bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of new p53 target microRNAs by bioinformatics and functional analysis
Authors: Bisio Alessandra , De Sanctis Veronica , Del Vescovo Valerio , Denti Michela A , Jegga Anil G , Inga Alberto , Ciribilli Yari
Published: November 2013

Background

The tumor suppressor p53 is a sequence-specific transcription factor that regulates an extensive network of coding genes, long non-coding RNAs and microRNAs, that establish intricate gene regulatory circuits influencing many cellular responses beyond the prototypical control of cell cycle, apoptosis and DNA repair.

Methods

Using bioinformatic approaches, we identified an additional group of candidate microRNAs (miRs) under direct p53 transcriptional control. To validate p53 family-mediated responsiveness of the newly predicted target miRs we first evaluated the potential for wild type p53, p63β and p73β to transactivate from p53 response elements (REs) mapped in the miR promoters, using an established yeast-based assay.

Results

The REs found in miR-10b, -23b, -106a, -151a, -191, -198, -202, -221, -320, -1204, -1206 promoters were responsive to p53 and 8 of them were also responsive to p63β or p73β. The potential for germline p53 mutations to drive transactivation at selected miR-associated REs was also examined. Chromatin Immuno-Precipitation (ChIP) assays conducted in doxorubicin-treated MCF7 cells and HCT116 p53+/+ revealed moderate induction of p53 occupancy at the miR-202, -1204, -1206, -10b RE-containing sites, while weak occupancy was observed for the miR-23b-associated RE only in MCF7 cells. RT-qPCR analyses cells showed modest doxorubicin- and/or Nutlin-dependent induction of the levels of mature miR-10b, -23b, -151a in HCT116 p53+/+ and MCF7 cells. The long noncoding RNA PVT1 comprising miR-1204 and −1206 was weakly induced only in HCT116 p53+/+ cells, but the mature miRs were not detected. miR-202 expression was not influenced by p53-activating stimuli in our cell systems.

Conclusions

Our study reveals additional miRs, particularly miR-10b and miR-151a, that could be directly regulated by the p53-family of transcription factors and contribute to the tuning of p53-induced responses.
The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities
Authors: Watanabe Susan M , Chen Min-Huei , Khan Mahfuz , Ehrlich Lorna , Kemal Kimdar Sherefa , Weiser Barbara , Shi Binshan , Chen Chaoping , Powell Michael , Anastos Kathryn , Burger Harold , Carter Carol A
Published: November 2013

Background

HIV-1 budding is directed primarily by two motifs in Gag p6 designated as late domain-1 and −2 that recruit ESCRT machinery by binding Tsg101 and Alix, respectively, and by poorly characterized determinants in the capsid (CA) domain. Here, we report that a conserved Gag p6 residue, S40, impacts budding mediated by all of these determinants.

Results

Whereas budding normally results in formation of single spherical particles ~100 nm in diameter and containing a characteristic electron-dense conical core, the substitution of Phe for S40, a change that does not alter the amino acids encoded in the overlapping pol reading frame, resulted in defective CA-SP1 cleavage, formation of strings of tethered particles or filopodia-like membrane protrusions containing Gag, and diminished infectious particle formation. The S40F-mediated release defects were exacerbated when the viral-encoded protease (PR) was inactivated or when L domain-1 function was disrupted or when budding was almost completely obliterated by the disruption of both L domain-1 and −2. S40F mutation also resulted in stronger Gag-Alix interaction, as detected by yeast 2-hybrid assay. Reducing Alix binding by mutational disruption of contact residues restored single particle release, implicating the perturbed Gag-Alix interaction in the aberrant budding events. Interestingly, introduction of S40F partially rescued the negative effects on budding of CA NTD mutations EE75,76AA and P99A, which both prevent membrane curvature and therefore block budding at an early stage.

Conclusions

The results indicate that the S40 residue is a novel determinant of HIV-1 egress that is most likely involved in regulation of a critical assembly event required for budding in the Tsg101-, Alix-, Nedd4- and CA N-terminal domain affected pathways.
Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes
Authors: Kochi Mitsugu , Fujii Masashi , Masuda Shinobu , Kanamori Noriaki , Mihara Yoshiaki , Funada Tomoya , Tamegai Hidenori , Watanabe Megumu , Suda Hiroshi , Takayama Tadatoshi
Published: November 2013

Background

The aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents.

Methods

The analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated.

Results

Positive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754).

Conclusion

The high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.
RaTrav: a tool for calculating mean first-passage times on biochemical networks
Authors: Torchala Mieczyslaw , Chelminiak Przemyslaw , Kurzynski Michal , Bates Paul A
Published: November 2013

Background

The concept of mean first-passage times (MFPTs) occupies an important place in the theory of stochastic processes, with the methods of their calculation being equally important in theoretical physics, chemistry and biology. We present here a software tool designed to support computational biology studies where Markovian dynamics takes place and MFPTs between initial and single or multiple final states in network-like systems are used. Two methods are made available for which their efficiency is strongly dependent on the topology of the defined network: the combinatorial Hill technique and the Monte Carlo simulation method.

Results

After a brief introduction to RaTrav, we highlight the utility of MFPT calculations by providing two examples (accompanied by Additional file 1) where they are deemed to be of importance: analysis of a protein-protein docking funnel and interpretation of the free energy transduction between two coupled enzymatic reactions controlled by the dynamics of transition between enzyme conformational states.

Conclusions

RaTrav is a versatile and easy to use software tool for calculating MFPTs across biochemical networks. The user simply prepares a text file with the structure of a given network, along with some additional basic parameters such as transition probabilities, waiting probabilities (if any) and local times (weights of edges), which define explicitly the stochastic dynamics on the network. The RaTrav tool can then be applied in order to compute desired MFPTs. For the provided examples, we were able to find the favourable binding path within a protein-protein docking funnel and to calculate the degree of coupling for two chemical reactions catalysed simultaneously by the same protein enzyme. However, the list of possible applications is much wider.
Gout with auricular tophi following anti-tuberculosis treatment: a case report
Authors: Chang Hsin-Jen , Wang Pa-Chun , Hsu Ying-Chieh , Huang Shih-Hung
Published: November 2013

Background

Auricular tophi are firm deposits of monosodium urate in crystal form, which may slowly develop in subcutaneous tissue of the ear. Ear is not usual locations for gout tophi, but when this growth does occur, helix and the antihelix are common sites.

Case presentation

We present a 64-year-old man who had multiple painless nodules over bilateral helix. An excisional biopsy was performed. Hematoxylin-eosin staining of biopsy specimens revealed a proteinaceous matrix that surrounded dissolved crystals, consistent with gout tophi. Bilateral auricular tophi are not common and may resemble a number of other diseases including squamous cell carcinomas, Kaposi’s sarcoma, epidermal and dermoid cysts, rheumatoid nodules. Biopsy should be performed to rule out malignancy.

Conclusions

Tophi of the auricle are usually asymptomatic but can become inflamed and occasionally ulcerate through the overlying skin. Chronic tophaceous gout is treated with dietary control and medication. Surgical excision is performed under local anesthetic if symptoms progression or cosmetically deformity is concerned.
Modeling the contrasting Neolithic male lineage expansions in Europe and Africa
Authors: Sikora Michael J , Colonna Vincenza , Xue Yali , Tyler-Smith Chris
Published: November 2013

Background

Patterns of genetic variation in a population carry information about the prehistory of the population, and for the human Y chromosome an especially informative phylogenetic tree has previously been constructed from fully-sequenced chromosomes. This revealed contrasting bifurcating and starlike phylogenies for the major lineages associated with the Neolithic expansions in sub-Saharan Africa and Western Europe, respectively.

Results

We used coalescent simulations to investigate the range of demographic models most likely to produce the phylogenetic structures observed in Africa and Europe, assessing the starting and ending genetic effective population sizes, duration of the expansion, and time when expansion ended. The best-fitting models in Africa and Europe are very different. In Africa, the expansion took about 12 thousand years, ending very recently; it started from approximately 40 men and numbers expanded approximately 50-fold. In Europe, the expansion was much more rapid, taking only a few generations and occurring as soon as the major R1b lineage entered Europe; it started from just one to three men, whose numbers expanded more than a thousandfold.

Conclusions

Although highly simplified, the demographic model we have used captures key elements of the differences between the male Neolithic expansions in Africa and Europe, and is consistent with archaeological findings.
Colonization patterns of soil microbial communities in the Atacama Desert
Authors: Crits-Christoph Alexander , Robinson Courtney K , Barnum Tyler , Fricke W Florian , Davila Alfonso F , Jedynak Bruno , McKay Christopher P , DiRuggiero Jocelyne
Published: November 2013

Background

The Atacama Desert is one of the driest deserts in the world and its soil, with extremely low moisture, organic carbon content, and oxidizing conditions, is considered to be at the dry limit for life.

Results

Analyses of high throughput DNA sequence data revealed that bacterial communities from six geographic locations in the hyper-arid core and along a North-South moisture gradient were structurally and phylogenetically distinct (ANOVA test for observed operating taxonomic units at 97% similarity (OTU0.03), P <0.001) and that communities from locations in the hyper-arid zone displayed the lowest levels of diversity. We found bacterial taxa similar to those found in other arid soil communities with an abundance of Rubrobacterales, Actinomycetales, Acidimicrobiales, and a number of families from the Thermoleophilia. The extremely low abundance of Firmicutes indicated that most bacteria in the soil were in the form of vegetative cells. Integrating molecular data with climate and soil geochemistry, we found that air relative humidity (RH) and soil conductivity significantly correlated with microbial communities’ diversity metrics (least squares linear regression for observed OTU0.03 and air RH and soil conductivity, P <0.001; UniFrac PCoA Spearman’s correlation for air RH and soil conductivity, P <0.0001), indicating that water availability and salt content are key factors in shaping the Atacama soil microbiome. Mineralization studies showed communities actively metabolizing in all soil samples, with increased rates in soils from the southern locations.

Conclusions

Our results suggest that microorganisms in the driest soils of the Atacama Desert are in a state of stasis for most of the time, but can potentially metabolize if presented with liquid water for a sufficient duration. Over geological time, rare rain events and physicochemical factors potentially played a major role in selecting micro-organisms that are most adapted to extreme desiccating conditions.
Utilization of oleo-chemical industry by-products for biosurfactant production
Authors: Bhardwaj Garima , Cameotra Swaranjit Singh , Chopra Harish Kumar
Published: November 2013

Biosurfactants are the surface active compounds produced by micro-organisms. The eco-friendly and biodegradable nature of biosurfactants makes their usage more advantageous over chemical surfactants. Biosurfactants encompass the properties of dropping surface tension, stabilizing emulsions, promoting foaming and are usually non- toxic and biodegradable. Biosurfactants offer advantages over their synthetic counterparts in many applications ranging from environmental, food, and biomedical, cosmetic and pharmaceutical industries. The important environmental applications of biosurfactants include bioremediation and dispersion of oil spills, enhanced oil recovery and transfer of crude oil. The emphasis of present review shall be with reference to the commercial production, current developments and future perspectives of a variety of approaches of biosurfactant production from the micro-organisms isolated from various oil- contaminated sites and from the by-products of oleo-chemical industry wastes/ by-products viz. used edible oil, industrial residues, acid oil, deodorizer distillate, soap-stock etc.
Evaluation of shear bond strength of orthodontic brackets using trans-illumination technique with different curing profiles of LED light-curing unit in posterior teeth
Authors: Heravi Farzin , Moazzami Saied Mostafa , Ghaffari Negin , Jalayer Javad , Bozorgnia Yasaman
Published: November 2013

Background

Although using light-cured composites for bonding orthodontic brackets has become increasingly popular, curing light cannot penetrate the metallic bulk of brackets and polymerization of composites is limited to the edges. Limited access and poor direct sight may be a problem in the posterior teeth. Meanwhile, effectiveness of the trans-illumination technique is questionable due to increased bucco-lingual thickness of the posterior teeth. Light-emitting diode (LED) light-curing units cause less temperature rise and lower risk to the pulpal tissue. The purpose of this study was to evaluate the clinical effectiveness of trans-illumination technique in bonding metallic brackets to premolars, using different light intensities and curing times of an LED light-curing unit.

Methods

Sixty premolars were randomly divided into six groups. Bonding of brackets was done with 40- and 80-s light curing from the buccal or lingual aspect with different intensities. Shear bond strengths of brackets were measured using a universal testing machine. Data were analyzed by one-way analysis of variance test and Duncan's post hoc test.

Results

The highest shear bond belonged to group 2 (high intensity, 40 s, buccal) and the lowest belonged to group 3 (low intensity, 40 s, lingual). Bond strength means in control groups were significantly higher than those in experimental groups.

Conclusions

In all experimental groups except group 6 (80 s, high intensity, lingual), shear bond strength was below the clinically accepted values. In clinical limitations where light curing from the same side of the bracket is not possible, doubling the curing time and increasing the light intensity during trans-illumination are recommended for achieving acceptable bond strengths.
NFAT3 and TGF-β/SMAD3 regulate the expression of miR-140 in osteoarthritis
Authors: Tardif Ginette , Pelletier Jean-Pierre , Fahmi Hassan , Hum David , Zhang Yue , Kapoor Mohit , Martel-Pelletier Johanne
Published: November 2013

Introduction

MicroRNAs (miRNAs) down-regulate their target genes. The intronic miR-140, present in the WW domain containing E3 ubiquitin protein ligase 2 (WWP2) gene, decreases the expression of genes that play detrimental roles in osteoarthritis (OA). As the expression level of miR-140 is significantly decreased in human OA chondrocytes, we investigated its regulation in those cells.

Methods

Gene expression in human chondrocytes was determined by quantitative polymerase chain reaction (qPCR) and gene silencing was done in OA chondrocytes by transient transfection with specific small interfering RNAs (siRNAs). Binding sites of the miR-140 regulatory sequence (rsmiR-140) were identified by mutagenesis and chromatin immunoprecipitation (ChIP) in OA chondrocytes. The effects of translocation on OA chondrocytes were determined by immunocytochemistry and qPCR.

Results

In contrast to miR-140, the expression of WWP2 was similar in both normal and OA cells, suggesting that miR-140 has an additional level of regulation. rsmiR-140 showed activity and predicted binding sites for nuclear matrix transcription factor 4 (NMP4), myc-associated zinc (MAZ), nuclear factor of activated T-cells (NFAT), and mothers against decapentaplegic homolog 3 (SMAD3). Silencing NFAT3 (P ≤0.01) and SMAD3 (P ≤0.05) differentially regulated miR-140 independently of WWP2. Silencing NFAT5 decreased both miR-140 and WWP2 (P ≤0.003 and P ≤0.05, respectively). NFAT3 activation increased and transforming growth factor-β (TGF-β) decreased rsmiR-140 activity. Mutagenesis of rsmiR-140 and ChIP assays identified binding sites at which NFAT3 (activator) and SMAD3 (repressor) directly regulated miR-140. TGF-β interfered with NFAT3 translocation, and subsequently with miR-140 expression.

Conclusions

This is the first study to provide evidence of a regulatory mechanism of miR-140 independent of WWP2, and new and differential roles for NFAT3 and SMAD3 in the OA process in the regulation of miR-140 transcription. Such knowledge could advance therapeutic strategies targeting OA.
Recursive integral time-extrapolation methods for waves: A comparative review
Authors: Du Xiang , Fowler Paul J. , Fletcher Robin P.
Published: November 2013

We compared several families of algorithms for recursive integral time-extrapolation (RITE) algorithms for waves in isotropic and anisotropic media. These methods allow simulating accurate wave extrapolation with little numerical dispersion even when using larger time steps than are usually possible for conventional finite-difference methods. These various RITE algorithms all share the use of mixed space/wavenumber-domain operators derived from Fourier integral solutions of single-mode wave equations. We evaluated a taxonomy for RITE methods based on how they approximated the influence of medium heterogeneity. One family of methods uses mixed-domain series expansions to provide accurate approximations to heterogeneous extrapolators even for large time steps. We compared several methods for deriving coefficients for such series approximations. Another family of methods uses interpolation between different homogeneous extrapolations to approximate heterogeneous time extrapolation. Such methods can be based on interpolating either the extrapolators themselves or interpolating between reference wavefields extrapolated using different homogeneous parameters. Interpolation methods work well for smooth media, but can suffer from oscillatory artifacts at large velocity discontinuities unless the time step is small. We tested numerical examples of the various families of RITE algorithms to determine their relative strengths and limitations.
Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish
Authors: Hruscha Alexander , Krawitz Peter , Rechenberg Alexandra , Heinrich Verena , Hecht Jochen , Haass Christian , Schmid Bettina
Published: November 2013

Gene modifications in animal models have been greatly facilitated through the application of targeted genome editing tools. The prokaryotic CRISPR/Cas9 type II genome editing system has recently been applied in cell lines and vertebrates. However, we still have very limited information about the efficiency of mutagenesis, germline transmission rates and off-target effects in genomes of model organisms. We now demonstrate that CRISPR/Cas9 mutagenesis in zebrafish is highly efficient, reaching up to 86.0%, and is heritable. The efficiency of the CRISPR/Cas9 system further facilitated the targeted knock-in of a protein tag provided by a donor oligonucleotide with knock-in efficiencies of 3.5-15.6%. Mutation rates at potential off-target sites are only 1.1-2.5%, demonstrating the specificity of the CRISPR/Cas9 system. The ease and efficiency of the CRISPR/Cas9 system with limited off-target effects make it a powerful genome engineering tool for in vivo studies.
Brain tumor specifies intermediate progenitor cell identity by attenuating β-catenin/Armadillo activity
Authors: Komori Hideyuki , Xiao Qi , McCartney Brooke M. , Lee Cheng-Yu
Published: November 2013

During asymmetric stem cell division, both the daughter stem cell and the presumptive intermediate progenitor cell inherit cytoplasm from their parental stem cell. Thus, proper specification of intermediate progenitor cell identity requires an efficient mechanism to rapidly extinguish the activity of self-renewal factors, but the mechanisms remain unknown in most stem cell lineages. During asymmetric division of a type II neural stem cell (neuroblast) in the Drosophila larval brain, the Brain tumor (Brat) protein segregates unequally into the immature intermediate neural progenitor (INP), where it specifies INP identity by attenuating the function of the self-renewal factor Klumpfuss (Klu), but the mechanisms are not understood. Here, we report that Brat specifies INP identity through its N-terminal B-boxes via a novel mechanism that is independent of asymmetric protein segregation. Brat-mediated specification of INP identity is critically dependent on the function of the Wnt destruction complex, which attenuates the activity of β-catenin/Armadillo (Arm) in immature INPs. Aberrantly increasing Arm activity in immature INPs further exacerbates the defects in the specification of INP identity and enhances the supernumerary neuroblast mutant phenotype in brat mutant brains. By contrast, reducing Arm activity in immature INPs suppresses supernumerary neuroblast formation in brat mutant brains. Finally, reducing Arm activity also strongly suppresses supernumerary neuroblasts induced by overexpression of klu. Thus, the Brat-dependent mechanism extinguishes the function of the self-renewal factor Klu in the presumptive intermediate progenitor cell by attenuating Arm activity, balancing stem cell maintenance and progenitor cell specification.
Peroxisome proliferator-activated receptor-γ interrupts angiogenic signal transduction via transrepression of platelet-derived growth factor-β receptor in hepatic stellate cells
Authors: Zhang Feng , Kong Desong , Chen Li , Zhang Xiaoping , Lian Naqi , Zhu Xiaojing , Lu Yin , Zheng Shizhong
Published: November 2013

Hepatic stellate cells (HSCs) are liver-specific pericytes with capabilities to recruit to vessels and secret pro-angiogenic cytokines and thus actively involved in pathologic vascularization during liver fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) is a switch molecule controlling HSC activation. Herein we investigated the PPARγ regulation of angiogenic signal transduction and the molecular mechanisms in HSCs. Primary rat HSCs and liver sinusoidal endothelial cells (LSECs) were isolated and used in this study. Using Boyden chamber assay and tubulogenesis assay, we found that focal adhesion kinase (FAK)/RhoA signaling activated by platelet-derived growth factor (PDGF) was required for HSC motility and associated vascularization. PDGF also simulated vascular endothelial growth factor (VEGF) expression and HSC-driven vascularization via signals mediated by extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Gain- and loss-of-function analyses demonstrated that activation of PPARγ interrupted FAK/RhoA, ERK and mTOR cascades and inhibited HSC-based vascularization. Molecular evidence further revealed that PPARγ attenuation of HSC angiogenic properties was dependent on inhibition of PDGF-β receptor expression. We concluded that PPARγ inhibited angiogenic signal transduction via transrepression of PDGF-β receptor leading to inhibited HSC motility, reduced VEGF expression, and thereby attenuated HSC-driven angiogenesis. PPARγ could be a molecular target for preventing vascular remolding in hepatic fibrosis.
The RhoGAP ARHGAP19 controls cytokinesis and chromosome segregation in T lymphocytes
Authors: David Muriel D. , Petit Dominique , Bertoglio Jacques
Published: November 2013

Small GTP-binding proteins of the Rho family orchestrate the cytoskeleton remodeling events required for cell division. Guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) promote cycling of Rho GTPases between the active GTP-bound and the inactive GDP-bound conformations. We report that ARHGAP19, a previously uncharacterized protein, is predominantly expressed in hematopoietic cells and is a critical actor of T lymphocyte division. Overexpression of ARHGAP19 in lymphocytes delays cell elongation and cytokinesis. Conversely, silencing of ARHGAP19 or expression of a GAP-deficient mutant induces precocious mitotic cell elongation and cleavage furrow ingression, as well as excessive blebbing. In relation with these phenotypes, we show that ARHGAP19 acts as a GAP for RhoA, and controls Citron and Myosin II recruitment to the plasma membrane of mitotic lymphocytes as well as Rock2-mediated phosphorylation of Vimentin, a critical determinant in stiffness and shape of lymphocytes. In addition to its effects on cell shape changes, silencing of ARHGAP19 in lymphocytes also impairs chromosome segregation.
A bacterial tubulovesicular network
Authors: Acehan Devrim , Santarella-Mellwig Rachel , Devos Damien P
Published: November 2013

We report the presence of a membranous tubulovesicular network in the planctomycete bacterium Gemmata obscuriglobus. This endomembrane system interacts with membrane coat proteins and is capable of protein internalization and degradation. Taken together, this suggests that the planctomycetal bacterium may illuminate the emergence of complex endomembrane systems.
Sphingomyelin synthase-related protein SMSr is a suppressor of ceramide-induced mitochondrial apoptosis
Authors: Tafesse Fikadu G. , Vacaru Ana M. , Bosma Elleke F. , Hermansson Martin , Jain Amrita , Hilderink Angelika , Somerharju Pentti , Holthuis Joost C. M.
Published: November 2013

Cells synthesize ceramides in the endoplasmic reticulum (ER) as precursors for sphingolipids to form an impermeable plasma membrane. As ceramides are engaged in apoptotic pathways, cells would need to monitor their levels closely to avoid killing themselves during sphingolipid biosynthesis. How this is accomplished remains to be established. Here we identify SMSr (SAMD8), an ER-resident ceramide phosphoethanolamine (CPE) synthase, as suppressor of ceramide-mediated cell death. Disruption of SMSr catalytic activity causes a rise in ER ceramides and their mislocalization to mitochondria, triggering a mitochondrial pathway of apoptosis. Blocking de novo ceramide synthesis, stimulating ceramide export from the ER, or targeting a bacterial ceramidase to mitochondria rescues SMSr-deficient cells from apoptosis. We also show that SMSr-catalysed CPE production, although required, is not sufficient to suppress ceramide-induced cell death and that SMSr-mediated ceramide homeostasis is critically dependent on the enzyme's N-terminal sterile α-motif or SAM domain. These results define ER ceramides as bona fide transducers of mitochondrial apoptosis and indicate a primary role of SMSr in monitoring ER ceramide levels to prevent inappropriate cell death during sphingolipid biosynthesis.
The conserved ciliary protein Bug22 controls planar beating ofChlamydomonasflagella
Authors: Meng Dan , Cao Muqing , Oda Toshiyuki , Kikkawa Masahide , Pan Junmin
Published: November 2013

Eukaryotic flagella and cilia may exhibit planar or non-planar beating, the mechanism underlying which is unknown. Chlamydomonas flagella beat in approximately the same plane either in asymmetric ciliary or symmetric flagellar waveforms. Each B tubule of number 1, 5 and 6 doublets of the flagellar axoneme possesses a beak-like structure. The number 5 and 6 beak structures are implicated in conversion of ciliary motion into flagellar motion. Here, we show that a null mutant of Bug22 converts asymmetric ciliary waveform into symmetric flagellar waveforms in three dimensions. Bug22 is localized approximately to the proximal half to two-thirds of the flagellum, similar to localization of beak-like structures. However, Bug22 associates with axonemal microtubules without apparent preference for any doublets shown by immunogold labeling. Interestingly, bug22 lacks all beak-like structures. We propose that one function of Bug22 is to regulate the anchoring of the beak-like structures to the doublet microtubules and confines flagellar beating in a plane.
Anoxia-mediated calcium release through the mitochondrial permeability transition pore silences NMDA receptor currents in turtle neurons
Authors: Hawrysh Peter John , Buck Leslie Thomas
Published: November 2013

Mammalian neurons are anoxia sensitive and rapidly undergo excitotoxic cell death when deprived of oxygen, mediated largely by Ca2+ entry through over-activation of N-methyl-d-aspartate receptors (NMDARs). This does not occur in neurons of the anoxia-tolerant western painted turtle, where a decrease in NMDAR currents is observed with anoxia. This decrease is dependent on a modest rise in cytosolic [Ca2+] ([Ca2+]c) that is mediated by release from the mitochondria. The aim of this study was to determine whether the mitochondrial permeability transition pore (mPTP) is involved in NMDAR silencing through release of mitochondrial Ca2+. Opening the mPTP during normoxia with atractyloside decreased NMDAR currents by releasing mitochondrial Ca2+, indicated by an increase in Oregon Green fluorescence. Conversely, the mPTP blocker cyclosporin A prevented the anoxia-mediated increase in [Ca2+]c and reduction in NMDAR currents. Mitochondrial membrane potential (Ψm) was determined using rhodamine-123 fluorescence and decreased with the onset of anoxia in a time frame that coincided with the increase in [Ca2+]c. Activation of mitochondrial ATP-sensitive potassium (mK+ATP) channels also releases mitochondrial Ca2+ and we show that activation of mK+ATP channels during normoxia with diazoxide leads to Ψm depolarization and inhibition with 5-hydroxydecanoic acid blocked anoxia-mediated Ψm depolarization. Ψm does not collapse during anoxia but rather reaches a new steady-state level that is maintained via ATP hydrolysis by the F1-F0 ATPase, as inhibition with oligomycin depolarizes Ψm further than the anoxic level. We conclude that anoxia activates mK+ATP channels, which leads to matrix depolarization, Ca2+ release via the mPTP, and ultimately silencing of NMDARs.
Monitoring ferumoxide-labelled neural progenitor cells and lesion evolution by magnetic resonance imaging in a model of cell transplantation in cerebral ischaemia
Authors: Panizzo Rachael A , Gadian David G , Sowden Jane C , Wells Jack A , Lythgoe Mark F , Ferretti Patrizia
Published: November 2013

Efficacy of neural stem/progenitor cell (NPC) therapies after cerebral ischaemia could be better evaluated by monitoring in vivo migration and distribution of cells post-engraftment in parallel with analysis of lesion volume and functional recovery. Magnetic resonance imaging (MRI) is ideally placed to achieve this, but still poses several challenges. We show that combining the ferumoxide MRI contrast agent Endorem with protamine sulphate (FePro) improves iron oxide uptake in cells compared to Endorem alone and is non-toxic. Hence FePro complex is a better contrast agent than Endorem for monitoring NPCs. FePro complex-labelled NPCs proliferated and differentiated normally in vitro, and upon grafting into the brain 48 hours post-ischaemia they were detected in vivo by MRI. Imaging over four weeks showed the development of a confounding endogenous hypointense contrast evolution at later timepoints within the lesioned tissue. This was at least partly due to accumulation within the lesion of macrophages and endogenous iron. Neither significant NPC migration, assessed by MRI and histologically, nor a reduction in the ischaemic lesion volume was observed in NPC-grafted brains.  Crucially, while MRI provides reliable information on engrafted cell location early after an ischaemic insult, pathophysiological changes to ischaemic lesions can interfere with cellular imaging at later timepoints.
Innovations and Sustainable Development Outline of Problems
Authors: Wronowska Gabriela
Published: November 2013

The topic dealt with in the paper is very timely and has assumed major importance from the viewpoint of development of research into economies based on sustainable development and application of research findings in specific solutions in the economy. The paper postulates that innovation is a fundamental and necessary instrument for implementing sustainable development throughout the whole economy. In order to confirm the thesis, first the paper attempts to identify the role of innovation in various areas of the economy. Secondly, it identifies the sources of innovation and areas of the economy which most require new innovative solutions. The study is based on literature, both domestic and foreign. The author analyses theoretical and empirical publications available on the market. Older publications turned out to be necessary and helpful in describing the evolution of the approach to sustainable development of the economy from a historical point of view. Newer works provide a basis for the compilation of a vast majority of the paper. The paper is a preliminary step in a more detailed research into various aspects of an economy based on sustainable development.
Czy polszczyznę mogą wzbogacić nowe typy struktur słowotwórczych?
Authors: Burkacka Iwona
Published: November 2013

Can Polish be enriched by new types of word-formative structures?

The paper presents some considerations on the lexical development of Polish. It concentrates on the issues of word-formative enlargement of vocabulary. Against the background of analogy, compensation, and extra- and intralinguistic borrowing, it discusses the possible continuants of feminine names (adjectives and diminutives), and of masculine names of professions that were traditionally reserved for women (e.g. kosmetyczka ‘beautician’, niania ‘nanny’). The paper does not only identify the extralinguistic factors, such as the rise of new naming needs or the phenomenon of linguistic fashion (e.g. structures with the prefix para-), but it also investigates the processes of erosion of morphotactic constraints, and of customary limitations.
Kryterium podmiotu przy wyodrębnianiu czasowników nieodmiennych przez osobę
Authors: Pluskota Karolina
Published: November 2013

The subject criterion in the identification of verbs uninflected for person

The paper discusses the problem of identification of a special type of modern Polish verbs that do not inflect for person. In the literature, they are known as czasowniki niewłaściwe, literally ‘improper verbs’, but the descriptions of their various interpretations lead to the conclusion that they can be no longer equated with verbs uninflected for person. The author proposes that the criterion of syntactic position of the subject can be used in their identification.
Życzenia i winszowanie jako akt mowy
Authors: Sikora Kazimierz
Published: November 2013

Wishing and congratulating as a speech act

The paper attempts to synthesize and revise the views on wishing and congratulating as specific speech acts which are represented in Polish by the performative verbs życzę, życzymy ‘I/we wish’, winszuję, winszujemy ‘I/we congratulate’, by optative formulas based on aspect operators (niech, oby, aby, żeby ‘let’, ‘so that’ &c.), and sometimes also by imperative sentences. It examines the conditions of fortuitousness of the wishes and their illocutive value, and especially the quite questionable honorific function of wishing formulas, and their connection with the linguistic relics of primitive magical thinking. The proposed interpretations emphasize the cultural and pragmatic function of wishes, rooted in history and tradition.
Integracyjne podejście funkcjonalne w dydaktyce przekładu prawniczego
Authors: Biel Łucja
Published: November 2013

Integrative functional approach in legal translation teaching

The paper introduces an integrative functional approach to legal translation teaching at translation programmes taught as part of Philology major. The approach is based on functionalism, professional realism of training, and social constructivism. The main objective is to train translators who are aware of their mediating role in intercultural and intersystemic communication, know how to produce a translation ‘fit for the purpose’, deal with terminological incongruity and overcome problems typical of the translation process. The approach requires a student-centred approach and autonomy of learners. The paper presents practical tasks which help foster the functional approach to translation and empower students by raising their self-efficacy.
Przekład tekstu naukowego i rola paratekstów
Authors: Piechnik Iwona
Published: November 2013

Translation of a scientific texts and role of paratexts

The article analyses translator’s problems and the role of different paratexts (such as footnotes, comments, forewords, afterwords and text on the cover of books) in the translation of specialized texts (scientific ones in particular). In this type of texts, the information is imperative to the reader, so every intervention of a translator makes the sense more clear in the translated work.
Status tłumacza i normy przekładu tekstów specjalistycznych w Rosji
Authors: Siniawska-Sujkowska Tatiana
Published: November 2013

The status of the translator and norms in specialized translation in Russia (on the basis of Recommendations for translators, clients and editors of written translations)

In the article the author describes the situation of specialized translators in Russia and analyzes Russian prescriptive document called Recommendations for translators, clients and editors of written translation, taking into consideration up-to-date translation theory and referring to Polish documents establishing norms of specialized translation.
The Value of Reputation in an Online Freelance Marketplace
Authors: Yoganarasimhan Hema
Published: November 2013

Online freelance marketplaces are websites that match buyers of electronically deliverable services with freelancers. Although freelancing has grown in recent years, it faces the classic “information asymmetry” problem—buyers face uncertainty over seller quality. Typically, these markets use reputation systems to alleviate this issue, but the effectiveness of these systems is open to debate. We present a dynamic structural framework to estimate the returns to seller reputations in freelance sites. In our model, a buyer decides in each period whether to choose a bid from her current set of bids, cancel the auction, or wait for more bids. In the process, she trades off sellers' price, reputation, and other attributes, as well as the costs of waiting and canceling. Our framework addresses dynamic selection, which can lead to underestimation of reputation, through two types of persistent unobserved heterogeneities: bid arrival rates and buyers' unobserved preference for bids. We apply our framework to data from a leading freelance firm. We find that buyers are forward looking, that they place significant weight on seller reputation, and that not controlling for dynamics and selection can bias reputation estimates. Using counterfactual simulations, we infer the dollar value of seller reputations and provide guidelines to managers of freelance firms.
Deciding Who Will Rule: Examining the Influence of Outside Noncore Directors on Executive Entrenchment
Authors: Kang Eugene , Kroll Mark
Published: November 2013

We examine the contingencies that sway independent noncore directors of S&P 500 firms to heed the norms of the corporate elite or the disciplining forces of the efficient directorial labor market in the context of executive entrenchment. We find support for the corporate elite perspective as the number of independent noncore directors is positively associated with an entrenchment index score. However, the positive association is moderated by contextual factors that influence whether these directors reflect the expectations of the corporate elite or the efficient directorial labor market. Specifically, this study shows that the association becomes more positive when these directors are highly embedded in the corporate elite network or have shorter board tenure but less positive when independent chief executive officer directors’ equity ownership is high. We also found a crossover interaction effect where the association is negative (positive) when firm performance is low (high). These results shed light on an underexplored group of independent directors that play an increasing role in the effective governance of publicly listed firms.
Twisting and turning: India’s telecommunications and media industries under the neo-liberal regime
Authors: Pendakur Manjunath
Published: November 2013

This paper traces the transformation of India’s telecommunications and media industries in the context of neo-liberal policies pursued by the state since 1991 to establish the supremacy of the market.

The growth of the capitalist enterprises, their expansion abroad, their entanglement with foreign capital and the closer ties to the multinationals are some of the features of this historic process. While the evidence indicates impressive short-term gains for the middle and upper classes, the larger structural questions linger. Nearly 400 million Indians out of the billion-plus population are languishing in crushing poverty as they attempt to climb up the economic ladder and grab the ephemeral promises made by the new, fast globalizing economy. The social costs of this economy, in which post-colonial India’s vision of a fair and just society are abandoned, have resulted in various upheavals and an unstable political economy.
A variational characterization of J-holomorphic curves
Authors: Arezzo Claudio , Sun Jun
Published: November 2013

In this paper, we prove that if the area functional of a surface Σ2 in a symplectic manifold

(

M

2
n

,

ω
¯

)

${(M^{2n},\bar{\omega })}$

has a critical point or has a compatible stable point in the same cohomology class, then it must be J-holomorphic. Inspired by a classical result of Lawson–Simons, we show how various restrictions of the stability assumption to variations of metrics in the space “projectively induced” metrics are enough to give the desired conclusion.
How (Not) to Lie with Benefit-Cost Analysis
Authors: Farrow Scott
Published: November 2013

Benefit-cost analysis is the applied side of welfare economics. Its broad use in support of public decisions draws both detractors and defenders. This tongue-in-cheek piece demonstrates that knowing how to lie provides insights into how not to lie; we assume the former is always accidental among economists and we hope it is so for others.
Pyrolysis gas-chromatography mass-spectrometry (Py-GC/MS) to identify compression wood in Pinus radiata saplings
Authors: Brennan Maree , McLean J. Paul , Klingberg Andreas , Altaner Clemens , Harris Philip J.
Published: November 2013

The potential of pyrolysis followed by gas-chromatography and mass-spectrometry (Py-GC/MS) was investigated for identifying compression wood (CW) in saplings of radiata pine (Pinus radiata) by examining samples of CW and opposite wood (OW). Phenolic compounds and anhydrosugars were identified among the pyrolysis products that provided information about the cell-wall polymers. Sample preparation, such as coarse-milling, fine-milling, and fine-milling followed by calcium-chloride treatment was also investigated. Fine-milling typically decreased the total yield of phenolic compounds compared with coarse-milling. Fine-milling followed by calcium-chloride washing significantly increased the proportions of pyrolysis products from polysaccharides, specifically from (1→4)-β-D-galactans that were of interest in distinguishing CW from OW. Six pyrolysis products were identified that were unique to the CW samples examined, including derivatives of (1→4)-β-D-galactans and H-units of lignin. Other pyrolysis products were identified that had significantly different proportions between the two wood types, and sometimes among samples of the same wood type.
Health-promoting lifestyle and its predictors among Iranian adolescent girls, 2013
Authors: Mirghafourvand Mojgan , Mohammad-Alizadeh-Charandabi Sakineh , Tavananezhad Nikta , Karkhaneh Mahsa
Published: November 2013

Introduction: Health-promoting behaviors have considerable effects on improving life quality and decreasing healthcare expenses. This study aimed to determine the status of health-promoting behaviors and its subscales, as well as its relationship with self-efficacy and some socio-demographic characteristics in adolescent Iranian girls.

Materials and methods: The participants in this study were 750 adolescent girls aged 14–18 years, living in the city of Sanandaj, Iran in 2013. Samples were selected randomly. Questionnaires used in the study were the “Adolescent Healthy Lifestyle” and “Sherer General Self-efficacy” questionnaires. Multivariate linear regresion analysis was used to determine predictors of health-promoting lifestyle.

Results: Mean total score of health-promoting lifestyles in adolescent girls was 3.51 (SD 0.55) and its observed scores ranged from 1 to 5. The highest and lowest mean scores were obtained for life appreciation and physical activity subscales, respectively. Self-efficacy had significant positive correlation with the total health-promoting lifestyle scores and all its subscales. The variables of self-efficacy, current disease, mother’s education, mother’s occupation, and sufficiency of income for expenses remained in the multivariate linear regresion model and were able to explain 21% of the observed variance of the total score for health-promoting lifestyle.

Conclusion: The findings show that adolescents “sometimes” or “often” show health-promoting behaviors. In addition to self-efficacy as the main predictor, some of the socio-demographic characteristics are also among the predictors of health behaviors. With consideration of adolescence years as a foundation for one’s future life, it is necessary to provide strategies to encourage a health-promoting lifestyle in adolescents.
Corrigendum to
Involution products in Coxeter groups
[J. Group Theory 14 (2011), no. 2, 251–259]
Authors: Hart Sarah B. , Rowley Peter J.
Published: November 2013

Corrigendum to http://dx.doi.org/10.1515/jgt.2010.053.