bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanocortin‐1 receptor‐targeting with radiolabeled cyclic α‐melanocyte‐stimulating hormone analogs for melanoma imaging
Authors: Raposinho Paula D. , Correia João D. G. , Oliveira Maria Cristina , Santos Isabel 
Published: July 2010

AbstractMelanoma is a type of skin cancer known for its high aggressiveness, early dissemination of metastases, and poor prognosis once metastasized. Thus, early diagnosis of melanoma is a key issue for increasing patient survival. The overexpression of melanocortin‐1 receptors (MC1R) in isolated melanoma cells and melanoma tissues led to the radiolabeling of several linear and cyclic MC analogs for melanoma imaging or therapy. Cyclization of α‐melanocyte stimulating hormone (α‐MSH) peptides has been successfully used to improve binding affinity and in vivo stability of peptides. Herein, we describe the different peptide cyclization strategies recently reported for radiolabeled α‐MSH analogs and discuss how such strategies affect MC1R binding affinity, pharmacokinetic profile, and MC1R‐melanoma imaging. This review also highlights how the nature of the radiometal and labeling approach influence those properties. Among the cyclized α‐MSH peptides reported, 99mTc/111In‐labeled metal‐cyclized and lactam bridge–cyclized peptides displayed the highest melanoma and lowest renal uptake values in B16/F1 melanoma‐bearing mice and became the most promising tools to be further explored as potential melanoma imaging probes. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 820–829, 2010.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The story of DNase II: A stifled death‐wish leads to self‐harm
Authors: Crow Yanick J. 
Published: July 2010

AbstractDNase II is an endonuclease which plays a fundamental role in the degradation of DNA from both apoptotic cells, and nuclei extruded from red blood cells during erythropoiesis: important tasks, considering that everyday 108–109 cells undergo apoptosis, and 1011 red blood cells are produced in the adult human. The DNase II‐null mouse demonstrates embryonic lethality due to type I interferon‐mediated erythroid precursor cell death triggered by undegraded nucleic acids. However, the mechanisms leading to such cytotoxicity are poorly understood. A study in the current issue of the European Journal of Immunology investigates the role of the death ligand TRAIL in this process. Although TRAIL is shown to be dispensable for the interferon‐induced apoptosis of erythroid cells in DNAse II−/− embryos, the authors have developed a useful strategy for further exploring this question in future studies. Interestingly, earlier studies by the same group showed that crossing the DNase II‐null mouse with a mouse deficient for the type I interferon receptor can rescue the lethal anaemia observed in the DNase II‐null embryos, but only at the cost of developing autoimmunity.
A mediational model of self‐esteem and social problem‐solving in anorexia nervosa
Authors: Paterson Gillian , Power Kevin , Collin Paula , Greirson David , Yellowlees Alex , Park Katy 
Published: July 2010

AbstractObjectivePoor problem‐solving and low self‐esteem are frequently cited as significant factors in the development and maintenance of anorexia nervosa. The current study examines the multi‐dimensional elements of these measures and postulates a model whereby self‐esteem mediates the relationship between social problems‐solving and anorexic pathology and considers the implications of this pathway.MethodFifty‐five inpatients with a diagnosis of anorexia nervosa and 50 non‐clinical controls completed three standardised multi‐dimensional questionnaires pertaining to social problem‐solving, self‐esteem and eating pathology.ResultsSignificant differences were yielded between clinical and non‐clinical samples on all measures. Within the clinical group, elements of social problem‐solving most significant to anorexic pathology were positive problem orientation, negative problem orientation and avoidance. Components of self‐esteem most significant to anorexic pathology were eating, weight and shape concern but not eating restraint. The mediational model was upheld with social problem‐solving impacting on anorexic pathology through the existence of low self‐esteem.ConclusionProblem orientation, that is, the cognitive processes of social problem‐solving appear to be more significant than problem‐solving methods in individuals with anorexia nervosa. Negative perceptions of eating, weight and shape appear to impact on low self‐esteem but level of restriction does not. Finally, results indicate that self‐esteem is a significant factor in the development and execution of positive or negative social problem‐solving in individuals with anorexia nervosa by mediating the relationship between those two variables. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.
Diffusion tensor imaging discriminates between glioblastoma and cerebral metastases in vivo
Authors: Byrnes Tiernan J. D. , Barrick Thomas R. , Bell B. Anthony , Clark Chris A. 
Published: July 2010

AbstractIn a prospective study, patients with a radiologically proven brain tumour underwent diffusion tensor imaging (DTI) prior to definitive diagnosis and treatment. Twenty‐eight patients with a histologically proven glioblastoma or metastasis were included in the study. Following the definition of regions of interest, DTI metrics [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for the tumour volume and the surrounding region of peritumoral oedema. These metrics were then subjected to logistic regression to investigate their ability to discriminate between glioblastomas and cerebral metastases. A cross‐validation was performed to investigate the ability of the model to predict tumour. The logistic regression analysis correctly distinguished glioblastoma in 15 of 16 cases (93.8%) and metastasis in 11 of 12 cases (91.7%). Cross‐validation resulted in the model correctly predicting 14 of 16 (87.5%) glioblastomas and 10 of 12 (83.3%) metastases studied. MD was significantly higher (p = 0.02) and FA was significantly lower (p = 0.04) within the oedema surrounding metastases than within the oedema around glioblastomas. MD was significantly higher (p = 0.02) within the tumour volume of the glioblastomas. Our results demonstrate that, when DTI metrics from the tumour volume and surrounding peritumoral oedema are studied in combination, glioblastoma can be reliably discriminated from cerebral metastases. Copyright © 2010 John Wiley & Sons, Ltd.
Protein–protein binding affinities by pulse proteolysis: Application to TEM‐1/BLIP protein complexes
Authors: Hanes Melinda S. , Ratcliff Kathleen , Marqusee Susan , Handel Tracy M. 
Published: July 2010

AbstractEfficient methods for quantifying dissociation constants have become increasingly important for high‐throughput mutagenesis studies in the postgenomic era. However, experimentally determining binding affinity is often laborious, requires large amounts of purified protein, and utilizes specialized equipment. Recently, pulse proteolysis has been shown to be a robust and simple method to determine the dissociation constants for a protein–ligand pair based on the increase in thermodynamic stability upon ligand binding. Here, we extend this technique to determine binding affinities for a protein–protein complex involving the β‐lactamase TEM‐1 and various β‐lactamase inhibitor protein (BLIP) mutants. Interaction with BLIP results in an increase in the denaturation curve midpoint, Cm, of TEM‐1, which correlates with the rank order of binding affinities for several BLIP mutants. Hence, pulse proteolysis is a simple, effective method to assay for mutations that modulate binding affinity in protein–protein complexes. From a small set (n = 4) of TEM‐1/BLIP mutant complexes, a linear relationship between energy of stabilization (dissociation constant) and ΔCm was observed. From this “calibration curve,” accurate dissociation constants for two additional BLIP mutants were calculated directly from proteolysis‐derived ΔCm values. Therefore, in addition to qualitative information, armed with knowledge of the dissociation constants from the WT protein and a limited number of mutants, accurate quantitation of binding affinities can be determined for additional mutants from pulse proteolysis. Minimal sample requirements and the suitability of impure protein preparations are important advantages that make pulse proteolysis a powerful tool for high‐throughput mutagenesis binding studies.
N‐terminal domain of the V‐ATPase a2‐subunit displays integral membrane protein properties
Authors: Merkulova Maria , McKee Mary , Dip Phat Vinh , Grüber Gerhard , Marshansky Vladimir 
Published: July 2010

AbstractV‐ATPase is a multisubunit membrane complex that functions as nanomotor coupling ATP hydrolysis with proton translocation across biological membranes. Recently, we uncovered details of the mechanism of interaction between the N‐terminal tail of the V‐ATPase a2‐subunit isoform (a2N1–402) and ARNO, a GTP/GDP exchange factor for Arf‐family small GTPases. Here, we describe the development of two methods for preparation of the a2N1–402 recombinant protein in milligram quantities sufficient for further biochemical, biophysical, and structural studies. We found two alternative amphiphilic chemicals that were required for protein stability and solubility during purification: (i) non‐detergent sulfobetaine NDSB‐256 and (ii) zwitterionic detergent FOS‐CHOLINE®12 (FC‐12). Moreover, the other factors including mild alkaline pH, the presence of reducing agents and the absence of salt were beneficial for stabilization and solubilization of the protein. A preparation of a2N1–402 in NDSB‐256 was successfully used in pull‐down and BIAcore™ protein–protein interaction experiments with ARNO, whereas the purity and quality of the second preparation in FC‐12 was validated by size‐exclusion chromatography and CD spectroscopy. Surprisingly, the detergent requirement for stabilization and solubilization of a2N1–402 and its cosedimentation with liposomes were different from peripheral domains of other transmembrane proteins. Thus, our data suggest that in contrast to current models, so called “cytosolic” tail of the a2‐subunit might actually be embedded into and/or closely associated with membrane phospholipids even in the absence of any obvious predicted transmembrane segments. We propose that a2N1–402 should be categorized as an integral monotopic domain of the a2‐subunit isoform of the V‐ATPase.
A filamentous phage display system for N‐linked glycoproteins
Authors: Çelik Eda , Fisher Adam C. , Guarino Cassandra , Mansell Thomas J. , DeLisa Matthew P. 
Published: July 2010

AbstractWe have developed a filamentous phage display system for the detection of asparagine‐linked glycoproteins in Escherichia coli that carry a plasmid encoding the protein glycosylation locus (pgl) from Campylobacter jejuni. In our assay, fusion of target glycoproteins to the minor phage coat protein g3p results in the display of glycans on phage. The glyco‐epitope displayed on phage is the product of biosynthetic enzymes encoded by the C. jejuni pgl pathway and minimally requires three essential factors: a pathway for oligosaccharide biosynthesis, a functional oligosaccharyltransferase, and an acceptor protein with a D/E‐X1‐N‐X2‐S/T motif. Glycosylated phages could be recovered by lectin chromatography with enrichment factors as high as 2 × 105 per round of panning and these enriched phages retained their infectivity after panning. Using this assay, we show that desired glyco‐phenotypes can be reliably selected by panning phage‐displayed glycoprotein libraries on lectins that are specific for the glycan. For instance, we used our phage selection to identify permissible residues in the −2 position of the bacterial consensus acceptor site sequence. Taken together, our results demonstrate that a genotype–phenotype link can be established between the phage‐associated glyco‐epitope and the phagemid‐encoded genes for any of the three essential components of the glycosylation process. Thus, we anticipate that our phage display system can be used to isolate interesting variants in any step of the glycosylation process, thereby making it an invaluable tool for genetic analysis of protein glycosylation and for glycoengineering in E. coli cells.
Cerebral folate deficiency
Authors: Hyland Keith , Shoffner John , Heales Simon J. 
Published: July 2010

AbstractCerebral folate deficiency (CFD) is defined as any neurological syndrome associated with a low cerebrospinal fluid (CSF) concentration of 5‐methyltetrahydrofolate (5MTHF) in the presence of normal peripheral folate status. CFD has a wide clinical presentation, with reported signs and symptoms generally beginning at around 4 months of age with irritability and sleep disturbances. These can be followed by psychomotor retardation, dyskinesia, cerebellar ataxia and spastic diplegia. Other signs may include deceleration of head growth, visual disturbances and sensorineural hearing loss. Identification of CFD is achieved by determining 5MTHF concentration in CSF. Once identified, CFD can in many cases be treated by administering oral folinic acid. Supplementation with folic acid is contraindicated and, if used, may exacerbate the CSF 5MTHF deficiency. Generation of autoantibodies against the folate receptor required to transport 5MTHF into CSF and mutations in the folate receptor 1 (FOLR1) gene have been reported to be causes of CFD. However, other mechanisms are probably also involved, as CFD has been reported in Aicardi‐Goutiere's and Rett syndromes and in mitochondriopathies. Several metabolic conditions and a number of widely used drugs can also lead to a decrease in the concentration of CSF 5MTHF, and these should be considered in the differential diagnosis if a low concentration of 5MTHF is found following CSF analysis.
Angiography suite concept for an interdisciplinary centre for cardiovascular interventions
Authors: Teichgräber Ulf K. M. , Wintzer Christian , Hamm Bernd 
Published: July 2010

AbstractA permanently mounted angiography suite in an operating room (OR) is considered to be a hybrid OR. However, regular use for angiographic interventions is restricted with this setup. We introduce an alternative use of space for the efficient utilisation of an angiographic suite outside the surgical unit. This concept includes three scenarios that describe a modification of the catheter suite according to the specific clinical demands by adapting the workflow.
Experiences in Common: Slavery and “Freedom” in the Process of Rio de Janeiro’s Working-Class Formation (1850–1910)
Authors: Mattos Marcelo Badaró 
Published: July 2010

SummaryThe present article is based on research into the process of working-class formation in Rio de Janeiro in the period between the end of the nineteenth century and the early years of the twentieth. It explores the significant shared experiences of workers subjected to slavery and “free” workers in the process of working-class formation, and aims to demonstrate that the history of that process in Brazil began while slavery still existed, and that through shared work and life experience in Rio de Janeiro, as in other Brazilian cities where slavery was strong during the nineteenth century, enslaved and “free” workers shared forms of organization and struggle, founding common values and expectations that were to have a central importance in later periods of class formation.
Transnational Experts in Social Reform, 1840–1880
Authors: Leonards Chris , Randeraad Nico 
Published: July 2010

SummaryWho were the people at the cutting edge of social reform in Europe between 1840 and 1880, and how were they connected? This article proposes a method to locate a transnational community of experts involved in social reform and focuses on the ways in which these experts shared and spread their knowledge across borders. After a discussion of the concepts of social reform, transnationalization, and transfer, we show how we built a database of visitors to social reform congresses in the period 1840–1880, and explain how we extracted a core group of experts from this database. This “congress elite” is the focus of the second part of this article, in which we discuss their travels, congress visits, publications, correspondence, and membership of learned and professional organizations. We argue that individual members of our elite, leaning on the prestige of their international contacts, shaped reform debates in their home countries. We conclude by calling for further research into the influence that the transnational elite were able to exert on concrete social reforms in different national frameworks in order to assess to what extent they can be regarded as an “epistemic community in the making”.
A Brave New World: The Left, Social Engineering, and Eugenics in Twentieth-Century Europe
Authors: Lucassen Leo 
Published: July 2010

SummaryThis article compares theories and social policies of social democrats and other representatives of the left-wing political spectrum in six European countries to explain why, in certain countries such as Sweden, Norway, and Switzerland, weak social groups became the target of illiberal and negative eugenic policy, especially isolation and sterilization, while elsewhere left-wing politicians and theorists were far less radical. One striking feature that emerges is the difference between acommunitarian-organicand aclass-boundform of socialism. Following Zygmunt Bauman, Michel Foucault, and James C. Scott, the article discerns a first variant of citizenship that is conditional and intended only for those with the right social attitude. Eugenics was perfectly consistent with such a view, since it offered a diagnosis and at the same time a cure. Prominent representatives of this approach were the Webbs in Britain and the Myrdals in Sweden. Such an organic-medical approach was less likely, however, in a more class-dependent variant of socialism embedded in a strong civil society. As long as social democrats and other leftist politicians believed social problems such as inequality and poverty were caused primarily by an unjust capitalist system, there was little cause for a eugenicist solution.
The Myosin Motor Domain of Fungal Chitin Synthase V Is Dispensable for Vesicle Motility but Required for Virulence of the Maize PathogenUstilago maydis
Authors: Treitschke Steffi , Doehlemann Gunther , Schuster Martin , Steinberg Gero 
Published: July 2010

AbstractClass V chitin synthases are fungal virulence factors required for plant infection. They consist of a myosin motor domain fused to a membrane-spanning chitin synthase region that participates in fungal cell wall formation. The function of the motor domain is unknown, but it might deliver the myosin chitin synthase-attached vesicles to the growth region. Here, we analyze the importance of both domains in Mcs1, the chitin synthase V of the maize smut fungus Ustilago maydis. By quantitative analysis of disease symptoms, tissue colonization, and single-cell morphogenic parameters, we demonstrate that both domains are required for fungal virulence. Fungi carrying mutations in the chitin synthase domain are rapidly recognized and killed by the plant, whereas fungi carrying a deletion of the motor domain show alterations in cell wall composition but can invade host tissue and cause a moderate plant response. We also show that Mcs1-bound vesicles exhibit long-range movement for up to 20 μm at a velocity of ~1.75 μm/s. Apical Mcs1 localization depends on F-actin and the motor domain, whereas Mcs1 motility requires microtubules and persists when the Mcs1 motor domain is deleted. Our results suggest that the myosin motor domain of ChsV supports exocytosis but not long-range delivery of transport vesicles.
Feeling Vulnerable? Indirect Risk Cues Differently Influence How Two Marsupials Respond to Novel Dingo Urine
Authors: Parsons Michael H. , Blumstein Daniel T. 
Published: July 2010

AbstractIn Tasmania, introduced predators are becoming more common. How Tasmanian prey respond to novel predator cues is of particular interest for their survival and management. Prey response to predator scents may depend on whether predator and prey share an evolutionary history and may be influenced by indirect risk cues such as perceived shelter or safety in the environment. To simultaneously explore the effects of indirect and direct risk cues (predator scent) on free‐living Tasmanian pademelons (Thylogale billardierii) and brush tail possums (Trichosurus vulpecula), we placed dingo (Canis lupus dingo) urine scents inside and outside a 25 ‐m2 selective feeding enclosure to mimic a heterogeneous risk landscape. Despite the lack of a historical relationship between dingoes and Tasmanian fauna, pademelons and possums demonstrated flight and vigilance when confronted with the novel scent outside the enclosure. According to our index of deterrence, number of successful entries/approaches, both species were deterred. However, responses inside the safe enclosure differed according to species. For instance, pademelons made more approaches/entries into the enclosure and fled more following approaches to scent marks both inside and outside the enclosure. In comparison, possums only exhibited similar responses outside the enclosure, and there was no effect of stimulus inside the safe compound. Our findings suggest that small animals may be pre‐adapted to avoid some predators they have not previously been in contact with, and that brush tail possums are more likely to respond to predation cues when exposed and vulnerable. Ultimately, the cumulative effects of direct and indirect risk cues may either increase or reduce a repellent response.
SUBCELLULAR DISTRIBUTION AND SOME PROPERTIES OF ACETYL‐COENZYME A HYDROLASE IN THE BRAIN
Authors: Matsuda T. , Yoshida H. 
Published: July 2010

Abstract—The detailed subcellular distribution and some properties of acetyl‐CoA hydrolase were studied in the rat brain. The brain homogenate (S1) hydrolysed acetyl‐CoA at a rate of approx 2·3 nmol/min/mg of protein at 37°C. The total activity of acetyl‐CoA hydrolase was distributed in the following order: soluble > mitochondrial > microsomal, synaptosomal > myelin fraction. The order of the specific activity of the enzyme was: soluble, microsomal > mitochondrial > synaptosomal > myelin fraction. The synaptic vesicle fraction (D) had relatively high specific activity among the intraterminal particulate fractions, having two or three times higher specific activity than that of the synaptic cytoplasmic membrane fraction (F or G). Attempts to de‐occlude acetyl‐CoA hydrolase in the particulate fraction showed that only the enzyme activity in the myelin fraction was increased markedly by the treatment with ether or Triton X‐100. Lineweaver‐Burk plots gave straight lines for each subcellular fraction and apparent Km values for acetyl‐CoA were between 0·1 and 0·2 mM. Neither diisopropyl fluorophosphate nor physostigmine at the concentration of 0·1 mm inhibited the enzyme activity.