bluuebunny/crossref_metadata_2025 huggingface dataset:
Midgut transcriptome profiling of Anoplophora glabripennis, a lignocellulose degrading cerambycid beetle
Authors: Scully Erin D , Hoover Kelli , Carlson John E , Tien Ming , Geib Scott M
Published: December 2013

Background

Wood-feeding insects often work in collaboration with microbial symbionts to degrade lignin biopolymers and release glucose and other fermentable sugars from recalcitrant plant cell wall carbohydrates, including cellulose and hemicellulose. Here, we present the midgut transcriptome of larvalAnoplophora glabripennis, a wood-boring beetle with documented lignin-, cellulose-, and hemicellulose- degrading capabilities, which provides valuable insights into how this insect overcomes challenges associated with feeding in woody tissue.

Results

Transcripts from putative protein coding regions of over 9,000 insect-derived genes were identified in theA. glabripennismidgut transcriptome using a combination of 454 shotgun and Illumina paired-end reads. The most highly-expressed genes predicted to encode digestive-related enzymes were trypsins, carboxylesterases, β-glucosidases, and cytochrome P450s. Furthermore, 180 unigenes predicted to encode glycoside hydrolases (GHs) were identified and included several GH 5, 45, and 48 cellulases, GH 1 xylanases, and GH 1 β-glucosidases. In addition, transcripts predicted to encode enzymes involved in detoxification were detected, including a substantial number of unigenes classified as cytochrome P450s (CYP6B) and carboxylesterases, which are hypothesized to play pivotal roles in detoxifying host tree defensive chemicals and could make important contributions toA. glabripennis’expansive host range. While a large diversity of insect-derived transcripts predicted to encode digestive and detoxification enzymes were detected, few transcripts predicted to encode enzymes required for lignin degradation or synthesis of essential nutrients were identified, suggesting that collaboration with microbial enzymes may be required for survival in woody tissue.

Conclusions

A. glabripennisproduces a number of enzymes with putative roles in cell wall digestion, detoxification, and nutrient extraction, which likely contribute to its ability to thrive in a broad range of host trees. This system is quite different from the previously characterized termite fermentation system and provides new opportunities to discover enzymes that could be exploited for cellulosic ethanol biofuel production or the development of novel methods to control wood-boring pests.
Analysis of banana transcriptome and global gene expression profiles in banana roots in response to infection by race 1 and tropical race 4 of Fusarium oxysporum f. sp. cubense
Authors: Li Chunqiang , Shao Jiaofang , Wang Yejun , Li Wenbin , Guo Dianjing , Yan Bin , Xia Yiji , Peng Ming
Published: December 2013

Background

Cavendish, the most widely grown banana cultivar, is relatively resistant to Race 1 ofFusarium oxysporumf. sp.cubense(Foc1) which caused widespread Panama disease during the first half of the 20thcentury but is susceptible to Tropical Race 4 of Foc (Foc TR4) which is threatening world banana production. The genome of the diploid speciesMusa acuminatawhich is the ancestor of a majority of triploid banana cultivars has recently been sequenced. Availability of banana transcriptomes will be highly useful for improving banana genome annotation and for biological research. The knowledge of global gene expression patterns influenced by infection of different Foc races will help to understand the host responses to the infection.

Results

RNA samples from different organs of the Cavendish cultivar were pooled for deep sequencing using the Illumina technology. Analysis of the banana transcriptome led to identification of over 842 genes that were not annotated by theMusagenome project. A large number of simple nucleotide polymorphisms (SNPs) and short insertions and deletion (indels) were identified from the transcriptome data. GFP-expressing Foc1 and Foc TR4 were used to monitor the infection process. Both Foc1 and Foc TR4 were found to be able to invade banana roots and spread to root vascular tissues in the first two days following inoculation. Digital gene expression (DGE) profiling analysis reveal that the infection by Foc1 and Foc TR4 caused very similar changes in the global gene expression profiles in the banana roots during the first two days of infection. The Foc infection led to induction of many well-known defense-related genes. Two genes encoding the ethylene biosynthetic enzyme ACC oxidase and several ethylene-responsive transcription factors (ERF) were among the strongly induced genes by both Foc1 and Foc TR4.

Conclusions

Both Foc1 and Foc TR4 are able to spread into the vascular system of banana roots during the early infection process and their infection led to similar gene expression profiles in banana roots. The transcriptome profiling analysis indicates that the ethylene synthetic and signalling pathways were activated in response to the Foc infection.
Reprogramming of lysosomal gene expression by interleukin-4 and Stat6
Authors: Brignull Louise M , Czimmerer Zsolt , Saidi Hafida , Daniel Bence , Villela Izabel , Bartlett Nathan W , Johnston Sebastian L , Meira Lisiane B , Nagy Laszlo , Nohturfft Axel
Published: December 2013

Background

Lysosomes play important roles in multiple aspects of physiology, but the problem of how the transcription of lysosomal genes is coordinated remains incompletely understood. The goal of this study was to illuminate the physiological contexts in which lysosomal genes are coordinately regulated and to identify transcription factors involved in this control.

Results

As transcription factors and their target genes are often co-regulated, we performed meta-analyses of array-based expression data to identify regulators whose mRNA profiles are highly correlated with those of a core set of lysosomal genes. Among the ~50 transcription factors that rank highest by this measure, 65% are involved in differentiation or development, and 22% have been implicated in interferon signaling. The most strongly correlated candidate was Stat6, a factor commonly activated by interleukin-4 (IL-4) or IL-13. Publicly available chromatin immunoprecipitation (ChIP) data from alternatively activated mouse macrophages show that lysosomal genes are overrepresented among Stat6-bound targets. Quantification of RNA from wild-type and Stat6-deficient cells indicates that Stat6 promotes the expression of over 100 lysosomal genes, including hydrolases, subunits of the vacuolar H+ATPase and trafficking factors. While IL-4 inhibits and activates different sets of lysosomal genes, Stat6 mediates only the activating effects of IL-4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL-4.

Conclusions

The current data establish Stat6 as a broadly acting regulator of lysosomal gene expression in mouse macrophages. Other regulators whose expression correlates with lysosomal genes suggest that lysosome function is frequently re-programmed during differentiation, development and interferon signaling.
Infarct quantification using 3D inversion recovery and 2D phase sensitive inversion recovery; validation in patients and ex vivo
Authors: Jablonowski Robert , Nordlund David , Kanski Mikael , Ubachs Joey , Koul Sasha , Heiberg Einar , Engblom Henrik , Erlinge David , Arheden Håkan , Carlsson Marcus
Published: December 2013

Background

Cardiovascular-MR (CMR) is the gold standard for quantifying myocardial infarction using late gadolinium enhancement (LGE) technique. Both 2D- and 3D-LGE-sequences are used in clinical practise and in clinical and experimental studies for infarct quantification. Therefore the aim of this study was to investigate if image acquisitions with 2D- and 3D-LGE show the same infarct size in patients and ex vivo.

Methods

Twenty-six patients with previous myocardial infarction who underwent a CMR scan were included. Images were acquired 10-20 minutes after an injection of 0.2 mmol/kg gadolinium-based contrast agent. Two LGE-sequences, 3D-inversion recovery (IR) and 2D-phase-sensitive (PS) IR, were used in all patients to quantify infarction size. Furthermore, six pigs with reperfused infarction in the left anterior descending artery (40 minutes occlusion and 4 hours of reperfusion) were scanned with 2D- and 3D-LGE ex vivo. A high resolution T1-sequence was used as reference for the infarct quantification ex vivo. Spearman’s rank-order correlation, Wilcoxon matched pairs test and bias according to Bland-Altman was used for comparison of infarct size with different LGE-sequences.

Results

There was no significant difference between the 2D- and 3D-LGE sequence in left ventricular mass (LVM) (2D: 115 ± 25 g; 3D: 117 ± 24 g: p = 0.35). Infarct size in vivo using 2D- and 3D-LGE showed high correlation and low bias for both LGE-sequences both in absolute volume of infarct (r = 0.97, bias 0.47 ± 2.1 ml) and infarct size as part of LVM (r = 0.94, bias 0.16 ± 2.0%). The 2D- and 3D-LGE-sequences ex vivo correlated well (r = 0.93, bias 0.67 ± 2.4%) for infarct size as part of the LVM. The IR LGE-sequences overestimated infarct size as part of the LVM ex vivo compared to the high resolution T1-sequence (bias 6.7 ± 3.0%, 7.3 ± 2.7% for 2D-PSIR and 3D-IR respectively, p < 0.05 for both).

Conclusions

Infarct quantification with 2D- and 3D-LGE gives similar results in vivo with a very low bias. IR LGE-sequences optimized for in vivo use yield an overestimation of infarct size when used ex vivo.
Genotypic characteristics of Mycobacterium tuberculosis isolated from household contacts of tuberculosis patients in the Philippines
Authors: Sia Irene G , Buckwalter Seanne P , Doerr Kelly A , Lugos Sonia , Kramer Rebecca , Orillaza-Chi Ruth , Quelapio Maria Imelda , Tupasi Thelma E , Wengenack Nancy L
Published: December 2013

Background

The Philippines has an extremely high rate of tuberculosis but little is known about M. tuberculosis genotypes and transmission dynamics in this country. The aim of this study was to determine the proportion of household contacts who develop active TB due to direct transmission from an index case in that household.

Methods

Mycobacterium tuberculosis isolates from household contacts of tuberculosis patients in the Philippines were characterized using restriction-fragment-length polymorphism analysis, spoligotyping, and mycobacterial interspersed repetitive units – variable number tandem repeats typing (12-loci) to determine their utility in elucidating transmission in an area of high tuberculosis prevalence. Drug susceptibility patterns for these isolates were also determined.

Results

Spoligotyping and MIRU-VNTR typing results matched in 10 (62.5%) of 16 index patient-household contact pairs while IS6110 fingerprints matched in only six (37.5%) pairs. Only 3/16 (18.8%) index patient-household contact pairs had identical drug susceptibility results.

Conclusions

Strain typing of M. tuberculosis isolates from household contacts in the Philippines indicates that transmission of strains does not necessarily occur directly from the index patient living in close proximity in the same household but rather that community-based transmission also frequently occurs. Accurate susceptibility testing of all isolates is necessary to insure optimal care of both the index patients and any culture-positive household contacts.
Molecular epidemiology of coagulase-negative Staphylococcus carriage in neonates admitted to an intensive care unit in Brazil
Authors: Ternes Yves Mauro , Lamaro-Cardoso Juliana , André Maria Cláudia Porfirio , Pessoa Vicente Porfírio , Vieira Maria Aparecida da Silva , Minamisava Ruth , Andrade Ana Lúcia , Kipnis André
Published: December 2013

Background

Nasal colonization with coagulase-negative Staphylococcus (CoNS) has been described as a risk factor for subsequent systemic infection. In this study, we evaluated the genetic profile of CoNS isolates colonizing the nares of children admitted to a neonatal intensive care unit (NICU).

Methods

We assessed CoNS carriage at admittance and discharge among newborns admitted to a NICU from July 2007 through May 2008 in one of the major municipalities of Brazil. Isolates were screened on mannitol salt agar and tryptic soy broth and tested for susceptibility to antimicrobials using the disc diffusion method. Polymerase chain reaction (PCR) was used to determine the species, the presence of the mecA gene, and to perform SCCmec typing. S. epidermidis and S. haemolyticus isolated from the same child at both admission and discharge were characterized by PFGE.

Results

Among 429 neonates admitted to the NICU, 392 (91.4%) had nasal swabs collected at both admission and discharge. The incidence of CoNS during the hospitalization period was 55.9% (95% confidence interval [CI]: 50.9-60.7). The most frequently isolated species were S. haemolyticus (38.3%) and S.epidermidis (38.0%). Multidrug resistance (MDR) was detected in 2.2% and 29.9% of the CoNS isolates, respectively at admittance and discharge (p = 0.053). The mecA gene was more prevalent among strains isolated at discharge (83.6%) than those isolated at admission (60%); overall, SCCmec type I was isolated most frequently. The length of hospitalization was associated with colonization by MDR isolates (p < 0.005). Great genetic diversity was observed among S. epidermidis and S. haemolyticus.

Conclusions

NICU represents an environment of risk for colonization by MDR CoNS. Neonates admitted to the NICU can become a reservoir of CoNS strains with the potential to spread MDR strains into the community.
Phenethyl isothiocyanate induces calcium mobilization and mitochondrial cell death pathway in cholangiocarcinoma KKU-M214 cells
Authors: Tusskorn Ornanong , Senggunprai Laddawan , Prawan Auemduan , Kukongviriyapan Upa , Kukongviriyapan Veerapol
Published: December 2013

Background

Phenethyl isothiocyanate (PEITC) is a cancer chemopreventive agent from cruciferous vegetables. Cholangiocarcinoma (CCA) is a chemo-resistant cancer with very poor prognosis. We evaluated the effects of PEITC on induction of apoptotic cell death in relation to cellular glutathione (GSH) and mitochondrial function of a CCA cell line, KKU-M214.

Methods

Cytotoxic effects of PEITC on a CCA cell line, KKU-M214, and a reference cell line, Chang cells were evaluated. To delineate mechanisms of cell death, the following parameters were measured; GSH and superoxide levels as the oxidative status parameters, apoptosis related proteins levels using Western blotting. Cellular free calcium level and mitochondrial transmembrane potential were also measured.

Results

PEITC induced apoptotic cell death of both KKU-M214 and Chang cells. After PEITC treatment, both cells showed decrease of Bcl-xl and increase of Bax levels. While KKU-M214 cells released AIF, Chang cells released cytochrome c, with subsequent activation of caspase 3 and 9, upon PEITC treatment. PEITC induced superoxide formation in both cells, although it seemed not play a role in cell death. PEITC caused GSH redox stress in different ways in two cell types, because N-acetylcysteine (NAC) prevented redox stress in Chang but not in KKU-M214 cells. The loss of mitochondrial transmembrane potential was induced by PEITC concurrent with GSH stress, but was not a primary cause of cell death. The rapid increase of free calcium level in cytosol was associated with cell death in both cell lines. These events were prevented by NAC in Chang cells, but not in KKU-M214 cells.

Conclusion

PEITC induced cell death KKU-M214 cells and Chang cells via increase of cellular calcium mobilization and activation of mitochondrial cell death pathway. The effects of PEITC on the redox stress was mediated via different ways in CCA and Chang cells because NAC could prevent redox stress in Chang cells, but not in KKU-M214 cells. The multiple effects of PEITC may be useful for the development of novel chemotherapy for CCA.
Phosphatidylinositol 3-Kinase dependent upregulation of the epidermal growth factor receptor upon Flotillin-1 depletion in breast cancer cells
Authors: Kurrle Nina , Ockenga Wymke , Meister Melanie , Völlner Frauke , Kühne Sina , John Bincy A , Banning Antje , Tikkanen Ritva
Published: December 2013

Background

Flotillin-1 and flotillin-2 are two homologous and ubiquitously expressed proteins that are involved in signal transduction and membrane trafficking. Recent studies have reported that flotillins promote breast cancer progression, thus making them interesting targets for breast cancer treatment. In the present study, we have investigated the underlying molecular mechanisms of flotillins in breast cancer.

Methods

Human adenocarcinoma MCF7 breast cancer cells were stably depleted of flotillins by means of lentivirus mediated short hairpin RNAs. Western blotting, immunofluorescence and quantitative real-time PCR were used to analyze the expression of proteins of the epidermal growth factor receptor (EGFR) family. Western blotting was used to investigate the effect of EGFR stimulation or inhibition as well as phosphatidylinositol 3-kinase (PI3K) inhibition on mitogen activated protein kinase (MAPK) signaling. Rescue experiments were performed by stable transfection of RNA intereference resistant flotillin proteins.

Results

We here show that stable knockdown of flotillin-1 in MCF7 cells resulted in upregulation of EGFR mRNA and protein expression and hyperactivation of MAPK signaling, whereas ErbB2 and ErbB3 expression were not affected. Treatment of the flotillin knockdown cells with an EGFR inhibitor reduced the MAPK signaling, demonstrating that the increased EGFR expression and activity is the cause of the increased signaling. Stable ectopic expression of flotillins in the knockdown cells reduced the increased EGFR expression, demonstrating a direct causal relationship between flotillin-1 expression and EGFR amount. Furthermore, the upregulation of EGFR was dependent on the PI3K signaling pathway which is constitutively active in MCF7 cells, and PI3K inhibition resulted in reduced EGFR expression.

Conclusions

This study demonstrates that flotillins may not be suitable as cancer therapy targets in cells that carry certain other oncogenic mutations such as PI3K activating mutations, as unexpected effects are prone to emerge upon flotillin knockdown which may even facilitate cancer cell growth and proliferation.
Clinical significance of palliative gastrectomy on the survival of patients with incurable advanced gastric cancer: a systematic review and meta-analysis
Authors: Sun Jingxu , Song Yongxi , Wang Zhenning , Chen Xiaowan , Gao Peng , Xu Yingying , Zhou Baosen , Xu Huimian
Published: December 2013

Background

Palliative gastrectomy for patients with advanced gastric cancer remains controversial. The objective of the present meta-analysis was to analyze survival outcomes and establish a consensus on whether palliative gastrectomy is suitable for patients with incurable advanced gastric cancer and which type of patients should be selected to receive palliative gastrectomy.

Methods

A literature search was conducted in PubMed, EMBASE and the Cochrane Library. The results for overall survival in the meta-analysis are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Of 1647 articles and abstracts reviewed, 14 studies with 3003 patients were eligible for the final analysis. The meta-analysis revealed that palliative gastrectomy is associated with a significantly improvement in overall survival (HR 0.56; 95%CI 0.39–0.80; p < 0.002) compared that of patients treated without palliative gastrectomy. An improvement in survival was also observed in patients with stage M1 gastric cancer who received palliative gastrectomy (HR 0.62; 95%CI 0.49–0.78; p < 0.0001), especially those with peritoneal dissemination (HR = 0.76, 95%CI 0.63–0.92), liver metastasis (HR = 0.41, 95%CI 0.30–0.55), or distant lymph-node metastasis (HR = 0.36, 95%CI 0.23–0.59). Combined hepatic resection may be beneficial for patients who under palliative gastrectomy (HR 0.30; 95%CI 0.15–0.61; p = 0.0008). The overall survival of patients who underwent palliative gastrectomy combined with chemotherapy was significantly improved (HR 0.63; 95%CI 0.47–0.84; p = 0.002).

Conclusions

From the results of the meta-analysis, palliative gastrectomy for patients with incurable advanced gastric cancer may be associated with longer survival, especially for patients with stage M1 gastric cancer. Combined hepatic resection for patients with liver metastasis and chemotherapy may be beneficial factors compared to simple palliative gastrectomy.
The association between indoor temperature and body mass index in children: the PIAMA birth cohort study
Authors: Scheffers Floor R , Bekkers Marga BM , Kerkhof Marjan , Gehring Ulrike , Koppelman Gerard H , Schipper Maarten , Haveman-Nies Annemien , Wijga Alet H
Published: December 2013

Background

Several experimental studies showed consistent evidence for decreased energy expenditure at higher ambient temperatures. Based on this, an association between thermal exposure and body weight may be expected. However, the effect of thermal exposure on body weight has hardly been studied. Therefore, this study investigated the association between indoor temperature and body mass index (BMI) in children in real life.

Methods

This longitudinal observational study included 3 963 children from the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort that started in 1996. These children were followed from birth until the age of 11 years. Winter indoor temperature (living room and bedroom) was reported at baseline and BMI z-scores were available at 10 consecutive ages. Missing data were multiply imputed. Associations between indoor temperature and BMI were analyzed using generalized estimating equations (GEE), adjusted for confounders and stratified by gender. In a subgroup of 104 children, bedroom temperature was also measured with data loggers.

Results

Mean reported living room and bedroom temperature were 20.3°C and 17.4°C, respectively. Reported and measured bedroom temperatures were positively correlated (r = 0.42, p = 0.001).

Neither reported living room temperature (-0.03 ≤ β ≥ 0.04) and bedroom temperature (-0.01 ≤ β ≥ 0.02) nor measured bedroom temperature (-0.04 ≤ β ≥ 0.05) were associated with BMI z-score between the age of 3 months and 11 years.

Conclusions

This study in children did not support the hypothesized association between indoor temperature and BMI in a real life setting.
Production and purification of polymerization-competent HIV-1 capsid protein p24 (CA) in NiCo21(DE3) Escherichia coli
Authors: Teow Sin Yeang , Mualif Siti Aisyah , Omar Tasyriq Che , Wei Chew Yik , Yusoff Narazah Mohd , Ali Syed A
Published: December 2013

Background

HIV genome is packaged and organized in a conical capsid, which is made up of ~1,500 copies of the viral capsid protein p24 (CA). Being a primary structural component and due to its critical roles in both late and early stages of the HIV replication cycle, CA has attracted increased interest as a drug discovery target in recent years. Drug discovery studies require large amounts of highly pure and biologically active protein. It is therefore desirable to establish a simple and reproducible process for efficient production of HIV-1 CA.

Result

In this work, 6-His-tagged wild type CA from HIV-1 (NL4.3) was expressed in rare tRNA-supplemented NiCo21(DE3) Escherichia coli, and its production was studied in shake flask culture condition of expression. Influences of various key cultivation parameters were examined to identify optimal conditions for HIV-1 CA production. It was found that a culture temperature of 22°C and induction with 0.05 mM IPTG at the early stage of growth were ideal, leading to a maximum biomass yield when grown in Super broth supplemented with 1% glucose. With optimized culture conditions, a final biomass concentration of ~27.7 g L-1 (based on optical density) was obtained in 12 hours post-induction, leading to a yield of about ~170 mg L-1 HIV-1 CA. A two-step purification strategy (chitin beads + IMAC) was employed, which efficiently removed metal affinity resin-binding bacterial proteins that contaminate recombinant His-tagged protein preparation, and resulted in highly pure HIV-1 CA. The purified protein was capable of polymerization when tested in an in vitro polymerization assay.

Conclusions

By using this optimized expression and purification procedure, milligram amounts of highly pure and polymerization-competent recombinant HIV-1 CA can be produced at the lab-scale and thus used for further biochemical studies.
The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer
Authors: Shakhssalim Nasser , Houshmand Massoud , Kamalidehghan Behnam , Faraji Abolfazl , Sarhangnejad Reza , Dadgar Sepideh , Mobaraki Maryam , Rosli Rozita , Sanati Mohammad Hossein
Published: December 2013

Background

Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues.

Methods

The DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis.

Results

From a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples.

Conclusion

Our study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.
A simple iterative positioning algorithm for client node localization in WLANs
Authors: Trevisan Luis M , Pellenz Marcelo E , Penna Manoel C , Souza Richard D , Fonseca Mauro SP
Published: December 2013

The ability to determine in real-time the geographic location of client nodes is an important tool in wireless networks, allowing instantaneous mobile tracking, implementation of location-aware services and also efficient channel and power allocation planning. Among existing classical cooperative localization techniques for wireless networks, the maximum likelihood estimator (MLE) is theoretically the best. However, the gradient-based algorithms that are commonly used for maximum likelihood estimation are quite sensitive to the initial values and cannot achieve the theoretical optimal performance. In this paper, we propose a new iterative positioning algorithm based on received signal strength information that employs a location ordering strategy and a numerical nonlinear optimization method. The algorithm performance is evaluated through simulation for different network scenarios. A real wireless network scenario is also implemented in order to demonstrate the algorithm effectiveness. The proposed algorithm, while presenting a simplified implementation, can achieve better positioning estimates than the classical MLE approach based on the conjugated gradient.
Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat
Authors: Furuya Motohide , Miyaoka Tsuyoshi , Tsumori Toshiko , Liaury Kristian , Hashioka Sadayuki , Wake Rei , Tsuchie Keiko , Fukushima Michiyo , Ezoe Satoko , Horiguchi Jun
Published: December 2013

Background

The pathophysiology of schizophrenia (SCZ) remains unclear, and its treatment is far from ideal. We have previously reported that yokukansan (YKS), which is a traditional Japanese medicine, is effective as an adjunctive therapy for SCZ. However, the mechanisms underlying the action of YKS have not yet been completely elucidated. A recent meta-analysis study has shown that adjuvant anti-inflammatory drugs are effective for SCZ treatment, and it has been proposed that some of the cognitive deficits associated with inflammation may in part be related to inflammation-induced reductions in adult hippocampal neurogenesis. Although certain ingredients of YKS have potent anti-inflammatory activity, no study has determined if YKS has anti-inflammatory properties.

Methods

Using the Gunn rat, which has been reported as a possible animal model of SCZ, we investigated whether YKS affects cognitive dysfunction in an object-location test and the suppression of microglial activation and neurogenesis in the hippocampus.

Results

We found that YKS ameliorated spatial working memory in the Gunn rats. Furthermore, YKS inhibited microglial activation and promoted neurogenesis in the hippocampal dentate gyrus of these rats. These results suggest that the ameliorative effects of YKS on cognitive deficits may be mediated in part by the suppression of the inflammatory activation of microglia.

Conclusions

These findings shed light on the possible mechanism underlying the efficacy of YKS in treating SCZ.
A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis
Authors: Ghosh Soma , Baloni Priyanka , Mukherjee Sumanta , Anand Praveen , Chandra Nagasuma
Published: December 2013

Background

The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis.

Results

The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration.

Conclusions

The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.
Sorbitol required for cell growth and ethanol production by Zymomonas mobilis under heat, ethanol, and osmotic stresses
Authors: Sootsuwan Kaewta , Thanonkeo Pornthap , Keeratirakha Nawapote , Thanonkeo Sudarat , Jaisil Prasit , Yamada Mamoru
Published: December 2013

Background

During ethanol fermentation, the ethanologenic bacterium, Zymomonas mobilis may encounter several environmental stresses such as heat, ethanol and osmotic stresses due to high sugar concentration. Although supplementation of the compatible solute sorbitol into culture medium enhances cell growth of Z. mobilis under osmotic stress, the protective function of this compound on cell growth and ethanol production by this organism under other stresses such as heat and ethanol has not been described yet. The formation of sorbitol in Z. mobilis was carried out by the action of the glucose-fructose oxidoreductase (GFOR) enzyme which is regulated by the gfo gene. Therefore, the gfo gene in Z. mobilis was disrupted by the fusion-PCR-based construction technique in the present study, and the protective function of sorbitol on cell growth, protein synthesis and ethanol production by Z. mobilis under heat, ethanol, and osmotic stresses was investigated.

Results

Based on the fusion-PCR-based construction technique, the gfo gene in Z. mobilis was disrupted. Disruption of the Z. mobilis gfo gene resulted in the reduction of cell growth and ethanol production not only under osmotic stress but also under heat and ethanol stresses. Under these stress conditions, the transcription level of pdc, adhA, and adhB genes involved in the pyruvate-to-ethanol (PE) pathway as well as the synthesis of proteins particularly in Z. mobilis disruptant strain were decreased compared to those of the parent. These findings suggest that sorbitol plays a crucial role not only on cell growth and ethanol production but also on the protection of cellular proteins from stress responses.

Conclusion

We showed for the first time that supplementation of the compatible solute sorbitol not only promoted cell growth but also increased the ethanol fermentation capability of Z. mobilis under heat, ethanol, and osmotic stresses. Although the molecular mechanism involved in tolerance to stress conditions after sorbitol supplementation is still unclear, this research has provided useful information for the development of the effective ethanol fermentation process particularly under environmental conditions with high temperature or high ethanol and sugar concentration conditions.
Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma
Authors: Somovilla-Crespo Beatriz , Alfonso-Pérez Manuel , Cuesta-Mateos Carlos , Carballo-de Dios Cristina , Beltrán Amada E , Terrón Fernando , Pérez-Villar Juan J , Gamallo-Amat Carlos , Pérez-Chacón Gema , Fernández-Ruiz Elena , Zapata Juan M , Muñoz-Calleja Cecilia
Published: December 2013

Background

The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model.

Methods

NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 μg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively.

Results

The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated.

Conclusions

The anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies.
XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway
Authors: Tian Xiao-Hong , Hou Wei-Jian , Fang Yan , Fan Jun , Tong Hao , Bai Shu-Ling , Chen Qu , Xu He , Li Yan
Published: December 2013

Background

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. The present treatment including surgery, chemotherapy and radiation, which have only 40% long-term cure rates, and usually cause tumor recurrence. Thus, looking for new effective and less toxic therapies has important significance. XAV939 is a small molecule inhibitor of tankyrase 1(TNKS1). The objective of this study is to investigate the effect of XAV939 on the proliferation and apoptosis of NB cell lines, and the related mechanism.

Methods

In the present study, we used both XAV939 treatment and RNAi method to demonstrate that TNKS1 inhibition may be a potential mechanism to cure NB. MTT method was used for determining the cell viability and the appropriate concerntration for follow-up assays. The colony formation assay, Annexin V staining and cell cycle analysis were used for detecting colony forming ability, cell apoptosis and the percentage of different cell cycle. The Western blot was used for detecting the expression of key proteins of Wnt/ beta-catenin (Wnt/β-catenin) signaling pathway.

Results

The results showed that TNKS1 inhibition decreased the viability of SH-SY5Y, SK-N-SH and IMR-32 cells, induced apoptosis in SH-SY5Y as well as SK-N-SH cells, and led to the accumulation of NB cells in the S and G2/M phase of the cell cycle. Moreover, we demonstrated TNKS1 inhibition may in part blocked Wnt/β-catenin signaling and reduced the expression of anti-apoptosis protein. Finally, we also demonstrated that TNKS1 inhibition decreased colony formation in vitro.

Conclusions

These findings suggested that TNKS1 may be a potential molecule target for the treatment of NB.
Information and output in agricultural markets: the role of market transparency
Authors: Ahlers Christian , Broll Udo , Eckwert Bernhard
Published: December 2013

This study is concerned with the impact of changes in market transparency on agricultural production levels. Market transparency is of central importance in the agri-food system as it affects the degree of uncertainty farmers face when taking economic decisions. In our study, we endogenize uncertainty by establishing a link between market transparency and the terms of contracting on the futures market. We find that a higher degree of market transparency leads to higher expected profits but does not increase agricultural production levels per se. However, when farmers have no access to futures markets, transparency does increase ex ante expected uility and output.
Multiple vacation policy for MX/Hk/1 queue with un-reliable server
Authors: Jain Madhu , Sharma Richa , Sharma Gokul Chandra
Published: December 2013

This paper studies the operating characteristics of an MX/Hk/1 queueing system under multiple vacation policy. It is assumed that the server goes for vacation as soon as the system becomes empty. When he returns from a vacation and there is one or more customers waiting in the queue, he serves these customers until the system becomes empty again, otherwise goes for another vacation. The breakdown and repair times of the server are assumed to follow a negative exponential distribution. By using a generating function, we derive various performance indices. The approximate formulas for the probability distribution of the waiting time of the customers in the system by using the maximum entropy principle (MEP) are obtained. This approach is accurate enough for practical purposes and is a useful method for solving complex queueing systems. The sensitivity analysis is carried out by taking a numerical illustration.
Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial
Authors: Bachmann Kai A , Trepte Constantin JC , Tomkötter Lena , Hinsch Andrea , Stork Jan , Bergmann Wilken , Heidelmann Lena , Strate Tim , Goetz Alwin E , Reuter Daniel A , Izbicki Jakob R , Mann Oliver
Published: December 2013

Introduction

Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study.

Methods

In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination.

Results

Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05).

Conclusions

TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.
Dendritic cells activated by double-stranded RNA induce arthritis via autocrine type I IFN signaling
Authors: Narendra Sudeep Chenna , Chalise Jaya Prakash , Höök Nina , Magnusson Mattias
Published: December 2013

Viral dsRNA can be found at the site of inflammation in RA patients, and intra-articular injection of dsRNA induces arthritis by activating type I IFN signaling in mice. Further, DCs, a major source of IFN-α, can be found in the synovium of RA patients. We therefore determined the occurrence of DCs in dsRNA-induced arthritis and their ability to induce arthritis. Here, we show, by immunohistochemistry, that cells expressing the pan-DC marker CD11c and the pDC marker 120G8 are present in the inflamed synovium in dsRNA-induced arthritis. Flt3L-generated and splenic DCs preactivated with dsRNA before intra-articular injection, but not mock-stimulated cells, clearly induced arthritis. Induction of arthritis was dependent on type I IFN signaling in the donor DCs, whereas IFNAR expression in the recipient was not required. Sorting of the Flt3L-DC population into cDCs (CD11c+, PDCA-1−) and pDCs (CD11c+, PDCA-1+) revealed that both subtypes were arthritogenic and produced type I IFN if treated with dsRNA. Taken together, these results demonstrate that viral nucleic acids can elicit arthritis by activating type I IFN signaling in DCs. Once triggered, autocrine type I IFN signaling in dsRNA-activated DCs is sufficient to propagate arthritis.
Effects of a novel schizophrenia risk variant rs7914558 atCNNM2on brain structure and attributional style
Authors: Rose Emma Jane , Hargreaves April , Morris Derek , Fahey Ciara , Tropea Daniela , Cummings Elizabeth , Caltagirone Carlo , Bossú Paola , Chiapponi Chiara , Piras Fabrizio , Spalletta Gianfranco , Gill Michael , Corvin Aiden , Donohoe Gary
Published: December 2013

Background

A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by whichCNNM2confers risk is unknown.

Aims

To determine the impact of the rs7914558 risk ‘A’ allele on measures of neurocognition, social cognition and brain structure.

Method

Patients with schizophrenia (n= 400) and healthy controls (n= 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n= 159) and an independent sample of Italian patients (n= 82) and healthy controls (n= 39).

Results

No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations betweenCNNM2and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples.

Conclusions

Although the biological role ofCNNM2in schizophrenia remains unknown, these data suggest that thisCNNM2risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established.
Going for the Cure: Patient Interest Groups and Health Advocacy in the United States
Authors: Keller Ann C. , Packel Laura
Published: December 2013

Citizen groups, though celebrated during their sudden arrival on the lobbying scene, are vastly outnumbered by groups representing elite, occupationally based interests. Sensitive to the odds that nonoccupational groups face, this study asks what factors have allowed patient groups to form and become active in federal politics. Using three distinct data sets — a survey of patient groups, content analysis of group websites, and in-depth interviews with group representatives and policy makers in Washington, DC — this study assesses the activities of patient groups in the United States and argues that patient advocacy organizations garner stability from the relatively easy provision of selective and solidary benefits. Larger patient groups are especially likely to make use of these structural advantages to pursue congressional lobbying strategies. However, even these groups seek out noncompetitive, distributive political environments. Moreover, the study finds that patient groups rarely form coalitions across diseases, forgoing the potential to collectively speak for shared patient interests.