bluuebunny/crossref_metadata_2025 huggingface dataset:
Caloric Restriction Primes Mitochondria for Ischemic Stress by Deacetylating Specific Mitochondrial Proteins of the Electron Transport Chain
Authors: Shinmura Ken , Tamaki Kayoko , Sano Motoaki , Nakashima-Kamimura Naomi , Wolf Alexander M. , Amo Taku , Ohta Shigeo , Katsumata Yoshinori , Fukuda Keiichi , Ishiwata Kyoko , Suematsu Makoto , Adachi Takeshi
Published: June 2011

Rationale:

Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD
+
-dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of specific mitochondrial proteins during CR preserves mitochondrial function and attenuates production of reactive oxygen species during ischemia/reperfusion.

Objective:

The objectives of the present study were (1) to investigate the effect of CR on mitochondrial function and mitochondrial proteome and (2) to investigate what molecular mechanisms mediate CR-induced cardioprotection.

Methods and Results:

Male 26-week-old Fischer344 rats were randomly divided into ad libitum–fed and CR (40% reduction) groups for 6 months. No change was observed in basal mitochondrial function, but CR preserved postischemic mitochondrial respiration and attenuated postischemic mitochondrial H
2
O
2
production. CR decreased the level of acetylated mitochondrial proteins that were associated with enhanced Sirtuin activity in the mitochondrial fraction. We confirmed a significant decrease in the acetylated forms of NDUFS1 and cytochrome
bc
1 complex Rieske subunit in the CR heart. Low-dose Resveratrol treatment mimicked the effect of CR on deacetylating them and attenuated reactive oxygen species production during anoxia/reoxygenation in cultured cardiomyocytes without changing the expression levels of manganese superoxide dismutase. Treatment with nicotinamide completely abrogated the effect of low-dose Resveratrol.

Conclusions:

These results strongly suggest that CR primes mitochondria for stress resistance by deacetylating specific mitochondrial proteins of the electron transport chain. Targeted deacetylation of NDUFS1 and/or Rieske subunit might have potential as a novel therapeutic approach for cardioprotection against ischemia/reperfusion.
AIP1 Prevents Graft Arteriosclerosis by Inhibiting Interferon-γ–Dependent Smooth Muscle Cell Proliferation and Intimal Expansion
Authors: Yu Luyang , Qin Lingfeng , Zhang Haifeng , He Yun , Chen Hong , Pober Jordan S. , Tellides George , Min Wang
Published: June 2011

Rationale:

ASK1-interacting protein-1 (AIP1), a Ras GTPase-activating protein family member, is highly expressed in endothelial cells and vascular smooth musccells (VSMCs). The role of AIP1 in VSMCs and VSMC proliferative disease is not known.

Objective:

We used mouse graft arteriosclerosis models characterized by VSMC accumulation and intimal expansion to determine the function of AIP1.

Methods and Results:

In a single minor histocompatibility antigen (male to female)–dependent aorta transplantation model, AIP1 deletion in the graft augmented neointima formation, an effect reversed in AIP1/interferon-γ receptor (IFN-γR) doubly-deficient aorta donors. In a syngeneic aortic transplantation model in which wild-type or AIP1-knockout mouse aortas were transplanted into IFN-γR–deficient recipients and in which neointima formation was induced by intravenous administration of an adenovirus that encoded a mouse IFN-γ transgene, donor grafts from AIP1-knockout mice enhanced IFN-γ–induced VSMC proliferation and neointima formation. Mechanistically, knockout or knockdown of AIP1 in VSMCs significantly enhanced IFN-γ–induced JAK-STAT signaling and IFN-γ–dependent VSMC migration and proliferation, 2 critical steps in neointima formation. Furthermore, AIP1 specifically bound to JAK2 and inhibited its activity.

Conclusions:

AIP1 functions as a negative regulator in IFN-γ–induced intimal formation, in part by downregulating IFN-γ-JAK2-STAT1/3–dependent migratory and proliferative signaling in VSMCs.
Enzymatic Single-Chain Antibody Tagging
Authors: Ta H.T. , Prabhu S. , Leitner E. , Jia F. , von Elverfeldt D. , Jackson Katherine E. , Heidt T. , Nair A.K.N. , Pearce H. , von zur Muhlen C. , Wang X. , Peter K. , Hagemeyer C.E.
Published: June 2011

Rationale:

Antibody-targeted delivery of imaging agents can enhance the sensitivity and accuracy of current imaging techniques. Similarly, homing of effector cells to disease sites increases the efficacy of regenerative cell therapy while reducing the number of cells required. Currently, targeting can be achieved via chemical conjugation to specific antibodies, which typically results in the loss of antibody functionality and in severe cell damage. An ideal conjugation technique should ensure retention of antigen-binding activity and functionality of the targeted biological component.

Objective:

To develop a biochemically robust, highly reproducible, and site-specific coupling method using the
Staphylococcus aureus
sortase A enzyme for the conjugation of a single-chain antibody (scFv) to nanoparticles and cells for molecular imaging and cell homing in cardiovascular diseases. This scFv specifically binds to activated platelets, which play a pivotal role in thrombosis, atherosclerosis, and inflammation.

Methods and Results:

The conjugation procedure involves chemical and enzyme-mediated coupling steps. The scFv was successfully conjugated to iron oxide particles (contrast agents for magnetic resonance imaging) and to model cells. Conjugation efficiency ranged between 50% and 70%, and bioactivity of the scFv after coupling was preserved. The targeting of scFv-coupled cells and nanoparticles to activated platelets was strong and specific as demonstrated in in vitro static adhesion assays, in a flow chamber system, in mouse intravital microscopy, and in in vivo magnetic resonance imaging of mouse carotid arteries.

Conclusions:

This unique biotechnological approach provides a versatile and broadly applicable tool for procuring targeted regenerative cell therapy and targeted molecular imaging in cardiovascular and inflammatory diseases and beyond.
Adults With Late Stage 3 Chronic Kidney Disease Are at High Risk for Prevalent Silent Brain Infarction
Authors: Chou Chia-Chi , Lien Li-Ming , Chen Wei-Hung , Wu Mai-Szu , Lin Shiue-Ming , Chiu Hou-Chang , Chiou Hung-Yi , Bai Chyi-Huey
Published: June 2011

Background and Purpose—

The close relationship between stroke and chronic kidney disease (CKD) has been well-documented. However, few studies have focused on silent brain infarction (SBI) in CKD. We investigated the prevalence of SBI in different stages of CKD.

Methods—

We included 1312 participants aged 30 to 93 years who came from either a random sample of residents or from a group of physically examined subjects in the same community. Basic information, clinical evaluations, laboratory tests, and MRI images were assessed. Subjects were divided into groups 1, 2, 3a, and 3b, corresponding to the estimated glomerular filtration rate (eGFR) levels of ≥90.0, 60.0 to 89.9, 45.0 to 59.9, and 30.0 to 44.9 mL/min/1.73 m
2
.

Results—

The crude prevalence was 4.7%: 2.6% (20 of 759 subjects) in group 1; 6.3% (32 of 506) in group 2; 12.9% (4 of 31) in group 3a; and 37.5% (6 of 16) in group 3b (
P
<0.001). Additionally, SBI also correlated with age, male sex, hypertension, diabetes, moderate carotid plaque, higher blood pressures, obesity, and levels of triglyceride, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and uric acid (all
P
<0.05). The effects for SBI risk in each eGFR group versus group 1 did not increase except for group 3b (OR, 9.34;
P
<0.001).

Conclusions—

A close association exists between SBI and eGFR. We have found a significant increase in prevalence of SBI when eGFR is between 30.0 and 44.9 mL/min/1.73 m
2
. Adults with late stage 3 CKD are at high risk for prevalent SBI.
A Southeastern South American Daily Gridded Dataset of Observed Surface Minimum and Maximum Temperature for 1961–2000
Authors: Tencer Bárbara , Rusticucci Matilde , Jones Phil , Lister David
Published: June 2011

This study presents a southeastern South American gridded dataset of daily minimum and maximum surface temperatures for 1961–2000. The data used for the gridding are observed daily data from meteorological stations in Argentina, Brazil, Paraguay, and Uruguay from the database of the European Community's Sixth Framework Programme A Europe–South America Network for Climate Change Assessment and Impact Studies in La Plata Basin (EU FP6 CLARIS LPB), with some additional data series. This gridded dataset is new for the region, not only for its spatial and temporal extension, but also for its temporal resolution. The region for which the gridded dataset has been developed is 20°–40°S, 45°–70°W, with a resolution of 0.5° latitude × 0.5° longitude. Since the methodology used produces an estimation of gridbox averages, the developed dataset is very useful for the validation of regional climate models. The comparison of gridded and observed data provides an evaluation of the usefulness of the interpolated data. According to monthly-mean values and daily variability, the methodology of interpolation developed during the EU FP6 ENSEMBLE-based predictions of climate changes and their impacts (ENSEMBLES) project for its application in Europe is also suitable for southeastern South America. Root-mean-square errors for the whole region are 1.77°C for minimum temperature and 1.13°C for maximum temperature. These errors are comparable to values obtained for Europe with the same methodology.
Impact of the Atlantic Meridional Overturning Circulation (AMOC) on Arctic Surface Air Temperature and Sea Ice Variability
Authors: Mahajan Salil , Zhang Rong , Delworth Thomas L.
Published: June 2011

The simulated impact of the Atlantic meridional overturning circulation (AMOC) on the low-frequency variability of the Arctic surface air temperature (SAT) and sea ice extent is studied with a 1000-year-long segment of a control simulation of the Geophysical Fluid Dynamics Laboratory Climate Model version 2.1. The simulated AMOC variations in the control simulation are found to be significantly anticorrelated with the Arctic sea ice extent anomalies and significantly correlated with the Arctic SAT anomalies on decadal time scales in the Atlantic sector of the Arctic. The maximum anticorrelation with the Arctic sea ice extent and the maximum correlation with the Arctic SAT occur when the AMOC index leads by one year. An intensification of the AMOC is associated with a sea ice decline in the Labrador, Greenland, and Barents Seas in the control simulation, with the largest change occurring in winter. The recent declining trend in the satellite-observed sea ice extent also shows a similar pattern in the Atlantic sector of the Arctic in the winter, suggesting the possibility of a role of the AMOC in the recent Arctic sea ice decline in addition to anthropogenic greenhouse-gas-induced warming. However, in the summer, the simulated sea ice response to the AMOC in the Pacific sector of the Arctic is much weaker than the observed declining trend, indicating a stronger role for other climate forcings or variability in the recently observed summer sea ice decline in the Chukchi, Beaufort, East Siberian, and Laptev Seas.
A New Enteral Diet, MHN‐02, Which Contains Abundant Antioxidants and Whey Peptide, Protects Against Carbon Tetrachloride–Induced Hepatitis
Authors: Takayanagi Takehiko , Sasaki Hajime , Kawashima Akihiro , Mizuochi Yuichiro , Hirate Hiroyuki , Sugiura Takeshi , Azami Takafumi , Asai Kiyofumi , Sobue Kazuya
Published: June 2011

Background: Inflammatory or oxidative stress is related to various diseases, including not only inflammatory diseases, but also diabetes, cancer, and atherosclerosis. The aim of this study was to evaluate the anti‐inflammatory effects of a new enteral diet, MHN‐02, which contains abundant antioxidants and whey peptide. The study also investigated the ability of MHN‐02 to attenuate lethality, liver injury, the production of inflammatory cytokines, and the production of oxidized products using a carbon tetrachloride–induced rat model of severe fulminant hepatitis. Methods: Male Sprague‐Dawley rats were fed either a control diet or the MHN‐02 diet for 14 days and injected with 2 mL/kg of carbon tetrachloride. Survival of rats was monitored from day 0 to day 3. To evaluate liver injury, inflammation, and oxidative stress, blood and liver samples were collected, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin 6, tumor necrosis factor–α, and superoxide dismutase activity as a free radical scavenger were measured. A portion of the liver was evaluated histologically. Results: The survival rates of rats receiving the MHN‐02 diet and the control diet were 90% and 55%, respectively. In the MHN‐02 diet group, levels of serum liver enzymes and serum cytokines were significantly lower than in the control group. Superoxide dismutase activity in the MHN‐02 diet was significantly higher in the MHN‐02 group. Pathological lesions were significantly larger in the control group. Conclusion: Supplementation of enteral diets containing whey peptide and antioxidants may protect against severe hepatitis.
ω‐3 Fatty Acids Have No Impact on Serum Lactate Levels After Major Gastric Cancer Surgery
Authors: Makay Ozer , Kaya Tayfun , Firat Ozgur , Sozbilen Murat , Caliskan Cemil , Gezer Gulten , Uyar Mehmet , Ersin Sinan
Published: June 2011

Background: Preoperative and intraoperative nutrition support in patients undergoing major surgery results in decreased incidence of morbidity and mortality. Studies investigating the role of ω‐3 fatty acids in these patients are increasing. Some are focused on perfusion at the cellular level. This study was undertaken to address the effect of postoperative administration of ω‐3 fatty acids on cellular hypoperfusion associated with major gastric surgery. Methods: Twenty‐six patients undergoing gastric cancer surgery were randomly assigned to receive parenteral nutrition (PN) supplemented with a combination of ω‐6 and ω‐3 fatty acids (Omegaven, 0.2 g/kg/d; Lipovenoes 10%, 0.6 g/kg/d) or with ω‐6 fatty acid (Lipovenoes 10%, 0.8 g/kg/d) for 5 days. Blood samples were taken preoperatively, postoperative day 1, and on the last day of PN therapy (day 5). Results: Patients receiving ω‐3 and ω‐6 fatty acids showed neither lower serum lactate levels nor lower rates of complications compared with patients receiving ω‐6 only. There were no statistically significant differences between the groups in other biochemical parameters, complications, or length of hospital stay or mortality. Conclusion: PN with ω‐3 fatty acid supplementation does not have a significant impact on cellular hypoperfusion and lactate clearance after major gastric surgery.
Human trafficking as a lever for feminist voices? Transformations of the Danish policy field of prostitution
Authors: Spanger Marlene
Published: June 2011

In Denmark, human trafficking has emerged as a central issue within the policy field of prostitution during the last decade. Taking a Foucauldian approach from a historical perspective, understanding the policy field of prostitution as a discursive terrain, the article analyses the thinking that lies behind policies on prostitution by identifying ruptures and discursive struggles which lead to transformations of the policy field. In particular, this article investigates how the problematization of human trafficking has created space for a feminist discourse breakthrough within the policy field of prostitution during the last decade. Asking how/where this ‘problem’ has been produced, what ways of speaking are permissible, and what is silenced, the article discusses limitations and possibilities within this policy field.
Gender-Based Differences in Outcome After Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction With Hamstring Tendon Autografts
Authors: Tohyama Harukazu , Kondo Eiji , Hayashi Riku , Kitamura Nobuto , Yasuda Kazunori
Published: June 2011

Background: Although previous studies suggested that female patients are predisposed to increase graft laxity compared with male patients after single-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons, there have been no studies specifically examining gender-based differences in outcome after anatomic double-bundle anterior cruciate ligament reconstruction with hamstring tendon autografts.

Hypotheses: (1) Female patients have significantly smaller hamstring graft diameters than do men for anatomic double-bundle anterior cruciate ligament reconstruction surgery; (2) female patients will have increased graft laxity compared with male patients after anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons.

Study Design: Cohort study; Level of evidence, 2.

Methods: The consecutive 174 patients who underwent anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons were enrolled. Of these patients, 49 women and 73 men were prospectively evaluated 2 years after surgery.

Results: The diameters for anteromedial and posterolateral grafts in the female group were significantly smaller than those in the male group. On Lachman testing, 98% of the female group and 97% of the male group were rated as negative. Regarding the pivot-shift test, 80% of the female group and 85% of the male group were rated as negative. No significant differences were found between the female and male groups in these tests. The average side-to-side differences in the KT-2000 knee ligament arthrometer values were 1.3 mm in the female group and 1.4 mm in the male group; this difference between females and males was not statistically significant. The average Lysholm scores were 96.7 points in the female group and 97.2 points in the male group. Thirty-five cases (73%) in the female group and 54 cases (74%) in the male group were graded as normal on the International Knee Documentation Committee (IKDC) evaluation. There were no significant differences in Lysholm score or IKDC evaluation between the female and male groups.

Conclusion: The results of assessment for ligament laxity at the 2-year postoperative evaluation in the female group were approximately identical to those of the male group after anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons. Therefore, the present study suggests that anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons provides satisfactory knee stability to female patients as well as male patients.
Modelling, parameter identification, and control of a shear mode magnetorheological device
Authors: Russo R , Terzo M
Published: June 2011

This paper describes theoretical and experimental studies of a shear mode magnetorheological fluid device. A testing procedure is used to measure the fundamental quantities needed to define a state space non-linear model and to identify its parameters. The obtained model is then validated by means of comparisons between modelling results and measurements. Finally, the model is used in the development of a time domain control scheme to regulate the transmitted torque.
‘Oh he was forgettable’: Construction of self identity through use of communicative coping behaviors in the discourse of persons with cognitive impairment
Authors: Saunders Pamela A. , de Medeiros Kate , Bartell Ashley
Published: June 2011

Communication involving persons with cognitive impairment (CI) associated memory issues requires particular attention in the clinical setting due to the sensitive and often difficult institutional work that must take place between the patient and his or her physician. An individual with CI is often tested for memory issues during the office visit, generating a potentially face-threatening situation. Said individual may attempt to preserve positive identity or ‘save face’ (Gumperz, 1982) by using communicative coping behaviors (CCBs). This study characterizes the use of CCBs (e.g., accounts and humor) by persons with CI in clinical interviews and provides important insight on how to improve doctor—patient communication involving people with CI. In order to describe and compare CCBs used by persons with cognitive impairment, and those used by cognitively normal individuals, verbatim, in-office transcripts from both groups were analyzed. Results showed that participants with CI used more memory accounts than cognitively normal individuals and similar amounts of humor in order to save face and construct a normal identity. These data help to inform doctors and caregivers regarding the ways in which persons with CI construct and preserve a positive sense of self-identity through communication.
Raindogs: performing the city
Authors: Pearson Mike
Published: June 2011

This article describes a multi-site, mediated performance entitled Raindogs achieved in Cardiff in 2002, and discusses the ways in which the presence and coexistence of such transient, aesthetic practices might reveal and pull into momentary focus aspects of the city’s fabric, its manifold temporalities and the diverse activities of its populace. Inter-textual in form and interdisciplinary in ambition, the article combines passages of creative writing with more sustained critical reflection that draws upon architectural planning, contemporary archaeology, forensics and performance analysis; it proposes performance as both a potential mode of enquiry and of interpretive exposition in enhancing public understanding of contemporary urban experiences. It suggests that the script of performance can itself contain moments of disciplinary perception – from local history, cultural geography; and that new forms of dramaturgy might both utilise and disclose the nature of pervasive phenomena of the city, such as surveillance – through the analogous use of media, refiguring the theatre auditorium as an oligopticon, a place from which only part of the city is seen, but seen well and site-specific performance as place-making as much as site-occupying.
Histones induce rapid and profound thrombocytopenia in mice
Authors: Fuchs Tobias A. , Bhandari Ashish A. , Wagner Denisa D.
Published: June 2011

Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage.
Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia
Authors: Maugeri Norma , Malato Simona , Femia Eti A. , Pugliano Mariateresa , Campana Lara , Lunghi Francesca , Rovere-Querini Patrizia , Lussana Federico , Podda GianMarco , Cattaneo Marco , Ciceri Fabio , Manfredi Angelo A.
Published: June 2011

Essential thrombocythemia (ET) and polycythemia vera (PV) are characterized by persistent platelet activation. The mechanisms involved in their clearance are poorly characterized. In the present study, we report that leukocytes were actively involved in platelet disposal in 51 patients with ET and 30 with PV, but not in 70 age- and sex-matched controls. The fraction of circulating neutrophils and monocytes that had phagocytosed platelets, as assessed by flow cytometry, was significantly higher in patients with PV or ET, independently of hydroxyurea treatment, than in controls. Platelet phagocytosis by circulating leukocytes was confirmed by confocal and electron microscopy. The lack of effect of hydroxyurea, which disrupts the P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction, suggests a P-selectin–independent mechanism. This hypothesis was confirmed in an ad hoc animal model based on the in vivo injection of activated platelets from P-selectin+/+ and P-selectin−/− mice. P-selectin expression was associated with an earlier and effective clearance of platelets by neutrophils. A second delayed, P-selectin–independent phase actively involved monocytes. Our results suggest that phagocytic clearance of platelets by leukocytes occurs in PV and ET, possibly involving P-selectin–dependent and -independent pathways, thus representing a novel mechanism to remove activated platelets from the circulation.
Supplementation with vitamin A early in life and subsequent risk of asthma
Authors: Checkley W. , West K.P. , Wise R.A. , Wu L. , LeClerq S.C. , Khatry S. , Katz J. , Christian P. , Tielsch J.M. , Sommer A.
Published: June 2011

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk.

In 2006–2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for <16 months during their pre-school years (1989–1991). The second cohort was born to mothers who received vitamin A, β-carotene or placebo before, during and after pregnancy (1994–1997). At follow-up, we asked about asthma symptoms and performed spirometry.

Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9–13 yrs and 6.6% in participants aged 14–23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p≥0.12 for all comparisons).

Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.
EST mining identifies proteins putatively secreted by the anthracnose pathogen Colletotrichum truncatum
Authors: Bhadauria Vijai , Banniza Sabine , Vandenberg Albert , Selvaraj Gopalan , Wei Yangdou
Published: June 2011

Background

Colletotrichum truncatumis a haploid, hemibiotrophic, ascomycete fungal pathogen that causes anthracnose disease on many economically important leguminous crops. This pathogen exploits sequential biotrophic- and necrotrophic- infection strategies to colonize the host. Transition from biotrophy to a destructive necrotrophic phase called the biotrophy-necrotrophy switch is critical in symptom development.C. truncatumlikely secretes an arsenal of proteins that are implicated in maintaining a compatible interaction with its host. Some of them might be transition specific.

Results

A directional cDNA library was constructed from mRNA isolated from infectedLens culinarisleaflet tissues displaying the biotrophy-necrotrophy switch ofC. truncatumand 5000 expressed sequence tags (ESTs) with an average read of > 600 bp from the 5-prime end were generated. Nearly 39% of the ESTs were predicted to encode proteins of fungal origin and among these, 162 ESTs were predicted to contain N-terminal signal peptides (SPs) in their deduced open reading frames (ORFs). The 162 sequences could be assembled into 122 tentative unigenes comprising 32 contigs and 90 singletons. Sequence analyses of unigenes revealed four potential groups: hydrolases, cell envelope associated proteins (CEAPs), candidate effectors and other proteins. Eleven candidate effector genes were identified based on features common to characterized fungal effectors, i.e. they encode small, soluble (lack of transmembrane domain), cysteine-rich proteins with a putative SP. For a selected subset ofCEAPsand candidate effectors, semiquantitative RT-PCR showed that these transcripts were either expressed constitutively in bothin vitroandin plantaor induced during plant infection. Using potato virus X (PVX) based transient expression assays, we showed that one of the candidate effectors, i. e. contig 8 that encodes a cerato-platanin (CP) domain containing protein, unlike CP proteins from other fungal pathogens was unable to elicit a hypersensitive response (HR).

Conclusions

The current study catalogues proteins putatively secreted at thein plantabiotrophy-necrotrophy transition ofC. truncatum. Some of these proteins may have a role in establishing compatible interaction with the host plant.
A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2genes
Authors: Hondow Heather L , Fox Stephen B , Mitchell Gillian , Scott Rodney J , Beshay Victoria , Wong Stephen Q ,   kConFab Investigators, Dobrovic Alexander
Published: June 2011

Background

Detection of mutations by DNA sequencing can be facilitated by scanning methods to identify amplicons which may have mutations. Current scanning methods used for the detection of germline sequence variants are laborious as they require post-PCR manipulation. High resolution melting (HRM) is a cost-effective rapid screening strategy, which readily detects heterozygous variants by melting curve analysis of PCR products. It is well suited to screening genes such as BRCA1 and BRCA2 as germline pathogenic mutations in these genes are always heterozygous.

Methods

Assays for the analysis of all coding regions and intron-exon boundaries of BRCA1 and BRCA2 were designed, and optimised. A final set of 94 assays which ran under identical amplification conditions were chosen for BRCA1 (36) and BRCA2 (58). Significant attention was placed on primer design to enable reproducible detection of mutations within the amplicon while minimising unnecessary detection of polymorphisms. Deoxyinosine residues were incorporated into primers that overlay intronic polymorphisms. Multiple 384 well plates were used to facilitate high throughput.

Results

169 BRCA1 and 239 BRCA2 known sequence variants were used to test the amplicons. We also performed an extensive blinded validation of the protocol with 384 separate patient DNAs. All heterozygous variants were detected with the optimised assays.

Conclusions

This is the first HRM approach to screen the entire coding region of the BRCA1 and BRCA2 genes using one set of reaction conditions in a multi plate 384 well format using specifically designed primers. The parallel screening of a relatively large number of samples enables better detection of sequence variants. HRM has the advantages of decreasing the necessary sequencing by more than 90%. This markedly reduced cost of sequencing will result in BRCA1 and BRCA2 mutation testing becoming accessible to individuals who currently do not undergo mutation testing because of the significant costs involved.
TRPV3 and TRPV4 Ion Channels are Not Major Contributors to Mouse Heat Sensation
Authors: Huang Susan M , Li Xiaoxin , Yu YinYin , Wang Juan , Caterina Michael J
Published: June 2011

Background:

The discovery of heat-sensitive Transient Receptor Potential Vanilloid (TRPV) ion channels provided a potential molecular explanation for the perception of innocuous and noxious heat stimuli. TRPV1 has a significant role in acute heat nociception and inflammatory heat hyperalgesia. Yet, substantial innocuous and noxious heat sensitivity remains in TRPV1 knockout animals. Here we investigated the role of two related channels, TRPV3 and TRPV4, in these capacities. We studied TRPV3 knockout animals on both C57BL6 and 129S6 backgrounds, as well as animals deficient in both TRPV3 and TRPV4 on a C57BL6 background. Additionally, we assessed the contributions of TRPV3 and TRPV4 to acute heat nociception and inflammatory heat hyperalgesia during inhibition of TRPV1.

Results:

TRPV3 knockout mice on the C57BL6 background exhibited no obvious alterations in thermal preference behavior. On the 129S6 background, absence of TRPV3 resulted in a more restrictive range of occupancy centered around cooler floor temperatures. TRPV3 knockout mice showed no deficits in acute heat nociception on either background. Mice deficient in both TRPV3 and TRPV4 on a C57BL6 background showed thermal preference behavior similar to wild-type controls on the thermal gradient, and little or no change in acute heat nociception or inflammatory heat hyperalgesia. Masking of TRPV1 by the TRPV1 antagonist JNJ-17203212 did not reveal differences between C57BL6 animals deficient in TRPV3 and TRPV4, compared to their wild-type counterparts.

Conclusions:

Our results support the notion that TRPV3 and TRPV4 likely make limited and strain-dependent contributions to innocuous warm temperature perception or noxious heat sensation, even when TRPV1 is masked. These findings imply the existence of other significant mechanisms for heat perception.
Human immunodeficiency virus infection and autoimmune hepatitis during highly active anti-retroviral treatment: a case report and review of the literature
Authors: Daas Hanady , Khatib Riad , Nasser Haitham , Kamran Farah , Higgins Martha , Saravolatz Louis
Published: June 2011

Introduction

The emergence of hepatic injury in patients with human immunodeficiency virus infection during highly active therapy presents a diagnostic dilemma. It may represent treatment side effects or autoimmune disorders, such as autoimmune hepatitis, emerging during immune restoration.

Case presentation

We present the case of a 42-year-old African-American woman with human immunodeficiency virus infection who presented to our emergency department with severe abdominal pain and was found to have autoimmune hepatitis. A review of the literature revealed 12 reported cases of autoimmune hepatitis in adults with human immunodeficiency virus infection, only three of whom were diagnosed after highly active anti-retroviral treatment was initiated. All four cases (including our patient) were women, and one had a history of other autoimmune disorders. In our patient (the one patient case we are reporting), a liver biopsy revealed interface hepatitis, necrosis with lymphocytes and plasma cell infiltrates and variable degrees of fibrosis. All four cases required treatment with corticosteroids and/or other immune modulating agents and responded well.

Conclusion

Our review suggests that autoimmune hepatitis is a rare disorder which usually develops in women about six to eight months after commencing highly active anti-retroviral treatment during the recovery of CD4 lymphocytes. It represents either re-emergence of a pre-existing condition that was unrecognized or a de novo manifestation during immune reconstitution.
Obstructive azoospermia as an unusual complication associated with herniorrhaphy of an omphalocele: a case report
Authors: Tsuchihashi Kazunari , Okubo Kazutoshi , Ichioka Kentaro , Soda Takeshi , Yoshimura Koji , Kanematsu Akihiro , Ogawa Osamu , Nishiyama Hiroyuki
Published: June 2011

Introduction

Iatrogenic damage to the seminal tract is one of the causes of obstructive azoospermia, which can be an indication for reconstruction surgery. We present a case of obstructive azoospermia as an unusual complication after neonatal herniorrhaphy of an omphalocele.

Case presentation

A 30-year-old Japanese man was diagnosed with obstructive azoospermia. He had undergone herniorrhaphy of an omphalocele immediately after birth. Reconstruction surgery of both seminal tracts was performed to pursue the possibility of naturally achieved pregnancy. Intra-operative findings demonstrated that both vasa deferentia were interrupted at the internal inguinal rings, although the abdominal end of the right vas leading to the seminal vesicle was found in the abdominal cavity. The discharge from the stump of the testicular end had no sperm, although the right epididymal tubules were dilated with motile sperm. Therefore, we performed right-sided vasovasostomy in the internal inguinal ring and ipsilateral epididymovasostomy simultaneously.

Conclusion

To the best of our knowledge, this is the first report describing obstructive azoospermia as an unusual complication of herniorrhaphy of an omphalocele. It is important to pay attention to the existence of seminal tracts in such surgery as well as in inguinal herniorrhaphy.
Metagenomic biomarker discovery and explanation
Authors: Segata Nicola , Izard Jacques , Waldron Levi , Gevers Dirk , Miropolsky Larisa , Garrett Wendy S , Huttenhower Curtis
Published: June 2011

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
Genetic variants in the MRPS30 region and postmenopausal breast cancer risk
Authors: Huang Ying , Ballinger Dennis G , Dai James Y , Peters Ulrike , Hinds David A , Cox David R , Beilharz Erica , Chlebowski Rowan T , Rossouw Jacques E , McTiernan Anne , Rohan Thomas , Prentice Ross L
Published: June 2011

Background

Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest.

Methods

We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction.

Results

The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343.

Conclusions

Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk.
Engaging Advocacy: Academic Freedom and Student Learning
Authors: Kunkel Charlotte A. , Radford-Hill Sheila
Published: June 2011

Scholars often debate the history of academic freedom, including efforts across the political spectrum to redefine its policies and practices. One fact that is sometimes overlooked in these debates is that students' educational experiences a re regularly and profoundly affected by how individual professors interpret their freedom to teach, conduct research, disseminate scholarship, speak in public on controversial issues, or criticize institutional policies and practices. Given that college professors use various definitions of academic freedom in their classrooms and that the politics surrounding their actions have become increasingly contentious, it is important to consider academic freedom from the perspective of college teachers in the United States. This essay therefore explores contemporary debates about academic freedom with respect to classroom teaching and student learning. The authors critique neoconservative practices of academic freedom and propose that advocacy—the passionate engagement of ideas leading to a principled stance—is a more pedagogically sound and ethically appropriate approach to engaging students in the classroom.
The New Modernist Studies: What's Left of Political Formalism?
Authors: Brzezinski Max
Published: June 2011

This article evaluates the methods and ideological positions that define the critical movement known as the New Modernist Studies (NMS). It treats the NMS as characteristic of recent attempts to politicize aesthetics within the corporate university. The piece argues that the NMS has consolidated its brand by strategically making anachronistic and shopworn claims for the relevance of modernist aesthetics for postmodern politics. The methodological hallmarks of the movement include the liberalization of previously radical political thought, the reduction of past theoretical interventions into portable dualisms and reified fixed principles, and the substitution of homological equivalences between aesthetics and politics in the place of mediating, dialectical, and/or constellating thought. While the NMS's self-branding impulse has generated popular, ready-to-apply models for new scholars in the humanities, it has also ironically brought many of its arguments closer in form to the positions of the neoliberal and neoconservative orthodoxies it positions itself against. In particular, its tendency to reduce politics to clashes between oppressive state powers and individuals seeking personal freedom limits its ability to push beyond the commonsense framework of the status quo.
Global Cultural Studies?
Authors: Szeman Imre
Published: June 2011

Does it make sense to speak of a global cultural studies? This review essay examines the apparent critical aversion to such a category by exploring the approaches taken by two books that consider the state of cultural studies in the global era. Ackbar Abbas and John Nguyet Erni's collection Internationalizing Cultural Studies: An Anthology (2005) is designed to open up North Atlantic–dominated cultural studies to approaches to the study of culture from other parts of the world. “Internationalizing” names a process (motivated by epistemic and political caution) that the editors see as essential to preserving the critical energy of cultural studies as its concepts and methodologies spread around the globe. In Culture in the Age of Three Worlds (2004), Michael Denning claims that the era of cultural studies has come to an end with the sociopolitical paradigm shift that moves us from the period of the Cold War to that of globalization. Through an interlinked series of essays published separately over fifteen years, he argues that the “cultural turn” that redefined the study of culture in the first world was mirrored by similar changes in the second and third worlds. The circumstances in which culture now exists are very different from those in the period that gave rise to cultural studies, necessitating new approaches to culture and politics. Taken together, these two books offer us important insights into how we examine culture in the context of globalization.
Design and Analysis of a Unimorph Piezoceramic Generator with Cantilever Structure in a Low-Frequency Environment
Authors: Wang S-H , Yao W-S , Laio W-S , Tsai M-C
Published: June 2011

Piezoelectric materials have the electromechanical capability of converting mechanical vibration energy into electrical energy and are utilized in sensors, generators, and actuator applications. However, with regard to compact-dimension applications, piezoelectric generators have to overcome some shortcomings, such as high voltage, low current, and relatively low power output. This article presents a design method of which the loading-weight vibration on the piezoelectric material can be transferred into an external force, and, additionally, an equivalent electric circuit method is used to calculate the electrical characteristics of piezoelectric material. Compared to the measurement, in a 4 Hz vibration environment with a 30 g loading mass, which is equivalent to a 0.5 N external force, the piezoelectric plate can generate an electric voltage of 19.8 V. A 2.7 per cent error rate of the output voltage in the equivalent force conversion is achieved. Finally, in order to demonstrate the accuracy of the theoretical analysis, a prototype hand-shaking piezoelectric generator is proposed, which is used to drive a wireless-switch device (5 V driving voltage). Experimental results show that the average electrical power of the hand-shaking piezoelectric generator is approximately 50 μW, and a 7 per cent stored power error rate is achieved when comparing the measurement and theoretical estimation.
A Computational Analysis of Bundle Trading Markets Design for Distributed Resource Allocation
Authors: Guo Zhiling , Koehler Gary J. , Whinston Andrew B.
Published: June 2011

Online auction markets play increasingly important roles for resource allocations in distributed systems. This paper builds upon a market-based framework presented by Guo et al. (Guo, Z., G. J. Koehler, A. B. Whinston. 2007. A market-based optimization algorithm for distributed systems. Management Sci. 53(8) 1345–1458), where a distributed system optimization problem is solved by self-interested agents iteratively trading bundled resources in a double auction market run by a dealer. We extend this approach to a dynamic, asynchronous Internet market environment and investigate how various market design factors including dealer inventory policies, market communication patterns, and agent learning strategies affect the computational market efficiency, market liquidity, and implementation. We prove finite convergence to an optimal solution under these various schemes, where individual rational and budget-balanced trading leads to an efficient auction outcome. Empirical investigations further show that the algorithmic implementation is robust to a number of dealer and agent manipulations and scalable to larger sizes and more complicated bundle trading markets. Interestingly, we find that, though both asynchronous communication and asymmetric market information negatively affect the speed of market convergence and lead to more agent welfare loss, agents' ability to predict market prices has a positive effect on both. Contrary to conventional wisdom that a dealer's intertemporal liquidity provisions improve market performance, we find that the dealer's active market intervention may not be desirable in a simple market trading environment where an inherent market liquidity effect dominates, especially when the dealer owns a significant amount of resources. Different from the traditional market insight, our trading data suggest that high trading volume does not correlate to low price volatility and quicker price discovery.