bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and analysis of in planta expressed genes of Magnaporthe oryzae
Authors: Kim Soonok , Park Jongsun , Park Sook-Young , Mitchell Thomas K , Lee Yong-Hwan
Published: March 2010

Background

Infection of plants by pathogens and the subsequent disease development involves substantial changes in the biochemistry and physiology of both partners. Analysis of genes that are expressed during these interactions represents a powerful strategy to obtain insights into the molecular events underlying these changes. We have employed expressed sequence tag (EST) analysis to identify rice genes involved in defense responses against infection by the blast fungusMagnaporthe oryzaeand fungal genes involved in infectious growth within the host during a compatible interaction.

Results

A cDNA library was constructed with RNA from rice leaves (Oryza sativacv. Hwacheong) infected withM. oryzaestrain KJ201. To enrich for fungal genes, subtraction library using PCR-based suppression subtractive hybridization was constructed with RNA from infected rice leaves as a tester and that from uninfected rice leaves as the driver. A total of 4,148 clones from two libraries were sequenced to generate 2,302 non-redundant ESTs. Of these, 712 and 1,562 ESTs could be identified to encode fungal and rice genes, respectively. To predict gene function, Gene Ontology (GO) analysis was applied, with 31% and 32% of rice and fungal ESTs being assigned to GO terms, respectively. One hundred uniESTs were found to be specific to fungal infection EST. More than 80 full-length fungal cDNA sequences were used to validateab initioannotated gene model ofM. oryzaegenome sequence.

Conclusion

This study shows the power of ESTs to refine genome annotation and functional characterization. Results of this work have advanced our understanding of the molecular mechanisms underpinning fungal-plant interactions and formed the basis for new hypothesis.
Genome dynamics of Bartonella grahamii in micro-populations of woodland rodents
Authors: Berglund Eva C , Ehrenborg Christian , Vinnere Pettersson Olga , Granberg Fredrik , Näslund Kristina , Holmberg Martin , Andersson Siv GE
Published: March 2010

Background

Rodents represent a high-risk reservoir for the emergence of new human pathogens. The recent completion of the 2.3 Mb genome of Bartonella grahamii, one of the most prevalent blood-borne bacteria in wild rodents, revealed a higher abundance of genes for host-cell interaction systems than in the genomes of closely related human pathogens. The sequence variability within the global B. grahamii population was recently investigated by multi locus sequence typing, but no study on the variability of putative host-cell interaction systems has been performed.

Results

To study the population dynamics of B. grahamii, we analyzed the genomic diversity on a whole-genome scale of 27 B. grahamii strains isolated from four different species of wild rodents in three geographic locations separated by less than 30 km. Even using highly variable spacer regions, only 3 sequence types were identified. This low sequence diversity contrasted with a high variability in genome content. Microarray comparative genome hybridizations identified genes for outer surface proteins, including a repeated region containing the fha gene for filamentous hemaggluttinin and a plasmid that encodes a type IV secretion system, as the most variable. The estimated generation times in liquid culture medium for a subset of strains ranged from 5 to 22 hours, but did not correlate with sequence type or presence/absence patterns of the fha gene or the plasmid.

Conclusion

Our study has revealed a geographic microstructure of B. grahamii in wild rodents. Despite near-identity in nucleotide sequence, major differences were observed in gene presence/absence patterns that did not segregate with host species. This suggests that genetically similar strains can infect a range of different hosts.
Chemogenomic and transcriptome analysis identifies mode of action of the chemosensitizing agent CTBT (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine)
Authors: Batova Monika , Klobucnikova Vlasta , Oblasova Zuzana , Gregan Juraj , Zahradnik Pavol , Hapala Ivan , Subik Julius , Schüller Christoph
Published: March 2010

Background

CTBT (7-chlorotetrazolo [5,1-c]benzo[1,2,4]triazine) increases efficacy of commonly used antifungal agents by an unknown mechanism. It increases the susceptibility of Saccharomyces cerevisiae, Candida albicans and Candida glabrata cells to cycloheximide, 5-fluorocytosine and azole antimycotic drugs. Here we elucidate CTBT mode of action with a combination of systematic genetic and transcriptome analysis.

Results

To identify the cellular processes affected by CTBT, we screened the systematic haploid deletion mutant collection for CTBT sensitive mutants. We identified 169 hypersensitive deletion mutants. The deleted genes encode proteins mainly involved in mitochondrial functions, DNA repair, transcription and chromatin remodeling, and oxidative stress response. We found that the susceptibility of yeast cells to CTBT depends on molecular oxygen. Transcriptome analysis of the immediate early response to CTBT revealed rapid induction of oxidant and stress response defense genes. Many of these genes depend on the transcription factors Yap1 and Cin5. Yap1 accumulates rapidly in the nucleus in CTBT treated cells suggesting acute oxidative stress. Moreover, molecular calculations supported a superoxide generating activity of CTBT. Superoxide production in vivo by CTBT was found associated to mitochondria as indicated by oxidation of MitoSOX Red.

Conclusion

We conclude that CTBT causes intracellular superoxide production and oxidative stress in fungal cells and is thus enhancing antimycotic drug effects by a secondary stress.
Dynamics of peptidergic secretory granule transport are regulated by neuronal stimulation
Authors: Sobota Jacqueline A , Mohler William A , Cowan Ann E , Eipper Betty A , Mains Richard E
Published: March 2010

Background

Peptidergic neurons store and secrete the contents of large dense core vesicles (LDCVs) from axon terminals and from dendrites. Secretion of peptides requires a highly regulated exocytotic mechanism, plus coordinated synthesis and transport of LDCVs to their sites of release. Although these trafficking events are critical to function, little is known regarding the dynamic behavior of LDCVs and the mechanisms by which their transport is regulated. Sensory neurons also package opiate receptors in peptide-containing LDCVs, which is thought to be important in pain sensation. Since peptide granules cannot be refilled locally after their contents are secreted, it is particularly important to understand how neurons support regulated release of peptides.

Results

A vector encoding soluble peptidylglycine α-hydroxylating monooxygenase fused to green fluorescent protein was constructed to address these questions in cultured primary peptidergic neurons of the trigeminal ganglion using time lapse confocal microscopy. The time course of release differs with secretagogue; the secretory response to depolarization with K+ is rapid and terminates within 15 minutes, while phorbol ester stimulation of secretion is maintained over a longer period. The data demonstrate fundamental differences between LDCV dynamics in axons and growth cones under basal conditions.

Conclusions

Under basal conditions, LDCVs move faster away from the soma than toward the soma, but fewer LDCVs travel anterograde than retrograde. Stimulation decreased average anterograde velocity and increases granule pausing. Data from antibody uptake, quantification of enzyme secretion and appearance of pHluorin fluorescence demonstrate distributed release of peptides all along the axon, not just at terminals.
Hypervariable intronic region in NCX1 is enriched in short insertion-deletion polymorphisms and showed association with cardiovascular traits
Authors: Kepp Katrin , Org Elin , Sõber Siim , Kelgo Piret , Viigimaa Margus , Veldre Gudrun , Tõnisson Neeme , Juhanson Peeter , Putku Margus , Kindmark Andreas , Kožich Viktor , Laan Maris
Published: March 2010

Background

Conserved non-coding regions (CNR) have been shown to harbor gene expression regulatory elements. Genetic variations in these regions may potentially contribute to complex disease susceptibility.

Methods

We targeted CNRs of cardiovascular disease (CVD) candidate gene, Na(+)-Ca(2+) exchanger (NCX1) with polymorphism screening among CVD patients (n = 46) using DHPLC technology. The flanking region (348 bp) of the 14 bp indel in intron 2 was further genotyped by DGGE assay in two Eastern-European CVD samples: essential hypertension (HYPEST; 470 cases, 652 controls) and coronary artery disease, CAD (CADCZ; 257 cases, controls 413). Genotype-phenotype associations were tested by regression analysis implemented in PLINK. Alignments of primate sequences were performed by ClustalW2.

Results

Nine of the identified NCX1 variants were either singletons or targeted by commercial platforms. The 14 bp intronic indel (rs11274804) was represented with substantial frequency in HYPEST (6.82%) and CADCZ (14.58%). Genotyping in Eastern-Europeans (n = 1792) revealed hypervariable nature of this locus, represented by seven alternative alleles. The alignments of human-chimpanzee-macaque sequences showed that the major human variant (allele frequency 90.45%) was actually a human-specific deletion compared to other primates. In humans, this deletion was surrounded by other short (5-43 bp) deletion variants and a duplication (40 bp) polymorphism possessing overlapping breakpoints. This indicates a potential indel hotspot, triggered by the initial deletion in human lineage. An association was detected between the carrier status of 14 bp indel ancestral allele and CAD (P = 0.0016, OR = 2.02; Bonferroni significance level alpha = 0.0045), but not with hypertension. The risk for the CAD development was even higher among the patients additionally diagnosed with metabolic syndrome (P = 0.0014, OR = 2.34). Consistent with the effect on metabolic processes, suggestive evidence for the association with heart rate, serum triglyceride and LDL levels was detected (P = 0.04).

Conclusions

Compared to SNPs targeted by large number of locus-specific and genome-wide assays, considerably less attention has been paid to short indel variants in the human genome. The data of genome dynamics, mutation rate and population genetics of short indels, as well as their impact on gene expressional profile and human disease susceptibility is limited. The characterization of NCX1 intronic hypervariable non-coding region enriched in human-specific indel variants contributes to this gap of knowledge.
The height-, weight-, and BMI-for-age of Polish school-aged children and adolescents relative to international and local growth references
Authors: Kulaga Zbigniew , Litwin Mieczysław , Tkaczyk Marcin , Różdżyńska Agnieszka , Barwicka Katarzyna , Grajda Aneta , Świąder Anna , Gurzkowska Beata , Napieralska Ewelina , Pan Huiqi
Published: March 2010

Background

The growth of children is an indicator of health and society's wellbeing. Growth references are useful in monitoring a child's growth, which is a very important part of child care. Poland's growth references are not updated regularly. Although several growth reference ranges have been developed in Poland over recent years, sampling was restricted to urban populations of major cities. The aim of this study was to assess how well Polish children match with, or diverge from, regional charts and to compare them with international growth references.

Methods

Four Polish and two international (WHO 2007 and USCDC2000) growth references were used to calculate the height, weight and BMI z-scores in a recent, large, population-representative sample of school-aged children and adolescents in Poland. The distributions of z-scores were analysed with descriptive and inferential statistical methods.

Results

Mean height z-scores calculated with the use of the WHO 2007 and USCDC2000 references were positive and significantly different from zero over the entire age range. The mean height z-score was closest to zero in the Poznan reference for boys (0.05) and Warszawa reference for girls (0.01). Median weight z-scores were positive under all weight references over the entire age range with only the exception of 18-year-old girls' weight z-score calculated relative to USCDC2000. Median BMI z-scores were positive in males in early childhood, decreasing with age. In the case of girls, the median BMI z-score calculated using WHO 2007 and USCDC2000 was close to zero in early childhood, decreased in adolescents and reached minimum values at age 18 years. Median BMI z-scores calculated with the use of the Lodz reference fluctuated between 0.05 and 0.2 over the studied age range.

Conclusions

In this contemporary sample of Polish school-aged children, distributions of height, weight and BMI differed from those of children from the international growth references. These differences should be considered when using the references. There exist certain limitations to the analysis of height, weight, and BMI z-scores when Polish regional references are used.
Doxorubicin-induced ovarian toxicity
Authors: Ben-Aharon Irit , Bar-Joseph Hadas , Tzarfaty Galia , Kuchinsky Lital , Rizel Shulamith , Stemmer Salomon M , Shalgi Ruth
Published: March 2010

Background

Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries.

Methods

Female mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin.

Results

A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation rate was observed one week after treatment, followed by a partial recovery at one month. Histological examination revealed positive staining of TUNEL and active caspase-3. We observed a significant reduction in the population of secondary and primordial follicles one month following treatment.

Conclusions

Our results may imply a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size, caused probably by an acute insult to the ovary.
Monitoring the regulation of gene expression in a growing organ using a fluid mechanics formalism
Authors: Merret Rémy , Moulia Bruno , Hummel Irène , Cohen David , Dreyer Erwin , Bogeat-Triboulot Marie-Béatrice
Published: March 2010

Background

Technological advances have enabled the accurate quantification of gene expression, even within single cell types. While transcriptome analyses are routinely performed, most experimental designs only provide snapshots of gene expression. Molecular mechanisms underlying cell fate or positional signalling have been revealed through these discontinuous datasets. However, in developing multicellular structures, temporal and spatial cues, known to directly influence transcriptional networks, get entangled as the cells are displaced and expand. Access to an unbiased view of the spatiotemporal regulation of gene expression occurring during development requires a specific framework that properly quantifies the rate of change of a property in a moving and expanding element, such as a cell or an organ segment.

Results

We show how the rate of change in gene expression can be quantified by combining kinematics and real-time polymerase chain reaction data in a mechanistic model which considers any organ as a continuum. This framework was applied in order to assess the developmental regulation of the two reference genes Actin11 and Elongation Factor 1-β in the apex of poplar root. The growth field was determined by time-lapse photography and transcript density was obtained at high spatial resolution. The net accumulation rates of the transcripts of the two genes were found to display highly contrasted developmental profiles. Actin11 showed pulses of up and down regulation in the accelerating and decelerating parts of the growth zone while the dynamic of EF1β were much slower. This framework provides key information about gene regulation in a developing organ, such as the location, the duration and the intensity of gene induction/repression.

Conclusions

We demonstrated that gene expression patterns can be monitored using the continuity equation without using mutants or reporter constructions. Given the rise of imaging technologies, this framework in our view opens a new way to dissect the molecular basis of growth regulation, even in non-model species or complex structures.
Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice
Authors: Harhausen Denise , Khojasteh Uldus , Stahel Philip F , Morgan B Paul , Nietfeld Wilfried , Dirnagl Ulrich , Trendelenburg George
Published: March 2010

Background

The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC) and its inhibitor-protein CD59.

Methods

Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death.

Results and Discussion

CD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO.

Conclusion

We conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.
Monitoring of clinical signs in goats with transmissible spongiform encephalopathies
Authors: Konold Timm , Bone Gemma E , Phelan Laura J , Simmons Marion M , González Lorenzo , Sisó Sílvia , Goldmann Wilfred , Cawthraw Saira , Hawkins Steve AC
Published: March 2010

Background

As there is limited information about the clinical signs of BSE and scrapie in goats, studies were conducted to describe the clinical progression of scrapie and BSE in goats and to evaluate a short clinical protocol for its use in detecting scrapie-affected goats in two herds with previously confirmed scrapie cases. Clinical assessments were carried out in five goats intracerebrally infected with the BSE agent as well as five reported scrapie suspects and 346 goats subject to cull from the two herds, 24 of which were retained for further monitoring. The brain and selected lymphoid tissue were examined by postmortem tests for disease confirmation.

Results

The sensitivity and specificity of the short clinical protocol in detecting a scrapie case in the scrapie-affected herds was 3.9% and 99.6%, respectively, based on the presence of tremor, positive scratch test, extensive hair loss, ataxia and absent menace response. All BSE- and scrapie-affected goats displayed abnormalities in sensation (over-reactivity to external stimuli, startle responses, pruritus, absent menace response) and movement (ataxia, tremor, postural deficits) at an advanced clinical stage but the first detectable sign associated with scrapie or BSE could vary between animals. Signs of pruritus were not always present despite similar prion protein genotypes. Clinical signs of scrapie were also displayed by two scrapie cases that presented with detectable disease-associated prion protein only in lymphoid tissues.

Conclusions

BSE and scrapie may present as pruritic and non-pruritic forms in goats. Signs assessed for the clinical diagnosis of scrapie or BSE in goats should include postural and gait abnormalities, pruritus and visual impairment. However, many scrapie cases will be missed if detection is solely based on the display of clinical signs. PrPdaccumulation in the brain appeared to be related to the severity of clinical disease but not to the display of individual neurological signs.
A systematic review of the use of theory in the design of guideline dissemination and implementation strategies and interpretation of the results of rigorous evaluations
Authors: Davies Philippa , Walker Anne E , Grimshaw Jeremy M
Published: March 2010

Background

There is growing interest in the use of cognitive, behavioural, and organisational theories in implementation research. However, the extent of use of theory in implementation research is uncertain.

Methods

We conducted a systematic review of use of theory in 235 rigorous evaluations of guideline dissemination and implementation studies published between 1966 and 1998. Use of theory was classified according to type of use (explicitly theory based, some conceptual basis, and theoretical construct used) and stage of use (choice/design of intervention, process/mediators/moderators, and post hoc/explanation).

Results

Fifty-three of 235 studies (22.5%) were judged to have employed theories, including 14 studies that explicitly used theory. The majority of studies (n = 42) used only one theory; the maximum number of theories employed by any study was three. Twenty-five different theories were used. A small number of theories accounted for the majority of theory use including PRECEDE (Predisposing, Reinforcing, and Enabling Constructs in Educational Diagnosis and Evaluation), diffusion of innovations, information overload and social marketing (academic detailing).

Conclusions

There was poor justification of choice of intervention and use of theory in implementation research in the identified studies until at least 1998. Future research should explicitly identify the justification for the interventions. Greater use of explicit theory to understand barriers, design interventions, and explore mediating pathways and moderators is needed to advance the science of implementation research.
Differential effects of selective HDAC inhibitors on macrophage inflammatory responses to the Toll-like receptor 4 agonist LPS
Authors: Halili Maria A , Andrews Melanie R , Labzin Larisa I , Schroder Kate , Matthias Gabriele , Cao Chun , Lovelace Erica , Reid Robert C , Le Giang T , Hume David A , Irvine Katharine M , Matthias Patrick , Fairlie David P , Sweet Matthew J
Published: March 2010

Selective inhibitor studies in macrophages implicate class II HDAC enzymes in TLR-mediated inflammatory pathways and class I HDACs as negative regulators.

Broad-spectrum inhibitors of HDACs are therapeutic in many inflammatory disease models but exacerbated disease in a mouse model of atherosclerosis. HDAC inhibitors have anti- and proinflammatory effects on macrophages in vitro. We report here that several broad-spectrum HDAC inhibitors, including TSA and SAHA, suppressed the LPS-induced mRNA expression of the proinflammatory mediators Edn-1, Ccl-7/MCP-3, and Il-12p40 but amplified the expression of the proatherogenic factors Cox-2 and Pai-1/serpine1 in primary mouse BMM. Similar effects were also apparent in LPS-stimulated TEPM and HMDM. The pro- and anti-inflammatory effects of TSA were separable over a concentration range, implying that individual HDACs have differential effects on macrophage inflammatory responses. The HDAC1-selective inhibitor, MS-275, retained proinflammatory effects (amplification of LPS-induced expression of Cox-2 and Pai-1 in BMM) but suppressed only some inflammatory responses. In contrast, 17a (a reportedly HDAC6-selective inhibitor) retained anti-inflammatory but not proinflammatory properties. Despite this, HDAC6−/− macrophages showed normal LPS-induced expression of HDAC-dependent inflammatory genes, arguing that the anti-inflammatory effects of 17a are not a result of inhibition of HDAC6 alone. Thus, 17a provides a tool to identify individual HDACs with proinflammatory properties.
The catalytic PI3K isoforms p110γ and p110δ contribute to B cell development and maintenance, transformation, and proliferation
Authors: Beer-Hammer Sandra , Zebedin Eva , von Holleben Max , Alferink Judith , Reis Bernhard , Dresing Philipp , Degrandi Daniel , Scheu Stefanie , Hirsch Emilio , Sexl Veronika , Pfeffer Klaus , Nürnberg Bernd , Piekorz Roland P
Published: March 2010

PI3K isoforms p110γ and p110δ are required for early B cell development, peripheral maintenance, transformation by the Abelson oncogene, and LPS-induced proliferation.

Class I PI3K-dependent signaling regulates cell proliferation, differentiation, and survival. Analysis of gene-deficient mice revealed specific roles for the hematopoietically expressed PI3K catalytic subunits, p110γ and p110δ, in development and function of T and B lymphocytes. However, the functional redundancy between these two PI3K isoforms in the B cell lineage remains unclear. Here, we demonstrate that p110δ and p110γ are expressed in B cells at early developmental stages. Normal B cell differentiation requires both isoforms, as p110γ/p110δ double deficiency causes an increased percentage of CD43hi/B220+/CD19− cells as compared with single deficiency. Interestingly, initial transformation efficiency of B cell precursors was strongly reduced in double-deficient cells following transformation by p185 bcr-abl or v-abl oncogenes as compared with single-deficient cells. The requirement of p110γ and p110δ in B cell development is underlined by reduced splenic B cell numbers of p110γ/p110δ double-deficient mice and of lethally irradiated wild-type mice reconstituted with double-deficient BM. Moreover, the peripheral maintenance of p110γ/p110δ double-deficient T and B cells was highly impaired following adoptive transfer of double-deficient splenocytes into wild-type mice. Functionally, LPS stimulation of splenocytes revealed proliferation defects resulting in decreased survival of p110γ/p110δ double-deficient B cells, which correlated with impaired induction of D-type cyclins and Bcl-XL. Surprisingly, this was not observed when purified B cells were analyzed, indicating a contribution of likely cell-extrinsic factor(s) to the impaired proliferation of double-deficient B cells. Thus, we provide novel evidence that p110γ and p110δ have overlapping and cell-extrinsic roles in the development, peripheral maintenance, and function of B cells.
STAT1-dependent IgG cell-surface expression in a human B cell line derived from a STAT1-deficient patient
Authors: Najjar Imen , Deglesne Pierre-Antoine , Schischmanoff Pierre Olivier , Fabre Emmanuelle E , Boisson-Dupuis Stéphanie , Nimmerjahn Falk , Bornkamm Georg W , Dusanter-Fourt Isabelle , Fagard Remi
Published: March 2010

A STAT1-dependent surface expression of IgGs is revealed in a human B cell line derived from a STAT1-deficient patient.

STAT1 is a key effector of cytokines involved in the resistance to pathogens; its identified transcriptional targets mediate the innate immune response involved in the defense against viruses and bacteria. Little is known about the role of STAT1 in adaptive immunity, including its impact on BCR or surface Ig expression. Analysis of this point is difficult in humans, as STAT1 deficiency is extremely rare. SD patients die early in childhood from a severe immunodeficiency. Herein, a SD B cell line obtained from a SD patient was compared with a B cell line from a STAT1-proficient subject in search of differences in surface Ig expression. In this SD B cell line, a complete absence of surface IgG was noted. The mRNA encoding the surface form of IgG was detected only in STAT1-proficient B cells; the mRNAs encoding the secreted and the surface forms were detected in SD and STAT1-proficient B cells. Re-expression of STAT1 in SD B cells restored surface IgG expression and a functional BCR. Conversely, shRNA silencing of STAT1 in B cells reduced considerably the expression of the surface IgG. Although limited to one B cell line, these results suggest that STAT1 may play an essential role in surface IgG expression in human B cells. Possible mechanisms involve regulation of mRNA splicing, transcription, or both. These observations extend the role of STAT1 further in adaptive immunity, including the regulation of BCR expression.
Human eosinophil granulocytes do not express the enzyme arginase
Authors: Luckner-Minden Claudia , Fischer Ina , Langhans Claus-Dieter , Schiller Martin , Kropf Pascale , Müller Ingrid , Hohlfeld Jens M , Ho Anthony D , Munder Markus
Published: March 2010

Human eosinophils lack the mechanism of arginase-mediated arginine depletion as a key immunosuppressive mechanism of neutrophil granulocytes.

Human polymorphonuclear PMN constitutively express the enzyme arginase I, which hydrolyzes arginine to ornithine and urea. This arginine consumption has been recognized as a key pathway of myeloid cell-mediated suppression of the adaptive immune system during inflammation, infection, and tumor growth. Eos granulocytes are crucial immunoregulatory and effector cells of allergic inflammation and infections with parasites and helminths and in a variety of tumors. Here, we analyzed if human Eos also express arginase with its potential immunosuppressive consequences. We show that human peripheral blood Eos do not express arginase I or II protein or arginase enzymatic activity. Correspondingly, no metabolism of arginine to ornithine can be detected in Eos-S. Neither Eos apoptosis nor cytokine-mediated cellular activation induces arginase in human Eos in vitro. Finally, we show that arginase activity and protein are also undetectable in Eos of allergic patients from peripheral blood or from BALF activated in vivo during allergic pulmonary inflammation. This work demonstrates a fundamental difference between neutrophil and Eos granulocytes. As Eos are not equipped with the immunosuppressive enzyme arginase, they cannot participate, via arginine limitation, in the suppression of the evolving adaptive immune response in allergy, infections, or tumor immunity.
Safe Practice Environment Chapter Proposed by United States Pharmacopeia; Sulfamethoxazole/Trimethoprim and Lisinopril Hyperkalemia
Authors: Cohen Michael R. , Smetzer Judy L.
Published: March 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Simvastatin and Amiodarone: Emergence of a Potentially Toxic Interaction
Authors: Backes James M. , Howard Patricia A.
Published: March 2010

This continuing feature updates readers on recent developments in cardiovascular pharmacotherapy. Cardiovascular disease remains the number 1 killer in the United States, and more clinical outcome trials have been conducted in cardiology than in any other field of medicine. Given this rapidly expanding knowledge base, if pharmacists stay current with developments in drug therapy, they can have a significant impact on prevention and treatment.
Panitumumab-Related Hypomagnesemia in Patients with Colorectal Cancer
Authors: Cheng Haiying , Gammon David , Dutton Traci M. , Piperdi Bilal
Published: March 2010

Purpose

Hypomagnesemia is an adverse reaction associated with epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies. Of the 2 EGFR antibodies approved by the US Food and Drug Administration—cetuximab and panitumumab—cetuximab-induced hypomagnesemia has been extensively characterized but panitumumab-induced hypomagnesemia has not.

Methods

In this retrospective study, the clinical course of hypomagnesemia is described in three 64- to 68-year-old men who received panitumumab monotherapy or panitumumab-plus-irinotecan therapy for colorectal cancer for 8 to 21 weeks.

Results

The onset of hypomagnesemia was variable, ranging from 1 week to 10 weeks following the initiation of panitumumab. Magnesium levels did not normalize until 4 to 8 weeks after discontinuation of the agent. Of the patients in the study, 2 had new onset of grade 3 hypomagnesemia 1 to 3 weeks after panitumumab was discontinued. Management was magnesium sulfate 2 g infusion weekly and magnesium oxide 1,200 mg oral repletion daily. With severe hypomagnesemia (grade 3 and higher) or significant diarrhea (grade 3 and higher), a daily infusion of magnesium sulfate 2 or 4 g was administered.

Conclusion

When administering panitumumab therapy, magnesium levels should be monitored from the initiation of the agent to at least 8 weeks following cessation. Hypomagnesemia usually can be managed with magnesium sulfate 2 to 4 g infusion weekly and magnesium oxide 1,200 mg oral repletion daily. Future research is warranted to identify simple and efficient strategies for monitoring and treating EGFR blockade with monoclonal antibody-associated hypomagnesemia.
Tigecycline-Induced Pancreatitis
Authors: Marshall S. Renee
Published: March 2010

Purpose

The intent of this case report is to heighten the awareness of the potential for tigecycline-induced pancreatitis.

Case Summary

A 55-year-old woman came to the emergency department with complaints of chest pain, and it was later found that the patient was bacteremic. Blood cultures grew Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus hominis. The patient was treated with several antibiotics, including tigecycline. Approximately 2 weeks following admission, the patient developed nausea, vomiting, fever, and loss of appetite. A gastroenterology consult revealed pancreatitis, and it was recommended that tigecycline be discontinued. Shortly after tigecycline discontinuation, the patient's symptoms resolved and the enzymes returned to normal.

Discussion

A review is presented of the available literature on mechanisms for tetracycline-induced pancreatitis based on tetracycline's interaction with a receptor on the 30s ribosomal subunit necessary for protein synthesis.

Conclusion

Because of the structural similarity between tigecycline and tetracycline, it is plausible that the same mechanism for tetracycline-induced pancreatitis could be the rationale for the episode of pancreatitis described in the case report presented here.
New Drugs Approved by the FDA; New Dosage Forms and Indications Approved by the FDA; Agents Pending FDA Approval; New Drug Applications Filed by Manufacturer; Supplemental Applications Filed by Manufacturer
Authors: Baker Danial E.
Published: March 2010

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let us know at hospitalpharmacy@drugfacts.com .
Automated Intravenous Preparation: Robots for the Pharmacy
Authors: Fox Brent I. , Felkey Bill G.
Published: March 2010

This month we address an emerging technology that we believe will one day be as common as automated dispensing cabinets. Automated, robotic intravenous preparation is not as new to the area of pharmacy as many may think. Recently, United States Pharmacopeia <797> regulations prompted serious consideration and evaluation of this technology by many pharmacy departments. This article provides an overview of the vendors, their products, and other considerations for your due diligence.
Electronic Prescribing
Authors: Weber Robert J. , Mark Scott M.
Published: March 2010

The Director's Forum series is written and edited by Michael Sanborn and Robert Weber and is designed for guiding pharmacy leaders in establishing patient-centered services in hospitals and health systems. Another specific goal of this column is addressing many of the key challenges that pharmacy directors currently face, while also providing information that will foster growth in pharmacy leadership and patient safety. As the use of electronic prescribing grows in health systems, pharmacy directors must be positioned to assist their organizations in a variety of ways when implementing and evaluating these systems. This installment of the Director's Forum provides a brief primer to electronic prescribing and its implications for improving the patient-centered provision of hospital pharmacy services.
Segundo de Chomn and the early years of cinema: a revisionist perspective
Authors: Batllori Joan M. Minguet
Published: March 2010

Segundo de Chomn is the Spanish film-maker from the silent era with a wider international dimension. But the study about him needs a permanent reformulation. First of all, due to the shortage of data about the specific moves in his career in the framework of cinema in its early years.
Secondly, due to the harmful nature of some clichs told about him (pioneer of Spanish cinema, the Spanish Mlis). This paper offers a starting point for a revision of Chomn's work, from theoretical considerations and particular films, including Le Vie et passion de N.S. Jess Christ, Le fils
du diable, Le courant lectrique or Symphonie bizarre.
Audio-visual communication degree conversion to the European Higher Education Area system in Catalonia
Authors: Montagut Marta
Published: March 2010

Spain is currently adapting its existing university system to European Higher Education Area guidelines for the 20092010 academic year. Against this background, we analyzed the development and transformation of the audio-visual communication degree currently offered in Catalan universities,
consisting of a hybrid of theoretical and practical knowledge applied in the audio-visual field. We describe research results based on the following data: audio-visual curricular content for eight Catalan universities, nine in-depth interviews conducted with heads of audio-visual communication
studies and a survey of 111 companies regarding labour market performance of audio-visual communication students on work experience programmes. On the basis of the results of our study we propose a solution to the problem of adapting audio-visual communication degrees to the European Higher
Education Area system, based on developing specialisation pathways for different job roles, media platforms and genres. The pathway option equips the degree with professional specificity and enables flexible curricula to be developed in accordance with the capacities of individual universities
and the demands of the private sector. The study also highlights the lack of definition in the job roles of audio-visual communication graduates and the difficulties in establishing differential skills for this course of studies.
Reviews
Authors: Green Laura , Olssen Mark , Turnbull Nick
Published: March 2010

To Speak is Never Neutral, Luce Irigaray (2002) London: Continuum, 277 pp., ISBN-0-8264-5905, paperback, 21.84Adorno's Concept of Life, Alastair Morgan (2007) London: Continuum, 9780826496133, Hardback, 70.00Uncovering Hidden Rhetorics: Social
Issues in Disguise, Barry Brummett (2008) Thousand Oaks, CA: Sage, ISBN 978-1-4129-5692-5, Paperback, 29.45
Communication between friends
Authors: O'Brien Dan
Published: March 2010

One kind of successful communication involves the transmission of knowledge from speaker to hearer. Such testimonial knowledge transmission is usually seen as conforming to three widely held epistemological approaches: reliabilism, impartialism and evidentialism. First, a speaker must be a reliable testifier in order that she transmits knowledge, and reliability is cashed out in terms of her likelihood of speaking the truth. Second, if a certain speaker's testimony has sufficient epistemic weight to be believed by hearer1, then it should also be believed by hearer2. Third, the normative constraint here is evidentially grounded: whether or not a hearer should believe a speaker depends on the evidence the hearer has that the speaker is telling the truth. I argue that there are cases of testimonial knowledge transmission that are incompatible with these three claims. This is when one accepts the testimony of an intimate friend.
Communication or Confrontation Heidegger and Philosophical Method
Authors: Blok Vincent
Published: March 2010

In this essay, we consider the philosophical method of reading and writing, of communication. Normally, we interpret the works of the great philosophers and explain them in papers and presentations. The thinking of Martin Heidegger has given us an indication of an entirely different
method of philosophical thinking. In the 1930s, he gave a series of lectures on Nietzsche. In them, he calls his own way of reading and writing a confrontation (Auseinandersetzung) with Nietzsche. We consider the specific character of confrontation, and in what ways it is different
from communication. First, we develop an answer to the question of how Heidegger reads Nietzsche. Does he give a charitable or a violent interpretation of Nietzsche and, if neither, how can his confrontation with Nietzsche be characterized? With this, we obtain an indication of the way we
have to read Heidegger, indeed, of philosophical reading and writing as such.
Audience Studies 2.0. On the theory, politics and method of qualitative audience research
Authors: Hermes Joke
Published: March 2010

Audience research, this paper suggests, is an excellent field to test the claims of Media Studies 2.0. Moreover, 2.0 claims are a good means to review qualitative audience research itself too. Working from a broad strokes analysis of the theory, politics and method of interpretative
research with audiences, it is argued that the new media ecology demands new roles of researchers, and an open approach to audiencehood as practice and innovative research method. The paper ends with a case study of the co-creation project of a research team and a Moroccan-Dutch Internet community-writing
team working together on an Internet telenovela.
Media Studies 2.0: a response
Authors: Gauntlett David
Published: March 2010

This article responds to the articles about Media Studies 2.0 featured in this special issue of Interactions. Key features of Media Studies 2.0 are restated: (1) Considerable changes in the media ecosystem, where internet-based technologies now blur the range of places where
users can encounter, interact with and contribute to media content; (2) The collapse of separate categories of producer and audience, as growing numbers of people become creators and curators of digital media; (3) A turn away from professional media productions, towards the everyday participatory
and creative possibilities of today's media.

The article notes William Merrin's sophisticated contributions to this debate, and goes on to consider some of the criticisms made about Media Studies 2.0. It notes that commentary in this field tends towards either celebration or condemnation
of new technologies, and suggests that a more measured discussion of the role of media in people's lives might prove more illuminating.
Media Studies 2.0: upgrading and open-sourcing the discipline
Authors: Merrin William
Published: March 2010

This paper argues that media studies needs to be upgraded to reflect contemporary changes in digital media. It argues that media studies was a product and reflection of the broadcast-era of media, being formed in and analysing a specific historical period of media production, distribution
and consumption. The rise of digital media, the transformation of old media into a digital form and ongoing developments in digital technology take us into a post-broadcast era, defined by new alignments of productive and distributive power and media consumption and use. This requires an upgraded
Media Studies 2.0, marked by the revision and updating of existing disciplinary knowledge; the foregrounding of contemporary changes and the development of new categories and concepts to understand these, and the open-sourcing of the discipline itself laying open its foundation, assumptions
and biases to enable its public to continually rewrite and improve its knowledge, to ensure its continued relevance in a rapidly changing era.
Critical Media Studies 2.0: an interactive upgrade
Authors: Andrejevic Mark
Published: March 2010

When it comes to the revolutionary promise of participatory media, the challenge faced by the proponents and practitioners of a Critical Media Studies 2.0 is not to assert (in all too familiar rhetoric) that, everything has changed, but rather to explain why, even in the face
of dramatic technological transformation, power relations remain largely unaltered. This essay explores some of the ways in which the social context has shifted to absorb and deflect the critical potential of interactive media and traces the outlines of a critical project for Media Studies
in the digital era. In particular, it argues that the automatic equation of interactivity with political critique and democratic empowerment represents an outdated way of thinking about the social role of information and communication technologies. Interactivity isn't automatically political
it needs to be made political if it is to live up to its promised potential. Consequently, critical Media Studies needs to develop new practices of sense making, an updated theory of exploitation, and a political economy for the digital era.
Beyond mediation: thinking the computer otherwise
Authors: Gunkel David J
Published: March 2010

Whatever Media Studies 2.0 involves, one thing is certain, there is a need to confront and deal with new technologies, most notably computers and computer networks. Despite the fact that the discipline has largely marginalized these innovations, there has been some effort to incorporate
the computer into both the theories and practices of media studies. This has been accomplished, at least in the United States, through the development of what is now called computer-mediated communication (CMC). CMC, which effectively understands the computer as a medium of human communication,
does not necessarily institute a significant paradigm shift in media studies but accommodates the new technologies to existing structures, methodologies, and models. This essay contests and critiques this approach. It reviews the development of CMC, identifies its structural limitations, and
provides an alternative understanding of the computer that has the potential to reorient the discipline in a much more radical fashion.
Critical theory 2.0 and im/materiality: the bug in the machinic flows
Authors: Taylor Paul A
Published: March 2010

The notion of Media Studies 2.0 is reassessed in the light of both past and present Critical Theory. It is argued that Media Studies 2.0 risks repeating the mistakes of earlier media studies by failing to engage adequately with stubbornly relevant critiques of mass society. A more sustained
recognition and interrogation of Critical Theory's analysis of technological processes is called for. Whilst writers such as Jean Baudrillard and Slavoj iek are presented as possible examples of a Critical Theory 2.0 to compensate for the worst excesses of Media Studies 2.0, it is suggested
that there is still much to be learnt from such Critical Theory 1.0 figures as Adorno, Heidegger, and Kracauer.