bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractory Nasopharyngeal Carcinoma: Positron Emission Tomography Combined with Computed Tomography–Guided 125I Seed Implantation Therapy after Repeated Traditional Radiochemotherapy
Authors: Zhang Fujun , Wu Ketong , Gao Fei , Zhang Weidong , Shi Feng , Li Chuanxing
Published: May 2013

Objective

To evaluate the feasibility of positron emission tomography combined with computed tomography (PET‐CT)–guided 125I seed implantation in the treatment of patients with refractory nasopharyngeal carcinoma after repeated traditional radiochemotherapy.

Study Design

Case series with chart review.

Setting

University medical center.

Subjects and Methods

A total of 26 patients (18 men, 8 women; mean age, 51.3 ± 10.8 years; totaling 53 lesions with an average diameter of 2.86 ± 1.61 cm) were treated by PET‐CT–guided 125I seed implantation. All of the patients received a PET‐CT scan 2 months after the treatment. Follow‐up was conducted for ~2 to 43 months (median, 28.2 months) to observe the local control rate, overall survival rate, and clinical complications.

Results

The local control rates of refractory nasopharyngeal carcinoma after repeated traditional radiochemotherapy after 3, 6, 12, 24, and 36 months were 90.6% (48/53), 79.3% (42/53), 71.7% (38/53), 62.3% (33/53), and 56.6% (30/53), respectively. The overall 1‐, 2‐, and 3‐year survival rates were 87.2%, 71.3%, and 56.5%, respectively, with a median survival time of 28.2 months. Of all patients, 19.2% (5/26) died of local recurrence and 15.4% (4/26) died of metastases. One patient died of hypertensive cerebral hemorrhage, and another patient died from cachexia and infection. The long‐term complications included hyperpigmentation at operative sites (n = 5), insensible feeling on the lateral cheek (n = 2), dryness of the oral cavity (n = 1), and headache (n = 1).

Conclusion

PET‐CT–guided 125I seed implantation is an acceptable and feasible method for treating refractory nasopharyngeal carcinoma with minimal damage and few complications.
My Patient is Short of Breath: Is there Pleural Fluid, and will PoCUS Help Drain it Safely?
Authors: Loubani Osama , Bowra Justin , Smith Andrew , Talbot Jo Ann , Jarman Bob , Atkinson Paul
Published: May 2013

Pathological pleural fluid is common in patients presenting to the emergency department, occurring in as many as 17% of patients presenting with shortness of breath, and as many as 20% of patients with blunt thoracic trauma. A typical chest X-ray may fail to identify as much as 175 mL of pleural fluid in the erect position, and as much as 500 mL in the supine position. Point-of-care ultrasound (PoCUS) on the other hand can detect as little as 20 mL of pleural fluid, and has consistently been shown to have sensitivities and specificities for the detection of pleural fluid close to 100% in both the trauma and critically ill populations. In addition, ultrasound identifies pleural fluid more rapidly than chest X-ray. PoCUS can be used to guide thoracentesis, resulting in improved success rates with decreased complications. Here we describe the evidence supporting the use of PoCUS in the management of pleural fluid collections.
Materials in the Field: Object-trajectories and Object-positions in the Field of Contemporary Art
Authors: Dominguez Rubio Fernando , Silva Elizabeth B.
Published: May 2013

The paper explores the central role of artworks in the field of contemporary art. It is based on an ethnographic study of the conservation laboratory at the Museum of Modern Art (MoMA) in New York and draws from three detailed case studies where the temporal and spatial trajectory of artworks led to processes of competition, collaboration, and repositioning among the agents involved in the acquisition, exhibition and conservation of these artworks. The study demonstrates the importance of artworks qua physical objects in the field of contemporary art, claiming attention to materiality in field theory and engaging with an object-oriented methodology in field analysis. Artworks are shown to intervene in field processes, both reproducing divisions and re-drawing boundaries within and between fields, and actualizing positions of individuals and institutions.
Genre, Boundary Drawing and the Classificatory Imagination
Authors: Beer David
Published: May 2013

This article suggests that the vitality of genre, and particularly music genre, is often missing from social and cultural research. This is despite its central presence as a structural force within increasingly popular forms of field analysis. To deal with this absence, the article draws upon conceptual material on everyday forms of classification and new forms of digital data. It is argued that the concept of a classificatory imagination might be used to develop a more contingent and transient vision of genre as a form of everyday cultural classification or as a structuring force in cultural fields. The article describes three problems facing cultural sociology in its use of genre categories. Two are briefly presented whilst the third is developed through a case study of hip hop. The article concludes with some reflections upon what this reveals about cultural boundary drawing and the impact of decentralized media upon genre formation.
On the Meaning of the PRC’s Development Since 1949
Authors: Raiklin Ernest G.
Published: May 2013

The purpose of this article is to search for answers to the following four questions: First, what is the social meaning of the People’s Republic of China’s (PRC) development prior to 1978? Second, how to interpret the Chinese social drive since 1978? Third, what is the balance sheet of the PRC’s development since 1949? Finally, on the basis of the exploration of China’s growth during the two periods, is it possible to extrapolate into a social structure of the country in the foreseeable future? In pursuing its objectives, the article does not judge China’s road as it should be from a theoretical point of view but simply examines it as it is or might be in practice. China’s development from 1949 to present has taken several socioeconomic forms: 1949-1958, from a prevalent nonstate feudalism to a dominant state feudalism; 1960-1966, elements of mixed capitalism within state feudalism; 1966-1976, the split within the state capitalist and feudal bureaucracies; since 1978, authoritarian state capitalism. Thus, the Chinese road turned out to be not that of “ socialist market economy with Chinese characteristics” but of state capitalist market economy with, of course, Chinese characteristics. It is argued that remarkable economic achievements of the PRC have not been due to “socialism” but due to various forms of capitalism and feudalism, which the circumstances have forced upon the country’s development.
Upper triangular operator matrices, asymptotic intertwining and Browder, Weyl theorems
Authors: Duggal Bhagwati P , Jeon In Ho , Kim In Hyoun
Published: May 2013

Given a Banach spaceX, letMC∈B(X⊕X)denote the upper triangular operator matrixMC=(AC0B), and letδAB∈B(B(X))denote the generalized derivationδAB(X)=AX−XB. Iflimn→∞∥δABn(C)∥1n=0, thenσx(MC)=σx(M0), whereσxstands for the spectrum or a distinguished part thereof (but not the point spectrum); furthermore, ifR=R1⊕R2∈B(X⊕X)is a Riesz operator which commutes withMC, thenσx(MC+R)=σx(MC), whereσxstands for the Fredholm essential spectrum or a distinguished part thereof. These results are applied to prove the equivalence of Browder’s (a-Browder’s) theorem forM0,MC,M0+RandMC+R. Sufficient conditions for the equivalence of Weyl’s (a-Weyl’s) theorem are also considered.

MSC:47B40, 47A10, 47B47, 47A11.
The role of retrotransposons in gene family expansions: insights from the mouse Abpgene family
Authors: Janoušek Václav , Karn Robert C , Laukaitis Christina M
Published: May 2013

Background

Retrotransposons have been suggested to provide a substrate for non-allelic homologous recombination (NAHR) and thereby promote gene family expansion. Their precise role, however, is controversial. Here we ask whether retrotransposons contributed to the recent expansions of the Androgen-binding protein (Abp) gene families that occurred independently in the mouse and rat genomes.

Results

Using dot plot analysis, we found that the most recent duplication in the Abp region of the mouse genome is flanked by L1Md_T elements. Analysis of the sequence of these elements revealed breakpoints that are the relicts of the recombination that caused the duplication, confirming that the duplication arose as a result of NAHR using L1 elements as substrates. L1 and ERVII retrotransposons are considerably denser in the Abp regions than in one Mb flanking regions, while other repeat types are depleted in the Abp regions compared to flanking regions. L1 retrotransposons preferentially accumulated in the Abp gene regions after lineage separation and roughly followed the pattern of Abp gene expansion. By contrast, the proportion of shared vs. lineage-specific ERVII repeats in the Abp region resembles the rest of the genome.

Conclusions

We confirmed the role of L1 repeats in Abp gene duplication with the identification of recombinant L1Md_T elements at the edges of the most recent mouse Abp gene duplication. High densities of L1 and ERVII repeats were found in the Abp gene region with abrupt transitions at the region boundaries, suggesting that their higher densities are tightly associated with Abp gene duplication. We observed that the major accumulation of L1 elements occurred after the split of the mouse and rat lineages and that there is a striking overlap between the timing of L1 accumulation and expansion of the Abp gene family in the mouse genome. Establishing a link between the accumulation of L1 elements and the expansion of the Abp gene family and identification of an NAHR-related breakpoint in the most recent duplication are the main contributions of our study.
Mining genes involved in the stratification of Paris Polyphyllaseeds using high-throughput embryo Transcriptome sequencing
Authors: Qi Jianjun , Zheng Na , Zhang Bing , Sun Peng , Hu Songnian , Xu Wenjuan , Ma Qin , Zhao Tingzhou , Zhou Lili , Qin Mingjian , Li Xianen
Published: May 2013

Background

Paris polyphylla var. yunnanensis is an important medicinal plant. Seed dormancy is one of the main factors restricting artificial cultivation. The molecular mechanisms of seed dormancy remain unclear, and little genomic or transcriptome data are available for this plant.

Results

In this study, massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform was used to generate a substantial sequence dataset for the P. polyphylla embryo. 369,496 high quality reads were obtained, ranging from 50 to 1146 bp, with a mean of 219 bp. These reads were assembled into 47,768 unigenes, which included 16,069 contigs and 31,699 singletons. Using BLASTX searches of public databases, 15,757 (32.3%) unique transcripts were identified. Gene Ontology and Cluster of Orthologous Groups of proteins annotations revealed that these transcripts were broadly representative of the P. polyphylla embryo transcriptome. The Kyoto Encyclopedia of Genes and Genomes assigned 5961 of the unique sequences to specific metabolic pathways. Relative expression levels analysis showed that eleven phytohormone-related genes and five other genes have different expression patterns in the embryo and endosperm in the seed stratification process.

Conclusions

Gene annotation and quantitative RT-PCR expression analysis identified 464 transcripts that may be involved in phytohormone catabolism and biosynthesis, hormone signal, seed dormancy, seed maturation, cell wall growth and circadian rhythms. In particular, the relative expression analysis of sixteen genes (CYP707A, NCED, GA20ox2, GA20ox3, ABI2, PP2C, ARP3, ARP7, IAAH, IAAS, BRRK, DRM, ELF1, ELF2, SFR6, and SUS) in embryo and endosperm and at two temperatures indicated that these related genes may be candidates for clarifying the molecular basis of seed dormancy in P. polyphlla var. yunnanensis.
Cytotoxicity and inflammatory potential of two Pseudomonas mosselii strains isolated from clinical samples of hospitalized patients
Authors: Leneveu-Jenvrin Charlène , Madi Amar , Bouffartigues Emeline , Biaggini Kelly , Feuilloley Marc , Chevalier Sylvie , Connil Nathalie
Published: May 2013

Background

The genus Pseudomonas includes a heterogeneous set of microorganisms that can be isolated from many different niches and nearly 100 different strains have been described. The best characterized bacterium is Pseudomonas aeruginosa which is the primary agent of opportunistic infection in humans, causing both acute and chronic infections. Other species like fluorescens, putida or mosselii have been sporadically isolated from hospitalized patients but their association with the pathology often remains unclear.

Results

This study focuses on the cytotoxicity and inflammatory potential of two strains of Pseudomonas mosselii (ATCC BAA-99 and MFY161) that were recently isolated from clinical samples of hospitalized patients. The behavior of these bacteria was compared to that of the well-known opportunistic pathogen P. aeruginosa PAO1. We found that P. mosselii ATCC BAA-99 and MFY161 are cytotoxic towards Caco-2/TC7 cells, have low invasive capacity, induce secretion of human β-defensin 2 (HBD-2), alter the epithelial permeability of differentiated cells and damage the F-actin cytoskeleton.

Conclusions

These data bring new insights into P. mosselii virulence, since this bacterium has often been neglected due to its rare occurrence in hospital.
The carrier rate and mutation spectrum of genes associated with hearing loss in South China hearing female population of childbearing age
Authors: Yin Aihua , Liu Chang , Zhang Yan , Wu Jing , Mai Mingqin , Ding Hongke , Yang Jiexia , Zhang Xiaozhuang
Published: May 2013

Background

Given that hearing loss occurs in 1 to 3 of 1,000 live births and approximately 90 to 95 percent of them are born into hearing families, it is of importance and necessity to get better understanding about the carrier rate and mutation spectrum of genes associated with hearing impairment in the general population.

Methods

7,263 unrelated women of childbearing age with normal hearing and without family history of hearing loss were tested with allele-specific PCR-based universal array. Further genetic testing were provided to the spouses of the screened carriers. For those couples at risk, multiple choices were provided, including prenatal diagnosis.

Results

Among the 7,263 normal hearing participants, 303 subjects carried pathogenic mutations included in the screening chip, which made the carrier rate 4.17%. Of the 303 screened carriers, 282 harbored heterozygous mutated genes associated with autosomal recessive hearing loss, and 95 spouses took further genetic tests. 8 out of the 9 couples harbored deafness-causing mutations in the same gene received prenatal diagnosis.

Conclusions

Given that nearly 90 to 95 percent of deaf and hard-of-hearing babies are born into hearing families, better understanding about the carrier rate and mutation spectrum of genes associated with hearing impairment in the female population of childbearing age may be of importance in carrier screening and genetic counseling.
N-glycosylation of ICAM-2 is required for ICAM-2-mediated complete suppression of metastatic potential of SK-N-AS neuroblastoma cells
Authors: Feduska Joseph M , Garcia Patrick L , Brennan Stephanie B , Bu Su , Council Leona N , Yoon Karina J
Published: May 2013

Background

Cell adhesion molecules (CAMs) are expressed ubiquitously. Each of the four families of CAMs is comprised of glycosylated, membrane-bound proteins that participate in multiple cellular processes including cell-cell communication, cell motility, inside-out and outside-in signaling, tumorigenesis, angiogenesis and metastasis. Intercellular adhesion molecule-2 (ICAM-2), a member of the immunoglobulin superfamily of CAMs, has six N-linked glycosylation sites at amino acids (asparagines) 47, 82, 105, 153, 178 and 187. Recently, we demonstrated a previously unknown function for ICAM-2 in tumor cells. We showed that ICAM-2 suppressed neuroblastoma cell motility and growth in soft agar, and induced a juxtamembrane distribution of F-actinin vitro. We also showed that ICAM-2 completely suppressed development of disseminated tumorsin vivoin a murine model of metastatic NB. These effects of ICAM-2 on NB cell phenotypein vitroandin vivodepended on the interaction of ICAM-2 with the cytoskeletal linker protein α-actinin. Interestingly, ICAM-2 did not suppress subcutaneous growth of tumors in mice, suggesting that ICAM-2 affects the metastatic but not the tumorigenic potential of NB cells. The goal of the study presented here was to determine if the glycosylation status of ICAM-2 influenced its function in neuroblastoma cells.

Methods

Because it is well documented that glycosylation facilitates essential steps in tumor progression and metastasis, we investigated whether the glycosylation status of ICAM-2 affected the phenotype of NB cells. We used site-directed mutagenesis to express hypo- or non-glycosylated variants of ICAM-2, by substituting alanine for asparagine at glycosylation sites, and compared the impact of each variant on NB cell motility, anchorage-independent growth, interaction with intracellular proteins, effect on F-actin distribution and metastatic potentialin vivo.

Results

Thein vitroandin vivophenotypes of cells expressing glycosylation site variants differed from cells expressing fully-glycosylated ICAM-2 or no ICAM-2. Most striking was the finding that mice injected intravenously with NB cells expressing glycosylation site variants survived longer (P ≤ 0.002) than mice receiving SK-N-AS cells with undetectable ICAM-2. However, unlike fully-glycosylated ICAM-2, glycosylation site variants did not completely suppress disseminated tumor development.

Conclusions

Reduced glycosylation of ICAM-2 significantly attenuated, but did not abolish, its ability to suppress metastatic properties of NB cells.
In vitro and in vivo evaluation of a photosensitive polyimide thin-film microelectrode array suitable for epiretinal stimulation
Authors: Jiang Xia , Sui Xiaohong , Lu Yiliang , Yan Yan , Zhou Chuanqing , Li Liming , Ren Qiushi , Chai Xinyu
Published: May 2013

Background

Epiretinal implants based on microelectro-mechanical system (MEMS) technology with a polyimide (PI) material are being proposed for application. Many kinds of non-photosensitive PIs have good biocompatibility and stability as typical MEMS materials for implantable electrodes. However, the effects of MEMS microfabrication, sterilization and implantation using a photosensitive polyimide (PSPI) microelectrode array for epiretinal electrical stimulation has not been extensively examined.

Methods

A novel PSPI (Durimide 7510) microelectrode array for epiretinal electrical stimulation was designed, fabricated based on MEMS processing and microfabrication techniques. The biocompatibility of our new microelectrode was tested in vitro using an MTT assay and direct contact tests between the microelectrode surface and cells. Electrochemical impedance characteristics were tested based on a three-electrode testing method. The reliability and stability was evaluated by a chronic implantation of a non-functional array within the rabbit eye. Histological examination and SEM were performed to monitor possible damage of the retina and microelectrodes. Electrically evoked potentials (EEPs) were recorded during the acute stimulation of the retina.

Results

The substrate was made of PSPI and the electrode material was platinum (Pt). The PSPI microelectrode array showed good biocompatibility and appropriate impedance characteristics for epiretinal stimulation. After a 6-month epiretinal implantation in the eyes of rabbits, we found no local retinal toxicity and no mechanical compression caused by the array. The Pt electrodes adhesion to the PSPI remained stable. A response to electrical stimuli was with recording electrodes lying on the visual cortex.

Conclusion

We provide a relevant design and fundamental characteristics of a PSPI microelectrode array. Strong evidences on testing indicate that implantation is safe in terms of mechanical pressure and biocompatibility of PSPI microelectrode arrays on the retina. The dual-layer process we used proffers considerable advantages over the more traditional single-layer approach and can accommodate much many electrode sites. This lays the groundwork for a future, high-resolution retinal prosthesis with many more electrode sites based on the flexible PSPI thin film substrate.
Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays
Authors: Fongaro Gislaine , Nascimento Mariana A do , Rigotto Caroline , Ritterbusch Giseli , da Silva Alessandra D’A , Esteves Paulo A , Barardi Célia R M
Published: May 2013

Background

Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system.

Methods

Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization.

Results

The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 102 HAdV genome copies per milliliter of infectious viral particles in the environmental water samples. The molecular characterization studies indicated that HAdV-2 was the prevalent serotype.

Conclusions

These results indicate a lack of proper public health measures. We suggest that HAdV can be efficiently used as a marker of environmental and drinking water contamination and ICC-RT-qPCR demonstrated greater sensitivity and speed of detection of infectious viral particles compared to PA.
Interferon-α sensitizes HBx-expressing hepatocarcinoma cells to chemotherapeutic drugs through inhibition of HBx-mediated NF-κB activation
Authors: Liu Yanning , Lou Guohua , Wu Wei , Shi Yu , Zheng Min , Chen Zhi
Published: May 2013

Background

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is characterized by high chemotherapy resistance; however, the underlying mechanism has not been fully clarified. In addition, HBx protein has been reported to play a key role in virus-mediated hepatocarcinogenesis. Therefore, the present study aims to investigate the role of HBx in the drug-resistance of HBV-related HCC and examine whether such drug-resistance can be reversed by IFN-α treatment.

Methods

We established HBx-expressing cells by liposome-mediated transfection of HBx into the Huh7 cell line. MTT, Annexin V/PI, and cell cycle assay were used for determining the cellular growth inhibition, apoptosis, and growth arrest, respectively, after treatment with chemical drug. We further used tumor-bearing mice model to compare the tumor growth inhibition efficacy of ADM and 5-FU between the Huh7-HBx group and the control group, as well as the ADM + IFN-α or ADM + IMD treated group and the ADM treated group. SQ-Real time-PCR was performed to analyze the expression of MDR-associated genes and anti-apoptotic genes. Moreover, immunofluorescence and Western blotting were used to determine the subcellular localization of p65 and the phosphorylation of IκBα.

Results

The IC50 values of Huh7-HBx cells against ADM and Amn were 2.317 and 1.828-folds higher than those of Huh7-3.1 cells, respectively. The apoptosis ratio and growth arrest was significantly lower in Huh7-HBx cells after treatment with ADM. The in vivo experiment also confirmed that the Huh7-HBx group was much more resistant to ADM or 5-FU than the control. Furthermore, the expression of MDR-associated genes, such as MDR1, MRP1, LRP1, and ABCG2, were significantly up-regulated in Huh7-HBx cells, and the NF-κB pathway was activated after HBx gene transfection in Huh7 cells. However, combined with IFN-α in ADM treatment, the HBx induced drug-resistance in Huh7-HBx cells can be partly abolished in in vitro and in vivo models. Moreover, we found that the NF-κB canonical pathway was affected by IFN-α treatment, and the expression of anti-apoptotic genes, such as Gadd45β, Survivin, and c-IAP-1 was down-regulated by IFN-α treatment in a dose-dependent manner.

Conclusions

HBx protein can induce MDR of HBV-related HCC by activating the NF-κB pathway, which can be partly abolished by IFN-α treatment.
‘Honeycomb appearance’ on three-dimensional transthoracic echocardiography as the landmark of left ventricular non-compaction: two case reports
Authors: Konishi Takao , Nagai Tomoo , Hamabe Akira , Arakawa Junko , Hisadome Hideki , Yoshida Mikoto , Tabata Hirotsugu
Published: May 2013

Introduction

Left ventricular non-compaction is a rare congenital heart disease, and is most commonly diagnosed via two-dimensional echocardiography according to echocardiographic criteria. Recently, transthoracic three-dimensional echocardiography has become available in the clinical setting.

Case presentation

We present two isolated cases of left ventricular non-compaction from Japan (in an 84-year-old woman and 47-year-old man) that were confirmed by two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography and cardiac magnetic resonance imaging. In both cases, three-dimensional echocardiography successfully demonstrated the trabecular meshwork of the left ventricle, referred to as a ‘honeycomb appearance’.

Conclusions

Three-dimensional echocardiography has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible with two-dimensional echocardiography. We further emphasize the clinical utility of three-dimensional echocardiography, which is not limited to just the observation of the trabeculations and inter-trabecular recesses, but can also visualize the trabecular meshwork with a ‘honeycomb appearance’.
Effect of salts on the Co-fermentation of glucose and xylose by a genetically engineered strain of Saccharomyces cerevisiae
Authors: Casey Elizabeth , Mosier Nathan S , Adamec Jiri , Stockdale Zachary , Ho Nancy , Sedlak Miroslav
Published: May 2013

Background

A challenge currently facing the cellulosic biofuel industry is the efficient fermentation of both C5 and C6 sugars in the presence of inhibitors. To overcome this challenge, microorganisms that are capable of mixed-sugar fermentation need to be further developed for increased inhibitor tolerance. However, this requires an understanding of the physiological impact of inhibitors on the microorganism. This paper investigates the effect of salts on Saccharomyces cerevisiae 424A(LNH-ST), a yeast strain capable of effectively co-fermenting glucose and xylose.

Results

In this study, we show that salts can be significant inhibitors of S. cerevisiae. All 6 pairs of anions (chloride and sulfate) and cations (sodium, potassium, and ammonium) tested resulted in reduced cell growth rate, glucose consumption rate, and ethanol production rate. In addition, the data showed that the xylose consumption is more strongly affected by salts than glucose consumption at all concentrations. At a NaCl concentration of 0.5M, the xylose consumption rate was reduced by 64.5% compared to the control. A metabolomics study found a shift in metabolism to increased glycerol production during xylose fermentation when salt was present, which was confirmed by an increase in extracellular glycerol titers by 4 fold. There were significant differences between the different cations. The salts with potassium cations were the least inhibitory. Surprisingly, although salts of sulfate produced twice the concentration of cations as compared to salts of chloride, the degree of inhibition was the same with one exception. Potassium salts of sulfate were less inhibitory than potassium paired with chloride, suggesting that chloride is more inhibitory than sulfate.

Conclusions

When developing microorganisms and processes for cellulosic ethanol production, it is important to consider salt concentrations as it has a significant negative impact on yeast performance, especially with regards to xylose fermentation.
Changing trends in surgery for Graves’ disease: A cohort comparison of those having surgery intended to preserve thyroid function with those having ablative surgery
Authors: Al-Adhami Ahmed , Snaith Ailsa C , Craig Wendy L , Krukowski Zygmunt H
Published: May 2013

Background

Surgery for Graves’ disease may be performed with the intent of preserving thyroid function (subtotal thyroidectomy) or ablating thyroid function (total thyroidectomy). This study examines the evolving practice in a specialist endocrine surgical unit.

Method

Longitudinal cohort study of patients undergoing surgery for Graves’ disease between 1986 and 2008. Outcome measures were thyroid failure, recurrent toxicity, recurrent laryngeal nerve (RLN) palsy, early reoperation and hypocalcaemia. Time to thyroid failure was analysed by potential predictors.

Results

Of 149 patients (129 female), 78 (52.3 percent) underwent subtotal thyroidectomy with the intention to preserve function (PF) and 71 (47.6 percent) total thyroidectomy with the intention to ablate thyroid function (AF). Mean duration of follow-up was 11.1 years; 14.8 years and 7.0 years respectively. Of 78 PF procedures: six (7.7 percent) patients suffered recurrent toxicity; 68 (87.2 percent) developed thyroid failure (four after treatment for recurrent toxicity); and eight (10 percent) remained euthyroid without replacement. Male gender and remnant gland weight were significant predictors of failure (P = 0.021 and 0.022 respectively). One patient developed permanent RLN palsy and one permanent hypocalcaemia. Of 71 AF procedures: one developed acute airway obstruction; one permanent RLN palsy; four permanent hypocalcaemia; and none developed recurrent toxicity. There were no deaths within a year of surgery. There was no statistically significant difference in complication rates.

Conclusion

Most PF resections resulted in eventual thyroid failure. The shift to ablative surgery virtually eliminated the need for lifelong specialist follow-up, albeit with an insignificant rise in permanent hypocalcaemia.
A genome scale metabolic network for rice and accompanying analysis of tryptophan, auxin and serotonin biosynthesis regulation under biotic stress
Authors: Dharmawardhana Palitha , Ren Liya , Amarasinghe Vindhya , Monaco Marcela , Thomason Jim , Ravenscroft Dean , McCouch Susan , Ware Doreen , Jaiswal Pankaj
Published: May 2013

Background

Functional annotations of large plant genome projects mostly provide information on gene function and gene families based on the presence of protein domains and gene homology, but not necessarily in association with gene expression or metabolic and regulatory networks. These additional annotations are necessary to understand the physiology, development and adaptation of a plant and its interaction with the environment.

Results

RiceCyc is a metabolic pathway networks database for rice. It is a snapshot of the substrates, metabolites, enzymes, reactions and pathways of primary and intermediary metabolism in rice. RiceCyc version 3.3 features 316 pathways and 6,643 peptide-coding genes mapped to 2,103 enzyme-catalyzed and 87 protein-mediated transport reactions. The initial functional annotations of rice genes with InterPro, Gene Ontology, MetaCyc, and Enzyme Commission (EC) numbers were enriched with annotations provided by KEGG and Gramene databases. The pathway inferences and the network diagrams were first predicted based on MetaCyc reference networks and plant pathways from the Plant Metabolic Network, using the Pathologic module of Pathway Tools. This was enriched by manually adding metabolic pathways and gene functions specifically reported for rice. The RiceCyc database is hierarchically browsable from pathway diagrams to the associated genes, metabolites and chemical structures. Through the integrated tool OMICs Viewer, users can upload transcriptomic, proteomic and metabolomic data to visualize expression patterns in a virtual cell. RiceCyc, along with additional species-specific pathway databases hosted in the Gramene project, facilitates comparative pathway analysis.

Conclusions

Here we describe the RiceCyc network development and discuss its contribution to rice genome annotations. As a case study to demonstrate the use of RiceCyc network as a discovery environment we carried out an integrated bioinformatic analysis of rice metabolic genes that are differentially regulated under diurnal photoperiod and biotic stress treatments. The analysis of publicly available rice transcriptome datasets led to the hypothesis that the complete tryptophan biosynthesis and its dependent metabolic pathways including serotonin biosynthesis are induced by taxonomically diverse pathogens while also being under diurnal regulation. The RiceCyc database is available online for free access at http://www.gramene.org/pathway/.
A tale of two systems: poisoning management in Iran and the United States
Authors: Mehrpour Omid , Zamani Nasim , Brent Jeffrey , Abdollahi Mohammad
Published: May 2013

Poisoning morbidity and mortality is high in the developing world. Systems for care of poisoned patients differ markedly between countries. In this paper a comparison of two very different systems for the care of poisoned patients, is presented. Specifically, the role of poison centers and poison treatment centers in the US and Iran are contrasted. A systematic literature search was undertaken utilizing the PubMed, Scopus, and Google Scholar and the keywords “poison centers”, “treatment” “Iran” “United States of America” and 100 publications were identified. From these, relevant data were found in 23 publications. The information was double-checked and data were summarized herein.

We find that the system of the care of poisoned patients relies heavily on certified poison centers in the US and that only a few hospitals have well developed medical toxicology services. In contrast, in Iran, the poison center system is somehow less developed and the care of poisoned patients is provided in centralized high volume hospital poison units.

Although both the US and Iran have highly developed systems for the care of poisoned patients they are distinctly different. Comparative studies based on these systems could provide important data for developing countries with more rudimentary poison control and treatment facilities.
Aging phenotypes in cultured normal human mammary epithelial cells are correlated with decreased telomerase activity independent of telomere length
Authors: Sputova Klara , Garbe James C , Pelissier Fanny A , Chang Eric , Stampfer Martha R , LaBarge Mark A
Published: May 2013

Background

Shortening of telomeres, which are essential for maintenance of genomic integrity, is a mechanism commonly associated with the aging process. Here we ascertained whether changes in telomere lengths or telomerase activity correlated with age in normal human mammary epithelial cells (HMEC), or with phenotypes of aging in breast. Accordingly, flow cytometry fluorescence in situ hybridization (flowFISH) was used to determine relative telomere lengths (RTL), and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP), in a collection of 41 primary HMEC strains established from women aged 16 to 91 years.

Results

RTL measurements of HMEC strains that were heterogeneous with respect to lineage composition revealed no significant associations between telomere length with age, maximum observed population doublings, or with lineage composition of the strains. However, within strains, luminal epithelial and cKit-expressing epithelial progenitor cells that were flow cytometry-enriched from individual HMEC strains exhibited significantly shorter telomeres relative to isogenic myoepithelial cells (P < 0.01). In unsorted strains, detectable telomerase activity did not correlate with RTL. Telomerase activity declined with age; the average age of strains that exhibited TRAP activity was 29.7 ± 3.9y, whereas the average age of strains with no detectable TRAP activity was 49.0 ± 4.9y (P < 0.01). Non-detectable TRAP activity also was correlated with phenotypes of aging previously described in HMEC strains; increased proportions of CD227-expressing luminal epithelial cells (P < 0.05) and cKit-expressing progenitor cells (P < 0.05).

Conclusions

Telomere shortening did not correlate with the chronological ages of HMEC strains, whereas decreased telomerase activity correlated with age and with lineage distribution phenotypes characteristic of aging.
Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model: in situ detection of 2-HG and α-KG
Authors: Navis Anna C , Niclou Simone P , Fack Fred , Stieber Daniel , van Lith Sanne , Verrijp Kiek , Wright Alan , Stauber Jonathan , Tops Bastiaan , Otte-Holler Irene , Wevers Ron A , van Rooij Arno , Pusch Stefan , von Deimling Andreas , Tigchelaar Wikky , van Noorden Cornelis JF , Wesseling Pieter , Leenders William PJ
Published: May 2013

Background

Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level.

Results

LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis.

Conclusions

The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations.
The consequences of measurement error when estimating the impact of obesity on income
Authors: O’Neill Donal , Sweetman Olive
Published: May 2013

This paper examines the consequences of using self-reported measures of BMI when estimating the effect of BMI on income for women using both Irish and US data. We find that self-reported BMI is subject to substantial measurement error and that this error deviates from classical measurement error. These errors cause the traditional least squares estimator to overestimate the relationship between BMI and income. We show that neither the conditional expectation estimator nor the instrumental variables approach adequately address the bias and briefly discuss alternative approaches that could be considered when faced with non-classical measurement error.

JEL codes

C13, C26, I14
Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers
Authors: Valentini Gabriele , Marcoccia Antonella , Cuomo Giovanna , Vettori Serena , Iudici Michele , Bondanini Francesco , Santoriello Carlo , Ciani Aldo , Cozzolino Domenico , De Matteis Giovanni Maria , Cappabianca Salvatore , Vitelli Filiberto , Spanò Alberto
Published: May 2013

Introduction

Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.

Methods

Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.

Results

Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.

Conclusion

These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.
Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens
Authors: Kuemmerle-Deschner Jasmin B , Wittkowski Helmut , Tyrrell Pascal N , Koetter Ina , Lohse Peter , Ummenhofer Katharina , Reess Fabian , Hansmann Sandra , Koitschev Assen , Deuter Christoph , Bialkowski Anja , Foell Dirk , Benseler Susanne M
Published: May 2013

Objectives

Muckle-Wells syndrome (MWS) is an autoinflammatory disease characterized by excessive interleukin-1 (IL-1) release, resulting in recurrent fevers, sensorineural hearing loss, and amyloidosis. IL-1 inhibition with anakinra, an IL-1 receptor antagonist, improves clinical symptoms and inflammatory markers. Subclinical disease activity is commonly observed. Canakinumab, a fully human IgG1 anti-IL-1β monoclonal antibody, can abolish excess IL-1β. The study aim was to analyze the efficacy and safety of these two anti-IL-1 therapies.

Methods

Two cohorts of patients with severe MWS and confirmed NLRP3 mutation were treated with anakinra and/or canakinumab. Clinical and laboratory features including ESR, CRP, SAA, and the neutrophil marker S100A12 were determined serially. Disease activity was captured by MWS disease activity scores (MWS-DAS). Remission was defined as MWS-DAS ≤5 plus normal CRP and SAA. Treatment efficacy and safety were analyzed.

Results

The study included 12 anakinra- and 14 canakinumab-treated patients; the median age was 33.5 years (3.0 years to 72.0 years); 57% were female patients. Both treatment regimens led to a significant reduction of clinical disease activity and inflammatory markers. At last follow-up, 75% of anakinra-treated and 93% of canakinumab-treated patients achieved remission. During follow-up, S100A12 levels mirrored recurrence of disease activity. Both treatment regimens had favorable safety profiles.

Conclusions

IL-1 blockade is an effective and safe treatment in MWS patients. MWS-DAS in combination with MWS inflammatory markers provides an excellent monitoring tool set. Canakinumab led to a sustained control of disease activity even after secondary failure of anakinra therapy. S100A12 may be a sensitive marker to detect subclinical disease activity.
Chronic pain in survivors of critical illness: a retrospective analysis of incidence and risk factors
Authors: Battle Ceri E , Lovett Simon , Hutchings Hayley
Published: May 2013

Introduction

Chronic pain has been reported in survivors of critical illness for many years after discharge from hospital. This study investigates the incidence and site of chronic pain in survivors of critical illness between 6 months and 1 year after hospitalization, including ICU admission. A retrospective analysis of the risk factors for chronic pain in this patient group was also completed.

Methods

A questionnaire method was used to investigate the incidence of chronic pain and the specific body parts affected. A retrospective study and multivariable analysis were used to investigate the risk factors for chronic pain in this patient group. All survivors of a general intensive care unit (ICU) in South Wales in a 6-month period were included in this study.

Results

Chronic pain was reported in 44% of all respondents. The shoulder was the most commonly reported joint affected by pain (22%). Risk factors for chronic pain between 6 months and 1 year after ICU discharge were increasing patient age and severe sepsis.

Conclusions

Chronic pain is a problem in survivors of critical illness, especially in the shoulder joint, and further studies are needed investigating therapeutic interventions that address this long-term problem.