bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases*
Authors: O'Hanlon Terrance P , Li Zhuoyan , Gan Lu , Gourley Mark F , Rider Lisa G , Miller Frederick W
Published: December 2011

Introduction

Although systemic autoimmune diseases (SAID) share many clinical and laboratory features, whether they also share some common features of pathogenesis remains unclear. We assessed plasma proteomic profiles among different SAID for evidence of common molecular pathways that could provide insights into pathogenic mechanisms shared by these diseases.

Methods

Differential quantitative proteomic analyses (one-dimensional reverse-phase liquid chromatography-mass spectrometry) were performed to assess patterns of plasma protein expression. Monozygotic twins (four pairs discordant for systemic lupus erythematosus, four pairs discordant for juvenile idiopathic arthritis and two pairs discordant for juvenile dermatomyositis) were studied to minimize polymorphic gene effects. Comparisons were also made to 10 unrelated, matched controls.

Results

Multiple plasma proteins, including acute phase reactants, structural proteins, immune response proteins, coagulation and transcriptional factors, were differentially expressed similarly among the different SAID studied. Multivariate Random Forest modeling identified seven proteins whose combined altered expression levels effectively segregated affected vs. unaffected twins. Among these seven proteins, four were also identified in univariate analyses of proteomic data (syntaxin 17, α-glucosidase, paraoxonase 1, and the sixth component of complement). Molecular pathway modeling indicated that these factors may be integrated through interactions with a candidate plasma biomarker, PON1 and the pro-inflammatory cytokine IL-6.

Conclusions

Together, these data suggest that different SAID may share common alterations of plasma protein expression and molecular pathways. An understanding of the mechanisms leading to the altered plasma proteomes common among these SAID may provide useful insights into their pathogeneses.
Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer
Authors: Jankowitz Rachel C , Cooper Kristine , Erlander Mark G , Ma Xiao-Jun , Kesty Nicole C , Li Hongying , Chivukula Mamatha , Brufsky Adam
Published: December 2011

Introduction

Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).

Methods

Tumor samples from 265 ER+LN- tamoxifen-treated patients were identified from a single academic institution's cancer research registry. The BCI assay was performed and scores were assigned based on a pre-determined risk model. Risk was assessed by BCI and AO and correlated to clinical outcomes in the patient cohort.

Results

BCI was a significant predictor of outcome in a cohort of 265 ER+LN- patients (median age: 56-y; median follow-up: 10.3-y), treated with adjuvant tamoxifen alone or tamoxifen with chemotherapy (32%). BCI categorized 55%, 21%, and 24% of patients as low, intermediate and high-risk, respectively. The 10-year rates of distant recurrence were 6.6%, 12.1% and 31.9% and of breast cancer-specific mortality were 3.8%, 3.6% and 22.1% in low, intermediate, and high-risk groups, respectively. In a multivariate analysis including clinicopathological factors, BCI was a significant predictor of distant recurrence (HR for 5-unit increase = 5.32 [CI 2.18-13.01; P = 0.0002]) and breast cancer-specific mortality (HR for a 5-unit increase = 9.60 [CI 3.20-28.80; P < 0.0001]). AO was significantly associated with risk of recurrence. In a separate multivariate analysis, both BCI and AO were significantly predictive of outcome. In a time-dependent (10-y) ROC curve accuracy analysis of recurrence risk, the addition of BCI+AO increased predictive accuracy in all patients from 66% (AO only) to 76% (AO+BCI) and in tamoxifen-only treated patients from 65% to 81%.

Conclusions

This study validates the prognostic performance of BCI in ER+LN- patients. In this characteristically low-risk cohort, BCI classified high versus low-risk groups with ~5-fold difference in 10-year risk of distant recurrence and breast cancer-specific death. BCI and AO are independent predictors with BCI having additive utility beyond standard of care parameters that are encompassed in AO.
Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC - PACS 01 randomized trial
Authors: Jacquemier Jocelyne , Boher Jean-Marie , Roche Henri , Esterni Benjamin , Serin Daniel , Kerbrat Pierre , Andre Fabrice , Finetti Pascal , Charafe-Jauffret Emmanuelle , Martin Anne-Laure , Campone Mario , Viens Patrice , Birnbaum Daniel , Penault-Llorca Frédérique , Bertucci François
Published: December 2011

Introduction

The PACS01 trial has demonstrated that a docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel's benefit.

Methods

Tumor samples from 1,099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested.

Results

Progesterone receptor-negativity (HR = 0.66; 95% CI 0.47 to 0.92, P = 0.013), and Ki67-positivity (HR = 1.53; 95% CI 1.12 to 2.08, P = 0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR = 0.51, 95% CI 0.33 to 0.79 for Ki67-positive versus HR = 1.10, 95% CI 0.75 to 1.61 for Ki67-negative tumors, P for interaction = 0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR = 1.16, 95% CI 0.73 to 1.84); the reduction in the relapse risk was 53% (HR = 0.47, 95% CI 0.22 to 1.01), 34% (HR = 0.66, 95% CI 0.37 to 1.19), and 12% (HR = 0.88, 95% CI 0.49 to 1.57) in the luminal B, HER2-overexpressing, and triple-negative subtypes, respectively.

Conclusions

In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67-positivity.
Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases
Authors: Adamo Barbara , Deal Allison M , Burrows Emily , Geradts Joseph , Hamilton Erika , Blackwell Kimberly L , Livasy Chad , Fritchie Karen , Prat Aleix , Harrell J Chuck , Ewend Matthew G , Carey Lisa A , Miller C Ryan , Anders Carey K
Published: December 2011

Introduction

Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway activation status and associations with time to distant recurrence (TTDR) and time to BCBMs. Similar analyses were also conducted among the subset of patients with triple-negative BCBMs.

Methods

p-AKT, p-S6, and PTEN expression was assessed with immunohistochemistry in 52 BCBMs and 12 matched primary BCs. Subtypes were defined as hormone receptor (HR)+/HER2-, HER2+, and triple-negative (TNBC). Survival analyses were performed by using a Cox model, and survival curves were estimated with the Kaplan-Meier method.

Results

Expression of p-AKT and p-S6 and lack of PTEN (PTEN-) was observed in 75%, 69%, and 25% of BCBMs. Concordance between primary BCs and matched BCBMs was 67% for p-AKT, 58% for p-S6, and 83% for PTEN. PTEN- was more common in TNBC compared with HR+/HER2- and HER2+. Expression of p-AKT, p-S6, and PTEN- was not associated with OS or survival after BCBMs (all, P > 0.06). Interestingly, among all patients, PTEN- correlated with shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in BCBMs was associated with poorer overall survival.

Conclusions

The PI3K pathway is active in most BCBMs regardless of subtype. Inhibition of this pathway represents a promising therapeutic strategy for patients with BCBMs, a group of patients with poor prognosis and limited systemic therapeutic options. Although expression of the PI3K pathway did not correlate with OS and survival after BCBM, PTEN- association with time to recurrence and OS (among patients with TNBC) is worthy of further study.
Early natural killer cell counts in blood predict mortality in severe sepsis
Authors: Andaluz-Ojeda David , Iglesias Verónica , Bobillo Felipe , Almansa Raquel , Rico Lucía , Gandía Francisco , Loma Ana Ma , Nieto Concepción , Diego Rosa , Ramos Epifanio , Nocito Mercedes , Resino Salvador , Eiros Jose M , Tamayo Eduardo , de Lejarazu Raul Ortiz , Bermejo-Martin Jesús F
Published: December 2011

Introduction

Host immunity should play a principal role in determining both the outcome and recovery of patients with sepsis that originated from a microbial infection. Quantification of the levels of key elements of the immune response could have a prognostic value in this disease.

Methods

In an attempt to evaluate the quantitative changes in the status of immunocompetence in severe sepsis over time and its potential influence on clinical outcome, we monitored the evolution of immunoglobulins (Igs) (IgG, IgA and IgM), complement factors (C3 and C4) and lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells (CD19+) and natural killer (NK) cells (CD3-CD16+CD56+)) in the blood of 50 patients with severe sepsis or septic shock at day 1, day 3 and day 10 following admission to the ICU.

Results

Twenty-one patients died, ten of whom died within the 72 hours following admission to the ICU. The most frequent cause of death (n = 12) was multiorgan dysfunction syndrome. At day 1, survivors showed significantly higher levels of IgG and C4 than those who ultimately died. On the contrary, NK cell levels were significantly higher in the patients who died. Survivors exhibited a progressive increase from day 1 to day 10 on most of the immunological parameters evaluated (IgG, IgA, IgM, C3, CD4+, CD8+ T cells and NK cells). Multivariate Cox regression analysis, including age, sex, APACHE II score, severe sepsis or septic shock status and each one of the immunological parameters showed that NK cell counts at day 1 were independently associated with increased risk of death at 28 days (hazard ratio = 3.34, 95% CI = 1.29 to 8.64; P = 0.013). Analysis of survival curves provided evidence that levels of NK cells at day 1 (> 83 cells/mm3) were associated with early mortality.

Conclusions

Our results demonstrate the prognostic role of NK cells in severe sepsis and provide evidence for a direct association of early counts of these cells in blood with mortality.
Circulating annexin V positive microparticles in patients after successful cardiopulmonary resuscitation
Authors: Fink Katrin , Feldbrügge Linda , Schwarz Meike , Bourgeois Natascha , Helbing Thomas , Bode Christoph , Schwab Tilmann , Busch Hans-Jörg
Published: December 2011

Introduction

Ischemia/reperfusion after cardiopulmonary resuscitation (CPR) induces systemic inflammatory response and activation of endothelium and coagulation, resulting in a post-cardiac arrest syndrome. We analysed circulating (annexin V+) microparticles and their conjugates in resuscitated patients.

Methods

36 patients after successful resuscitation, 20 control patients with stable cardiac disease and 15 healthy subjects were included prospectively. Two blood samples were drawn, one immediately and one 24 hours after return of spontaneous circulation (ROSC) to detect (annexin V+) monocyte-derived microparticles (MMPs) or procoagulant (annexin V+) platelet-derived microparticles (PMPs) and conjugates of endothelial-derived (annexin V+) microparticles (EMPs) with monocytes (EMP-MC) or platelets (EMP-PC). Measurements were performed by flow cytometric analysis. Additionally, the effect of isolated microparticles on cultured endothelial cells was assessed by ELISA.

Results

MMPs were significantly elevated immediately after ROSC compared to the cardiological control group (control; p < 0.01) and healthy subjects (healthy; p < 0.05) and persisted to be elevated in the following 24 hours after CPR (p < 0.05 vs. control and healthy, respectively). Procoagulant PMPs increased within the first 24 hours after ROSC (p < 0.01 vs. control and p < 0.005 vs. healthy). Conjugates of EMP with monocytes and platelets were both significantly elevated immediately after CPR (EMP-MC: p < 0.05 vs. control and p < 0.05 vs. healthy; EMP-PC: p < 0.05 vs. control and p < 0.05 vs. healthy), while only EMP-MC showed persisting high levels within 24 hours after CPR (p < 0.05 vs. control and p < 0.01 vs. healthy). MMP levels of ≥1.0/μL 24 hours after CPR predicted adverse outcome at 20 days (p < 0.05). Furthermore, isolated microparticles circulating in CPR patients early after ROSC led to enhanced endothelial apoptosis ex vivo compared to those of the healthy controls (p < 0.005).

Conclusions

Resuscitated patients show substantially increased levels of different (annexin V+) microparticles and their conjugates immediately and 24 hours after cardiopulmonary resuscitation, suggesting an early onset of inflammation, an ongoing endothelial activation and a procoagulatory state. Additionally, microparticles of CPR patients may contribute to endothelial apoptosis. These results point to an involvement of microparticles in the development of the post-cardiac arrest syndrome.
mRNA-based approach to monitor recombinant gamma-interferon restoration of LPS-induced endotoxin tolerance
Authors: Turrel-Davin Fanny , Venet Fabienne , Monnin Cécile , Barbalat Véronique , Cerrato Elisabeth , Pachot Alexandre , Lepape Alain , Alberti-Segui Christine , Monneret Guillaume
Published: December 2011

Introduction

It is now well accepted that sepsis is associated with the development of a pronounced immunosuppressive state, characterized by severe immune alterations (e.g. reduced proliferative capacity, endotoxin tolerance, apoptosis) participating in increased mortality and susceptibility to nosocomial infections. Efforts are currently aimed at restoring a functional immune response in septic patients. Successful therapy depends on the identification of appropriate immunostimulatory drugs and on the development of suitable biomarkers that could be used to stratify patients and to follow response to treatment.

Methods

In this study, we evaluated the ex vivo effect of recombinant interferon gamma (rIFN-γ) in restoring monocyte functionality (endotoxin-induced Tumor Necrosis Factor-α production) in a two-hit model of endotoxin tolerance (ET) with peripheral blood mononuclear cells from healthy volunteers and in whole blood of septic shock patients. Importantly, we used quantitative-reverse transcription polymerase-chain reaction to monitor the effect of rIFN-γ on the expression of seven genes known to participate in ET (TNF-α, IL-10, HLA-DRA, CIITA, IRAK-M, ABIN-3 and LY64).

Results

Expression analysis of those genes confirmed the presence of an immunosuppression state and the ex vivo restoration of immune functions by rIFN-γ. We show for the first time that rIFN-γ is able to bypass, at the mRNA level, the effect of negative regulators of the LPS signalling pathway such as IRAK-M, ABIN-3 and LY 64.

Conclusions

Overall, mRNA expressions of a panel of genes could represent promising candidates for the ex vivo evaluation of rIFN-γ effect on monocyte functionality. This ex vivo translational research study demonstrates the potential of a mRNA-based approach to successfully monitor drug efficacy.
IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and mortality of severe sepsis
Authors: Nakada Taka-aki , Russell James A , Boyd John H , Walley Keith R
Published: December 2011

Introduction

Interleukin 17A (IL17A) plays a key role in host defense against microbial infection including Gram-positive bacteria. Genetic factors contribute to the host defense, but the role of IL17A single nucleotide polymorphisms (SNPs) has not yet been investigated in severe sepsis. Therefore, we hypothesized that SNPs in the IL17A gene alter susceptibility to infection and clinical outcome of severe sepsis.

Methods

We tested for the association of IL17A SNPs with susceptibility to infection and clinical outcome of severe sepsis using two cohorts of European ancestry (derivation cohort, St Paul's Hospital (SPH), n = 679; validation cohort, Vasopressin and Septic Shock Trial (VASST), n = 517). The primary outcome variable was susceptibility to Gram-positive bacterial infection. The secondary outcome variable was 28-day mortality.

Results

Of four tested IL17A tag SNPs (rs4711998, rs8193036, rs2275913, rs1974226), rs1974226 SNP was associated with altered susceptibility to Gram-positive infection in the derivation SPH cohort (corrected P = 0.014). Patients having the rs1974226 GG genotype were more susceptible to Gram-positive infection, compared to AG/AA genotype in the two cohorts of severe sepsis (SPH, P = 0.0036, odds ratio (OR) 2.19, 95% confidence interval (CI) 1.28-3.72; VASST, P = 0.011, OR 1.95, 95%CI 1.16-3.27) and in the subgroup having lung infection (P = 0.017, OR 1.90, 95%CI 1.12-3.21). Furthermore, the IL17A rs1974226 G allele was associated with increased 28-day mortality in two cohorts (SPH, adjusted OR 1.44, 95%CI 1.04-2.02, P = 0.029; VASST, adjusted OR 1.67, 95%CI 1.17-2.40, P = 0.0052).

Conclusions

IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and 28-day mortality of severe sepsis.
Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration
Authors: Colson Pascal H , Bernard Cedric , Struck Joachim , Morgenthaler Nils G , Albat Bernard , Guillon Gilles
Published: December 2011

Introduction

Post cardiac surgery vasodilatation (PCSV) is possibly related to a vasopressin deficiency that could relate to chronic stimulation of adeno-hypophysis. To assess vasopressin system activation, a perioperative course of copeptin and vasopressin plasma concentrations were studied in consecutive patients operated on for cardiac surgery.

Methods

Sixty-four consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass were studied. Hemodynamic, laboratory and clinical data were recorded before and during cardiopulmonary bypass, and at the eighth postoperative hour (H8). At the same time, blood was withdrawn to determine plasma concentrations of arginine vasopressin (AVP, radioimmunoassay) and copeptin (immunoluminometric assay). PCSV was defined as mean arterial blood pressure < 60 mmHg with cardiac index ≥ 2.2 l/min/m2, and was treated with norepinephrine to restore mean blood pressure > 60 mmHg. Patients with PCSV were compared with the other patients (controls). Student's t test, Fisher's exact test, or nonparametric tests (Mann-Whitney, Wilcoxon) were used when appropriate. Correlation between AVP and copeptin was evaluated and receiver-operator characteristic analysis assessed the utility of preoperative copeptin to distinguish between controls and PCSV patients.

Results

Patients who experienced PCSV had significantly higher copeptin plasma concentration before cardiopulmonary bypass (P < 0.001) but lower AVP concentrations at H8 (P < 0.01) than controls. PCSV patients had preoperative hyponatremia and decreased left ventricle ejection fraction, and experienced more complex surgery (redo). The area under the receiver-operator characteristic curve of preoperative copeptin concentration was 0.86 ± 0.04 (95% confidence interval = 0.78 to 0.94; P < 0.001). The best predictive value for preoperative copeptin plasma concentration was 9.43 pmol/l with a sensitivity of 90% and a specificity of 77%.

Conclusions

High preoperative copeptin plasma concentration is predictive of PSCV and suggests an activation of the AVP system before surgery that may facilitate depletion of endogenous AVP stores and a relative AVP deficit after surgery.
Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity
Authors: Rasmussen Markus , Sundström Magnus , Kultima Hanna Göransson , Botling Johan , Micke Patrick , Birgisson Helgi , Glimelius Bengt , Isaksson Anders
Published: December 2011

We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.
RNA-seq in grain unveils fate of neo- and paleopolyploidization events in bread wheat (Triticum aestivum L.)
Authors: Pont Caroline , Murat Florent , Confolent Carole , Balzergue Sandrine , Salse Jérôme
Published: December 2011

Background

Whole genome duplication is a common evolutionary event in plants. Bread wheat (Triticum aestivum L.) is a good model to investigate the impact of paleo- and neoduplications on the organization and function of modern plant genomes.

Results

We performed an RNA sequencing-based inference of the grain filling gene network in bread wheat and identified a set of 37,695 non-redundant sequence clusters, which is an unprecedented resolution corresponding to an estimated half of the wheat genome unigene repertoire. Using the Brachypodium distachyon genome as a reference for the Triticeae, we classified gene clusters into orthologous, paralogous, and homoeologous relationships. Based on this wheat gene evolutionary classification, older duplicated copies (dating back 50 to 70 million years) exhibit more than 80% gene loss and expression divergence while recent duplicates (dating back 1.5 to 3 million years) show only 54% gene loss and 36 to 49% expression divergence.

Conclusions

We suggest that structural shuffling due to duplicated gene loss is a rapid process, whereas functional shuffling due to neo- and/or subfunctionalization of duplicates is a longer process, and that both shuffling mechanisms drive functional redundancy erosion. We conclude that, as a result of these mechanisms, half the gene duplicates in plants are structurally and functionally altered within 10 million years of evolution, and the diploidization process is completed after 45 to 50 million years following polyploidization.
Adding an Extra Dimension to What Students See through the Light Microscope: A Lab Exercise Demonstrating Critical Analysis for Microscopy Students
Authors: Garrill Ashley
Published: December 2011

This article describes an undergraduate lab exercise that demonstrates the importance of students thinking critically about what they see through a microscope. The students are given growth data from tip-growing organisms that suggest the cells grow in a pulsatile manner. The students then critique this data in several exercises that incorporate aspects of a problem-based learning approach, envisaging growth not just in two dimensions, but in three dimensions. For some cells, what appears to be pulsatile growth could also be explained by growth at a constant rate up and down in the z-axis. Depending on the diffraction pattern generated by the tip of the cell, this movement in the z-axis could go undetected. This raises the possibility that pulsatile growth seen in some species may be an artifact generated by the limitations of the light microscope. Students were subsequently asked to rate their awareness of the need to think critically about what they see through a microscope, using a scale of 1 (unaware) to 5 (very much aware). Prior to doing the lab exercise, the mean rating was 2.7; this increased to 4.4 after the lab. The students also indicated a likelihood of being more critical in their thinking in other aspects of their biology curriculum.
Osmosis and Diffusion Conceptual Assessment
Authors: Fisher Kathleen M. , Williams Kathy S. , Lineback Jennifer Evarts
Published: December 2011

Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified from the previously published Diffusion and Osmosis Diagnostic Test (DODT) and some newly developed items. The ODCA, a validated instrument containing fewer items than the DODT and emphasizing different content areas within the realm of osmosis and diffusion, better aligns with our curriculum. Creation of the ODCA involved removal of six DODT item pairs, modification of another six DODT item pairs, and development of three new item pairs addressing basic osmosis and diffusion concepts. Responses to ODCA items testing the same concepts as the DODT were remarkably similar to responses to the DODT collected from students 15 yr earlier, suggesting that student mastery regarding the mechanisms of diffusion and osmosis remains elusive.
The Oasis Poets: Perpetrators, Victims, and Soldier Testimony
Authors: Rowland Antony
Published: December 2011

This article examines the categories of victim and perpetrator testimony in relation to the writing contained in the Salamander Oasis Trust archive in the Imperial War Museum at Duxford. In Dimensions of the Holocaust, Elie Wiesel famously commented that the Holocaust produced the new literary genre of testimony. Although critics — such as James Young in Writing and Rewriting the Holocaust — have pointed out that testamentary accounts abound in relation to many other wars and atrocities, studies of testimony have — following Wiesel — mainly focused on the Holocaust. In this article, I explore British soldiers' poetic accounts of the Second World War in the Oasis archive, which contains around 20,000 items by over 200 authors. The concepts of victim and perpetrator testimony are both relevant and problematized in relation to soldier testimony. Clearly, the origin of the terms “victim” and “perpetrator” lies in a judicial context, but with the development of critical discussions about testimony outside the courtroom — as in the notion of literary testimony — the efficacy of these terms has been questioned. For Primo Levi, the trace of legal discourse is important, since it allows us to distinguish his tormentors from his fellow prisoners. However, Levi himself introduced the notion of the “grey zone” in which the “guilt” of, for example, the Sonderkommando does not sit easily with legal notions of criminality. In relation to soldier testimony, these categories are similarly vexed, since — as the variety of writing in the Oasis archive attests — an Allied recruit, as a reluctant conscript, or subsequently traumatized individual, or even a violator of the Geneva Convention, could be considered a victim. Sometimes the categories blur within an individual poem, as when Oasis writers celebrate the killing of German soldiers, but then also engage with troubling memories that surface in relation to such events after the war. Who (or what) is a perpetrator in the context of soldier testimony (as opposed to a perpetrator of genocide)? Should the term only be used in a legal sense, or should critical discussions of literary testimony draw on the dictionary definition of a perpetrator as an instigator of (potentially heinous) acts, which may include — whatever the pertinent definition of criminality — the killing of others in combat (OED, 2nd ed.)? Is a soldier only ever a victim (a common descriptor of soldiers after Vietnam and the advent of PTSD in 1980) or something between these two testamentary categories? And — most pertinent for this article — is there such a thing as a perpetrator voice, perspective, or aesthetic when the poet dispassionately records enemy deaths, or — as in Keith Douglas's “Elegy for an 88 Gunner” — voyeuristically mulls over the corpse of an enemy soldier? This article addresses such questions in relation to both the canonical poet Keith Douglas and other, relatively unknown, writers in the Oasis archive.
Queerness, Norms, Utopia
Authors: Rosenberg Jordana , Villarejo Amy
Published: December 2011

Extending the recent rapprochement among queer studies, Marxist theory, and political economy, this special issue of GLQ responds to the current crisis of capitalism. Contributors consider how methodologies of queer studies are specially poised to reveal the global, historical, and social dimensions of capitalist economic relations. Using queer hermeneutical tools in combination with globalization studies, secularization studies, and queer of color critique, contributors examine global economic history and the ideological collusion of capitalist production and biological reproduction. The Introduction explores the ways in which capitalism is only made possible by systems of racial, sexual, and national exploitation; further, we seek to interrupt the commonsensical presumption that recuperation from periods of crisis depends on the increasingly violent reassertion of these forms of exploitation. Turning our attention to the set of crises defining the period we understand as neoliberal capitalism—the long wave of recessions and dispossessions stretching from the 1970s to the present—we explore the shared queer and Marxist commitment to concepts of utopia and theories of totality as frameworks for strenuously negating and moving beyond current conditions. By providing an expansive theoretical perspective on current and historical economic patterns, we hope to illuminate and advance our understanding of the complex structures of global capitalism.
Perverse Justice
Authors: Jakobsen Janet R.
Published: December 2011

“Perverse Justice” considers sexual relations of production as they contribute to the neoliberal order of things. Specifically, the essay explores the imbrications of heteronormativity, Protestantism, and secularized global capital. By taking sex seriously as part and parcel of the relations of production, rather than as a realm of reproduction analogous to or functional for production, it is possible to develop a new understanding of both economic value and the values of social change, including justice, peace, and freedom. Through analyses of policy from the administrations of Barack Obama and George W. Bush, as well as the World Bank, this essay explores whether and how perversity might be an effective agent of economic justice.
Ideological Fantasies
Authors: Freccero Carla
Published: December 2011

“Ideological Fantasies” is an argument for the continued importance of thinking Marxism and psychoanalysis together in the conjunction of “queer” and “capital.” Both, within a certain Western tradition, are preoccupied with understanding how ideology fashions subjectivities. By revisiting a textual scene in the genealogy of capitalism where commodity fetishism makes its appearance as a rhetorical construction—Leon Battista Alberti's treatise on the family—I show how ideology works phantasmically to “eternalize” or “universalize” historical contingency, even as the historicization of this fantasy (its relegation to the “origins” of kinship and exchange) produces the effect of concealing the repeated return of the same in late capitalism. Commodity fetishism is the name of one of the most explicit figural convergences of psychoanalysis and Marxism, and its critical genealogy continues to be haunted by spectral appearances of gender, sexuality, and racialization, particularly where the to-be-commodified object is concerned. What I focus on is how a particular—and multiply displaced—subjectivity inhabits the scene of commodity fetishism and how commodity fetishism structures and marks not only the objects but also the subjects of exchange, creating “real abstractions” that have not ceased to perform their ideological work.
“If I Turn into a Boy, I Don't Think I Want Huevos”
Authors: Cacho Lisa Marie
Published: December 2011

Carla Trujillo's novel What Night Brings, set in the mid- to late 1960s, critiques Chicano cultural nationalist narratives for too easily entangling racial emasculation with economic exclusion and domestic violence. Considering how this critique of male violence can also be appropriated by the state, I contemplate how we might read differently to find alternative ways to analyze family-centered politics that enable us to “disidentify” with the state and delegitimate its monopoly on violence.
Queer Value
Authors: Wesling Meg
Published: December 2011

This essay addresses how an interrogation of the concept of value can make room for a materialist reading of sexuality that goes beyond the identifiably “queer” to address the historical specificity of capital's investment in formations of sexual identity. The production of sexuality, through which unpredictable constellations of desire, knowledge, and practice become concretized into limited models of sexual identity, is bound up in the way capital produces the subjects accommodated to its own needs. Thus “queer value” sutures together two domains too often understood to operate autonomously: the psychic realm of desire and the material realm of accumulation and exchange. If we take seriously the notion of affect in relation to labor, then the daily, repetitive performances through which bodies are socially legible as gendered (whether coded as queer or straight) constitute a kind of affectively necessary labor—that is, the compulsory repetition of gender as performance might usefully be understood as a form of self-conscious labor that produces value, both material and social. It is the realm of affect that renders such performances to seem as though they are spontaneous, the reflection of the subject himself or herself rather than the internalized form of subjection through which each individual becomes legible as a social subject.
Queer Media Loci: Israel/Palestine
Authors: Ma Ming-Yuen S. , Juhasz Alexandra
Published: December 2011

Although queer Israeli cinema is often perceived as symptomatically expressing Israeli society and its gay politics, this article argues that the recent success of Israeli films abroad can be attributed to their inclusion within the global network of film festivals and art houses. Israeli films have been thriving as part of “world cinema” by adopting a formula that Thomas Elsaesser has labeled “self-othering” or “self-exoticizing,” in which they expose local issues, such as the Israeli-Palestinian conflict and ultraorthodox Jewish communities, to the gaze of the other. We suggest that many Israeli queer films offer a double exoticization, adding a gay twist to the familiar formula of Israeli self-othering, or providing an exotic locale to revitalize otherwise worn-out gay narratives. Additionally, we look at films that challenge this formula from within the festival network and suggest that we should also examine our own position as film scholars writing about queer Israeli cinema to a global academic community.
Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism
Authors: Sahoo Pabitra K. , Murawala Prayag , Sawale Pravin T. , Sahoo Manas R. , Tripathi Mukesh M. , Gaikwad Swati R. , Seshadri Vasudevan , Joseph Jomon
Published: December 2011

Cells often respond to diverse environmental stresses by inducing stress granules (SGs) as an adaptive mechanism. SGs are generally assembled as a result of aggregation of mRNAs stalled in a translational pre-initiation complex, mediated by a set of RNA-binding proteins such as G3BP and TIA-1. SGs may serve as triage centres for storage, translation re-initiation or degradation of specific mRNAs. However, the mechanism involved in the modulation of their assembly/disassembly is unclear. Here we report that Wnt signalling negatively regulates SG assembly through Dishevelled (Dvl), a cytoplasmic Wnt effector. Overexpression of Dvl2, an isoform of Dvl, leads to impairment of SG assembly through a DEP domain dependent mechanism. Intriguingly, the Dvl2 mutant K446M, which corresponds to an analogous mutation in Drosophila Dishevelled DEP domain (dsh1) that results in defective PCP pathway, fails to antagonize SG assembly. Furthermore, we show that Dvl2 exerts the antagonistic effect on SG assembly through a mechanism involving Rac1-mediated inhibition of RhoA. Dvl2 interacts with G3BP, a downstream component of Ras signalling involved in SG assembly, and functional analysis suggests a model wherein the Dvl-Rac1-RhoA axis regulates G3BP's SG-nucleating activity. Collectively, these results define an antagonistic effect of Wnt signalling on SG assembly, and reveal a novel role for Wnt/Dvl pathway in the modulation of mRNA functions.
AQP2 is necessary for vasopressin- and forskolin-mediated filamentous actin depolymerization in renal epithelial cells
Authors: Yui Naofumi , Lu Hua Jenny , Bouley Richard , Brown Dennis
Published: December 2011

Remodeling of the actin cytoskeleton is required for vasopressin (VP)-induced aquaporin 2 (AQP2) trafficking. Here, we asked whether VP and forskolin (FK)-mediated F-actin depolymerization depends on AQP2 expression. Using various MDCK and LLC-PK1 cell lines with different AQP2 expression levels, we performed F-actin quantification and immunofluorescence staining after VP/FK treatment. In MDCK cells, in which AQP2 is delivered apically, VP/FK mediated F-actin depolymerization was significantly correlated with AQP2 expression levels. A decrease of apical membrane associated F-actin was observed upon VP/FK treatment in AQP2 transfected, but not in untransfected cells. There was no change in basolateral actin staining under these conditions. In LLC-PK1 cells, which deliver AQP2 basolaterally, a significant VP/FK mediated decrease in F-actin was also detected only in AQP2 transfected cells. This depolymerization response to VP/FK was significantly reduced by siRNA knockdown of AQP2. By immunofluorescence, an inverse relationship between plasma membrane AQP2 and membrane-associated F-actin was observed after VP/FK treatment again only in AQP2 transfected cells. This is the first report showing that VP/FK mediated F-actin depolymerization is dependent on AQP2 protein expression in renal epithelial cells, and that this is not dependent on the polarity of AQP2 membrane insertion.
Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1
Authors: Chen Ku-Chung , Hsieh I-Chung , Hsi Edward , Wang Yung-Song , Dai Chia-Yen , Chou Wen-Wen , Juo Suh-Hang Hank
Published: December 2011

Lectin-like oxidized LDL receptor-1 (LOX-1) is a surface scavenger receptor for oxidized low-density lipoprotein (oxLDL). Several transcription factors have been reported to regulate LOX-1 expression. MicroRNAs are small noncoding RNAs that control gene expression, but there have been no reports of LOX-1 expression being regulated by microRNAs. Because the microRNA let-7g has been predicted to bind to LOX-1 mRNA, we investigated whether let-7g can regulate LOX-1 expression. Our experiments first demonstrated that oxLDL can reduce let-7g expression. We later confirmed that there is a let-7g binding site on the 3′-untranslated region of LOX-1 mRNA. We showed that intracellular Ca2+-activated protein kinase C is involved in the oxLDL–LOX-1–let-7g pathway. Bioinformatics predicted that the let-7g promoter has a binding site for the transcriptional repressor OCT-1. We used a promoter assay and chromatin immunoprecipitation to confirm this binding. Consequently, knockdown of OCT-1 was found to increase let-7g expression. Transfection of let-7g inhibited oxLDL-induced LOX-1 and OCT-1 expression, cell proliferation and migration. Mice fed with a high-fat diet showed a decrease in let-7g and an increase in LOX-1 and OCT-1. A study on humans showed the serum levels of let-7g are lower in subjects with hypercholesterolemia compared with normal controls. Our findings identify a negative feedback regulation between let-7g and LOX-1, and indicate that let-7g could be a target to treat cardiovascular disease.
Crossed cerebellar hyperperfusion after MELAS attack followed up by whole brain continuous arterial spin labeling perfusion imaging
Authors: Tsujikawa Tetsuya , Yamamoto Tatsuya , Ikawa Masamichi , Yoneda Makoto , Kimura Hirohiko
Published: December 2011

Crossed cerebellar hyperperfusion (CCH) is detected in patients with epilepsy by brain perfusion studies including single photon emission computed tomography and positron emission tomography. In addition, brain perfusion can be studied with arterial spin labeling (ASL), which is a non-invasive MRI perfusion method that quantitatively measures cerebral blood flow per unit tissue mass. We followed up a 47-year-old patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by continuous arterial spin labeling technique, which showed crossed cerebellar hyperperfusion after acute stroke-like episode. This cerebellar hyperperfusion normalized in the follow-up.
CT-guided percutaneous drainage within intervertebral space for pyogenic spondylodiscitis with psoas abscess
Authors: Matsumoto Tomohiro , Yamagami Takuji , Morishita Hiroyuki , Iida Shigeharu , Asai Shunsuke , Masui Koji , Yamazoe Shoichi , Sato Osamu , Nishimura Tsunehiko
Published: December 2011

Background

Reports on CT-guided percutaneous drainage within the intervertebral space for pyogenic spondylodiscitis with a secondary psoas abscess are limited.

Purpose

To evaluate CT-guided percutaneous drainage within the intervertebral space for pyogenic spondylodiscitis and a secondary psoas abscess in which the two sites appear to communicate.

Material and Methods

Eight patients with pyogenic spondylodiscitis and a secondary psoas abscess showing communication with the intradiscal abscess underwent CT-guided percutaneous drainage within the intervertebral space. The clinical outcome was retrospectively assessed.

Results

An 8-French pigtail catheter within the intervertebral space was successfully placed in all patients. Seven patients responded well to this treatment. The one remaining patient who had developed septic shock before the procedure died on the following day. The mean duration of drainage was 32 days (13–70 days). Only one patient with persistent back pain underwent surgery for stabilization of the spine after the improvement of inflammation. Among seven patients responding well, long-term follow-up (91–801 days, mean 292 days) was conducted in six patients excluding one patient who died of asphyxiation due to aspiration unrelated to the procedure within 30 days after the procedure. In these six patients, no recurrence of either pyogenic spondylodiscitis or the psoas abscess was noted.

Conclusion

CT-guided percutaneous drainage within the intervertebral space can be effective for patients with pyogenic spondylodiscitis and a secondary psoas abscess if the psoas abscess communicates with the intradiscal abscess.
Retrospective review of hand-based splinting for zone II extensor pollicis longus tendon repairs using an early active motion rehabilitation regimen
Authors: van Veenendaal Penelope M , Moate Fiona A
Published: December 2011

Introduction

Forearm-based splints have been traditionally used for extensor pollicis longus (EPL) tendon repairs for zones T II–T V (T is used to represent thumb extensor tendon zones). Limited literature exists on hand-based splinting in the rehabilitation of zone T II EPL tendon repairs. This retrospective review of five case studies highlights the anatomical justification and the outcome of rehabilitation of zone T II EPL surgical repairs using a static hand-based thumb extension splint.

Methods

In this study, five patients were retrospectively reviewed. All patients attended hand therapy for initial treatment within three days postoperatively. The postoperative interphalangeal joint mobilization regimen utilized in this study was early active motion (EAM). Outcomes measured in the study were reliable and valid, including goniometry measurement at week 4, week 6 and week 8 postoperatively for range of motion, total active motion (TAM), Dargan's criteria assessing extensor lag and White's assessment of interphalangeal joint range of motion.

Results

The results demonstrated that a hand-based splint did not create undue stress on the EPL tendon repair, as there was no incidence of rupture. Hyperextension of EPL was within 8° compared with the non-injured thumb. ‘Excellent’ and ‘good’ categories were achieved when applying TAM criteria, White's assessment and Dargan's criteria.

Conclusion

A hand-based splint with an EAM regimen is a viable treatment option for zone T II EPL surgical repairs instead of a long forearm-based splint. Further research is warranted with a larger sample and using a control group.
Outcome of zone 2 flexor tendon injuries: Kleinert versus controlled active motion therapy regimens
Authors: Prowse Phoebe , Nixon Matt , Constantinides Joannis , Hunter Janet , Henry Angela , Feldberg Lore
Published: December 2011

Introduction

No single optimal regimen for the rehabilitation of flexor tendon injuries has yet been determined. We aimed to evaluate if a change in rehabilitation from a modified Kleinert to a controlled active motion (CAM) regimen had an effect on outcomes in a regional plastic surgery unit. We did this by comparing ruptures and range of movement of zone 2 repairs following both Kleinert and CAM regimens.

Methods

We performed a retrospective case series review, analysing data collected prospectively between 2004 and 2007. During 2004 and 2005, patients were rehabilitated with a modified Kleinert regimen, and during 2006 and 2007 a CAM regimen was used. We looked at total active motion (TAM) and ruptures at 12-week follow-up for all zone 2 repairs, and compared the two regimens.

Results

There were 38 patients with 42 injured digits in the Kleinert group, and 34 patients with 39 injured digits in the CAM group. There was no statistically significant difference in TAM achieved between the Kleinert and CAM regimens overall (70% versus 72% of normal in each group respectively, P = 0.70 t-test). Patients over 30 years old achieved significantly worse outcomes in the Kleinert group than in the CAM group ( P = 0.03). One digit ruptured following a Kleinert regimen (2.6%) compared with four digits in the CAM group (11.7%).

Conclusion

In this study, we found no overall difference in outcome following a Kleinert or CAM rehabilitation regimen. Rupture rates were higher in the CAM group by four-fold. In our patients those over 30 years had poorer outcomes when rehabilitated with a Kleinert regimen.