bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global changes in gene expression associated with phenotypic switching of wild yeast
Authors: Šťovíček Vratislav , Váchová Libuše , Begany Markéta , Wilkinson Derek , Palková Zdena 
Published: February 2014

Abstract

Background

Saccharomyces cerevisiae strains isolated from natural settings form structured biofilm colonies that are equipped with intricate protective mechanisms. These wild strains are able to reprogram themselves with a certain frequency during cultivation in plentiful laboratory conditions. The resulting domesticated strains switch off certain protective mechanisms and form smooth colonies that resemble those of common laboratory strains.

Results
Here, we show that domestication can be reversed when a domesticated strain is challenged by various adverse conditions; the resulting feral strain restores its ability to form structured biofilm colonies. Phenotypic, microscopic and transcriptomic analyses show that phenotypic transition is a complex process that affects various aspects of feral strain physiology; it leads to a phenotype that resembles the original wild strain in some aspects and the domesticated derivative in others. We specify the genetic determinants that are likely involved in the formation of a structured biofilm colonies. In addition to FLO11, these determinants include genes that affect the cell wall and membrane composition. We also identify changes occurring during phenotypic transitions that affect other properties of phenotypic strain-variants, such as resistance to the impact of environmental stress. Here we document the regulatory role of the histone deacetylase Hda1p in developing such a resistance.

Conclusions
We provide detailed analysis of transcriptomic and phenotypic modulations of three related S. cerevisiae strains that arose by phenotypic switching under diverse environmental conditions. We identify changes specifically related to a strain’s ability to create complex structured colonies; we also show that other changes, such as genome rearrangement(s), are unrelated to this ability. Finally, we identify the importance of histone deacetylase Hda1p in strain resistance to stresses.
Arginine deiminase pathway is far more important than urease for acid resistance and intracellular survival in Laribacter hongkongensis: a possible result of arc gene cassette duplication
Authors: Xiong Lifeng , Teng Jade LL , Watt Rory M , Kan Biao , Lau Susanna KP , Woo Patrick CY 
Published: February 2014

Abstract

Background

Laribacter hongkongensis is a Gram-negative, urease-positive bacillus associated with invasive bacteremic infections in liver cirrhosis patients and fish-borne community-acquired gastroenteritis and traveler’s diarrhea. Its mechanisms of adaptation to various environmental niches and host defense evasion are largely unknown. During the process of analyzing the L. hongkongensis genome, a complete urease cassette and two adjacent arc gene cassettes were found. We hypothesize that the urease cassette and/or the arc gene cassettes are important for L. hongkongensis to survive in acidic environment and macrophages. In this study, we tested this hypothesis by constructing single, double and triple non-polar deletion mutants of the urease and two arc gene cassettes of L. hongkongensis using the conjugation-mediated gene deletion system and examining their effects in acidic environment in vitro, in macrophages and in a mouse model.

Results
HLHK9∆ureA, HLHK9∆ureC, HLHK9∆ureD and HLHK9∆ureE all exhibited no urease activity. HLHK9∆arcA1 and HLHK9∆arcA2 both exhibited arginine deiminase (ADI) activities, but HLHK9∆arcA1/arcA2 double deletion mutant exhibited no ADI activity. At pH 2 and 3, survival of HLHK9∆arcA1/arcA2 and HLHK9∆ureA/arcA1/arcA2 were markedly decreased (p < 0.001) but that of HLHK9∆ureA was slightly decreased (p < 0.05), compared to wild type L. hongkongensis HLHK9. Survival of HLHK9∆ureA/arcA1/arcA2 and HLHK9∆arcA1/arcA2 in macrophages were also markedly decreased (p < 0.001 and p < 0.01 respectively) but that of HLHK9∆ureA was slightly decreased (p < 0.05), compared to HLHK9, although expression of arcA1, arcA2 and ureA genes were all upregulated. Using a mouse model, HLHK9∆ureA exhibited similar survival compared to HLHK9 after passing through the murine stomach, but survival of HLHK9∆arcA1/arcA2 and HLHK9∆ureA/arcA1/arcA2 were markedly reduced (p < 0.01).

Conclusions
In contrast to other important gastrointestinal tract pathogens, ADI pathway is far more important than urease for acid resistance and intracellular survival in L. hongkongensis. The gene duplication of the arc gene cassettes could be a result of their functional importance in L. hongkongensis.
Physical violence during pregnancy and pregnancy outcomes in Ghana
Authors: Pool Michelle Sharon , Otupiri Easmon , Owusu-Dabo Ellis , de Jonge Ank , Agyemang Charles 
Published: February 2014

Abstract

Background
In pregnancy, violence can have serious health consequences that could affect both mother and child. In Ghana there are limited data on this subject. We sought to assess the relationship between physical violence during pregnancy and pregnancy outcomes (early pregnancy loss, perinatal mortality and neonatal mortality) in Ghana.

Method
The 2008 Ghana Demographic and Health Survey data were used. For the domestic violence module, 2563 women were approached of whom 2442 women completed the module. After excluding missing values and applying the weight factor, 1745 women remained. Logistic regression analysis was performed to assess the relationship between physical violence in pregnancy and adverse pregnancy outcomes with adjustments for potential confounders.

Results
About five percent of the women experienced violence during their pregnancy. Physical violence in pregnancy was positively associated with perinatal mortality and neonatal mortality, but not with early pregnancy loss. The differences remained largely unchanged after adjustment for age, parity, education level, wealth status, marital status and place of residence: adjusted odds ratios were 2.32; 95% CI: 1.34-4.01 for perinatal mortality, 1.86; 95% CI: 1.05-3.30 for neonatal mortality and 1.16; 95% CI: 0.60-2.24 for early pregnancy loss.

Conclusion
Our findings suggest that violence during pregnancy is related to adverse pregnancy outcomes in Ghana. Major efforts are needed to tackle violence during pregnancy. This can be achieved through measures that are directed towards the right target groups. Measures should include education, empowerment and improving socio-economic status of women.
PKC α regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer
Authors: Liu Jiao , Kong Chui-ze , Gong Da-xin , Zhang Zhe , Zhu Yu-yan 
Published: February 2014

Abstract

Background
Netrin-1 and its receptor UNC5B play important roles in angiogenesis, embryonic development, cancer and inflammation. However, their expression patttern and biological roles in bladder cancer have not been well characterized. The present study aims to investigating the clinical significance of PKC α, netrin-1 and UNC5B in bladder cancer as well as their association with malignant biological behavior of cancer cells.

Methods
Netrin-1 and UNC5B expression was examined in 120 bladder cancer specimens using immunohistochemistry and in 40 fresh cancer tissues by western blot. Immunofluorescence was performed in cancer cell lines. PKC α agonist PMA and PKC siRNA was employed in bladder cancer cells. CCK-8, wound healing assays and flow cytometry analysis were used to examine cell proliferation, migration and cell cycle, respectively.

Results
Netrin-1 expression was positively correlated with histological grade, T stage, metastasis and poor prognosis in bladder cancer tissues. Immunofluorescence showed elevated netrin-1 and decreased UNC5B expression in bladder cancer cells compared with normal bladder cell line. Furthermore, cell proliferation, migration and cell cycle progression were promoted with PMA treatment while inhibited by calphostin C. In addition, PMA treatment could induce while calphostin C reduce netrin-1 expression in bladder cancer cells.

Conclusions
The present study identified netrin-1/UNC5B, which could be regulated by PKC signaling, was important mediators of bladder cancer progression.
Molecular analysis of hyperthermophilic endoglucanase Cel12B from Thermotoga maritima and the properties of its functional residues
Authors: Shi Hao , Zhang Yu , Wang Liangliang , Li Xun , Li Wenqian , Wang Fei , Li Xiangqian 
Published: February 2014

Abstract

Background
Although many hyperthermophilic endoglucanases have been reported from archaea and bacteria, a complete survey and classification of all sequences in these species from disparate evolutionary groups, and the relationship between their molecular structures and functions are lacking. The completion of several high-quality gene or genome sequencing projects provided us with the unique opportunity to make a complete assessment and thorough comparative analysis of the hyperthermophilic endoglucanases encoded in archaea and bacteria.

Results
Structure alignment of the 19 hyperthermophilic endoglucanases from archaea and bacteria which grow above 80°C revealed that Gly30, Pro63, Pro83, Trp115, Glu131, Met133, Trp135, Trp175, Gly227 and Glu229 are conserved amino acid residues. In addition, the average percentage composition of residues cysteine and histidine of 19 endoglucanases is only 0.28 and 0.74 while it is high in thermophilic or mesophilic one. It can be inferred from the nodes that there is a close relationship among the 19 protein from hyperthermophilic bacteria and archaea based on phylogenetic analysis. Among these conserved amino acid residues, as far as Cel12B concerned, two Glu residues might be the catalytic nucleophile and proton donor, Gly30, Pro63, Pro83 and Gly227 residues might be necessary to the thermostability of protein, and Trp115, Met133, Trp135, Trp175 residues is related to the binding of substrate. Site-directed mutagenesis results reveal that Pro63 and Pro83 contribute to the thermostability of Cel12B and Met133 is confirmed to have role in enhancing the binding of substrate.

Conclusions
The conserved acids have been shown great importance to maintain the structure, thermostability, as well as the similarity of the enzymatic properties of those proteins. We have made clear the function of these conserved amino acid residues in Cel12B protein, which is helpful in analyzing other undetailed molecular structure and transforming them with site directed mutagenesis, as well as providing the theoretical basis for degrading cellulose from woody and herbaceous plants.
Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release
Authors: Gliga Anda R , Skoglund Sara , Odnevall Wallinder Inger , Fadeel Bengt , Karlsson Hanna L 
Published: February 2014

Abstract

Background
Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity.

Methods
BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and γH2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS).

Results
The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no γH2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4–7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity.

Conclusions
This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a ‘Trojan horse’ effect.
A potential mechanism for extracellular matrix induction of breast cancer cell normality
Authors: Bruno Robert D , Smith Gilbert H 
Published: February 2014

AbstractExtracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.
Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study
Authors: Donati Abele , Damiani Elisa , Luchetti Michele Maria , Domizi Roberta , Scorcella Claudia , Carsetti Andrea , Gabbanelli Vincenzo , Carletti Paola , Bencivenga Rosella , Vink Hans , Adrario Erica , Piagnerelli Michael , Gabrielli Armando , Pelaia Paolo , Ince Can 
Published: February 2014

Abstract
Introduction
Microvascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2) delivery but rarely improves tissue O2 uptake in patients with sepsis. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused RBCs on microcirculation in patients with sepsis.

Methods
In a prospective randomized trial, 20 patients with sepsis were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2 saturation (StO2) and tissue hemoglobin index (THI) were determined with near-infrared spectroscopy, and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage, and glycocalyx compounds (syndecan-1, hyaluronan, and heparan sulfate) were measured in the serum.

Results
No differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When within-group changes were examined, microcirculatory improvement was observed only in patients who received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01), and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2 upslope increased in both groups. StO2 and StO2 downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03).

Conclusions
This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in patients with sepsis, although it suggests a more favorable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings.

Trial registration
ClinicalTrials.gov, NCT01584999
Flagellin and LPS each restores rat lymphocyte populations after colorectal irradiation
Authors: Lacave-Lapalun Jean-Victor , Benderitter Marc , Linard Christine 
Published: February 2014

AbstractRadiation-induced gastrointestinal toxicity, including its shift of the immune balance, remains a major limitation to delivering tumoricidal doses of abdominal radiation therapy. This study evaluates the effect on the colon's innate and adaptive immune responses to moderate irradiation doses and the therapeutic possibilities of maintaining immune homeostasis. We investigated whether administration of the TLR4 agonist LPS or of the TLR5 agonist flagellin, 3 days after a single 20-Gy colorectal irradiation, modified recruitment of neutrophils, NK cells, or CD4+ or CD8+ T cells, 7 days postirradiation. Flow cytometric analysis showed that LPS and flagellin reduced irradiation-induced neutrophil infiltration and normalized NK frequency. LPS normalized the CD4+ population and enhanced the CD8+ population, whereas flagellin maintained the radiation-induced elevation in the frequencies of both. Irradiation also modified TLR4 and TLR5 expression on the surface of both populations, but LPS and flagellin each subsequently normalized them. LPS and flagellin were strong inducers of Th1 cytokines (IL-12p35, IL-12p40, and IFN-γ) and thus, contributed to a shift from the Th2 polarization induced by irradiation toward a Th1 polarization, confirmed by an increase of the T-bet:GATA3 ratio, which assesses the Th1 or Th2 status in mixed cell populations. LPS and flagellin treatment resulted in overexpression of FoxP3, IL-2Rα (CD25), IL-2, and OX40, all expressed specifically and involved in high levels of Treg cell expansion. We observed no variation in Treg function-related expression of IL-10 or CTLA-4. These data suggest that the use of TLR ligands limits the effects of irradiation on innate and adaptive immunity.
Cot/tpl2 participates in the activation of macrophages by adiponectin
Authors: Sanz-Garcia Carlos , Nagy Laura E , Lasunción Miguel A , Fernandez Margarita , Alemany Susana 
Published: February 2014

AbstractWhereas the main function of APN is to enhance insulin activity, it is also involved in modulating the macrophage phenotype. Here, we demonstrate that at physiological concentrations, APN activates Erk1/2 via the IKKβ-p105/NF-κΒ1-Cot/tpl2 intracellular signal transduction cassette in macrophages. In peritoneal macrophages stimulated with APN, Cot/tpl2 influences the ability to phagocytose beads. However, Cot/tpl2 did not modulate the known capacity of APN to decrease lipid content in peritoneal macrophages in response to treatment with oxLDL or acLDL. A microarray analysis of gene-expression profiles in BMDMs exposed to APN revealed that APN modulated the expression of ∼3300 genes; the most significantly affected biological functions were the inflammatory and the infectious disease responses. qRT-PCR analysis of WT and Cot/tpl2 KO macrophages stimulated with APN for 0, 3, and 18 h revealed that Cot/tpl2 participated in the up-regulation of APN target inflammatory mediators included in the cytokine–cytokine receptor interaction pathway (KEGG ID 4060). In accordance with these data, macrophages stimulated with APN increased secretion of cytokines and chemokines, including IL-1β, IL-1α, TNF-α, IL-10, IL-12, IL-6, and CCL2. Moreover, Cot/tpl2 also played an important role in the production of these inflammatory mediators upon stimulation of macrophages with APN. It has been reported that different types of signals that stimulate TLRs, IL-1R, TNFR, FcγR, and proteinase-activated receptor-1 activate Cot/tpl2. Here, we demonstrate that APN is a new signal that activates the IKKβ-p105/NF-κΒ1-Cot/tpl2-MKK1/2-Erk1/2 axis in macrophages. Furthermore, this signaling cassette modulates the biological functions triggered by APN in macrophages.
Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors
Authors: Antón Luis C , Yewdell Jonathan W 
Published: February 2014

AbstractMHC class I molecules display oligopeptides on the cell surface to enable T cell immunosurveillance of intracellular pathogens and tumors. Speed is of the essence in detecting viruses, which can complete a full replication cycle in just hours, whereas tumor detection is typically a finding-the-needle-in-the-haystack exercise. We review current evidence supporting a nonrandom, compartmentalized selection of peptidogenic substrates that focuses on rapidly degraded translation products as a main source of peptide precursors to optimize immunosurveillance of pathogens and tumors.
Zwischen religiöser Ideologie und religiösem Fundamentalismus
Authors: Fischer Johannes 
Published: February 2014

Abstract According to a wide-spread opinion, protestant ethics is based on its Christian understanding of reality. Hence the task of protestant ethics is seen in the deduction and justification of moral judgments about ethically controversial questions from premises of the Christian faith. The present contribution offers an in-depth critique of this predominant view. Its assumption is that this concept is based on a wrong understanding of both moral and religion. Either one is connected to the presence of reality (»Wirklichkeitspräsenz«); thus the relation between the two has to be determined within the horizon of the presence of reality instead of theoretical deductions and constructs.
Zur gesellschaftlichen Bedeutung von Kirchenräumen in Zeiten religiöser Relativierung
Authors: Körs Anna 
Published: February 2014

ZusammenfassungIn Zeiten von Globalisierung, Pluralisierung und Säkularisierung werden auch religiöse Räume und ihre Bedeutungen neu verhandelt. Kirchenräume sind nicht nur Gotteshäuser, sondern - gerade durch ihre Bedeutungsvarianz sowie als Erinnerungs- und Gefühlsräume - wichtige symbolische Orte der Gesellschaft. Dabei ist ihre Wirksamkeit weder materialistisch durch den Kirchenraum noch konstruktivistisch durch den Kirchenbesucher zu erklären, sondern entsteht erst in der interrelationalen Verbindung aus beiden. In einer netzwerktheoretischen Deutung des Kirchenraums wird seine relationale Wirkungskraft deutlich sowie sein besonderes Potential als gesellschaftliche Gestaltungkraft und im interreligiösen Dialog.
The Characters of Mo-MoSi2 Functionally Graded Coating
Authors: Zhang Ying-Yi , Li Yun-Gang , Qi Yuan-Hong , Zou Zong-Shu 
Published: February 2014

AbstractMo-MoSi2 functionally graded coating on Mo substrate is prepared by siliconizing technology. The characters of Mo-MoSi2 functionally graded coating are analyzed by SEM, EDS, GDS and XRD. The result shows that Mo-MoSi2 functionally graded coating is dense and smooth, without pore and crack defects, gradient coating and Mo matrix achieve good metallurgy bond. The silicon molybdenum atom ratios (Si/Mo) in functionally graded coating appear three changing regularities. When the Si/Mo of outer layer are from 6:1 to 2:1, the surface phase is constituted by MoSi2 and Si; when the Si/Mo of interlayer is about 2:1, the interlayer phase is constituted by MoSi2; when the Si/Mo of transitional layer are from 2:1 to 0:1, the transitional layer phase is constituted by Mo5Si3 and Mo. The phase structure of Mo-MoSi2 functionally graded coating from outside to inside is outer layer MoSi2 + Si, interlayer MoSi2 and transitional layer Mo5Si3 + Mo3Si three-layer structure. The thermodynamic calculation results are consistent with the experimental results substantially.