bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

AbstractViral 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

BackgroundA 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.AimsTo determine the impact of the rs7914558 risk ‘A’ allele on measures of neurocognition, social cognition and brain structure.MethodPatients 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).ResultsNo 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.ConclusionsAlthough 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

AbstractCitizen 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.
Locomotion- and mechanics-mediated tactile sensing: antenna reconfiguration simplifies control during high-speed navigation in cockroaches
Authors: Mongeau Jean-Michel , Demir Alican , Lee Jusuk , Cowan Noah J. , Full Robert J. 
Published: December 2013

SUMMARYAnimals can expend energy to acquire sensory information by emitting signals and/or moving sensory structures. We propose that the energy from locomotion itself could permit control of a sensor, whereby animals use the energy from movement to reconfigure a passive sensor. We investigated high-speed, antenna-mediated tactile navigation in the cockroach Periplaneta americana. We discovered that the passive antennal flagellum can assume two principal mechanical states, such that the tip is either projecting backward or forward. Using a combination of behavioral and robotic experiments, we demonstrate that a switch in the antenna's state is mediated via the passive interactions between the sensor and its environment, and this switch strongly influences wall-tracking control. When the tip of the antenna is projected backward, the animals maintain greater body-to-wall distance with fewer body collisions and less leg–wall contact than when the tip is projecting forward. We hypothesized that distally pointing mechanosensory hairs at the tip of the antenna mediate the switch in state by interlocking with asperities in the wall surface. To test this hypothesis, we performed laser ablation of chemo-mechanosensory hairs and added artificial hairs to a robotic antenna. In both the natural and artificial systems, the presence of hairs categorically increased an antenna's probability of switching state. Antennal hairs, once thought to only play a role in sensing, are sufficient for mechanically reconfiguring the state of the entire antenna when coupled with forward motion. We show that the synergy between antennal mechanics, locomotion and the environment simplifies tactile sensing.
Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal
Authors: Martinez Bridget , Soñanez-Organis José G. , Vázquez-Medina José Pablo , Viscarra Jose A. , MacKenzie Duncan S. , Crocker Daniel E. , Ortiz Rudy M. 
Published: December 2013

SUMMARYFood deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5–7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic–pituitary–thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism.
Maintaining acoustic communication at a cocktail party: heterospecific masking noise improves signal detection through frequency separation
Authors: Siegert M. E. , Römer H. , Hartbauer M. 
Published: December 2013

SUMMARYWe examined acoustic masking in a chirping katydid species of the Mecopoda elongata complex due to interference with a sympatric Mecopoda species where males produce continuous trills at high amplitudes. Frequency spectra of both calling songs range from 1 to 80 kHz; the chirper species has more energy in a narrow frequency band at 2 kHz and above 40 kHz. Behaviourally, chirper males successfully phase-locked their chirps to playbacks of conspecific chirps under masking conditions at signal-to-noise ratios (SNRs) of −8 dB. After the 2 kHz band in the chirp had been equalised to the level in the masking trill, the breakdown of phase-locked synchrony occurred at a SNR of +7 dB. The remarkable receiver performance is partially mirrored in the selective response of a first-order auditory interneuron (TN1) to conspecific chirps under these masking conditions. However, the selective response is only maintained for a stimulus including the 2 kHz component, although this frequency band has no influence on the unmasked TN1 response. Remarkably, the addition of masking noise at 65 dB sound pressure level (SPL) to threshold response levels of TN1 for pure tones of 2 kHz enhanced the sensitivity of the response by 10 dB. Thus, the spectral dissimilarity between masker and signal at a rather low frequency appears to be of crucial importance for the ability of the chirping species to communicate under strong masking by the trilling species. We discuss the possible properties underlying the cellular/synaptic mechanisms of the ‘novelty detector’.