Polyblends of an electroactive biomaterial consisting of a biodegradable polyester - PHBV and a carboxylate polythiophene derivative, the poly(3-thiophene ethyl acetate) - PTAcEt have been prepared ...and applied as a substrate for tissue engineering. The biodegradable polymer was used as a matrix for polythiophene. Thermal, electrical, optical and morphological properties as well as viability and cell adhesion (
in vitro
assays) were investigated. Blend films exhibited high flexibility, resistance to handling and a semiconducting character, since they preserved the individual properties of each polymer. Besides, the incorporation of PTAcEt (up to 12%) has led to improvements in the thermal stability and in the crystallinity degree of the bioactive matrix. Qualitative morphological analysis showed irregular and porous surfaces; important features for growth and cell adhesion. Viability assays indicated that the polyblends promoted superior cell proliferation after 72 h exposure to mammalian cells when compared to a pure PHBV matrix. Therefore, PTAcEt showed low cytotoxicity allowing cell growth. The adhesion study revealed that the cells were able to adhere to the surface and proliferate inside the cavities of the substrate. The results indicate that the 88 : 12% (PHBV : PTAcEt) blend is a promising candidate for use as scaffold in the biomedical area.
Polyblend films based on poly(3-hydroxybutirate-
co
-valerate) and poly(3-thiophene ethyl acetate) - PHBV/PTAcEt showed low cytotoxicity, good adhesion and mammalian cell proliferation. The physical-chemical properties were explored.
Summary Background Many randomised controlled trials have investigated the effect of adjuvant chemotherapy in operable non-small-cell lung cancer. We undertook two comprehensive systematic reviews ...and meta-analyses to establish the effects of adding adjuvant chemotherapy to surgery, or to surgery plus radiotherapy. Methods We included randomised trials, not confounded by additional therapeutic differences between the two groups and that started randomisation on or after Jan 1, 1965, which compared surgery plus adjuvant chemotherapy versus surgery alone, or surgery plus adjuvant radiotherapy and chemotherapy versus surgery plus adjuvant radiotherapy. Updated individual patient data were collected, checked, and included in meta-analyses stratified by trial. The primary endpoint was overall survival, defined as time from randomisation until death by any cause. All analyses were by intention to treat. Findings The first meta-analysis of surgery plus chemotherapy versus surgery alone was based on 34 trial comparisons and 8447 patients (3323 deaths). We recorded a benefit of adding chemotherapy after surgery (hazard ratio HR 0·86, 95% CI 0·81–0·92, p<0·0001), with an absolute increase in survival of 4% (95% CI 3–6) at 5 years (from 60% to 64%). The second meta-analysis of surgery plus radiotherapy and chemotherapy versus surgery plus radiotherapy was based on 13 trial comparisons and 2660 patients (1909 deaths). We recorded a benefit of adding chemotherapy to surgery plus radiotherapy (HR 0·88, 95% CI 0·81–0·97, p=0·009), representing an absolute improvement in survival of 4% (95% CI 1–8) at 5 years (from 29% to 33%). In both meta-analyses we noted little variation in effect according to the type of chemotherapy, other trial characteristics, or patient subgroup. Interpretation The addition of adjuvant chemotherapy after surgery for patients with operable non-small-cell lung cancer improves survival, irrespective of whether chemotherapy was adjuvant to surgery alone or adjuvant to surgery plus radiotherapy. Funding UK Medical Research Council, Institut Gustave-Roussy, Programme Hospitalier de Recherche Clinique (AOM 05 209), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.
OBJECTIVES
The purpose of this study was to determine whether the response to ventricular pacing during tachycardia is useful for differentiating atypical atrioventricular node re-entrant tachycardia ...(AVNRT) from orthodromic reciprocating tachycardia (ORT) using a septal accessory pathway.
BACKGROUND
Although it is usually possible to differentiate atypical AVNRT from ORT using a septal accessory pathway, a definitive diagnosis is occasionally elusive.
METHODS
In 30 patients with atypical AVNRT and 44 patients with ORT using a septal accessory pathway, the right ventricle was paced at a cycle length 10 to 40 ms shorter than the tachycardia cycle length (TCL). The ventriculo-atrial (VA) interval and TCL were measured just before pacing. The interval between the last pacing stimulus and the last entrained atrial depolarization (stimulus-atrial S-A interval) and the post-pacing interval (PPI) at the right ventricular apex were measured on cessation of ventricular pacing.
RESULTS
All 30 patients with atypical AVNRT and none of the 44 patients with ORT using a septal accessory pathway had an S-A–VA interval >85 ms and PPI–TCL >115 ms.
CONCLUSIONS
The S-A–VA interval and PPI–TCL are useful in distinguishing atypical AVNRT from ORT using a septal accessory pathway.
During vertebrate gastrulation, mesodermal and ectodermal cells undergo convergent extension, a process characterised by prominent cellular rearrangements in which polarised cells intercalate along ...the medio-lateral axis leading to elongation of the antero-posterior axis. Recently, it has become evident that a noncanonical Wnt/Frizzled (Fz)/Dishevelled (Dsh) signalling pathway, which is related to the planar-cell-polarity (PCP) pathway in flies, regulates convergent extension during vertebrate gastrulation. Here we isolate and functionally characterise a zebrafish homologue of Drosophila prickle (pk), a gene that is implicated in the regulation of PCP. Zebrafish pk1 is expressed maternally and in moving mesodermal precursors. Abrogation of Pk1 function by morpholino oligonucleotides leads to defective convergent extension movements, enhances the silberblick (slb)/wnt11 and pipetail (Ppt)/wnt5 phenotypes and suppresses the ability of Wnt11 to rescue the slb phenotype. Gain-of-function of Pk1 also inhibits convergent extension movements and enhances the slb phenotype, most likely caused by the ability of Pk1 to block the Fz7-dependent membrane localisation of Dsh by downregulating levels of Dsh protein. Furthermore, we show that pk1 interacts genetically with trilobite (tri)/strabismus to mediate the caudally directed migration of cranial motor neurons and convergent extension. These results indicate that, during zebrafish gastrulation Pk1 acts, in part, through interaction with the noncanonical Wnt11/Wnt5 pathway to regulate convergent extension cell movements, but is unlikely to simply be a linear component of this pathway. In addition, Pk1 interacts with Tri to mediate posterior migration of branchiomotor neurons, probably independent of the noncanonical Wnt pathway.
DNA cytosine methylation (5mC) is indispensable for a number of cellular processes, including retrotransposon silencing, genomic imprinting, and X chromosome inactivation in mammalian development. ...Recent studies have focused on 5-hydroxymethylcytosine (5hmC), a new epigenetic mark or intermediate in the DNA demethylation pathway. However, 5hmC itself has no role in pluripotency maintenance in mouse embryonic stem cells (ESCs) lacking
Dnmt1
,
3a
, and
3b
. Here, we demonstrated that 5hmC accumulated on euchromatic chromosomal bands that were marked with di- and tri-methylated histone H3 at lysine 4 (H3K4me2/3) in mouse ESCs. By contrast, heterochromatin enriched with H3K9me3, including mouse chromosomal G-bands, pericentric repeats, human satellite 2 and 3, and inactive X chromosomes, was not enriched with 5hmC. Therefore, enzymes that hydroxylate the methyl group of 5mC belonging to the Tet family might be excluded from inactive chromatin, which may restrict 5mC to 5hmC conversion in euchromatin to prevent nonselective de novo DNA methylation.
BRN2 transcription factor is associated with the development of malignant melanoma. The cytotoxic activities and cell death mechanism against B16F10-Nex2 cells were determined with synthetic peptide ...R18H derived from the POU domain of the BRN2 transcription factor.
To determine the cell death mechanisms and in vivo activity of peptide R18H derived from the POU domain of the BRN2 transcription factor against B16F10-Nex2 cells.
Cell viability was determined by the MTT method. C57Bl/6 mice were challenged with B16F10-Nex2 cells and treated with R18H. To identify the type of cell death, we used TUNEL assay, Annexin V and PI, Hoechst, DHE, and determination of caspase activation and cytochrome c release. Transmission electron microscopy was performed to verify morphological alterations after peptide treatment.
Peptide R18H displayed antitumor activity in the first hours of treatment and the EC50% was calculated for 2 and 24h, being 0.76 ± 0.045 mM and 0.559 ± 0.053 mM, respectively. After 24h apoptosis was evident, based on DNA degradation, chromatin condensation, increase of superoxide anion production, phosphatidylserine translocation, activation of caspases 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. The peptide cytotoxic activity was not affected by necroptosis inhibitors and treated cells did not release LDH in the extracellular medium. Moreover, in vivo antitumor activity was observed following treatment with peptide R18H.
Peptide R18H from BRN2 transcription factor induced apoptosis in B16F10-Nex2 and displayed antitumor activity in vivo.
Sequencing plant genomes are often challenging because of their complex architecture and high content of repetitive sequences. Sugarcane has one of the most complex genomes. It is highly polyploid, ...preserves intact homeologous chromosomes from its parental species and contains >55% repetitive sequences. Although bacterial artificial chromosome (BAC) libraries have emerged as an alternative for accessing the sugarcane genome, sequencing individual clones is laborious and expensive. Here, we present a strategy for sequencing and assembly reads produced from the DNA of pooled BAC clones. A set of 178 BAC clones, randomly sampled from the SP80-3280 sugarcane BAC library, was pooled and sequenced using the Illumina HiSeq2000 and PacBio platforms. A hybrid assembly strategy was used to generate 2,451 scaffolds comprising 19.2 MB of assembled genome sequence. Scaffolds of ≥20 Kb corresponded to 80% of the assembled sequences, and the full sequences of forty BACs were recovered in one or two contigs. Alignment of the BAC scaffolds with the chromosome sequences of sorghum showed a high degree of collinearity and gene order. The alignment of the BAC scaffolds to the 10 sorghum chromosomes suggests that the genome of the SP80-3280 sugarcane variety is ∼19% contracted in relation to the sorghum genome. In conclusion, our data show that sequencing pools composed of high numbers of BAC clones may help to construct a reference scaffold map of the sugarcane genome.
Regularly recurring phenomena are a common and important part of life. Such rhythmic behaviors are often seen in nonliving systems under far-from-equilibrium conditions. The study of simple nonliving ...systems provides clues for improving our understanding of the origin of biological rhythms. Here, we focus on the spontaneous oscillation of surface tension associated with an intermittent Marangoni convective flow generated by two types of surfactants, those that are partially soluble (long chain alcohols) and insoluble (lipids) in water. In this system, we find that the collective motions of two surfactants interact with each other in a systematic manner to control a stable periodic motion: the alcohol molecules (donor) produce a Marangoni flow, and the lipid molecules (acceptor) in a monolayer push the flow back. The shape of the surface tension oscillation can be explained by the viscoelastic properties of the acceptor surfactant, whereas the period of the surface tension oscillation has been explained by the physical properties of the donor surfactant. A recently developed time-resolved X-ray surface scattering technique enables the dynamic structure of the water surface under flow to be determined. We have repeatedly observed that lipid molecules at the air–water interface become regularly oriented normal to the surface at every onset of the Marangoni convective flow.
PDF
