bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil mediated smooth muscle cell loss precedes allograft vasculopathy
Authors: King Chelsey L , Devitt Jennifer J , Lee Timothy DG , Hancock Friesen Camille L
Published: June 2010

Background

Cardiac allograft vasculopathy (AV) is a pathological process of vascular remodeling leading to late graft loss following cardiac transplantation. While there is consensus that AV is alloimmune mediated, and evidence that the most important alloimmune target is medial smooth muscle cells (SMC), the role of the innate immune response in the initiation of this disease is still being elucidated. As ischemia reperfusion (IR) injury plays a pivotal role in the initiation of AV, we hypothesize that IR enhances the early innate response to cardiac allografts.

Methods

Aortic transplants were performed between fully disparate mouse strains (C3H/HeJ and C57BL/6), in the presence of therapeutic levels of Cyclosporine A, as a model for cardiac AV. Neutrophils were depleted from some recipients using anti-PMN serum. Grafts were harvested at 1,2,3,5d and 1,2wk post-transplant. Ultrastructural integrity was examined by transmission electron microscopy. SMC and neutrophils were quantified from histological sections in a blinded manner.

Results

Grafts exposed to cold ischemia, but not transplanted, showed no medial SMC loss and normal ultrastructural integrity. In comparison, allografts harvested 1d post-transplant exhibited > 90% loss of SMC (p < 0.0001). SMC partially recovered by 5d but a second loss of SMC was observed at 1wk. SMC loss at 1d and 1wk post-transplant correlated with neutrophil influx. SMC loss was significantly reduced in neutrophil depleted recipients (p < 0.01).

Conclusions

These novel data show that there is extensive damage to medial SMC at 1d post-transplant. By depleting neutrophils from recipients it was demonstrated that a portion of the SMC loss was mediated by neutrophils. These results provide evidence that IR activation of early innate events contributes to the etiology of AV.
Churg-Strauss syndrome following cessation of allergic desensitization vaccination: a case report
Authors: Masjedi Mohammad Reza , Tafti Saeid Fallah , Cheraghvandi Ali , Fayazi Nader , Talischi Firouzeh , Mokri Bahareh
Published: June 2010

Introduction

Churg-Strauss syndrome is a vasculitis of medium to small sized vessels. Diagnosis is mainly clinical with findings of asthma, eosinophilia, rhinosinusitis and signs of vasculitis in major organs.

Case presentation

We present a case of a 19-year-old Persian male who developed signs and symptoms of this syndrome related to hyposensitization treatments for allergy control.

Conclusions

No unifying etiology for the disease can be presented as it is found associated with environmental factors, medications, infections and is even considered a variant of asthma with predisposition to vasculitic involvement. Therefore, it is important to recognize this disease and be aware of underdiagnosis because of emphasis on pathologic evidence. Here, we present a case of allergic desensitization causing Churg-Strauss syndrome in the absence of other known factors.
Clinical significance of the expression of connexin26 in colorectal cancer
Authors: Nomura Shinya , Maeda Kiyoshi , Noda Eiji , Inoue Toru , Fukunaga Shinya , Nagahara Hisashi , Hirakawa Kosei
Published: June 2010

Background

Connexin26 (Cx26) is one of the connexins (Cxs) family members which form gap junction channels. Cx26 is considered to be a tumor suppressor gene. However, recent studies revealed that over expression of Cx26 is associated with a poor prognosis in several human cancers. This study investigated the correlation between Cx26 expression and the clinicopathological features and P53 expression in colorectal cancer.

Methods

One hundred and fifty-three patients who underwent a curative resection were studied. Tissue samples were investigated by immunohistochemical staining using antibodies for Cx26 and P53. Moreover, apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining.

Results

Cx26 expression was found in 83 cases (54.2%) and P53 expression in 71 cases (46.4%). A correlation was observed between the Cx26 expression and recurrence, histology, and p53 expression (P < 0.05). Cx26 positive tumors had significantly longer survival than Cx26 negative tumors (P < 0.05). A multivariate Cox analysis demonstrated that Cx26 expression was an independent prognostic factor (P < 0.05). However, no significant correlation was observed between Cx26 and AI.

Conclusion

This study suggests that Cx26 expression is an independent prognostic factor in patients that undergo a curative resection of colorectal cancer.
MYEOV (myeloma overexpressed gene) drives colon cancer cell migration and is regulated by PGE2
Authors: Lawlor Garrett , Doran Peter P , MacMathuna Padraic , Murray David W
Published: June 2010

Introduction

We have previously reported that Myeov (MYEloma OVerexpressed gene) expression is enhanced in colorectal cancer (CRC) and that it promotes CRC cell proliferation and invasion. The role of Myeov in CRC migration is unclear. ProstaglandinE2 (PGE 2) is a known factor in promoting CRC carcinogenesis. The role of PGE 2 in modulating Myeov expression has also not been defined.

Aim

To assess the role of Myeov expression in CRC cell migration and to evaluate the role of PGE 2 in Myeov bioactivity.

Methods

siRNA mediated Myeov knockdown was achieved in T84 CRC cells. Knockdown was assessed using quantitative real time PCR. The effect of knockdown on CRC cell migration was assessed using a scratch wound healing assay. Separately, T84 cells were treated with PGE 2 (0.00025 μ M, 0.1 μ M and 1 μ M) from 30 min to 3 hours and the effect on Myeov gene expression was assessed using real time PCR.

Results

Myeov knockdown resulted in a significant reduction in CRC cell migration, observable as early as 12 hours (P < 0.05) with a 39% reduction compared to control at 36 hours (p < 0.01). Myeov expression was enhanced after treatment with PGE 2, with the greatest effect seen at 60 mins for all 3 PGE 2 doses. This response was dose dependent with a 290%, 550% & 1,000% increase in Myeov expression for 0.00025 μ M, 0.1 μ M and 1 μ M PGE 2 respectively.

Conclusion

In addition to promoting CRC proliferation and invasion, our findings indicate that Myeov stimulates CRC cell migration, and its expression may be PGE 2 dependant.
The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET
Authors: Schneider-Kolsky Michal E , Hart Stewart , Fox Jane , Midolo Peter , Stuckey John , Hofman Michael , Ganju Vinod
Published: June 2010

Introduction

The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]flourodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer.

Methods

Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy.

Results

Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B.

Conclusions

Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols.
Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development
Authors: Oloumi Arusha , Maidan Mykola , Lock Frances E , Tearle Howard , McKinney Steven , Muller William J , Aparicio Samuel AJR , Dedhar Shoukat
Published: June 2010

Introduction

Breast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascade that regulates cell growth and survival. Interestingly, mammary-specific expression of either one of these proteins has been shown to promote mammary tumorigenesis. In light of our recent findings and to investigate the potential interaction between Wnt and ILK proteins during mammary tumor formation and progression, we established a transgenic mouse model that expresses both Wnt and ILK in mammary epithelial cells.

Methods

A novel transgenic mouse model with mammary-specific expression of both Wnt1 and ILK was generated by crossing the two previously characterized mouse models, MMTV-Wnt1 and MMTV-ILK. The resulting MMTV-Wnt/ILK mice were closely monitored for tumor development and growth, as well as for the tumor onset. The molecular phenotypes of both tumors and premalignant mammary glands were investigated by using biochemical and global gene-expression analysis approaches.

Results

A significant acceleration in mammary tumor incidence and growth was observed in the MMTV-Wnt/ILK mice. Pre-neoplastic mammary glands also display lobuloalveolar hyperplasia and an increase in ductal epithelium proliferation. Apart from elevated expression of Wnt/ILK targets, such as β-catenin and cyclin D1, gene-expression profiling identified the surprising activation of the FOXA1 transcription factor. Upregulation of FOXA1, which is also known as the molecular marker of differentiated mammary luminal cells, was consistent with the expansion of the enriched luminal progenitor population or CD29loCD24hiCD61+ cells in MMTV-Wnt/ILK tumors.

Conclusions

These results show cooperation between Wnt1 and ILK transgenes during mammary carcinogenesis, leading to changes in a transcriptional network, which could dictate a specific breast cancer phenotype with enhanced growth dynamics. The MMTV-Wnt/ILK can be used as a model to identify further the genes downstream of the estrogen receptor-β/FOXA1 and to investigate the mechanisms targeting the expansion of the luminal progenitor cells leading to hyperplasia and tumorigenesis.
Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer
Authors: Creighton Chad J , Fu Xiaoyong , Hennessy Bryan T , Casa Angelo J , Zhang Yiqun , Gonzalez-Angulo Ana Maria , Lluch Ana , Gray Joe W , Brown Powell H , Hilsenbeck Susan G , Osborne C Kent , Mills Gordon B , Lee Adrian V , Schiff Rachel
Published: June 2010

Introduction

Accumulating evidence suggests that both levels and activity of the estrogen receptor (ER) and the progesterone receptor (PR) are dramatically influenced by growth-factor receptor (GFR) signaling pathways, and that this crosstalk is a major determinant of both breast cancer progression and response to therapy. The phosphatidylinositol 3-kinase (PI3K) pathway, a key mediator of GFR signaling, is one of the most altered pathways in breast cancer. We thus examined whether deregulated PI3K signaling in luminal ER+ breast tumors is associated with ER level and activity and intrinsic molecular subtype.

Methods

We defined two independent molecular signatures of the PI3K pathway: a proteomic (reverse-phase proteomic array) PI3K signature, based on protein measurement for PI3K signaling intermediates, and a PI3K transcriptional (mRNA) signature based on the set of genes either induced or repressed by PI3K inhibitors. By using these signatures, we scored each ER+ breast tumor represented in multiple independent expression-profiling datasets (four mRNA, n = 915; one protein, n = 429) for activation of the PI3K pathway. Effects of PI3K inhibitor BEZ-235 on ER expression and activity levels and cell growth were tested by quantitative real-time PCR and cell proliferation assays.

Results

Within ER+ tumors, ER levels were negatively correlated with the PI3K activation scores, both at the proteomic and transcriptional levels, in all datasets examined. PI3K signature scores were also higher in ER+ tumors and cell lines of the more aggressive luminal B molecular subtype versus those of the less aggressive luminal A subtype. Notably, BEZ-235 treatment in four different ER+ cell lines increased expression of ER and ER target genes including PR, and treatment with IGF-I (which signals via PI3K) decreased expression of ER and target genes, thus further establishing an inverse functional relation between ER and PI3K. BEZ-235 had an additional effect on tamoxifen in inhibiting the growth of a number of ER+ cell lines.

Conclusions

Our data suggest that luminal B tumors have hyperactive GFR/PI3K signaling associated with lower ER levels, which has been correlated with resistance to endocrine therapy. Targeting PI3K in these tumors might reverse loss of ER expression and signaling and restore hormonal sensitivity.
Echocardiography: a help in the weaning process
Authors: Caille Vincent , Amiel Jean-Bernard , Charron Cyril , Belliard Guillaume , Vieillard-Baron Antoine , Vignon Philippe
Published: June 2010

Introduction

To evaluate the ability of transthoracic echocardiography (TTE) to detect the effects of spontaneous breathing trial (SBT) on central hemodynamics and to identify indices predictive of cardiac-related weaning failure.

Methods

TTE was performed just before and at the end of a 30-min SBT in 117 patients fulfilling weaning criteria. Maximal velocities of mitral E and A waves, deceleration time of E wave (DTE), maximal velocity of E' wave (tissue Doppler at the lateral mitral annulus), and left ventricular (LV) stroke volume were measured. Values of TTE parameters were compared between baseline (pressure support ventilation) and SBT in all patients and according to LV ejection fraction (EF): >50% (n = 58), 35% to 50% (n = 30), and <35% (n = 29). Baseline TTE indices were also compared between patients who were weaned (n = 94) and those who failed (n = 23).

Results

Weaning failure was of cardiac origin in 20/23 patients (87%). SBT resulted in a significant increase in cardiac output and E/A, and a shortened DTE. At baseline, DTE was significantly shorter in patients with LVEF <35% when compared to other subgroups (median [25th-75th percentiles]: 119 ms [90-153]; vs. 187 ms [144-224] vs. 174 ms [152-193]; P < 0.01) and E/E' was greater (7.9 [5.4-9.1] vs. 6.0 [5.3-9.0] vs. 5.2 [4.7-6.0]; P < 0.01). When compared to patients who were successfully weaned, those patients who failed exhibited at baseline a significantly lower LVEF (36% [27-55] vs. 51% [43-55]: P = 0.04) and higher E/E' (7.0 [5.0-9.2] vs. 5.6 [5.2-6.3]: P = 0.04).

Conclusions

TTE detects SBT-induced changes in central hemodynamics. When performed by an experienced operator prior to SBT, TTE helps in identifying patients at high risk of cardiac-related weaning failure when documenting a depressed LVEF, shortened DTE and increased E/E'. Further studies are needed to evaluate the impact of this screening strategy on the weaning process and patient outcome.
A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes
Authors: De Cegli Rossella , Romito Antonio , Iacobacci Simona , Mao Lei , Lauria Mario , Fedele Anthony O , Klose Joachim , Borel Christelle , Descombes Patrick , Antonarakis Stylianos E , di Bernardo Diego , Banfi Sandro , Ballabio Andrea , Cobellis Gilda
Published: June 2010

Background

Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.

Results

To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis.

Conclusions

We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.
Use of Bisphosphonates and Risk of Postmenopausal Breast Cancer
Authors: Rennert Gad , Pinchev Mila , Rennert Hedy S.
Published: June 2010

Purpose

Bisphosphonates are commonly used for the treatment of osteoporosis and for prevention and treatment of skeletal lesions due to malignancy. However, the association between the use of bisphosphonates and the risk of developing breast cancer has not been reported.

Patients and Methods

The Breast Cancer in Northern Israel Study is a population-based case-control study in northern Israel of patients with breast cancer and age-, clinic-, and ethnic-group matched controls. Use of bisphosphonates was assessed in 4,039 postmenopausal patients and controls, members of Clalit Health Services, using pharmacy records.

Results

The use of bisphosphonates for longer than 1 year before diagnosis, but not for shorter than 1 year, was associated with a significantly reduced relative risk of breast cancer (odds ratio [OR], 0.61; 95% CI, 0.50 to 0.76). This association remained significant after adjustment for age, fruit, and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, use of calcium supplements, hormone replacement therapy use, number of pregnancies, months of breast feeding, and age at first pregnancy (OR, 0.72; 95% CI, 0.57 to 0.90). Breast cancer risk did not change further if bisphosphonates were used for more years. Breast tumors identified in bisphosphonates users were more often estrogen receptor positive and less often poorly differentiated.

Conclusion

The use of bisphosphonates for longer than 1 year was associated with a 28% relative reduction in the risk of postmenopausal breast cancer. Tumors developing under bisphosphonates treatment tended to have a favorable prognostic factors profile.
Adoption of Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer: A Population-Based Outcomes Study
Authors: Booth Christopher M. , Shepherd Frances A. , Peng Yingwei , Darling Gail E. , Li Gavin , Kong Weidong , Mackillop William J.
Published: June 2010

Purpose

Since 2004, several clinical trials have demonstrated that adjuvant chemotherapy (ACT) improves survival in patients with early-stage non–small-cell lung cancer (NSCLC). Here, we evaluate the uptake of ACT and its impact on outcomes in the general population of Ontario, Canada.

Methods

All patients diagnosed with NSCLC in Ontario from 2001 to 2006 who underwent surgical resection (n = 6,304) were identified using the Ontario Cancer Registry. We linked electronic records of treatment to the registry. We described uptake of ACT and compared survival of all patients with surgically resected NSCLC diagnosed from 2001 to 2003 with patients diagnosed from 2004 to 2006. As a proxy measure of ACT-related toxicity, we evaluated hospitalizations within 6 months of surgery.

Results

Demographic, disease, and treatment-related characteristics did not differ between the 2001 to 2003 and 2004 to 2006 study cohorts. Over the study period, the proportion of patients receiving ACT increased from 7% (192 of 2,950 patients) to 31% (1,032 of 3,354 patients; P < .001). The proportion of patients admitted to hospital within 6 months of surgery remained stable and (36% in the 2001 to 2003 cohort and 37% in the 2004 to 2006 cohort). However, within 2 years of surgery, there was a 33% reduction in the proportion of patients admitted to hospital with metastatic disease (P < .001). During the study period, there was a substantial improvement in 4-year survival among surgically resected patients, from 52.5% (2001 to 2003) to 56.1% (2004 to 2006; P = .001).

Conclusion

There has been a rapid uptake of ACT for NSCLC, which was not associated with an increased rate of hospitalization. The adoption of ACT was associated with a substantial improvement in overall survival, suggesting that the benefits seen in clinical trials are generalizable to the general population.
The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline
Authors: Coleman Hope A. , Labrador Juan-Pablo , Chance Rebecca K. , Bashaw Greg J.
Published: June 2010

Slits and their Roundabout (Robo) receptors mediate repulsive axon guidance at the Drosophila ventral midline and in the vertebrate spinal cord. Slit is cleaved to produce fragments with distinct signaling properties. In a screen for genes involved in Slit-Robo repulsion, we have identified the Adam family metalloprotease Kuzbanian (Kuz). Kuz does not regulate midline repulsion through cleavage of Slit, nor is Slit cleavage essential for repulsion. Instead, Kuz acts in neurons to regulate repulsion and Kuz can cleave the Robo extracellular domain in Drosophila cells. Genetic rescue experiments using an uncleavable form of Robo show that this receptor does not maintain normal repellent activity. Finally, Kuz activity is required for Robo to recruit its downstream signaling partner, Son of sevenless (Sos). These observations support the model that Kuz-directed cleavage is important for Robo receptor activation.
Crooked, Coiled and Crimpled are three Ly6-like proteins required for proper localization of septate junction components
Authors: Nilton Anna , Oshima Kenzi , Zare Fariba , Byri Sunitha , Nannmark Ulf , Nyberg Kevin G. , Fehon Richard G. , Uv Anne E.
Published: June 2010

Cellular junction formation is an elaborate process that is dependent on the regulated synthesis, assembly and membrane targeting of constituting components. Here, we report on three Drosophila Ly6-like proteins essential for septate junction (SJ) formation. SJs provide a paracellular diffusion barrier and appear molecularly and structurally similar to vertebrate paranodal septate junctions. We show that Crooked (Crok), a small GPI-anchored Ly6-like protein, is required for septa formation and barrier functions. In embryos that lack Crok, SJ components are produced but fail to accumulate at the plasma membrane. Crok is detected in intracellular puncta and acts tissue-autonomously, which suggests that it resides in intracellular vesicles to assist the cell surface localization of SJ components. In addition, we demonstrate that two related Ly6 proteins, Coiled (Cold) and Crimpled (Crim), are required for SJ formation and function in a tissue-autonomous manner, and that Cold also localizes to intracellular vesicles. Specifically, Crok and Cold are required for correct membrane trafficking of Neurexin IV, a central SJ component. The non-redundant requirement for Crok, Cold, Crim and Boudin (Bou; another Ly6 protein that was recently shown to be involved in SJ formation) suggests that members of this conserved family of proteins cooperate in the assembly of SJ components, possibly by promoting core SJ complex formation in intracellular compartments associated with membrane trafficking.
Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs
Authors: Lin Yao-Tang , Kincaid Rodney P. , Arasappan Dhivya , Dowd Scot E. , Hunicke-Smith Scott P. , Sullivan Christopher S.
Published: June 2010

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus that encodes 12 precursor microRNAs (pre-miRNAs) that give rise to 17 different known ∼22-nucleotide (nt) effector miRNAs. Like all herpesviruses, KSHV has two modes of infection: (1) a latent mode whereby only a subset of viral genes are expressed and (2) a lytic mode during which the full remaining viral genes are expressed. To date, KSHV miRNAs have been mostly identified via analysis of cells that are undergoing latent infection. Here, we developed a method to profile small RNAs (∼18–75 nt) from populations of cells undergoing predominantly lytic infection. Using two different next-generation sequencing platforms, we cloned and sequenced both pre-miRNAs and derivative miRNAs. Our analysis shows that the vast majority of viral and host 5p miRNAs are co-terminal with the 5′ end of the cloned pre-miRNAs, consistent with both being defined by microprocessor cleavage. We report the complete repertoire (25 total) of 5p and 3p derivative miRNAs from all 12 previously described KSHV pre-miRNAs. Two KSHV pre-miRNAs, pre-miR-K12-8 and pre-miR-K12-12, encode abundant derivative miRNAs from the previously unreported strands of the pre-miRNA. We identify several novel small RNAs of low abundance, including viral miRNA-offset-RNAs (moRNAs), and antisense viral miRNAs (miRNA-AS) that are encoded antisense to previously reported KSHV pre-miRNAs. Finally, we observe widespread antisense transcription relative to known coding sequences during lytic replication. Despite the enormous potential to form double-stranded RNA in KSHV-infected cells, we observe no evidence for the existence of abundant viral-derived small interfering RNAs (siRNAs).
SL2-like spliced leader RNAs in the basal nematode Prionchulus punctatus: New insight into the evolution of nematode SL2 RNAs
Authors: Harrison Neale , Kalbfleisch Andreas , Connolly Bernadette , Pettitt Jonathan , Müller Berndt
Published: June 2010

Spliced-leader (SL) trans-splicing has been found in all molecularly characterized nematode species to date, and it is likely to be a nematode synapomorphy. Most information regarding SL trans-splicing has come from the study of nematodes from a single monophyletic group, the Rhabditida, all of which employ SL RNAs that are identical to, or variants of, the SL1 RNA first characterized in Caenorhabditis elegans. In contrast, the more distantly related Trichinella spiralis, belonging to the subclass Dorylaimia, utilizes a distinct set of SL RNAs that display considerable sequence diversity. To investigate whether this is true of other members of the Dorylaimia, we have characterized SL RNAs from Prionchulus punctatus. Surprisingly, this revealed the presence of a set of SLs that show clear sequence similarity to the SL2 family of spliced leaders, which have previously only been found within the rhabditine group (which includes C. elegans). Expression of one of the P. punctatus SL RNAs in C. elegans reveals that it can compete specifically with the endogenous C. elegans SL2 spliced leaders, being spliced to the pre-mRNAs derived from downstream genes in operons, but does not compete with the SL1 spliced leaders. This discovery raises the possibility that SL2-like spliced leaders were present in the last common ancestor of the nematode phylum.
A structural database for k-turn motifs in RNA
Authors: Schroeder Kersten T. , McPhee Scott A. , Ouellet Jonathan , Lilley David M.J.
Published: June 2010

The kink-turn (k-turn) is a common structural motif in RNA that introduces a tight kink into the helical axis. k-turns play an important architectural role in RNA structures and serve as binding sites for a number of proteins. We have created a database of known and postulated k-turn sequences and three-dimensional (3D) structures, available via the internet. This site provides (1) a database of sequence and structure, as a resource for the RNA community, and (2) a tool to enable the manipulation and comparison of 3D structures where known.
The Ballot Box and Beyond: The (Im)Possibilities of White Antiracist Organizing
Authors: Middlebrook Jeb Aram
Published: June 2010

This article considers the role of white people in multiracial social justice movements through an examination of a community event by white antiracists in Los Angeles in 2008 called The Ballot Box and Beyond: Race, Elections, and the Making of History. The event is examined in relation to the question of the white voter in the 2008 presidential election, the rise of diversity workshops and the academic study of whiteness, and the resurgence of white supremacist and radical right-wing organizing. The article places the event within a long, but relatively unknown, history of white people organizing other white people against racism in the United States as part of a larger, multiracial movement to challenge the white supremacist system, and argues for a nuanced understanding of the ways white supremacy and antiracism operate to bring otherwise disparate racial histories and groups into conversation and alliance.
"You trade in a man for the man": Domestic Violence and the U.S. Welfare State
Authors: Kandaswamy Priya
Published: June 2010

The Family Violence Option, an amendment that sought to mitigate the effects that "welfare reform" would have on victims of domestic violence, embodied the quintessential arguments for feminist reform. Accepting the larger transformations within the welfare system as inevitable, mainstream feminist activists chose to link their political claims to both a law and order agenda that emphasized criminalizing individual acts of violence rather than addressing structural violence and to neoliberal forms of governance that emphasized individual rehabilitation and labor discipline as the solutions to economic inequality. In analyzing the political struggle over the Family Violence Option during the mid-1990s, this essay demonstrates the many pitfalls of looking to the state to protect women from violence in a context in which the state is itself a major perpetrator of gendered violence and advocates instead for the necessity of feminist social movements that challenge rather than accommodate state violence.
All in the Family?: Asian American Designers and the Boundaries of Creative Labor
Authors: Tu Thuy Linh Nguyen
Published: June 2010

This article examines the ways Asian American designers imagine their relationship to Asian garment workers and considers the discursive and performative acts that have enabled them to transform obligatory encounters within the marketplace into voluntary relationships that exceed the realm of economic exchange. These include most prominently a performance of kinship that rewrites Asian sewers and contractors into "uncles" and "aunties" who "help out" Asian American designers because they are "their girls." I argue that these exchanges constitute a form of gift-giving that created social bonds and obligations whose functions, while utilitarian, were never purely rational or solely economic. I demonstrate how the performance of the family generated a sense of familiarity and intimacy—between differently located workers and between their different forms of labor—that allowed these constituencies to activate "ethnicity" and "community" across a range of differences.
Locating the Mississippi: Landscape, Nature, and National Territoriality at the Mississippi Headwaters
Authors: Heyman Rich
Published: June 2010

This study of the scientific production of nature at the Mississippi headwaters at Lake Itasca, Minnesota shows how national imaginings of geography were territorialized in the landscape and made available to an imagined national community. The exploration of the Mississippi, the establishment of its source, and the creation and maintenance of the headwaters landscape are all part of the geographic project of making the territory of the nation appear as a collection of timeless natural objects, a cultural process that accompanied the violent appropriation of indigenous land through which national territory was acquired. Because of the symbolic importance of the Mississippi River, its social construction as a "natural" object played a key role in constituting national territory, an imperialist project that simultaneously depended on and helped erase indigenous conceptions of and claims on the land. The landscape at Itasca State Park sustains this process and keeps it alive today.
Art History in the Temple
Authors: Platt Verity
Published: June 2010

This paper tackles a prime site of contestation in the struggle to understand Greco-Roman notions of "art"—that of religion. The adoption of connoisseurial practices such as collecting and art-history writing in the Hellenistic period has often been yoked to a narrative of increasing secularization. Yet a broad range of sculpture, ekphrastic poetry and epigraphy demonstrates that art-historical erudition and the scholarly apparatus of catalog and citation are often employed in religious contexts, too. Here they are not simply grafted onto earlier cultic activity, but testify to an active negotiation of the relationship between the sacred and the scholarly, the ritual and the aesthetic, that modern scholars risk oversimplifying in their urge to identify intellectual and museological trends ancestral to our own institutional practices.
Introduction. Notes on a Margin: British Women Writers and Acts of Annotation
Authors: Shapira Yael , Yaggi Miranda M.
Published: June 2010

The special issue of Partial Answers devoted to British women writers is organized around the theme of marginalia, a concept that shifts attention away from the commonplace critical understanding of "margin" as merely an indicator of status and toward the intellectual work that occurs within it. The relation of "margin" to "center" articulates the position that women authors have historically occupied vis-à-vis a male tradition of literary creation; however, the margin is also a space of possibility that invites women authors to enter into an intellectual exchange with this tradition and to generate their own responses to it. The introduction surveys the essays collected in the issue as reflecting in different ways on the complex literary and discursive effects of women's liminal locations.
Dorothy Sayers and the Case of the Shell-Shocked Detective
Authors: Freedman Ariela
Published: June 2010

Through readings of contemporary medical accounts of shell shock alongside Dorothy L. Sayers' (1893-1957) popular detective novels, this essay argues that through the character of Peter Wimsey, a veteran of the World War I and a survivor of shell shock, Sayers not only participates in the creation of a new kind of male literary protagonist, distinguished by his vulnerability rather than virility, but also intervenes in a contemporary debate about the place of a shell-shocked soldier in post-war society. While the medical literature aligned the doctor, detective, and policeman against the soldier, shell shock victim, and criminal, Sayers exposes and revises the implied alignment of shell shock and criminality, using shell shock as the pre-condition for the creation of an empathic, flawed, and profoundly modern detective in a traumatized and diminished post-war England.
"Speaking on the Edge of My Tomb": The Epistolary Life and Death of Catherine Talbot
Authors: Rasmussen Celia Barnes
Published: June 2010

Bluestocking Catherine Talbot is now perhaps best known as the closest and most "angelic" friend of the learned Mrs. Elizabeth Carter, poet, translator, and prolific letter-writer. But Talbot's literary afterlife as a relatively marginal figure in Carter's illustrious career is hardly accidental. Hers are the only letters placed alongside Carter's in the volumes published by Montagu Pennington after Carter's death, and yet she is introduced to us (and remains throughout) Carter's "deceased friend." The letters chart her painful decline and then repeatedly eulogize her after death, keeping her memory alive. Though the letters are obsessed with Catherine Talbot, living and dead, Talbot's is always a voice from the past, from memory, from the margins, and that voice serves an important function: it becomes a way for Carter to represent the unrepresentable, death.
Rebecca West and the Meaning of Exile
Authors: Schweizer Bernard
Published: June 2010

Rebecca West was a protean artist (author of, among other works, Black Lamb and Grey Falcon [1941]), a leading public intellectual, and a visionary commentator on the twentieth century. This paper shows the connection between her major philosophical, spiritual, and political ideas and her attitude towards exile. Following a brief historical overview of the main kinds of responses to the state of exile, from Ovid's laments to modernist celebrations, I document Rebecca West's fear of exile, so powerful that it could override even her dominant philosophy of process, her revisionist thinking, and her love of metaphor. Twentieth-century artists and thinkers tended to associated the state of exile with heightened artistic creativity, linking it with epistemological "privilege" (Simmel), or seeing it as instrumental to self-invention (Olsson). For West these ideas were not acceptable. Her patriotism, determinism, existentialism, and essentialism combined with her encounters with refugees during the 1940s and the 1950s to bring about a powerful conviction regarding the misery of exile, one that challenged other parts of her own belief system.
Charlotte Smith's Exilic Persona
Authors: Hart Monica Smith
Published: June 2010

The essay argues that typical readings of Smith as a poet writing in a traditional Romantic mode, creating lyrics that depict a melancholic individual subject drawing inspiration and education from the natural world, risk marginalizing her. Recognizing exile as both biographical reality and literary trope is central to an understanding of Smith's verse, for she also wrote poetry with a significant political agenda, one that distinguishes her from her early Romantic contemporaries and challenges the parameters of English Romantic nationalist discourse.
"Making the Prude" in Charlotte Brontë's Villette
Authors: Kent Julia D.
Published: June 2010

This essay explores one version of a recurring pattern in the Victorian novel, the tendency to compare English and French models of national character. While many novelists, including Charlotte Brontë, portray French women as possessing an immoral theatricality, and deploying deceptive "public" personae that contrast with the Englishwoman's devotion to her national and domestic homes, Brontë's Villette endows French theater with the power to question British national gender ideals.
The Four Minute Men and Early Twentieth-Century Public Speaking Pedagogy
Authors: Sproule J. Michael
Published: June 2010

In the forum section of Volume 12:4 (Winter 2009) of Rhetoric & Public Affairs, Professor Lisa Mastrangelo wrote about "World War I, Public Intellectuals, and the Four Minute Men: Convergent Ideals of Public Speaking and Civic Participation." Responding to her essay are four well-known scholars of rhetorical education—J. Michael Sproule, William Keith, Kari Whittenberger-Keith, and Robert Danisch .
Educational Consortia in a Knowledge Economy: Collaboration, Competition, and Organizational Equilibrium
Authors: Flora Bethany H. , Hirt Joan B.
Published: June 2010

In today’s knowledge economy, collaboration and competition are critical in success. New postsecondary organizations have emerged in the higher education landscape, including consortiums and inter-institutional and interdisciplinary partnerships. One new organization is the Higher Education Center (HEC) in which multiple institutions partner to share resources while delivering separate academic programs. In many ways, the HEC can inform our knowledge of higher education as a whole since the HEC is comprised of public and private institutions that must compete and collaborate to ensure organizational survival. In this case study, the authors explored one such center’s internal dynamics.
Toward a Spiritual Praxis: The Role of Spirituality among Faculty of Color Teaching for Social Justice
Authors: Shahjahan Riyad Ahmed
Published: June 2010

There is scant research literature on the interconnection between spirituality and the practices of faculty of color teaching social justice in the higher education classroom. This paper is based on a qualitative study that examined 15 spiritually minded activist scholars (who are all racially minoritized) in Canadian universities. The analysis focuses on how such scholars integrate spirituality into their teaching practices. This paper presents three themes: (a) responding to students in the classroom, (b) centering spirituality in the curriculum, and (c) the perils of incorporating a spiritually based pedagogy.
Disequilibrium and Resolution: The Nonlinear Effects of Diversity Courses on Well-Being and Orientations toward Diversity
Authors: Bowman Nicholas A.
Published: June 2010

Recent literature suggests that participating in college diversity courses contributes to numerous positive outcomes. However, dealing with diversity issues is a difficult and novel experience for many students; therefore, some of the benefits of diversity coursework may accrue only after taking multiple courses. In a large multi-institutional sample, students who take one diversity course generally do not show greater gains in well-being and orientations toward diversity than those who take no courses. However, students who take two or more courses experience substantial benefits. Moreover, these effects vary somewhat by race, family income, and gender. Implications for practice are discussed.
Anthropomorphism in Sign Languages: A Look at Poetry and Storytelling with a Focus on British Sign Language
Authors: Sutton-Spence Rachel , Napoli Donna Jo
Published: June 2010

The work presented here considers some linguistic methods used in sign anthropomorphism. We find a cline of signed anthropomorphism that depends on a number of factors, including the skills and intention of the signer, the animacy of the entities represented, the form of their bodies, and the form of vocabulary signs referring to those entities. We consider four main factors that allow signers to anthropomorphize the whole range of entities (from animate to inanimate): the linguistic base that allows such play, the ability of the nonmanuals to anthropomorphize even when the manual articulators are signing in an ordinary way, the range of possibilities for both manual and nonmanual articulators when the signer engages in (almost) complete embodiment of the nonhuman character, and how nonhumans are portrayed as communicating via sign language.
Schoolization: An Account of the Origins of Regional Variation in British Sign Language
Authors: Quinn Gary
Published: June 2010

British Sign Language has a number of regional variations. This article examines the role of residential schools in the development of sign variants. Citing data collected during interviews with members of the Lancaster and Morecambe Deaf community (who of necessity attended schools elsewhere), it explores the peer-to-peer transmission of sign forms in schools and the influence of these forms in the communities to which the pupils returned on leaving school (coining the term schoolization for this phenomenon). It discusses the effect the closure of such residential schools will have on the acquisition and transmission of BSL.
Analytical Performance of 4 Automated Assays for Measurement of Cystatin C
Authors: Li Jinong , Dunn Willard , Breaud Autumn , Elliott Debra , Sokoll Lori J , Clarke William
Published: June 2010

BACKGROUND

We evaluated the analytical performance of 4 cystatin C assays (Siemens N Latex on BNII, Roche Tina-quant on Cobas c501, Genzyme on Cobas c501, and Tosoh ST AIA-PACK on Tosoh AIA-600II) according to guidelines published by the Clinical and Laboratory Standards Institute.

METHODS

We evaluated total imprecision, limit of detection, and limit of quantification for each assay using patient serum pools and linearity/recovery using serial dilutions of a patient serum pool with cystatin C–free serum. We compared patients (n = 102) using the Siemens assay as a comparison method.

RESULTS

All assays had limits of detection and quantification <0.08 and <0.39 mg/L, respectively. Total CVs were generally higher than the manufacturers' claims for all assays. The Roche assay overrecovered cystatin C, particularly at low concentrations (mean recovery 119%, 142% at 0.587 mg/L). Deming regression equations were y = 1.184x + 0.089, Sy|x = 0.246 for Genzyme; y = 0.937x + 0.231, Sy|x = 0.231 for Roche; and y = 1.010x + 0.216, Sy|x = 0.115 for Tosoh. The Genzyme assay appeared to report higher results than the Siemens assay, which is consistent with a higher reference interval specified by the manufacturer.

CONCLUSIONS

Although all assays were acceptable for clinical use, their diagnostic performances were not optimal. Limitations include imprecision greater than claimed, overrecovery for the Roche assay on low concentration samples, and differences in results for patient samples. The latter situation requires assay-specific cystatin C–based glomerular filtration rate prediction equations at least until calibration is standardized using the international cystatin C calibrator now being developed.
Evaluation of Oligonucleotide Sequence Capture Arrays and Comparison of Next-Generation Sequencing Platforms for Use in Molecular Diagnostics
Authors: Hoppman-Chaney Nicole , Peterson Lisa M , Klee Eric W , Middha Sumit , Courteau Laura K , Ferber Matthew J
Published: June 2010

BACKGROUND

Next-generation DNA sequencing (NGS) techniques have the potential to revolutionize molecular diagnostics; however, a thorough evaluation of these technologies is necessary to ensure their performance meets or exceeds that of current clinical sequencing methods.

METHODS

We evaluated the NimbleGen Sequence Capture 385K Human Custom Arrays for enrichment of 22 genes. We sequenced each sample on both the Roche 454 Genome Sequencer FLX (GS-FLX) and the Illumina Genome Analyzer II (GAII) to compare platform performance.

RESULTS

Although the sequence capture method allowed us to rapidly develop a large number of sequencing assays, we encountered difficulty enriching G+C–rich regions. Although a high proportion of reads consistently mapped outside of the targeted regions, >80% of targeted bases for the GAII and >30% of bases for the GS-FLX were covered by a read depth of ≥20, and >90% of bases for the GAII and >80% of bases for the GS-FLX were covered by a read depth of ≥5. We observed discrepancies among sequence variants identified by the different platforms.

CONCLUSIONS

Although oligonucleotide arrays are quick and easy to develop, some problematic regions may evade capture, necessitating sequential redesigning for complete optimization. Neither sequencing technology was able to detect every variant identified by Sanger sequencing because of well-known drawbacks of the NGS technologies. The rapidly decreasing error rates and costs of these technologies, however, coupled with advancing bioinformatic capabilities, make them an attractive option for molecular diagnostics in the very near future.