorion during early placental development
Authors: Watson Erica D. , Hughes Martha , Simmons David G. , Natale David R.C. , Sutherland Ann E. , Cross James C.
Published: March 2012

Immunofluorescence staining of actin (red), keratin 18 (green) and DNA (blue) in Mrj‐/‐ trophoblast stem cells cultured in the absence of growth factors. From Watson et al., Developmental Dynamics 240:2505–2519, 2011.
Fibroblast growth factor and bone morphogenetic protein signaling are required for specifying prechondrogenic identity in neural crest‐derived mesenchyme and initiating the chondrogenic program
Authors: Kumar Megha , Ray Poulomi , Chapman Susan C.
Published: March 2012

The pharyngeal endoderm is hypothesized as the source of local signals that specify the identity of neural crest‐derived mesenchyme in the arches. Sox9 is induced and maintained in prechondrogenic cells during condensation formation and endochondral ossification. Using explant culture, we determined that pharyngeal endoderm was sufficient, but not necessary for specifying prechondrogenic identity, as surrounding tissues including the otic vesicle can compensate for signals from the pharyngeal endoderm. Multiple Fgf genes are expressed specifically in the pharyngeal endoderm subjacent to the neural crest‐derived mesenchyme. Fibroblast growth factor (FGF) signaling is both sufficient and required for specification of Sox9 expression and specification of prechondrogenic identity, as demonstrated by the addition of recombinant FGF protein or the FGF receptor inhibitor (SU5402) to explanted tissue, respectively. However, FGF signaling cannot maintain Sox9 expression or initiate the chondrogenic program as indicated by the absence of Col2a1 transcripts. Bone morphogenetic protein (BMP) 4 signaling can induce and maintain Sox9 expression in isolated mesenchyme, but only in combination with FGF signaling induce Col2a1 expression, and thus, chondrogenesis. Given the spatiotemporal expression patterns of FGFs and BMPs in the pharyngeal arches, we suggest that this may represent a general mechanism of local signals specifying prechondrogenic identity and initiation of the chondrogenic program. Developmental Dynamics 241:1091–1103, 2012. © 2012 Wiley Periodicals, Inc.
Peri‐implantation lethality in mice lacking the PGC‐1‐related coactivator protein
Authors: He Xin , Sun Chen , Wang Feng , Shan Aijing , Guo Ting , Gu Weiqiong , Cui Bin , Ning Guang
Published: March 2012

Background: Members of the PPARγ coactivator‐1 (PGC‐1) family are central transcriptional coactivators that regulate cell metabolic processes ranging from mitochondrial biogenesis to oxidative respiration. PGC‐1‐related coactivator (PPRC1 or PRC), initially identified as a member of the PGC‐1 family, is believed to regulate mitochondria biogenesis, respiration pathways, and cell proliferation. However, its physiological role is not clearly understood. Here, we investigate the biological functions of PPRC1 in vivo using PPRC1 deficient mice generated by gene targeting. Results: Homozygous deficient PPRC1 mice failed to form egg cylinders and died after implantation but before embryonic day 6.5, whereas mice heterozygous for PPRC1 were viable, fertile and indistinguishable from their wild‐type littermates. Furthermore, PPRC1 mRNA was expressed at the embryonic stage before implantation and was rapidly up‐regulated during the first day of embryoid body formation. The PPRC1 mRNA was then subsequently down‐regulated, although its precise function at this stage of development was unclear. Conclusions: This is the first study to suggest a nonredundant role for PPRC1 in mouse early embryonic development. Developmental Dynamics 241:975–983, 2012. © 2012 Wiley Periodicals, Inc.
Normalized shape and location of perturbed craniofacial structures in the Xenopus tadpole reveal an innate ability to achieve correct morphology
Authors: Vandenberg Laura N. , Adams Dany S. , Levin Michael
Published: March 2012

Background: Embryonic development can often adjust its morphogenetic processes to counteract external perturbation. The existence of self‐monitoring responses during pattern formation is of considerable importance to the biomedicine of birth defects, but has not been quantitatively addressed. To understand the computational capabilities of biological tissues in a molecularly tractable model system, we induced craniofacial defects in Xenopus embryos, then tracked tadpoles with craniofacial deformities and used geometric morphometric techniques to characterize changes in the shape and position of the craniofacial structures. Results: Canonical variate analysis revealed that the shapes and relative positions of perturbed jaws and branchial arches were corrected during the first few months of tadpole development. Analysis of the relative movements of the anterior‐most structures indicates that misplaced structures move along the anterior–posterior and left–right axes in ways that are significantly different from their normal movements. Conclusions: Our data suggest a model in which craniofacial structures use a measuring mechanism to assess and adjust their location relative to other local organs. Understanding the correction mechanisms at work in this system could lead to the better understanding of the adaptive decision‐making capabilities of living tissues and suggest new approaches to correct birth defects in humans. Developmental Dynamics 241:863–878, 2012. © 2012 Wiley Periodicals, Inc.
Incomplete splicing, cell division defects, and hematopoietic blockage in dhx8 mutant zebrafish
Authors: English Milton A. , Lei Lin , Blake Trevor , Wincovitch Stephen M. , Sood Raman , Azuma Mizuki , Hickstein Dennis , Liu P. Paul
Published: March 2012

Background: Vertebrate hematopoiesis is a complex developmental process that is controlled by genes in diverse pathways. To identify novel genes involved in early hematopoiesis, we conducted an ENU (N‐ethyl‐N‐nitrosourea) mutagenesis screen in zebrafish. The mummy (mmy) line was investigated because of its multiple hematopoietic defects. Results: Homozygous mmy embryos lacked circulating blood cell types and were dead by 30 hr post‐fertilization (hpf). The mmy mutants did not express myeloid markers and had significantly decreased expression of progenitor and erythroid markers in primitive hematopoiesis. Through positional cloning, we identified a truncation mutation in dhx8 in the mmy fish. dhx8 is the zebrafish ortholog of the yeast splicing factor prp22, which is a DEAH‐box RNA helicase. mmy mutants had splicing defects in many genes, including several hematopoietic genes. mmy embryos also showed cell division defects as characterized by disorganized mitotic spindles and formation of multiple spindle poles in mitotic cells. These cell division defects were confirmed by DHX8 knockdown in HeLa cells. Conclusions: Together, our results confirm that dhx8 is involved in mRNA splicing and suggest that it is also important for cell division during mitosis. This is the first vertebrate model for dhx8, whose function is essential for primitive hematopoiesis in developing embryos. Developmental Dynamics 241:879–889, 2012. © 2012 Wiley Periodicals, Inc.
Eating disorder not otherwise specified presentation in the US population
Authors: Le Grange Daniel , Swanson Sonja A. , Crow Scott J. , Merikangas Kathleen R.
Published: March 2012

Objective:

To examine prevalence and clinical correlates of eating disorder not otherwise specified (EDNOS) in the US population.

Method:

Two cross‐sectional surveys of adults and adolescents used the WHO CIDI to assess DSM‐IV criteria for anorexia nervosa (AN), bulimia nervosa (BN), and EDNOS.

Results:

Lifetime prevalence of EDNOS was 4.78% in adolescents and 4.64% in adults. The majority of adolescents and adults with an eating disorder presented with EDNOS. Three‐quarters of participants with EDNOS met criteria for comorbid disorders, while one‐quarter endorsed suicidality. Severity correlates were equally prevalent in EDNOS and AN, whereas comparisons between EDNOS and BN varied by specific correlate and sample. Adolescents with subthreshold AN (SAN) endorsed more anxiety than AN (p < .05), and adolescents and adults with SAN endorsed more suicidal plans than AN (p's < .05).

Discussion:

Findings increase our understanding of the clinical relevance of EDNOS. Eating disorder diagnostic nomenclature requires modification to capture the full spectrum. © 2012 by Wiley Periodicals, Inc. Int J Eat Disord 2012.
Recruitment and retention in an adolescent anorexia nervosa treatment trial
Authors: Brownstone Lisa , Anderson Kristen , Beenhakker Judy , Lock James , Le Grange Daniel
Published: March 2012

Objective:

To investigate recruitment and retention for a randomized controlled trial (RCT) of adolescent anorexia nervosa (AN), as prior studies suggest that these are significant hurdles to completing meaningful RCTs in this population.

Method:

Retrospective analyses of recruitment and retention rates were conducted for a multisite RCT of family‐based treatment (FBT) versus adolescent‐focused therapy (AFT) recruiting adolescents between 12 and 18 years of age with AN.

Results:

Adolescent participants were recruited from a variety of both medical and nonmedical sources. Recruitment goals were met in time (October 2004–March 2007). Percent retention rates were high across both treatment types (84% for FBT and 92% for AFT), and these rates did not differ significantly.

Discussion:

These results reveal that recruitment and retention of adolescent patients with AN to RCTs are feasible in contrast to the experience in adult studies. It is likely that characteristics of our clinical programs make recruitment easier than in other settings, e.g., child and adolescent focused, specialized eating disorders program with an emphasis on outpatient treatment, recognized leaders in the field, and a history of clinical excellence with this population. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012; 45:812–815)
Night eating in obese treatment‐seeking hispanic patients with and without binge eating disorder
Authors: Grilo Carlos M. , Milsom Vanessa A. , Morgan Peter T. , White Marney A.
Published: March 2012

Objective:

To examine the frequency of night eating (NE) and its relation to binge eating disorder (BED), eating‐disorder psychopathology, depression, and metabolic variables in treatment‐seeking obese Hispanic men and women.

Method:

A consecutive series of 79 obese monolingual Spanish‐speaking‐only Hispanic patients with BED (N= 40) and without BED (N= 39) were reliably assessed by bilingual research‐clinicians using Spanish‐language versions of semistructured interviews and measures.

Results:

Overall, 38% (N= 30) of the 79 patients reported regular NE (≥4 days/month). NE and BED were significantly associated; 70% (21/30) of NE versus 18% (9/49) of non‐NE had BED. Patients with NE reported greater frequency of binge‐eating and higher levels of eating‐disorder psychopathology and depression than non‐NE patients; group differences in eating disorder psychopathology and depression levels persisted after controlling for BED status. The NE and non‐NE groups did not differ significantly in BMI or metabolic variables.

Discussion:

In obese treatment‐seeking Hispanic patients, NE and BED were significantly associated and NE was associated with heightened eating‐disorder psychopathology and depression even after controlling for BED status. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012; 45:787–791)
High fat feeding exacerbates endoplasmic reticulum stress and beta cell demise
Authors: Cnop Miriam
Published: March 2012

A growing body of evidence suggests that the insulin‐producing beta cells in the pancreas are susceptible to saturated fatty acid‐induced endoplasmic reticulum (ER) stress and apoptosis, and that this may contribute to the development of diabetes. In this issue of the European Journal of Lipid Science and Technology, Guo et al. [p. 233–234] report on accelerated beta cell dysfunction and death induced by high fat feeding of the Ncb5or knockout mouse, which lacks the ER‐associated NADH‐cytochrome b5 oxidoreductase and has impaired fatty acid desaturation.
Total Synthesis of Macrosphelide M from Diacetone Glucose
Authors: Sharma Gangavaram V. M. , Reddy Post Sai
Published: March 2012

The total synthesis of macrosphelide M is described. The key steps include the preparation of the acid and alcohol fragments from diacetone glucose and (S)‐malic acid, respectively, followed by Yamaguchi esterification and macrocyclization of the tris‐olefin by ring‐closing metathesis. Finally, one‐pot deprotection of the PMB and TBS groups with TiCl4 results in the target. The C‐3/C‐4 stereocenters of diacetone glucose are used for the introduction of four stereocenters, whereas the fifth stereocenter is realized from (S)‐malic acid.
Lipase‐Catalyzed Kinetic Resolution of 2‐Phenylethanol Derivatives and Chiral Oxa‐Pictet–Spengler Reaction as the Key Steps in the Synthesis of Enantiomerically Pure Tricyclic Amines
Authors: Ketterer Christian , Wünsch Bernhard
Published: March 2012

A series of 5,6,7,8,9,10‐hexahydro‐5,9‐epoxybenzocycloocten‐6‐amines have been synthesized and pharmacologically evaluated in receptor binding studies (σ1, σ2, NMDA, κ, and μ receptors). The first key step of the synthesis was a chiral oxa‐Pictet–Spengler reaction with enantiomerically pure 2‐phenylethanol derivatives (S)‐ and (R)‐14. After transformation of the dimethylamide 18 into the ester 19, the tricyclic system 20 was established by Dieckmann cyclization reaction. Finally, amino moieties were introduced diastereoselectively into the 6‐position by reductive amination and SN2 reaction. The enantiomerically pure building blocks (S)‐14 (>99.0 % ee) and (R)‐14 (98.4 % ee) were synthesized by enantioselective acetylation of racemic alcohol 14 catalyzed by Pseudomonas fluorescens lipase and enantioselective hydrolysis of racemic acetate 16 catalyzed by Candida rugosa lipase. The absolute configurations were determined by theoretical calculations of the specific optical rotation and CD spectra, as well as by X‐ray crystal structure analysis of (S,S,S)‐25 by the three‐beam interference method. Although enantiomerically pure dimethylamines (S,R,S)‐ and (R,S,R)‐29 with an axial amino moiety showed low‐to‐moderate affinity towards σ1 and σ2 receptors, a promising σ2 affinity (Ki = 2.9 μM) was found for (S,S,S)‐24 with an equatorially oriented dimethylamino group.
A lattice Boltzmann method for viscous free surface waves in two dimensions
Authors: Zhao Zhuangming , Huang Ping , Li Yineng , Li Junmin
Published: March 2012

We propose a new method based on the combination of the lattice Boltzmann equation (LBE) and the kinematic boundary condition (KBC) method to simulate viscous free surface wave in two dimensions. In our method, the flow field is modeled by LBE, whereas the free surface is explicitly tracked by the local height function, which is calculated by the KBC method. The free surface boundary condition (FSBC) for LBE is revised from previous researches. Interpolation‐supplemented lattice Boltzmann (ISLB) method is introduced, which enables our approach to be applied on arbitrary, nonuniform mesh grids. Five cases are simulated respectively to validate the LBE–KBC method: the stationary flow and the solitary waves simulated by the revised‐FSBC are more accurate than the one obtained by the former‐FSBC; numerical results of standing waves show that our method is compatible to the existing two‐dimensional finite‐volume scheme; cases of small amplitude Stokes wave and waves traveling over a submerged bar show good agreement on wave celerity, wavelength, wave amplitude and wave period between numerical results and corresponding analytical solutions and/or experiment data.Copyright © 2012 John Wiley & Sons, Ltd.
A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity
Authors: Lavretsky H. , Epel E.S. , Siddarth P. , Nazarian N. , Cyr N. St. , Khalsa D.S. , Lin J. , Blackburn E. , Irwin M.R.
Published: March 2012

Background

This study examined the effects of brief daily yogic meditation on mental health, cognitive functioning, and immune cell telomerase activity in family dementia caregivers with mild depressive symptoms.

Methods

Thirty‐nine family dementia caregivers (mean age 60.3 years old (SD = 10.2)) were randomized to practicing Kirtan Kriya or listening to relaxation music for 12 min per day for 8 weeks. The severity of depressive symptoms, mental and cognitive functioning were assessed at baseline and follow‐up. Telomerase activity in peripheral blood mononuclear cells (PMBC) was examined in peripheral PBMC pre‐intervention and post‐intervention.

Results

The meditation group showed significantly lower levels of depressive symptoms and greater improvement in mental health and cognitive functioning compared with the relaxation group. In the meditation group, 65.2% showed 50% improvement on the Hamilton Depression Rating scale and 52% of the participants showed 50% improvement on the Mental Health Composite Summary score of the Short Form‐36 scale compared with 31.2% and 19%, respectively, in the relaxation group (p < 0.05). The meditation group showed 43% improvement in telomerase activity compared with 3.7% in the relaxation group (p = 0.05).

Conclusion

This pilot study found that brief daily meditation practices by family dementia caregivers can lead to improved mental and cognitive functioning and lower levels of depressive symptoms. This improvement is accompanied by an increase in telomerase activity suggesting improvement in stress‐induced cellular aging. These results need to be confirmed in a larger sample. Copyright © 2012 John Wiley & Sons, Ltd.
Characteristic patterns of altered DNA methylation predict emergence of human hepatocellular carcinoma
Authors: Nishida Naoshi , Kudo Masatoshi , Nagasaka Takeshi , Ikai Iwao , Goel Ajay
Published: March 2012

We aimed to identify the specific subset of tumor suppressor genes (TSGs) that are methylation-silenced during the earliest steps of hepatocarcinogenesis, and to further evaluate whether these genes can serve as predictive biomarkers of hepatocellular carcinoma (HCC) emergence. A total of 482 liver tissues including 177 pairs of HCCs and matched nontumor livers and 128 liver biopsies from chronic hepatitis C (CHC) patients were analyzed for quantitative methylation analysis in 24 TSG promoters and three MINT loci. The tumors were classified as early, less-progressed, and highly progressed HCCs using histology and radiological approaches. A subset of TSGs that harbored distinctly high levels of methylation in early HCCs were selected. Based on the methylation profiles of these genes, Kaplan-Meier analyses were performed to determine time-to-HCC occurrence in CHC patients. Subsequently, multivariate analysis was performed using age, gender, fibrosis stage, and number of methylated TSGs as covariates. Among TSGs analyzed, a subset of eight TSGs (
HIC1, GSTP1, SOCS1, RASSF1, CDKN2A, APC, RUNX3
, and

PRDM2
) demonstrated a distinct cluster by hierarchical clustering and receiver operating characteristic analyses. This subset of TSGs showed significantly higher methylation levels in the early HCCs (
P

< 0.0001). In the CHC patients, methylation frequencies in these TSGs were associated with shorter time-to-HCC occurrence (
P

< 0.0001), and number of methylated genes was an independent risk factor for HCC (hazard ratio = 5.21, 95% confidence interval = 2.25–11.76,

P

= 0.0002).

Conclusion:

Epigenetic inactivation of a subset of TSGs plays a critical role in the earliest steps of hepatocarcinogenesis. Furthermore, epigenetic inactivation of these genes in CHC provides a prognostic value for determining the risk for developing HCC later in life.
NF‐κB inhibition significantly upregulates the norepinephrine transporter system, causes apoptosis in pheochromocytoma cell lines and prevents metastasis in an animal model
Authors: Pacak Karel , Sirova Marta , Giubellino Alessio , Lencesova Lubomira , Csaderova Lucia , Laukova Marcela , Hudecova Sona , Krizanova Olga
Published: March 2012

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are specific types of neuroendocrine tumors that originate in the adrenal medulla or sympathetic/parasympathetic paraganglia, respectively. Although these tumors are intensively studied, a very effective treatment for metastatic PHEO or PGL has not yet been established. Preclinical evaluations of novel therapies for these tumors are very much required. Therefore, in this study we tested the effect of triptolide (TTL), a potent nuclear factor‐kappaB (NF‐κB) inhibitor, on the cell membrane norepinephrine transporter (NET) system, considered to be the gatekeeper for the radiotherapeutic agent 131I‐metaiodobenzylguanidine (131I‐MIBG). We measured changes in the mRNA and protein levels of NET and correlated them with proapoptotic factors and metastasis inhibition. The study was performed on three different stable PHEO cell lines. We found that blocking NF‐κB with TTL or capsaicin increased both NET mRNA and protein levels. Involvement of NF‐κB in the upregulation of NET was verified by mRNA silencing of this site and also by using NF‐κB antipeptide. Moreover, in vivo treatment with TTL significantly reduced metastatic burden in an animal model of metastatic PHEO. The present study for the first time shows how NF‐κB inhibitors could be successfully used in the treatment of metastatic PHEO/PGL by a significant upregulation of NET to increase the efficacy of 131I‐MIBG and by the induction of apoptosis.
Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients
Authors: Avraham Ayelet , Uhlmann Ronit , Shperber Aino , Birnbaum Miriam , Sandbank Judith , Sella Avishay , Sukumar Saraswati , Evron Ella
Published: March 2012

Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the “methylation sensitive PCR and high resolution melting,” we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.
Quantum dots hold promise for early cancer imaging and detection
Authors: Pericleous Pericles , Gazouli Maria , Lyberopoulou Anna , Rizos Spyros , Nikiteas Nikolaos , Efstathopoulos Efstathios P
Published: March 2012

Despite all major breakthroughs in recent years of research concerning the complex events that lead to cancer expression and metastasis, we are not yet able to effectively treat cancer that has spread to vital organs. The various clinical phases originating from cancer diagnosis through treatment and prognosis require a comprehensive understanding of these events, to utilise pre‐symptomatic, minimally invasive and targeted cancer management techniques. Current imaging modalities such as ultrasound, computed tomography, magnetic resonance imaging and gamma scintigraphy facilitate the pre‐operative study of tumours, but they have been rendered unable to visualise cancer in early stages, due to their intrinsic limitations. The semiconductor nanocrystal quantum dots (QDs) have excellent photo‐physical properties, and the QDs‐based probes have achieved encouraging developments in cellular (in vitro) and in vivo molecular imaging. However, the same unique physical and chemical properties which renowned QDs attractive may be associated with their potentially catastrophic effects on living cells and tissues. There are critical issues that need to be further examined to properly assess the risks associated with the manufacturing and use of QDs in cancer management. In this review, we aim to describe the current utilisation of QDs as well as their future prospective to decipher and confront cancer.
Peak and time‐integrated shear rates independently predict flow‐mediated dilation
Authors: Stoner Lee , McCully Kevin K.
Published: March 2012

Background:

To determine whether peak and time‐integrated shear rates independently predict flow‐mediated dilation (FMD).

Methods:

Eleven physically active (25±5 years old) male subjects were tested. FMD was defined as the shear rate‐diameter relationship. Hierarchical linear modeling was used to estimate brachial artery diameter change with repeated measures of shear rate nested within each subject. Two models were tested: 1) FMD was induced using ischemia‐induced hyperemia (2, 4, 6, and 10 minutes); and 2) FMD was induced following transient (ischemia) and steady‐state (forearm heating and handgrip exercise) increases in shear rate. For both models we determined whether peak, in addition to time‐integrated shear rates, explained a significant portion of variation for diameter change.

Results:

Model 1: Time integrated shear rates explained most of the variation for diameter change. However, peak shear rate explained an additional significant portion of variation. Model 2: The transient condition resulted in significantly (p = 0.012) smaller diameter change per shear rate change than the steady‐state condition. However, when specifying peak shear rate as a covariate, the difference between conditions became nonsignificant (p = 0.138).

Conclusions:

Peak and time‐integrated shear rates independently predict FMD. Future studies using the FMD test should consider both parameters. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012;
Planning and designing the care transitions innovation (C‐Train) for uninsured and Medicaid patients
Authors: Englander Honora , Kansagara Devan
Published: March 2012

BACKGROUND:

Uninsured and Medicaid patients are particularly vulnerable as they transition from hospital to home. Transitional care improvement programs require time and capital, incentives for which may be unclear for those lacking a third‐party payor. This article describes our experience developing a hospital‐funded transitional care program for uninsured and Medicaid patients.

METHODS:

We performed an inpatient needs assessment, convened multi‐stakeholder work groups, and engaged institutional change‐agents to inform program development and a business case.

RESULTS:

We mapped needs to specific program elements, including a transitional care nurse, pharmacy consult and provision of medications for uninsured patients, medical home linkages including community payment for medical homes, and monthly quality improvement meetings. A business case was informed by local needs and utilization data, and compelled the hospital to invest in up‐front resources for this population.

DISCUSSION:

We are studying our program's impact on 30‐day readmission and emergency department rates through a clustered, randomized controlled trial. Lessons from our experience may be useful to others aiming to improve care for socioeconomically disadvantaged patients. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine
Standardized AP radiographs do not provide reliable diagnostic measures for the assessment of acetabular retroversion
Authors: Wassilew Georgi I. , Heller Markus O. , Diederichs Gerd , Janz Viktor , Wenzl Markus , Perka Carsten
Published: March 2012

Diagnosis of acetabular retroversion is essential in femoroacetabular impingement (FAI), but its assessment from radiographs is complicated by pelvic tilt and the two‐dimensional nature of plain films. We performed a study to validate the diagnostic accuracy of the cross‐over sign (COS) and the posterior wall sign (PWS) in identifying acetabular retroversion. COS and PWS were evaluated from radiographs and computed tomography (CT) scans as the standard of reference in 50 hips of subjects with symptoms of FAI. A CT‐based method using three‐dimensional (3D) models was developed to measure the COS, PWS, true acetabular version, and pelvic tilt relative to the anterior pelvic plane. The new CT‐based method aimed to eliminate errors resulting from variations in the position and orientation of the pelvis during imaging. A low level of agreement for COS and PWS was found between radiographs and CT scans. A positive COS strongly correlated with pelvic tilt. These results suggest that COS and PWS determined from anteroposterior radiographs are considerably limited by pelvic tilt and inherent limitations of radiographs. Their use as the sole basis for deciding whether or not surgical intervention is indicated seems questionable. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1369–1376, 2012
The natural compound Alizarin as an osteotropic drug for the treatment of bone tumors
Authors: Fotia Caterina , Avnet Sofia , Granchi Donatella , Baldini Nicola
Published: March 2012

Despite significant clinical improvements, conventional therapies for bone cancer treatment are limited by significant systemic toxicity and lack of specific targeting. In this study, we considered Alizarin, a natural hydroxyanthraquinone derived from madder root with high affinity to calcium and remarkable osteotropic features, as a novel approach for bone cancer treatment. Due to its antitumor properties, as demostrated in colon cancer cells, and to its tropism to bone, Alizarin may be an ideal drug to reduce bone tumor growth. We demonstrated that low dosages of Alizarin strongly inhibited the osteosarcoma (IC50 for Saos‐2, MG‐63, and U‐2 OS cells, 27.5, 29.0, and 69.9 µg/ml, respectively) and breast carcinoma (IC50 for MDA‐MB‐231 cells, 62.1 µg/ml) cell proliferation in vitro. Importantly, Alizarin had a significantly lower inhibitory activity on normal cells (IC50 for MSC, 828.6 µg/ml), thereby revealing a selective activity towards malignant cells. Furthermore, we found that Alizarin acted through the inhibition of ERK phosphorylation and cell cycle arrest in the S‐phase. Finally, Alizarin significantly and strongly impaired both osteosarcoma and breast cancer tumorigenesis. Our results highlight a selective and effective inhibitory activity of Alizarin towards cancerous cells, laying the basis for further studies to investigate its application in bone cancer therapy. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1486–1492, 2012
Neural‐differentiated mesenchymal stem cells incorporated into muscle stuffed vein scaffold forms a stable living nerve conduit
Authors: Hassan Nur Hidayah , Sulong Ahmad Fadzli , Ng Min‐Hwei , Htwe Ohnmar , Idrus Ruszymah B. H. , Roohi Sharifah , Naicker Amaramalar S. , Abdullah Shalimar
Published: March 2012

Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35–75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post‐implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1674–1681, 2012