bluuebunny/crossref_metadata_2025_split 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract

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

Abstract
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.
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

SUMMARYMammalian 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.
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.