A new look at acid catalyzed deacetylation of carbohydrates : A regioselective synthesis and reactivity of 2-O-acetyl aryl glycopyranosides

Abstract In the present work we report that acetyl groups of per – acetylated aryl glycosides have different reactivity during the acidic deacetylation using HCl/EtOH in CHCl3, which leads to preferential deacetylation at O-3, O-4 and O-6. Thereby, the one-step preparation of 2-O-acetyl aryl glycosides with simple aglycon was accomplished for the first time. It was proved that the found reagent is to be general and unique for the preparation of series of 2-О-acetyl aryl glycosides. We have determined the influence of both carbohydrate moiety and the aglycon on the selectivity of deacetylation reaction by kinetic experiments. Using DFT/B3LYP/6-31G(d,p) and semi-empirical АМ1 methods we have found that the highest activation barrier is for 2-О-acetyl group. This completely explains the least reactivity of 2-О-acetyl group.Peer reviewe

Information flow during gene activation by signaling molecules: ethylene transduction in Arabidopsis cells as a study system

<p>Abstract</p> <p>Background</p> <p>We study root cells from the model plant <it>Arabidopsis thaliana </it>and the communication channel conformed by the ethylene signal transduction pathway. A basic equation taken from our previous work relates the probability of expression of the gene <it>ERF</it>1 to the concentration of ethylene.</p> <p>Results</p> <p>The above equation is used to compute the Shannon entropy (<it>H</it>) or degree of uncertainty that the genetic machinery has during the decoding of the message encoded by the ethylene specific receptors embedded in the endoplasmic reticulum membrane and transmitted into the nucleus by the ethylene signaling pathway. We show that the amount of information associated with the expression of the master gene <it>ERF</it>1 (Ethylene Response Factor 1) can be computed. Then we examine the system response to sinusoidal input signals with varying frequencies to determine if the cell can distinguish between different regimes of information flow from the environment. Our results demonstrate that the amount of information managed by the root cell can be correlated with the frequency of the input signal.</p> <p>Conclusion</p> <p>The ethylene signaling pathway cuts off very low and very high frequencies, allowing a window of frequency response in which the nucleus reads the incoming message as a sinusoidal input. Out of this window the nucleus reads the input message as an approximately non-varying one. From this frequency response analysis we estimate: a) the gain of the system during the synthesis of the protein ERF1 (~-5.6 dB); b) the rate of information transfer (0.003 bits) during the transport of each new ERF1 molecule into the nucleus and c) the time of synthesis of each new ERF1 molecule (~21.3 s). Finally, we demonstrate that in the case of the system of a single master gene (<it>ERF</it>1) and a single slave gene (<it>HLS</it>1), the total Shannon entropy is completely determined by the uncertainty associated with the expression of the master gene. A second proposition shows that the Shannon entropy associated with the expression of the <it>HLS</it>1 gene determines the information content of the system that is related to the interaction of the antagonistic genes <it>ARF</it>1, 2 and <it>HLS</it>1.</p

C9ORF72 hexanucleotide repeat expansion in ALS patients from the Central European Russia population

Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analyzed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. The presence of a large (>40) repeat expansion was found in 15% of familial ALS cases (3 of 20 unrelated familial cases) and 2.5% of sporadic ALS cases (6 of 238) but in none of control cases. These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central Europea

Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions

<p>Abstract</p> <p>Background</p> <p>Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.</p> <p>Results</p> <p>To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-κB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies.</p> <p>To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA.</p> <p>Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced false positives at least at higher stringencies.</p> <p>Conclusion</p> <p>Based on this analysis, SiteGA adds substantial specificity even to optimized PWMs and may be considered for large-scale genome analysis. It adds to the range of techniques available for TFBS prediction, and EPD analysis has led to a list of genes which appear to be regulated by the above TFs.</p

The relationship of seminal transforming growth factor-β1 and interleukin-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment

It has been proposed that the transforming growth factor (TGF)-β1 present in seminal plasma (SP) triggers a female immune response favorable for implantation. We hypothesize that seminal interleukin (IL)-18, a cytokine that can potentially cause implantation failure, interferes with the beneficial effect of TGF-β1. This study aims to determine whether the levels of seminal TGF-β1 and IL-18 are associated with reproductive outcomes in patients exposed to SP during in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI). A prospective study, which included 71 couples undergoing IVF/ICSI was carried out. Female patients were exposed to their partners’ SP via timed intercourse before the day of ovum pick-up (OPU) and also subjected to intravaginal SP application just after OPU. Quantitative measurements of total TGF-β1 (active plus latent) as well as IL-18 were determined by FlowCytomix™ technology in the SP to be used for intravaginal applications. Comparison of SP cytokine profiles between pregnant and non-pregnant groups revealed that pregnancy was correlated with a lower concentration of IL-18 (P = 0.018) and lower content per ejaculate for both of IL-18 (P = 0.0003) and TGF-β1 (P = 0.047). The ratio of TGF-β1-to-IL-18 concentration was significantly higher in the pregnant than in the non-pregnant group (P = 0.026). This study supports the notion that two key cytokines TGF-β1 and IL-18, both present in SP are associated with reproductive outcomes in female patients exposed to SP during IVF/ICSI treatment

CuCoMgAlO_x Mixed Oxides as Selective Catalysts for the Hydrogenation of Furan Compounds

Single phase CuCoMgAl-layered hydroxides were obtained by making fine adjustment to their composition through changing the (Co + Cu)/Mg = 0.5; 1; 2; 3 and Co/Cu = 0.5; 1; 2 ratios. The rise of Co/Cu in systems contributed to the increase in their thermal stability. CuCoMgAl-catalysts showed high selectivity of carbonyl group hydrogenation in furfural and 5-hydroxymethylfurfural. In furfural hydrogenation, the selectivity to furfuryl alcohol was more than 99%, and in 5-hydroxymethylfurfural hydrogenation, the selectivity to 2,5-hydroxymethyl furfural was 95%. The surface of the samples with different Co/Cu after calcination and reduction was the same and had a «core-shell» structure (TEM). «Core» consisted of Cu and Co metallic particles. «Shell» consisted of CuCoMgAlOx mixed no-stoichiometric spinel oxides. There was no sintering or change in size of the metallic particles after the reaction. For the sample with Co/Cu = 1, their phase composition after reaction remained unchangeable. The increase of Co/Cu led to the formation of an X-ray amorphous phase after the reaction. This suggests the decrease in structural stability of this sample. The obtained results prove the prospects of using bimetallic CoCu-systems for hydrogenation of furan aldehydes, and opens up new directions for further research and improvement

Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations

JAK2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9, and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), CALR mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the CALR mutation. In 16 from 24 (69.6%) cases, with combined CALR and JAK2 mutations, V617F allele burden was lower than 1%. A combination of JAK2 V617F with MPL W515L/K was also observed in 1 out of 1348 cases, only. JAK2 allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load JAK2 V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of CALR. The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells

Nanoparticles Carrying Conserved Regions of Influenza A Hemagglutinin, Nucleoprotein, and M2 Protein Elicit a Strong Humoral and T Cell Immune Response and Protect Animals from Infection

Current influenza vaccines are mainly strain-specific and have limited efficacy in preventing new influenza A strains. Efficient control of infection can potentially be achieved through the development of broad-spectrum vaccines based on conserved antigens. A combination of several such antigens, including the conserved region of the second subunit of the hemagglutinin (HA2), the extracellular domain of the M2 protein (M2e), and epitopes of nucleoprotein (NP), which together can elicit an antibody- and cell-mediated immune response, would be preferred for vaccine development. In this study, we obtained recombinant virus-like particles formed by an artificial self-assembling peptide (SAP) carrying two epitopes from NP, tandem copies of M2e and HA2 peptides, along with a T helper Pan DR-binding epitope (PADRE). Fusion proteins expressed in Escherichia coli self-assembled in vitro into spherical particles with a size of 15–35 nm. Immunization of mice with these particles induced strong humoral immune response against M2e and the entire virus, and lead to the formation of cytokine-secreting antigen-specific CD4+ and CD8+ effector memory T cells. Immunization provided high protection of mice against the lethal challenge with the influenza A virus. Our results show that SAP-based nanoparticles carrying conserved peptides from M2, HA, and NP proteins of the influenza A virus, as well as T helper epitope PADRE, can be used for the development of universal flu vaccines