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The recombinant FrtR protein was purified, and conserved DNA binding motifs were determined using electrophoretic mobility shift and DNase I footprinting assays. Finally, a series of mutant and complement strains were constructed to perform the minimum inhibitory concentration (MIC) assays, which indicated that frtP upregulation led to the increase of fluoride sensitivity. Collectively, our results indicate that FrtR is an important transcription factor regulating the frtP expression in S. learn more mutans, thus affecting the intrinsic fluoride tolerance. Therefore, this study provides novel insights into a potential target to increase the S. mutans sensitivity to fluoride for a better prevention of dental caries.Objective The development of electrode arrays able to reliably record brain electrical activity is a critical issue in brain machine interface (BMI) technology. In the present study we undertook a comprehensive physico-chemical, physiological, histological and immunohistochemical characterization of new single-walled carbon nanotubes (SWCNT)-based electrode arrays grafted onto medium-density polyethylene (MD-PE) films. Approach The long-term electrical stability, flexibility, and biocompatibility of the SWCNT arrays were investigated in vivo in laboratory rats by two-months recording and analysis of subdural electrocorticogram (ECoG). Ex-vivo characterization of a thin flexible and single probe SWCNT/polymer electrode is also provided. Main results The SWCNT arrays were able to capture high quality and very stable ECoG signals across 8 weeks. The histological and immunohistochemical analyses demonstrated that SWCNT arrays show promising biocompatibility properties and may be used in chronic conditions. The SWCNT-based arrays are flexible and stretchable, providing low electrode-tissue impedance, and, therefore, high compliance with the irregular topography of the cortical surface. Finally, reliable evoked synaptic local field potentials in rat brain slices were recorded using a special SWCNT-polymer-based flexible electrode. Significance The results demonstrate that the SWCNT arrays grafted in MD-PE are suitable for manufacturing flexible devices for subdural ECoG recording and might represent promising candidates for long-term neural implants for epilepsy monitoring or neuroprosthetic BMI.A convergent synthesis via the late-stage serine ligation of naturally occurring calcium-dependent antibiotic CDA3a and its analogues has been developed, which allowed us to readily synthesize the analogues with the variation on the lipid tail. Some analogues were found to show 100-500-fold higher antimicrobial activity than the natural compound CDA3a against drug resistant bacteria. This study will enhance our understanding of CDA3a and provide valuable antibacterial lead candidates for further development.Accurate determination of the binding affinity of the ligand to the receptor remains a difficult problem in computer-aided drug design. Here we study and compare the efficiency of the Jarzynski's equality combined with steered molecular dynamics (SMD) and the linear interaction energy (LIE) method by assessing the binding affinity of 23 small compounds to six receptors, including beta-lactamase, thrombin, factor Xa, HIV-1 protease (HIV), myeloid cell leukemia-1 (MCL-1) and cyclin dependent kinase 2 (CDK-2) proteins. It was shown that the Jarzynski's non-equilibrium binding free energy correlates with the available experimental data with the correlation level R=0.89, 0.86, 0.83, 0.80, 0.83 and 0.81 for six data sets, while for the binding free energy obtained by the LIE method, we have R = 0.73, 0.80, 0.42, 0.23, 0.85, and 0.01. Therefore, Jarzynski's equality is recommended to use for ranking binding affinities as it provides accurate and robust results. In contrast, LIE is not as reliable as Jarzynski's equality, and it should be used with caution, especially when it comes to new systems.Both cattle (Bos taurus) and sheep (Ovis aries) belong to the Bovidae family but to different subfamilies, Bovinae and Caprinae, respectively. From a chromosomal point of view, apart from the already known centric fusions (that occurred during the evolutionary process in the Bovidae family) and the small differences in the chromosome classification, the 2 karyotypes are very similar in banding patterns. In this study, the combination of bioinformatics techniques and physical mapping of DNA markers enabled the identification of a micro-rearrangement, a small inversion involving bovine chromosome 21 (BTA21) and the corresponding sheep chromosome 18 (OAR18). The aim of this study was the cytogenetic characterization of this difference in genomic assemblies between cattle and sheep in this single chromosome region. To verify the inversion in FISH experiments, we used the BACs 442H08 and 222H03 from the INRA library and BACs 134H22 and 436P08 from the sheep-specific CHORI library. The results confirmed the presence of the inverted fragment in sheep compared to the cattle genome. Genomic rearrangements may have consequences depending on their influence on gene activity, but in this case no gene or transcribed DNA portion seemed to be involved. In conclusion, we showed for the first time, concerning autosomes, that besides the already known centric fusions also other differences exist between the bovine and sheep karyotypes. Furthermore, we demonstrated that the combination of a bioinformatics approach and physical mapping is a valid tool for the identification of currently unknown rearrangements between related species.PLCzeta(ζ) initiates Ca2+ oscillations and egg activation at fertilization in mammals, but studies in mouse eggs fertilized by PLCζ knockout (KO) sperm imply that there is another slow acting factor causing Ca2+ release. Here, I propose a hypothesis for how this second sperm factor might cause Ca2+ oscillations in mouse eggs.Introduction Myelodysplastic syndromes (MDS) include various hematologic abnormalities characterized by chronic cytopenia due to disruption in cellular differentiation. This study aims to evaluate the prognostic value of PLR in patients with MDS. Material and methods Clinical-laboratory findings and the results of bone marrow biopsies of MDS patients before treatment were recorded. p value of less then 0.05 was considered statistically significant. SPSS version 20.0 was used for statistical analysis. Results The study included 62 patients with median follow-up time of 62.8±4.5 months and median age of 68.5 years. In 13 patients, acute leukemia was transformed. In these subjects, a PLR cut-off level of 46 was established for mortality (p=0.015). We found a significant relationship between PLR and multilineage series with the presence of dysplasia (p=0.017). The survival analysis showed a decreased survival in cases with dysplasia in two and/or more series, transformation into acute leukemia, and thrombocytopenia.
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