bluuebunny/crossref_metadata_2025_split huggingface dataset:
LIVING LIKE THE LAITY? THE NEGOTIATION OF RELIGIOUS STATUS IN THE CITIES OF LATE MEDIEVAL ITALY
Authors: Andrews Frances 
Published: November 2010

ABSTRACTFramed by consideration of images of treasurers on the books of the treasury in thirteenth-century Siena, this article uses evidence for the employment of men of religion in city offices in central and northern Italy to show how religious status (treated as a subset of ‘clerical culture’) could become an important object of negotiation between city and churchmen, a tool in the repertoire of power relations. It focuses on the employment of men of religion as urban treasurers and takes Florence in the late thirteenth and early fourteenth centuries as a principal case study, but also touches on the other tasks assigned to men of religion and, very briefly, on evidence from other cities (Bologna, Brescia, Como, Milan, Padua, Perugia and Siena). It outlines some of the possible arguments deployed for this use of men of religion in order to demonstrate that religious status was, like gender, more contingent and fluid than the norm-based models often relied on as a shorthand by historians. Despite the powerful rhetoric of lay–clerical separation in this period, the engagement of men of religion in paid, term-bound urban offices inevitably brought them closer to living like the laity.
Mechanical vibratory stimulation of feline forepaw skin induces long‐lasting potentiation in the secondary somatosensory cortex
Authors: Kawakami Yoriko , Miyata Mariko , Oshima Tomokazu 
Published: November 2010

AbstractWe investigated the long‐lasting effects of mechanical vibratory stimulation of the skin on the excitability of feline cortical neurons in the forelimb areas of the primary (SI) and secondary (SII) somatosensory cortices. Conditioning mechanical stimuli were 300 bursts of 10 pulses at 200 Hz delivered with a 10‐s interburst interval from a mechanical stimulator. Test field potentials and unit discharges were evoked by electrical stimulation to the ventral posterolateral thalamic nucleus (VPL) or by single mechanical stimuli applied to the skin. In SII, the mechanical burst stimulation to the skin increased the amplitudes of field potentials and the frequency of unit discharges elicited by single mechanical stimuli applied to the skin. The vibratory conditioning stimulus also produced a similar potentiation of the VPL‐evoked field potentials (126–139% increase in amplitude, P < 0.05) with an associated increase in firing rates of extracellularly recorded neuronal activity (117%, P < 0.001). These potentiations persisted through the entire experimental period of 120 min. The translaminar current source density analysis calculated from the VPL‐evoked field potentials increased to 127% of the control value (P < 0.01). In contrast, in SI we observed no significant changes in the field potential amplitudes or in the currents generated in superficial layers (91–117%). Taken together with the previous finding that tetanic electrical stimulation of VPL induces long‐lasting potentiation of the VPL‐evoked cortical responses in SII but not of those in SI, the present results suggest that SII has a large capacity for the rapid functional plasticity involved in the learning that occurs during repeated tactile experiences.
Environmental tuning of mutation rates
Authors: Saint‐Ruf Claude , Matic Ivan 
Published: November 2010

SummaryThrough their life cycles, bacteria experience many different environments in which the relationship between available energy resources and the frequency and the nature of various stresses is highly variable. In order to survive in such changeable environments, bacteria must balance the need for nutritional competence with stress resistance. In Escherichia coli natural populations, this is most frequently achieved by changing the regulation of the RpoS sigma factor‐dependent general stress response. One important secondary consequence of altered regulation of the RpoS regulon is the modification of mutation rates. For example, under nutrient limitation during stationary phase, the high intracellular concentration of RpoS diminishes nutritional competence, increases stress resistance, and, by downregulating the mismatch repair system and downregulating the expression of the dinB gene (coding for PolIV translesion synthesis polymerase) increases mutation rates. The reduction of the intracellular concentration of RpoS has exactly opposite effects on nutritional competence, stress resistance and mutation rates. Therefore, the natural selection that favours variants having the highest fitness under different environmental conditions results in high variability of stress‐associated mutation rates in those variants.
A database view of naturally occurring antimicrobial peptides: nomenclature, classification and amino acid sequence analysis.
Authors: Wang G. S. , Li X. , Zasloff M. 
Published: November 2010

Abstract

The nomenclature and classification of naturally occurring antimicrobial peptides (AMPs) are complex and have not been fully standardized. The Antimicrobial Peptide Database (http://aps.unmc.edu/AP/main.php) is a useful tool that facilitates peptide naming and classification. The names of AMPs are normally derived from peptide properties, source species or a combination of both. In the database, AMPs are classified based on source organisms (protozoa, bacteria, archaea, fungi, plants and animals), biological activities (antibacterial, antifungal, antiviral, antiparasitic, spermicidal and insecticidal), peptide features (charge, length, hydrophobic residue content, chemical modification and threedimensional structure), binding targets (membranes and non-membranes) and mechanisms of action of the peptides. This database also enables bioinformatic analysis of AMPs that reveals amino acid composition signatures as well as frequently occurring residues.
Database-aided prediction and design of novel antimicrobial peptides.
Authors: Wang G. S. 
Published: November 2010

Abstract

The isolation and characterization of potent antimicrobial peptides from natural sources has opened a new avenue to the development of future antimicrobials. To further expand the peptide space, new antimicrobial peptides can be predicted or designed based on natural peptide templates. By using the knowledge derived from mature peptides, propeptides, or both (i.e. precursor proteins), a variety of peptide prediction tools have been developed. Furthermore, bacteriocins are predicted under the genomic context by considering not only the peptide itself, but also the accompanying genes for its expression, processing and export. This chapter also discusses database-aided peptide design based on database screening, sequence shuffl ing, grammar-based design and de novo design. Finally, major strategies for improving peptide selectivity and stability are highlighted.
Discovery of novel antimicrobial peptides using combinatorial chemistry and high-throughput screening.
Authors: Wimley W. C. 
Published: November 2010

Abstract

The field of antimicrobial peptide (AMP) research has now spanned three decades, in which hundreds of AMPs have been discovered, designed or engineered. Yet despite a vast literature, obvious structure-function relationships are rare and this has created a bottleneck in the discovery of novel AMPs. Instead of rigorous structure-function principles, AMP activity may be best addressed using the physical chemistry concept of 'interfacial activity', a concept that does not help one predict or engineer AMP activity. In this chapter, I address one method of circumventing this engineering bottleneck: combinatorial chemistry and high-throughput screening. Combinatorial methods are first discussed from the perspective of library synthesis techniques, for both indexed and non-indexed methods. This is followed by a discussion of available high-throughput screening techniques. Finally, I address the accomplishments to date generated using combinatorial chemistry and high-throughput screening and future directions the field may take. Combinatorial chemistry and high-throughput screening are powerful and effective tools for discovering novel AMPs. The future of this field holds great promise.
Lung infection: shifting the equilibrium towards the free and active form of human LL-37 and the design of alternative antimicrobial agents.
Authors: Janmey P. A. , Bucki R. 
Published: November 2010

Abstract

Under disease conditions, human LL-37 and other cationic antimicrobial factors are expressed but inactive due to their binding to anionic polyelectrolytes such as DNA, F-actin or acidic polysaccharides. This chapter discusses the basis for this electrostatic interaction and alternative strategies that liberate LL-37 and other amphipathic cations from the bound state so that they are available to fight invading pathogenic bacteria. The potential of this approach for therapeutic use is discussed.
Plastids Contain a Second Sec Translocase System with Essential Functions
Authors: Skalitzky Courtney A. , Martin Jonathan R. , Harwood Jessica H. , Beirne John J. , Adamczyk Benjamin J. , Heck Gregory R. , Cline Kenneth , Fernandez Donna E. 
Published: November 2010

AbstractProteins that are synthesized on cytoplasmic ribosomes but function within plastids must be imported and then targeted to one of six plastid locations. Although multiple systems that target proteins to the thylakoid membranes or thylakoid lumen have been identified, a system that can direct the integration of inner envelope membrane proteins from the stroma has not been previously described. Genetics and localization studies were used to show that plastids contain two different Sec systems with distinct functions. Loss-of-function mutations in components of the previously described thylakoid-localized Sec system, designated as SCY1 (At2g18710), SECA1 (At4g01800), and SECE1 (At4g14870) in Arabidopsis (Arabidopsis thaliana), result in albino seedlings and sucrose-dependent heterotrophic growth. Loss-of-function mutations in components of the second Sec system, designated as SCY2 (At2g31530) and SECA2 (At1g21650) in Arabidopsis, result in arrest at the globular stage and embryo lethality. Promoter-swap experiments provided evidence that SCY1 and SCY2 are functionally nonredundant and perform different roles in the cell. Finally, chloroplast import and fractionation assays and immunogold localization of SCY2-green fluorescent protein fusion proteins in root tissues indicated that SCY2 is part of an envelope-localized Sec system. Our data suggest that SCY2 and SECA2 function in Sec-mediated integration and translocation processes at the inner envelope membrane.
Measurement of apoptosis in cytological specimens by flow cytometry: comparison of Annexin V, caspase cleavage and dUTP incorporation assays
Authors: Dong H. P. , Holth A. , Ruud M. G. , Emilsen E. , Risberg B. , Davidson B. 
Published: November 2010

H. P. Dong, A. Holth, M. G. Ruud, E. Emilsen, B. Risberg and B. DavidsonMeasurement of apoptosis in cytological specimens by flow cytometry: comparison of annexin V, caspase cleavage and dUTP incorporation assaysObjective:  To compare the performance of different assays for measuring apoptosis in cytological specimens.Methods:  Apoptosis was assessed in 27 specimens (22 effusions, five fine needle aspirates; 20 malignant, seven reactive) using flow cytometry, applying assays for the measurement of annexin V expression, caspase‐3 and ‐8 cleavage and deoxynucleotidyl transferase deoxyuridine triphosphates (dUTP) incorporation. Results were studied for differences between reactive and malignant specimens, as well as performance across assays.Results:  Wide variation in the degree of apoptosis was observed in both benign and malignant specimens using all assays. However, the percentage of annexin V‐positive cells was higher compared with those showing caspase cleavage or dUTP incorporation in the majority of cases, irrespective of specimen type. Comparative analysis of benign and malignant specimens showed no significant differences in expression of any of the studied parameters. However, tumour cells and reactive mesothelial cells in pleural effusions had a significantly lower level of dUTP incorporation compared with their counterparts in peritoneal specimens (P = 0.001).Conclusions:  The present data are in agreement with our previous observation in ovarian carcinoma effusions, that measurement of apoptosis by the annexin V assay provides higher expression values than those obtained by other assays, suggesting that this assay does not accurately reflect the degree of apoptosis in benign or malignant cells in effusions.
Strain origin drives virulence and persistence ofXylella fastidiosain alfalfa
Authors: Lopes J. R. S. , Daugherty M. P. , Almeida R. P. P. 
Published: November 2010

Generalist pathogens frequently exist as a complex of genetically differentiated strains, which can differ in virulence and transmissibility. A description of the extent to which strain variability mediates host species competence is needed to understand disease dynamics for systems with both host and pathogen strain diversity. This study tested the hypothesis that strain‐specific variation of a generalist vector‐borne plant pathogen,Xylella fastidiosa, affects disease severity in alfalfa (Medicago sativa) and competence of this crop as a reservoir host. Alfalfa seedlings were inoculated with one of 23X. fastidiosaisolates collected from different hosts, eight identified as belonging to an almond strain, and the remainder from a grape strain. Pathogen population, symptom severity and infection incidence were compared over five successive harvests. Infected plant size, measured mainly by plant height, internode length and above ground biomass, was reduced up to 50% compared to buffer‐inoculated controls, and more severe symptoms were observed at later harvests and for higher pathogen populations. Grape isolates had higher bacterial populations within alfalfa than almond isolates. In addition, infection with grape isolates resulted in more severe alfalfa stunting than that caused by almond isolates. Moreover, there was a strong positive relationship between isolate multiplication rate and both symptom severity and infection persistence (i.e. maintenance of chronic infection within host). Isolates with low initial populations had low incidence at the final harvest, with one isolate dying out altogether. The results showed thatX. fastidiosa‐genetic diversity contributed to variation in alfalfa disease severity. The results also suggest that pathogen strain may mediate host competence via differences in bacterial population density and persistence.
Metformin inhibits P‐glycoprotein expression via the NF‐κB pathway and CRE transcriptional activity through AMPK activation
Authors: Kim Hyung Gyun , Hien Tran Thi , Han Eun Hee , Hwang Yong Pil , Choi Jae Ho , Kang Keon Wook , Kwon Kwang‐il , Kim Bong‐Hee , Kim Sang Kyum , Song Gye Yong , Jeong Tae Cheon , Jeong Hye Gwang 
Published: November 2010

BACKGROUND AND PURPOSE The expression of P‐glycoprotein (P‐gp), encoded by the multidrug resistance 1 (MDR1) gene, is associated with the emergence of the MDR phenotype in cancer cells. We investigated whether metformin (1,1‐dimethylbiguanide hydrochloride) down‐regulates MDR1 expression in MCF‐7/adriamycin (MCF‐7/adr) cells.EXPERIMENTAL APPROACH MCF‐7 and MCF‐7/adr cells were incubated with metformin and changes in P‐gp expression were determined at the mRNA, protein and functional level. Transient transfection assays were performed to assess its gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action.KEY RESULTS Metformin significantly inhibited MDR1 expression by blocking MDR1 gene transcription. Metformin also significantly increased the intracellular accumulation of the fluorescent P‐gp substrate rhodamine‐123. Nuclear factor‐κB (NF‐κB) activity and the level of IκB degradation were reduced by metformin treatment. Moreover, transduction of MCF‐7/adr cells with the p65 subunit of NF‐κB induced MDR1 promoter activity and expression, and this effect was attenuated by metformin. The suppression of MDR1 promoter activity and protein expression was mediated through metformin‐induced activation of AMP‐activated protein kinase (AMPK). Small interfering RNA methods confirmed that reduction of AMPK levels attenuates the inhibition of MDR1 activation associated with metformin exposure. Furthermore, the inhibitory effects of metformin on MDR1 expression and cAMP‐responsive element binding protein (CREB) phosphorylation were reversed by overexpression of a dominant‐negative mutant of AMPK.CONCLUSIONS AND IMPLICATIONS These results suggest that metformin activates AMPK and suppresses MDR1 expression in MCF‐7/adr cells by inhibiting the activation of NF‐κB and CREB. This study reveals a novel function of metformin as an anticancer agent.
Phosphatidylinositol 3‐kinase affects mitochondrial function in part through inducing peroxisome proliferator‐activated receptor γ coactivator‐1β expression
Authors: Gao Minghui , Wang Junjian , Wang Wenxian , Liu Jinsong , Wong Chi‐Wai 
Published: November 2010

BACKGROUND AND PURPOSE Hyperactivation of phosphatidylinositol 3‐kinase (PI3K), commonly observed in cancer, is believed to promote cancer cell growth and survival. Appropriate mitochondrial function is an integral part of cellular function. How PI3K affects mitochondrial homeostasis is not fully understood.EXPERIMENTAL APPROACH Mitochondrial mass, membrane potential and reactive oxygen species (ROS) were quantified by three different fluorogenic probes. Gene expression at the levels of mRNA and protein were measured by quantitative RT‐PCR and Western analysis.KEY RESULTS Using the PI3K inhibitors LY294002 and PI103, we found that suppressing PI3K activity altered mitochondrial function. Specifically, LY294002 and PI103 suppressed the mRNA expression levels of mitochondrial regulators nuclear respiratory factors 1 and 2 (NRF1 and NRF2). As NRF1 and NRF2 are under the transcriptional control of peroxisome proliferator‐activated receptor γ coactivators‐1α and ‐1β (PGC‐1α and PGC‐1β), we found that suppressing PI3K activity selectively reduced both the mRNA and protein levels of PGC‐1β but not PGC‐1α. Reducing PGC‐1β expression also led to reduced mRNA expression levels of uncoupling protein 1, 2 (UCP1 and UCP2) and superoxide dismutase 2. Correspondingly, mitochondrial membrane potential (Δψm) and ROS levels were increased. Finally, we partially blunted the LY294002‐mediated growth suppression by using an antioxidant or over‐expressing PGC‐1β.CONCLUSIONS AND IMPLICATIONS PI3K regulates mitochondrial homeostasis in part through PGC‐1β and blocking this pathway induces ROS to arrest cell growth at the G1 phase.
Status epilepticus in fragile X syndrome
Authors: Gauthey Magali , Poloni Claudia B. , Ramelli Gian‐Paolo , Roulet‐Perez Eliane , Korff Christian M. 
Published: November 2010

SummaryEpilepsy is frequent in fragile X syndrome (FXS), the most common cause of inherited mental retardation. Status epilepticus (SE), however, seems exceptional in FXS, particularly as an initial epileptic manifestation. To our knowledge, SE was reported in only four FXS patients. We report the clinical features and electroencephalography (EEG) findings of five children with FXS, who presented with SE as their initial seizure.
STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome—Result of Japanese cohort study
Authors: Otsuka Motoko , Oguni Hirokazu , Liang Jao‐Shwann , Ikeda Hiroko , Imai Katsumi , Hirasawa Kyoko , Imai Kaoru , Tachikawa Emiko , Shimojima Keiko , Osawa Makiko , Yamamoto Toshiyuki 
Published: November 2010

SummaryWe performed STXBP1 mutation analyses in 86 patients with various types of epilepsies, including 10 patients with OS, 43 with West syndrome, 2 with Lennox‐Gastaut syndrome, 12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 5 with other undetermined types of epilepsy. In all patients, the etiology was unknown, but ARX and CDKL5 mutations were negative in all cases. All coding exons of STXBP1 were analyzed by direct‐sequencing. Two de novo nucleotide alterations of STXBP1 were identified in two patients with Ohtahara and West syndrome, respectively. No de novo or deleterious mutations in STXBP1 were found in the remaining 84 patients with various types of symptomatic epilepsies. This is the first case report showing that STXBP1 mutations caused West syndrome from the onset of epilepsy. STXBP1 analysis should be considered as an etiology of symptomatic West syndrome without explainable cause.
The impact of maternal depressive symptoms on health‐related quality of life in children with epilepsy: A prospective study of family environment as mediators and moderators
Authors: Ferro Mark A. , Avison William R. , Karen Campbell M. , Speechley Kathy N. 
Published: November 2010

SummaryPurpose:  To examine the impact of maternal depressive symptoms (DS) on health‐related quality of life (HRQL) in children with new‐onset epilepsy and to identify family factors that moderate and mediate this relationship during the first 24 months after epilepsy diagnosis.Methods:  A sample of 339 mother–child dyads recruited from pediatric neurologists across Canada in the Health‐related Quality of Life in Children with Epilepsy Study. Mothers’ and neurologists’ reports were collected at four times during the 24‐month follow‐up. Mothers’ DS were measured using the Center for Epidemiological Studies Depression Scale (CES‐D) and children’s HRQL using the Quality of Life in Childhood Epilepsy (QOLCE). Data were modeled using individual growth curve modeling.Key Findings:  Maternal DS were observed to have a negative impact on QOLCE scores at 24 months (β = −0.47, p < 0.0001) and the rate of change in QOLCE scores during follow‐up (β = −0.04, p = 0.0250). This relationship was moderated by family resources (β = 0.25, p = 0.0243), and the magnitude of moderation varied over time (β = 0.09, p = 0.0212). Family functioning and demands partially mediated the impact of maternal DS on child HRQL (β = −0.07, p = 0.0007; β = −0.12, p = 0.0006).Significance:  Maternal DS negatively impact child HRQL in new‐onset epilepsy during the first 24 months after diagnosis. This relationship is moderated by family resources and mediated by family functioning and demands. By adopting family centered approaches, health care professionals may be able to intervene at the maternal or family level to promote more positive outcomes in children.
Drug monitoring of lamotrigine and oxcarbazepine combination during pregnancy
Authors: Wegner Ilse , Edelbroek Peter , De Haan Gerrit‐Jan , Lindhout Dick , Sander Josemir W. 
Published: November 2010

SummaryLittle is known about pregnancy‐induced alterations in the pharmacokinetics of the newer antiepileptic drugs, especially when used in combinations. Two women receiving combination therapy of lamotrigine (LTG) and oxcarbazepine (OXC) were followed prospectively during pregnancy and puerperium. Steady‐state concentrations of LTG and the active metabolite of OXC, 10‐hydroxycarbazepine (MHD), were measured at regular intervals using a dried blood spot method, and clearances were calculated. A strong effect of pregnancy on the clearance of both LTG and MHD was seen. An increase in seizure frequency occurred in both women. This stresses the importance of therapeutic drug monitoring of LTG and MHD during pregnancy. In case of breakthrough seizures or increased seizure frequency, dosage adjustment of both drugs may be required.