bluuebunny/crossref_metadata_2025 huggingface dataset:
Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag
Authors: Woods Matthew W , Kelly Jenna N , Hattlmann Clayton J , Tong Jessica GK , Xu Li S , Coleman Macon D , Quest Graeme R , Smiley James R , Barr Stephen D
Published: December 2011

Background

The identification and characterization of several interferon (IFN)-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5) that blocks a unique late stage of the HIV-1 life cycle.

Results

HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV) Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus.

Conclusions

HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.
Immunopathogenesis of primary biliary cirrhosis: an old wives' tale
Authors: Smyk Daniel S , Rigopoulou Eirini I , Lleo Ana , Abeles Robin D , Mavropoulos Athanasios , Billinis Charalambos , Invernizzi Pietro , Bogdanos Dimitrios P
Published: December 2011

Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the autoimmune destruction of the small intrahepatic bile ducts. The disease has an unpredictable clinical course, but may progress to fibrosis and cirrhosis. Although medical treatment with urseodeoxycholic acid is largely successful, some patients may progress to liver failure requiring liver transplantation. PBC is characterised by the presence of disease specific anti-mitochondrial (AMA) antibodies, which are pathognomonic for PBC development. The disease demonstrates an overwhelming female preponderance and virtually all women with PBC present in middle age. The reasons for this are unknown; however several environmental and immunological factors may be involved. As the immune systems ages, it become less self tolerant, and mounts a weaker response to pathogens, possibly leading to cross reactivity or molecular mimicry. Some individuals display immunological changes which encourage the development of autoimmune disease. Risk factors implicated in PBC include recurrent urinary tract infection in females, as well as an increased prevalence of reproductive complications. These risk factors may work in concert with and possibly even accelerate, immune system ageing, contributing to PBC development. This review will examine the changes that occur in the immune system with ageing, paying particular attention to those changes which contribute to the development of autoimmune disease with increasing age. The review also discusses risk factors which may account for the increased female predominance of PBC, such as recurrent UTI and oestrogens.
The objective assessment of cough frequency: accuracy of the LR102 device
Authors: Leconte Sophie , Liistro Giuseppe , Lebecque Patrick , Degryse Jean-Marie
Published: December 2011

Background

The measurement of cough frequency is problematic and most often based on subjective assessment. The aim of the study was to assess the accuracy of the automatic identification of cough episodes by LR102, a cough frequency meter based on electromyography and audio sensors.

Methods

Ten adult patients complaining of cough were recruited in primary care and hospital settings. Participants were asked to wear LR102 for 4 consecutive hours during which they were also filmed.

Results

Measures of cough frequency by LR102 and manual counting were closely correlated (r = 0.87 for number of cough episodes per hour; r = 0.89 for number of single coughs per hour) but LR102 overestimated cough frequency. Bland-Altman plots indicate that differences between the two measurements were not influenced by cough frequency.

Conclusions

LR102 offers a useful estimate of cough frequency in adults in their own environment, while significantly reducing the time required for analysis.
The contribution of traditional healers' clinics to public health care system in Addis Ababa, Ethiopia: a cross-sectional study
Authors: Birhan Wubet , Giday Mirutse , Teklehaymanot Tilahun
Published: December 2011

Background

Ethiopian people have been using traditional medicine since time immemorial with 80% of its population dependent on traditional medicines. However, the documentation of traditional healers' clinics contribution to modern public health system in cosmopolitan cities is scanty. Studies conducted so far are limited and focused on the perceptions and practices of modern and traditional health practitioners about traditional medicine. Thus, a cross sectional study was conducted from February to May 2010 to assess the contribution of traditional healers' clinics to public health care system in Addis Ababa.

Materials and methods

Ten traditional healers who were willing to participate in the study and 306 patients who were visiting these traditional healers' clinics were interviewed using two types of semi-structured questionnaires. Data were summarized using percentages, tables and bar chart.

Results

The diseases mostly treated by traditional healers were wound, inflammation, herpes zoster, hemorrhoids, fracture, paralysis, back-pain, liver diseases, cancer and eczema. This study showed that traditional healers' clinics considerably contribute to public health care in Addis Ababa. Fifty two percent of patients reported that traditional healers' clinics were their first choice when they faced health problems. The reasons for visiting these clinics were 175 (57.2%) efficacy, 109 (35.6%) dissatisfaction with modern medicine, 10 (3.3%) dissatisfaction with modern medicine and efficacy, 6 (2.0%) cost and 6 (2.0%) dissatisfaction and cost. Females (55.2%), young age (20-40 years, 65.0%), never married (56.9%), orthodox (73.9%), Amhara (52.3%), educational status above grade 12 (34.6%) and government employees (29.4%) were frequent visitors. Healers reported that there was no form of cooperation with modern health professionals. The reasons were lack of motivation to collaborate and communicate with modern health service workers. Family based apprenticeship was the sources of knowledge for majority of the healers.

Conclusions

The study conducted showed that for the majority of patients interviewed traditional healers' clinics were one of the options to solve their health problems that indicated the considerable contribution of these clinics to the public health care system in Addis Ababa. Nevertheless, in this study the contribution of traditional healers' clinics to the public health system would have been better shown if individuals who are not users of the traditional healers' clinics were included in the interview. However, the study might be useful as a base line data for future evaluation of the significance of traditional healers' clinics for public health system and the services rendered in these clinics.
Protocol: high throughput silica-based purification of RNA from Arabidopsis seedlings in a 96-well format
Authors: Salvo-Chirnside Eliane , Kane Steven , Kerr Lorraine E
Published: December 2011

The increasing popularity of systems-based approaches to plant research has resulted in a demand for high throughput (HTP) methods to be developed. RNA extraction from multiple samples in an experiment is a significant bottleneck in performing systems-level genomic studies. Therefore we have established a high throughput method of RNA extraction from Arabidopsis thaliana to facilitate gene expression studies in this widely used plant model. We present optimised manual and automated protocols for the extraction of total RNA from 9-day-old Arabidopsis seedlings in a 96 well plate format using silica membrane-based methodology. Consistent and reproducible yields of high quality RNA are isolated averaging 8.9 μg total RNA per sample (~20 mg plant tissue). The purified RNA is suitable for subsequent qPCR analysis of the expression of over 500 genes in triplicate from each sample. Using the automated procedure, 192 samples (2 × 96 well plates) can easily be fully processed (samples homogenised, RNA purified and quantified) in less than half a day. Additionally we demonstrate that plant samples can be stored in RNAlater at -20°C (but not 4°C) for 10 months prior to extraction with no significant effect on RNA yield or quality. Additionally, disrupted samples can be stored in the lysis buffer at -20°C for at least 6 months prior to completion of the extraction procedure providing a flexible sampling and storage scheme to facilitate complex time series experiments.
Dynamic proteomic profiling of a unicellular cyanobacterium CyanotheceATCC51142 across light-dark diurnal cycles
Authors: Aryal Uma K , Stöckel Jana , Krovvidi Ravi K , Gritsenko Marina A , Monroe Matthew E , Moore Ronald J , Koppenaal David W , Smith Richard D , Pakrasi Himadri B , Jacobs Jon M
Published: December 2011

Background

Unicellular cyanobacteria of the genus Cyanothece are recognized for their ability to execute nitrogen (N2)-fixation in the dark and photosynthesis in the light. An understanding of these mechanistic processes in an integrated systems context should provide insights into how Cyanothece might be optimized for specialized environments and/or industrial purposes. Systems-wide dynamic proteomic profiling with mass spectrometry (MS) analysis should reveal fundamental insights into the control and regulation of these functions.

Results

To expand upon the current knowledge of protein expression patterns in Cyanothece ATCC51142, we performed quantitative proteomic analysis using partial ("unsaturated") metabolic labeling and high mass accuracy LC-MS analysis. This dynamic proteomic profiling identified 721 actively synthesized proteins with significant temporal changes in expression throughout the light-dark cycles, of which 425 proteins matched with previously characterized cycling transcripts. The remaining 296 proteins contained a cluster of proteins uniquely involved in DNA replication and repair, protein degradation, tRNA synthesis and modification, transport and binding, and regulatory functions. Functional classification of labeled proteins suggested that proteins involved in respiration and glycogen metabolism showed increased expression in the dark cycle together with nitrogenase, suggesting that N2-fixation is mediated by higher respiration and glycogen metabolism. Results indicated that Cyanothece ATCC51142 might utilize alternative pathways for carbon (C) and nitrogen (N) acquisition, particularly, aspartic acid and glutamate as substrates of C and N, respectively. Utilization of phosphoketolase (PHK) pathway for the conversion of xylulose-5P to pyruvate and acetyl-P likely constitutes an alternative strategy to compensate higher ATP and NADPH demand.

Conclusion

This study provides a deeper systems level insight into how Cyanothece ATCC51142 modulates cellular functions to accommodate photosynthesis and N2-fixation within the single cell.
Model-based clustering reveals vitamin D dependent multi-centrality hubs in a network of vitamin-related proteins
Authors: Nguyen Thanh-Phuong , Scotti Marco , Morine Melissa J , Priami Corrado
Published: December 2011

Background

Nutritional systems biology offers the potential for comprehensive predictions that account for all metabolic changes with the intricate biological organization and the multitudinous interactions between the cellular proteins. Protein-protein interaction (PPI) networks can be used for an integrative description of molecular processes. Although widely adopted in nutritional systems biology, these networks typically encompass a single category of functional interaction (i.e., metabolic, regulatory or signaling) or nutrient. Incorporating multiple nutrients and functional interaction categories under an integrated framework represents an informative approach for gaining system level insight on nutrient metabolism.

Results

We constructed a multi-level PPI network starting from the interactions of 200 vitamin-related proteins. Its final size was 1,657 proteins, with 2,700 interactions. To characterize the role of the proteins we computed 6 centrality indices and applied model-based clustering. We detected a subgroup of 22 proteins that were highly central and significantly related to vitamin D. Immune system and cancer-related processes were strongly represented among these proteins. Clustering of the centralities revealed a degree of redundancy among the indices; a repeated analysis using subsets of the centralities performed well in identifying the original set of 22 most central proteins.

Conclusions

Hierarchical and model-based clustering revealed multi-centrality hubs in a vitamin PPI network and redundancies among the centrality indices. Vitamin D-related proteins were strongly represented among network hubs, highlighting the pervasive effects of this nutrient. Our integrated approach to network construction identified promiscuous transcription factors, cytokines and enzymes - primarily related to immune system and cancer processes - representing potential gatekeepers linking vitamin intake to disease.
De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome
Authors: Min Xiao , Na Zhang , Yanan Liu , Chunrui Li
Published: December 2011

Acute megakaryoblastic leukemia (AMKL) is a type of acute myeloid leukemia (AML), in which majority of the blasts are megakaryoblastic. De novo AMKL in adulthood is rare, and carries very poor prognosis. We here report a 45-year-old woman with de novo AMKL with BCR/ABL rearrangement and der(16)t(1;16)(q21;q23) translocation but negative for t(9;22) Ph chromosome. Upon induction chemotherapy consisting of homoharringtonine, cytarabine and daunorubicin, the patient achieved partial hematological remission. The patient was then switched to imatinib plus one cycle of CAG regimen (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor), and achieved complete remission (CR). The disease recurred after 40 days and the patient eventually died of infection. To the best of our knowledge, this is the first report of de novo AMKL with p210 BCR/ABL and der(16)t(1;16)(q21;q23) translocation but not t(9;22) Ph chromosome.
Enhancer-driven chromatin interactions during development promote escape from silencing by a long non-coding RNA
Authors: Korostowski Lisa , Raval Anjali , Breuer Gillian , Engel Nora
Published: December 2011

Background

Gene regulation in eukaryotes is a complex process entailing the establishment of transcriptionally silent chromatin domains interspersed with regions of active transcription. Imprinted domains consist of clusters of genes, some of which exhibit parent-of-origin dependent monoallelic expression, while others are biallelic. The Kcnq1 imprinted domain illustrates the complexities of long-range regulation that coexists with local exceptions. A paternally expressed repressive non-coding RNA, Kcnq1ot1, regulates a domain of up to 750 kb, encompassing 14 genes. We study how the Kcnq1 gene, initially silenced by Kcnq1ot1, undergoes tissue-specific escape from imprinting during development. Specifically, we uncover the role of chromosome conformation during these events.

Results

We show that Kcnq1 transitions from monoallelic to biallelic expression during mid gestation in the developing heart. This transition is not associated with the loss of methylation on the Kcnq1 promoter. However, by exploiting chromosome conformation capture (3C) technology, we find tissue-specific and stage-specific chromatin loops between the Kcnq1 promoter and newly identified DNA regulatory elements. These regulatory elements showed in vitro activity in a luciferase assay and in vivo activity in transgenic embryos.

Conclusions

By exploring the spatial organization of the Kcnq1 locus, our results reveal a novel mechanism by which local activation of genes can override the regional silencing effects of non-coding RNAs.
Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets
Authors: Cohen Ruth , Stammes Marieke A , de Roos Inge HC , Stigter-van Walsum Marijke , Visser Gerard WM , van Dongen Guus AMS
Published: December 2011

Background

Photoimmunodetection, in which monoclonal antibodies [mAbs] are labeled with fluorescent dyes, might have clinical potential for early detection and characterization of cancer. For this purpose, the dye should be coupled in an inert way to mAb. In this study, different equivalents of IRDye800CW, a near-infrared fluorescent dye, were coupled to 89Zr-labeled cetuximab and bevacizumab, and conjugates were evaluated in biodistribution studies. Radiolabeled mAbs were used to allow accurate quantification for assessment of the number of dye groups that can be coupled to mAbs without affecting their biological properties.

Methods

89Zr-cetuximab and 89Zr-bevacizumab, containing 0.5 89Zr-desferal group per mAb molecule, were incubated with 1 to 10 eq IRDye800CW at pH 8.5 for 2 h at 35°C, and 89Zr-mAb-IRDye800CW conjugates were purified by a PD10 column using 0.9% NaCl as eluent. HPLC analysis at 780 nm was used to assess conjugation efficiency. In vitro stability measurements were performed in storage buffer (0.9% NaCl or PBS) at 4°C and 37°C and human serum at 37°C. 89Zr-mAb-IRDye800CW conjugates and 89Zr-mAb conjugates (as reference) were administered to nude mice bearing A431 (cetuximab) or FaDu (bevacizumab) xenografts, and biodistribution was assessed at 24 to 72 h after injection.

Results

Conjugation efficiency of IRDye800CW to 89Zr-mAbs was approximately 50%; on an average, 0.5 to 5 eq IRDye800CW was conjugated. All conjugates showed optimal immunoreactivity and were > 95% stable in storage buffer at 4°C and 37°C and human serum at 37°C for at least 96 h. In biodistribution studies with 89Zr-cetuximab-IRDye800CW, enhanced blood clearance with concomitant decreased tumor uptake and increased liver uptake was observed at 24 to 72 h post-injection when 2 or more eq of dye had been coupled to mAb. No significant alteration of biodistribution was observed 24 to 48 h after injection when 1 eq of dye had been coupled. 89Zr-bevacizumab-IRDye800CW showed a similar tendency, with an impaired biodistribution when 2 eq of dye had been coupled to mAb.

Conclusion

Usage of 89Zr-mAbs allows accurate quantification of the biodistribution of mAbs labeled with different equivalents of IRDye800CW. Alteration of biodistribution was observed when more than 1 eq of IRDye800CW was coupled to mAbs.
Critical illness induces alternative activation of M2 macrophages in adipose tissue
Authors: Langouche Lies , Marques Mirna B , Ingels Catherine , Gunst Jan , Derde Sarah , Vander Perre Sarah , D'Hoore André , Van den Berghe Greet
Published: December 2011

Introduction

We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown.

Methods

We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients.

Results

Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels.

Conclusions

Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2 macrophages, which have local anti-inflammatory and insulin sensitizing features. This M2 macrophage accumulation may contribute to the previously observed protective metabolic activity of adipose tissue during critical illness.
The draft genome of the carcinogenic human liver fluke Clonorchis sinensis
Authors: Wang Xiaoyun , Chen Wenjun , Huang Yan , Sun Jiufeng , Men Jingtao , Liu Hailiang , Luo Fang , Guo Lei , Lv Xiaoli , Deng Chuanhuan , Zhou Chenhui , Fan Yongxiu , Li Xuerong , Huang Lisi , Hu Yue , Liang Chi , Hu Xuchu , Xu Jin , Yu Xinbing
Published: December 2011

Background

Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome.

Results

We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines.

Conclusions

This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control.
Suppressed Prostate Epithelial Development with Impaired Branching Morphogenesis in Mice Lacking Stromal Fibromuscular Androgen Receptor
Authors: Lai Kuo-Pao , Yamashita Shinichi , Vitkus Spencer , Shyr Chih-Rong , Yeh Shuyuan , Chang Chawnshang
Published: December 2011

Using the cre-loxP system, we generated a new mouse model [double stromal androgen receptor knockout (dARKO)] with selectively deleted androgen receptor (AR) in both stromal fibroblasts and smooth muscle cells, and found the size of the anterior prostate (AP) lobes was significantly reduced as compared with those from wild-type littermate controls. The reduction in prostate size of the dARKO mouse was accompanied by impaired branching morphogenesis and partial loss of the infolding glandular structure. Further dissection found decreased proliferation and increased apoptosis of the prostate epithelium in the dARKO mouse AP. These phenotype changes were further confirmed with newly established immortalized prostate stromal cells (PrSC) from wild-type and dARKO mice. Mechanistically, IGF-1, placental growth factor, and secreted phosphoprotein-1 controlled by stromal AR were differentially expressed in PrSC-wt and PrSC-ARKO. Moreover, the conditioned media (CM) from PrSC-wt promoted prostate epithelium growth significantly as compared with CM from PrSC-dARKO. Finally, adding IGF-1/placental growth factor recombinant proteins into PrSC-dARKO CM was able to partially rescue epithelium growth. Together, our data concluded that stromal fibromuscular AR could modulate epithelium growth and maintain cellular homeostasis through identified growth factors.
The Expression and Role of Hyperpolarization-Activated and Cyclic Nucleotide-Gated Channels in Endocrine Anterior Pituitary Cells
Authors: Kretschmannova Karla , Kucka Marek , Gonzalez-Iglesias Arturo E. , Stojilkovic Stanko S.
Published: December 2011

Pituitary cells fire action potentials independently of external stimuli, and such spontaneous electrical activity is modulated by a large variety of hypothalamic and intrapituitary agonists. Here, we focused on the potential role of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in electrical activity of cultured rat anterior pituitary cells. Quantitative RT-PCR analysis showed higher level of expression of mRNA transcripts for HCN2 and HCN3 subunits and lower expression of HCN1 and HCN4 subunits in these cells. Western immunoblot analysis of lysates from normal and GH3 immortalized pituitary cells showed bands with appropriate molecular weights for HCN2, HCN3, and HCN4. Electrophysiological experiments showed the presence of a slowly developing hyperpolarization-activated inward current, which was blocked by Cs+ and ZD7288, in gonadotrophs, thyrotrophs, somatotrophs, and a fraction of lactotrophs, as well as in other unidentified pituitary cell types. Stimulation of adenylyl cyclase and addition of 8-Br-cAMP enhanced this current and depolarized the cell membrane, whereas 8-Br-cGMP did not alter the current and hyperpolarized the cell membrane. Both inhibition of basal adenylyl cyclase activity and stimulation of phospholipase C signaling pathway inhibited this current. Inhibition of HCN channels affected the frequency of firing but did not abolish spontaneous electrical activity. These experiments indicate that cAMP and cGMP have opposite effects on the excitability of endocrine pituitary cells, that basal cAMP production in cultured cells is sufficient to integrate the majority of HCN channels in electrical activity, and that depletion of phosphatidylinositol 4,5-bisphosphate caused by activation of phospholipase C silences them.
Coming to Terms
Authors: Lecklider Aaron
Published: December 2011

This review essay places several recent works on homosexuality and the Left within a broader history of scholarly engagement with queer radicalism. Books by Daniel Hurewitz, Terence Kissack, Gary Holcomb, and Kevin Floyd together represent a grappling with defining queer leftist studies. Their works build on the contributions of several generations of scholarship and envision avenues for mapping future studies of radical queer communities, culture, and politics in the United States.
ABT-737 synergizes with Bortezomib to kill melanoma cells
Authors: Reuland Steven N. , Goldstein Nathaniel B. , Partyka Katie A. , Smith Shilo , Luo Yuchun , Fujita Mayumi , Gonzalez Rene , Lewis Karl , Norris David A. , Shellman Yiqun G.
Published: December 2011

The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-XL, and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib) in vitro and in vivo, and further evaluated the mechanisms of action. Results showed that ABT-737 alone induced modest cytotoxicity in melanoma cells, but only at higher doses. Knock-down of the anti-apoptotic proteins Bcl-2, Bcl-XL, or Mcl-1 with siRNAs demonstrated that Mcl-1 is the critical mediator of melanoma's resistance to ABT-737 treatment. However, ABT-737 displayed strong synergistic lethality when combined with Bortezomib. Immunoblot analyses demonstrated that Bortezomib increased expression of Noxa, a pro-apoptotic Bcl-2 member that antagonizes Mcl-1. Additionally, siRNA-mediated inhibition of Noxa expression protected melanoma cells from cytotoxicity induced by the combination treatment. These results demonstrate that Bortezomib synergizes with ABT-737 by neutralizing Mcl-1's function via increased levels of Noxa. In a xenograft mouse model, although drug doses were limited due to toxicity, ABT-737 or Bortezomib slowed melanoma tumor growth compared to the control, and the drug combination significantly decreased growth compared to either drug alone. These data imply that less toxic drugs fulfilling a function similar to Bortezomib to neutralize Mcl-1 are promising candidates for combination with ABT-737 for treating melanomas.
Digital tomosynthesis for aortic arch calcification evaluation: performance comparison with chest radiography with CT as the reference standard
Authors: Kim Eun Young , Chung Myung Jin , Choe Yeon Hyeon , Lee Kyung Soo
Published: December 2011

Background

Recently developed digital tomosynthesis has shown improved detection of pulmonary lesions with a radiation dose comparable to conventional CR but with a much lower radiation dose than CT.

Purpose

To compare the diagnostic performance of digital tomosynthesis (DT) with that of chest radiography (CR) for the detection of aortic arch calcification (AAC).

Material and Methods

The study included 100 patients who underwent multidetector computed tomography (MDCT), DT, and CR (DT and CR were obtained within one week of CT examination). We evaluated and compared the diagnostic performances of DT and CR for the detection of AAC with MDCT as the reference standard. The extent (four grades 0–3) of AAC on DT and CR was also compared with CT calcium score. Inter-observer agreement was analyzed by using kappa statistics.

Results

On DT, overall accuracy for AAC was superior to that of CR (94% and 71%, respectively, P < 0.01). Inter-observer agreement was good with DT and CR (kappa values = 0.74 and 0.62, respectively) for the presence of AAC, and good with DT and moderate with CR (kappa value = 0.64 and 0.53, respectively) for AAC grading. The overall correlation coefficient on AAC grading between DT and CT (calcium score) was superior to that between CR and CT (0.90 and 0.60, respectively).

Conclusion

DT is superior to CR for detection and extent evaluation of AAC.
Atypical pleural tuberculosis presenting as an isolated pleural tuberculoma
Authors: Hwang Sook Min , Rho Ji Young , Yoo Seung Min , Jung Hae Kyoung , Cho Sang Ho
Published: December 2011

Pleural tuberculosis is the most common extrapulmonary manifestation of tuberculosis, and is generally characterized by an effusion. The effusion is usually unilateral and residual pleural thickening or calcification is also observed in some cases. Manifestations of multiple pleural tuberculomas without associated effusion and history of tuberculosis or antituberculous therapy are rare and an isolated pleural tuberculoma is exceedingly rare. Herein, we report the first documented case of an isolated pleural tuberculoma, diagnosed by chest CT and pathological findings. Although rare, an isolated pleural tuberculoma should be added to the differential diagnosis of focal nodular pleural tumors, particularly in areas of high tuberculosis prevalence.
Dorsal agenesis of the pancreas – a rare cause of abdominal pain and insulin-dependent diabetes
Authors: Lång Kristina , Lasson Åke , Müller Markus F , Thorlacius Henrik , Toth Ervin , Olsson Rolf
Published: December 2011

Dorsal agenesis of the pancreas is a rare congenital disorder. We report a case of a 65-year-old man with mild abdominal pain and insulin-dependent diabetes mellitus. Computed tomography (CT) of the abdomen showed a short pancreas with no pancreatic tissue ventral to the splenic vein. Magnetic resonance cholangiopancreatography (MRCP) visualized the absence of a dorsal duct system and confirmed the suspicion of complete agenesis of the dorsal pancreas. Endoscopic ultrasound (EUS) was also performed to rule out pancreatic malignancy.
The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography
Authors: Zhang Yan , Tang Jie , Li Yan-mi , Fei Xiang , He En-hui , Li Qiu-yang , Shi Huai-yin
Published: December 2011

Background

Elasticity is an important characteristic of tissue. During an elastography examination, various strain images of lesions are observed, and a suitable classification of strain patterns (SP) may provide vital diagnostic information about lesions. Numerous studies have shown that ultrasound elastography can improve the detection of prostate cancer, but the diagnostic value of SP classification has not yet been fully evaluated.

Purpose

To investigate the contribution of SP on the characterization of prostate peripheral zone lesions by transrectal real-time tissue elastography (TRTE) in combination with conventional transrectal ultrasonography (TRUS).

Material and Methods

One hundred and seventy-one patients with suspected prostate cancer underwent TRUS and TRTE examinations. The SPs of the suspicious lesions were classified into five scores by TRTE according to the degree and distribution of strain. All findings were confirmed by transrectal systematic 12-core biopsies and targeted biopsies for suspicious areas detecting by TRUS and/or TRTE.

Results

One hundred and forty-eight of 171 patients had high-quality TRTE imaging and were included into the study. When a cut-off point of SP score III was used, the area under the receiver-operating characteristic curve (AUC) was, respectively, 0.75 (95% CI: 0.67–0.83), 0.85 (95% CI: 0.78–0.91) and 0.84 (95% CI: 0.77–0.91) for the diagnosis of prostate cancer by TRUS, TRTE and TRTE + TRUS. A linear tendency of SP and Gleason scores was observed in scores III-V. The detection rate of prostate cancer using TRTE-targeted biopsy (75.8%) was significantly higher than that of systematic 12-core biopsy plus TRUS-targeted biopsy (14.5%) ( P = 0.00).

Conclusion

This study suggests the significant contribution of SP on characterization of prostate peripheral zone lesions and the improvement of TRTE-targeted biopsy on detection of prostate cancer.
Early return to work and improved range of motion with modified relative motion splinting: a retrospective comparison with immobilization splinting for zones V and VI extensor tendon repairs
Authors: Hirth Melissa J , Bennett Kate , Mah Eldon , Farrow Hamish C , Cavallo Andrew V , Ritz Morris , Findlay Michael W
Published: December 2011

Introduction

There is a lack of evidence on the best method for rehabilitating extensor tendon injuries in zones V and VI. The purpose of this study was to evaluate the outcomes of modified relative motion splinting compared with immobilization following repair of extensor tendons in zones V and VI.

Methods

A retrospective analysis compared the outcomes of relative motion splinting with immobilization. Sixteen patients (16 fingers) were treated by conventional immobilization splinting for four weeks (immobilization group) followed by mobilization with avoidance of ‘at-risk/heavy’ activities for a further 4–6 weeks. Twenty-three patients (23 fingers) were treated with the modified relative motion splint (mRMS group) during the day and a resting splint worn overnight for the first four weeks. The relative motion splint was continued for ‘at-risk/heavy’ activities for a further 4–6 weeks.

Results

The mRMS group demonstrated statistically significant improvement in range of motion compared with the immobilization group. This effect was most marked at six weeks ( P = 0.0194, two-way mixed ANOVA) with the mRMS group achieving a 12% higher mean percentage total active motion ( P = 0.0076, Mann-Whitney U test). Results were similar for both groups 12 weeks postoperatively. Differences in return to work times between groups were statistically significant ( P = 0.0062, Mann-Whitney U test). Average return to work was 9.4 weeks for the immobilization group and 3.3 weeks for the mRMS group, equating to a 42 days earlier return to work for the mRMS group. There was no incidence of tendon rupture in either group.

Conclusion

This study demonstrates that modified relative motion splintage (finger based without wrist component) can be applied in the postoperative management of single zone V or VI extensor tendon repairs. The main advantages of this protocol, compared with immobilization include the small simple splint design, and straightforward patient instructions that enable earlier mobilization, functional hand use and return to both daily living and work.
Paleoenvironment of Lower Silurian Black Shale and its Significance to the Potential of Shale Gas, Southeast of Chongqing, China
Authors: Guo Ling , Jiang Zaixing , Zhang Jinchuan , Li Yuxi
Published: December 2011

Black shale is studied because of its economic value, paleoclimatic and paleogeographic significance. Due intensive development southeast of Chongqing, Longmaxi black shale, characterized by thickness in excess of 100 m, is becoming a location of concentrated research interest for shale gas exploration in China. The paleoenvironment, mineral composition, elements and reservoir characteristics of black shale of the Lower Silurian Longmaxi formation southeast of Chongqing were obtained by cores, outcrops, slices analysis, X-ray diffraction and X-ray fluorescence spectrum. The results show that Longmaxi black shale, including turbidite and suspended sediment, is deposited primarily in deep water. The sum of SiO2, Al2O3 and Fe2O3 content ranges from 73.82% to 90.54% by weight; quartz, feldspar and clay minerals are the dominant minerals in the rocks, ranging from 56% to 100%. Trace element contents of Mo (7.71 μg/g) and U (5.97 μg/g) are higher than that of earth crust and mudstone, the indexes of the anoxic reducing environment in the Longmaxi stage in the study area. The relative sea level of the Lower Silurian Longmaxi period, which correlates to total organic carbon content, experienced two rise-and-fall cycles; meanwhile, the reducibility of the ancient sea waters experienced a similar period of rise-and-fall cycles. Total organic carbon content is quite higher near the maximum flooding surface in study area. After mineral analysis, the reservoir property was found to be similar to the Ohio shale that provided the first commercial gas production in the United States, thereby inspiring and instructing shale gas exploration and exploitation southeast of Chongqing.
Active Acoustic Systems for the Control of Room Acoustics
Authors: Poletti M. A.
Published: December 2011

The acoustic design of auditoria involves the specification of the room geometry and boundary properties, and any additional acoustic elements such as reflectors or diffusers, to usefully direct sound to produce a desired subjective experience, quantified by measurable acoustic parameters. This design must take into account the reflection of sound within the stage area, the early reflections from the stage to the audience and the reverberant response of the room. The sound produced by the audience can also be an important consideration. Active acoustic systems provide an alternative approach to controlling subjective experience. They use microphones, electronic processors and loudspeakers to create reflections and reverberation in addition to those produced by the naturally-occurring sound field. The acoustic properties can be changed instantly, and the enhanced acoustic properties of the auditorium can typically be varied over a wider range than can be produced by variable passive techniques. The design of active acoustics follows that of passive approaches, but rather than the physical arrangement of the room surfaces, it commences with an existing passive space with some minimum acoustic condition, and requires the arrangement of microphones to detect relevant sound and the choice of processors and loudspeaker positions to direct it usefully back into the room to produce a desired set of acoustic parameters. While active systems have historically been developed with the goal of enhancing either the stage or audience sound, they must generally provide the same control of sound as passive acoustic design. This paper discusses the principles of active acoustic systems and how they are used to achieve the required range of control. A survey of current commercial systems is given and some implications for the future of live performance are explored.
Improvement of the Acoustics under the Balcony in Auditoria Using the Electro-Acoustic Method—A Study with a Full-Scale Model
Authors: Watanabe Takayuki , Ikeda Masahiro
Published: December 2011

In auditoria, the acoustical properties of audience areas located under balconies are regarded as inferior to the main area. This is caused by the reduction of direct and reflected sound energy due to the smaller open area and the reduction of diffusive energy due to the limited acoustical space. In this paper, a new electro-acoustic system is proposed to compensate for this acoustical condition. The proposed system is a non-regenerative system and consists of directional microphones, head amps, a convolver, a matrix processor, amplifiers, and ceiling loudspeakers located under the balcony. The loudspeakers, located at positions corresponding to measurement points across the balcony, recreate the reflecting sound from above the balcony area, which otherwise fail to reach to the listeners under the balcony. The authors have examined the proposed system's performance via two methods: acoustical measurement using a full-scale model and a corresponding psycho-acoustical experiment. The results showed that the energy of the reflections from above the system was the same or more than that without the balcony, and the decay curve with the system was almost the same as that without the balcony. The MUSHRA method was used in the psycho-acoustical experiment, which focused on the evaluation of apparent source width (ASW) and listener envelopment (LEV). The results of the experiment show that the system is significantly better for all tests to the use of no system and that the system is superior to a standerd PA (delay system).
New Acoustical Parameters and Visualization Techniques to Analyze the Spatial Distribution of Sound in Music Spaces
Authors: Bassuet Alban
Published: December 2011

An important factor in our appreciation of music in a hall is the perception of the spatial distribution of sound, influenced by room shape and form. This paper investigates new techniques for visualizing 3D impulse responses and two new spatial indicators are proposed: LH (ratio of low lateral versus high lateral energy), FR (ratio of front lateral versus rear lateral energy). Different room shape characteristics are illustrated from B-format measurements conducted in a selection of famous music spaces such as old and new recital and concert halls, and sacred music spaces.
Microencapsulating and Banking Living Cells for Cell‐Based Medicine
Authors: Zhang Wujie , He Xiaoming
Published: December 2011

A major challenge to the eventual success of the emerging cell‐based medicine such as tissue engineering, regenerative medicine, and cell transplantation is the limited availability of the desired cell sources. This challenge can be addressed by cell microencapsulation to overcome the undesired immune response (i.e., to achieve immunoisolation) so that non‐autologous cells can be used to treat human diseases, and by cell/tissue preservation to bank living cells for wide distribution to end users so that they are readily available when needed in the future. This review summarizes the status quo of research in both cell microencapsulation and banking the microencapsulated cells. It is concluded with a brief outlook of future research directions in this important field.
Recent Advances and History of Vitreous Surgery
Authors: Mimura Tatsuya , Nakashizuka Takayuki , Mori Mikiro
Published: December 2011

There have been tremendous advances in the small‐gauge pars plana vitrectomy (PPV) systems. This review provides an overview of the recent advances and state of the art of vitreous surgery. The two most innovative advancements that have been developed in this area are the small‐gauge cutter and the new illuminating systems. Compared to the traditional 20‐gauge PPV, transconjunctival sutureless small‐gauge PPV is a safe and effective strategy to treat a variety of vitreoretinal diseases. Chandelier illumination allows better visualisation of vitreous for bimanual surgery. The small‐gauge PPV provides benefits in terms of less inflammation, less patient discomfort, and faster recovery of the visual acuity.
Therapeutic Capsule Endoscopy: Opportunities and Challenges
Authors: Rasouli Mahdi , Lin Lin , Prima Kencana Andy , Wong Kai-Juan , Tan Su-Lim , Ho Khek Yu , Phee Soo Jay
Published: December 2011

The increasing demand for non‐invasive (or less‐invasive) monitoring and treatment of medical conditions has attracted both physicians and engineers to work together and investigate new methodologies. Wireless capsule endoscopy is a successful example of such techniques which has become an accepted routine for diagnostic inspection of the gastrointestinal tract. This method offers a non‐invasive alternative to traditional endoscopy and provides the opportunity for exploring distal areas of the small intestine which are otherwise not accessible. Despite these advantages, wireless capsule endoscopy is still limited in functionality compared to traditional endoscopy. Wireless capsule endoscopes with advanced functionalities, such as biopsy or drug delivery, are highly desirable. In this article, the current status of wireless capsule endoscopy is reviewed together with some of its possible therapeutic applications as well as the existing challenges.