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This work provides new insight into assembling of phenol in various solvents and competition between different kinds of interactions. To examine both weak and strong interactions, we selected a series of non-aromatic and aromatic solvents. Infrared spectra were measured at low (0.05 M) and high (2 M) phenol content. In addition, we performed density functional theory calculations of the structures and harmonic vibrational spectra of 1:1 complexes of phenol with the solvents and the associates of phenol from dimer to tetramer. Based on these results, we divided the solvents into three groups. The first group consists of non-aromatic solvents weakly interacting with phenol. Depending on the concentration, molecules of phenol in these solvents remain non-bonded or self-associated. In diluted solutions of phenol in chlorinated non-aromatic solvents do not appear free OH groups, since they are involved in a weak OH···Cl interaction. It is of note that in diluted solutions of phenol in tetramethyl ethylene both the non-bonded and bonded OH coexists due to solvent–solvent interactions. The second group consists of aromatic solvents with methyl or chlorine substituents. At low concentration, the molecules of phenol are involved in the phenol–solvent OH···π interaction and the strength of these interactions depends on the solvent properties. At a higher phenol content an equilibrium exists between phenol–solvent OH···π and phenol–phenol OH···OH interactions. Finally, the third group includes the aromatic and non-aromatic solvents with highly polar group (C≡N). In these solvents, regardless of the concentration all molecules of phenol are involved in the solute–solvent OH···NC interaction. Comparison of the experimental and theoretical band parameters reveals that molecules of phenol in non-aromatic solvents prefer the cyclic associates, while in the aromatic solvents they tend to form the linear associates.

Short modified oligonucleotides that bind in a sequence-specific way to messenger RNA essential for bacterial growth could be useful to fight bacterial infections. One such promising oligonucleotide is peptide nucleic acid (PNA), a synthetic DNA analog with a peptide-like backbone. However, the limitation precluding the use of oligonucleotides, including PNA, is that bacteria do not import them from the environment. We have shown that vitamin B12, which most bacteria need to take up for growth, delivers PNAs to Escherichia coli cells when covalently linked with PNAs. Vitamin B12 enters E. coli via a TonB-dependent transport system and is recognized by the outer-membrane vitamin B12-specific BtuB receptor. We engineered the E. coli ΔbtuB mutant and found that transport of the vitamin B12-PNA conjugate requires BtuB. Thus, the conjugate follows the same route through the outer membrane as taken by free vitamin B12. From enhanced sampling all-atom molecular dynamics simulations, we determined the mechanism of conjugate permeation through BtuB. BtuB is a β-barrel occluded by its luminal domain. The potential of mean force shows that conjugate passage is unidirectional and its movement into the BtuB β-barrel is energetically favorable upon luminal domain unfolding. Inside BtuB, PNA extends making its permeation mechanically feasible. BtuB extracellular loops are actively involved in transport through an induced-fit mechanism. We prove that the vitamin B12 transport system can be hijacked to enable PNA delivery to E. coli cells.

Yellow onion waste from industrial peeling was used to obtain three pure preparations: protocatechuic acid (PA), quercetin diglycosides (QD) and quercetin monoglycosides (QM). PA contained 61% protocatechuic acid, QD contained 35% quercetin diglucosides, mainly quercetin-3,4'-diglucoside, and QM contained 41% monoglucosides, mainly quercetin-4'-glucoside. The highest antioxidant activity was shown by PA. The effects of preparations on the digestive functions of the gastrointestinal tract of rats as well as the biochemical parameters and antioxidant capacity of the blood in model research on Wistar rats sustained by a high-fat diet were assessed (5 groups per 8 animals). The results of the present experiment showed that different onion phenolic preparations differently modulated the enzymatic activity of faecal (P < 0.001) and caecal (P < 0.001) microbiota. For instance, the QD preparation but not QM efficiently reduced the faecal and caecal bacterial β-glucuronidase activity. Both protocatechuic acid and quercetin monoglycosides showed a beneficial effect by regulating blood lipids (reduction of TC (P < 0.001) and TG (P < 0.001), non-HDL increase in HDL (P < 0.001)), thereby lowering the risk factors for atherosclerotic lesions AI (P = 0.038) and AII (P = 0.013). In addition, onion phenols showed a strong antioxidant effect, however, with a different mechanism: protocatechuic acid via serum ACL (P = 0.033) increase and hepatic GSSG (P = 0.070) decrease, QM via ACW (P < 0.001) increase and hepatic TBARS (P = 0.002) decrease, and QD via serum ACW increase and hepatic GSSG decrease. It can be concluded that onion polyphenols with a lower molar weight, i.e. QM more preferably affect the blood lipid profile than QD. However QD more efficiently reduced the faecal and caecal bacterial β-glucuronidase activity.

Mid-infrared (MIR) and near-infrared (NIR) spectra of crystalline menadione (vitamin K3) were measured and analyzed with aid of quantum chemical calculations. The calculations were carried out using the harmonic approach for the periodic model of crystal lattice and the anharmonic DVPT2 calculations applied for the single molecule model. The theoretical spectra accurately reconstructed the experimental ones permitting for reliable assignment of the MIR and NIR bands. For the first time, a detailed analysis of the NIR spectrum of a molecular system based on a naphthoquinone moiety was performed to elucidate the relationship between the chemical structure of menadione and the origin of the overtones and combination bands. In addition, the importance of these bands during interpretation of the MIR spectrum was demonstrated. The overtones and combination bands contribute to 46.4% of the total intensity of menadione in the range of 3600–2600 cm−1. Evidently, these bands play a key role in shaping of the C-H stretching region of MIR spectrum. We have shown also that the spectral regions without fundamentals may provide valuable structural information. For example, the theoretical calculations reliably reconstructed numerous overtones and combination bands in the 4000–3600 and 2800–1800 cm−1 ranges. These results, provide a comprehensive origin of the fundamentals, overtones and combination bands in the NIR and MIR spectra of menadione, and the relationship of these spectral features with the molecular structure.

Near-infrared (NIR) spectra of phenol in a series of non-aromatic and aromatic solvents were recorded to study the competition between various types of solute–solute and solute–solvent interactions. Depending on the phenol concentration, the free OH and OH involved in the OH⋯OH interactions in the dimers and higher associates are present in cyclohexane solutions. On the other hand, free OH does not appear in Cl-containing solvents since at a low phenol content the OH groups participate in the OH⋯Cl interactions. In CCl4 and tetrachloroethylene this interaction is weak, while in chlorobenzene the strength of this interaction is higher. In the aromatic solvents the solute–solute OH⋯OH interactions compete with the solute–solvent OH⋯π and aromatic CH⋯OH ones. Consequently, the degree of self-association of phenol in aromatic solvents is smaller than that in non-aromatic ones. The strength of the OH⋯π interactions increases with growing electron-donating ability of the substituents in the benzene derivatives. This observation obtained from the NIR spectra is in line with the results of the theoretical calculations (DFT). A clear correlation appears between the number of methyl groups in aromatic solvents and the population of the free OH groups. The methyl groups are steric hindrances and impede the formation of the OH⋯OH and OH⋯π interactions. Our results suggest the presence of aromatic CH⋯OH solute–solvent interactions, not observed in previous studies. NIR spectroscopy appears to be a powerful tool for exploration of free and weakly-bonded OH groups.

Sugar beet (Beta vulgaris subsp. vulgaris) is the exclusive source of sugar in the form of sucrose in temperate climate zones. Sugar beet is grown there as an annual crop from spring to autumn because of the damaging effect of freezing temperatures to taproot tissue. A collection of hybrid and non-hybrid sugar beet cultivars was tested for winter survival rates and freezing tolerance. Three genotypes with either low or high winter survival rates were selected for detailed study of their response to frost. These genotypes differed in the severity of frost injury in a defined inner region in the upper part of the taproot, the so-called pith. We aimed to elucidate genotype- and tissue-dependent molecular processes during freezing and combined analyses of sugar beet anatomy and physiology with transcriptomic and metabolite profiles of leaf and taproot tissues at low temperatures. Freezing temperatures induced strong downregulation of photosynthesis in leaves, generation of reactive oxygen species (ROS), and ROS-related gene expression in taproots. Simultaneously, expression of genes involved in raffinose metabolism, as well as concentrations of raffinose and its intermediates, increased markedly in both leaf and taproot tissue at low temperatures. The accumulation of raffinose in the pith tissue correlated with freezing tolerance of the three genotypes. We discuss a protective role for raffinose and its precursors against freezing damage of sugar beet taproot tissue.

Association of 1-hexanol in n-hexane has been studied by measurements of nonlinear dielectric effect (NDE) and near-infrared (NIR) spectroscopy. Besides, the dipole moments of selected open and cyclic associates were determined by DFT (density functional theory) calculations. All measurements were performed in the whole range of mole fractions with a step of 0.1. From numerical fitting of the dielectric data we obtained populations of all species present in the mixture. Our results do not support common opinion about the exceptional role of cyclic tetramers. The most abundant cyclic species are trimers and population of the cyclic associates rapidly decreases with increasing size of associates. The variations in population of open associates are more complex and for mole fractions of 1-hexanol > 0.1 the relationships have a maximum, which shifts towards higher associates. In pure 1-hexanol this maximum is close to seven. From analysis of the dielectric data it results that at lower alcohol content dominate the cyclic species. When the concentration of 1-hexanol increases the equilibrium shifts towards formation of the linear associates. From NIR spectra we determined the overall population of the free OH in monomers and open associates. Next, these values were used for estimation of an average length of the open associates. It appears that an averaged size of the open associates determined from NIR spectra is higher than that from the dielectric data and these differences are more pronounced when the concentration of 1-hexanol increases. We discuss possible explanations of this observation. Assuming that the actual size of the open associates is between those obtained from both methods, one can estimate that the size of open associates is ranging from 3 to 15 in pure 1-hexanol. It seems that the higher associates are stabilized by interaction of the aliphatic chains.

Hydrothermal reaction of copper nitrate, 1,2-phenylenediacetic acid (pdaH2), and flexible dipyridylamide ligands afforded four new coordination polymers with diverse structural topologies, as characterized by single crystal X-ray diffraction. {[Cu(pda)(hdn)(H2O)2]·2H2O}n (1, hdn = N,N′-(hexane-1,6-diyl)dinicotinamide) shows 1D ribbon motifs. In contrast, [Cu(pda)(hdin)]n (2, hdin = N,N′-(hexane-1,6-diyl)diisonicotinamide) presents a rare example of a five-fold interpenetrated 4-connected 658 cds 3D topology. [Cu(pda)(bdn)]n (3, bdn = N,N′-(butane-1,4-diyl)dinicotinamide) displays an unprecedented 3,5-connected binodal (63)(6783) 3D topology with embedded {Cu(OCO)}n axial-equatorial bridged chain motifs. {[Cu(pda)(bpfp)(H2O)]·4H2O}n (4, bpfp = N,N′-(bis-4-pyridylformyl)piperazine) shows rectangular (4,4) grid submotifs. All four materials were assayed as heterogeneous catalysts for the degradation of Congo Red (CR) in aqueous suspension under ultraviolet irradiation; only compound 3 catalyzed the degradation. Thermal properties of 1–4 are also discussed herein.

To our best knowledge, this is the first spectroscopic study of small heterogeneity at a molecular level in binary mixtures of aliphatic and aromatic hydrocarbons. The composition-dependent spectra of benzene/toluene, benzene/n‑hexane, benzene/cyclohexane, n‑hexane/n‑heptane and n‑hexane/cyclohexane mixtures were recorded by NIR transmission technique in the whole range of mole fractions. A comprehensive exploration of the experimental data was performed by two-dimensional correlation analysis (2DCOS) and chemometric methods. In addition, we calculated excess NIR molar absorption spectra and parameter of ER, which allows for comparison of the degree of deviation from ideality for various mixtures. Our results reveal that all studied mixtures deviate from the ideal mixture. The extent of these deviations is small for the mixtures were both components are aromatic or aliphatic and increases for aromatic/aliphatic mixtures. In addition, molecular shapes have an important effect on the degree of deviation from the ideal mixture. As expected, benzene/n‑hexane is the most non-ideal mixture, while behavior of n‑hexane/n‑heptane and benzene/toluene mixtures is close to the ideal one. Our results suggest that in the mixtures with the largest deviations from ideality are present homoclusters of both components and heteroclusters. The heteroclusters exist in the whole range of compositions, while the homoclusters appears above a certain concentration limit. If both components of the mixture are similar, the molecules with equal probability form the homo- and heteroclusters. In the case of unlike components, the molecules prefer to form the homoclusters. The homoclusters of both components in the mixture are similar as those observed in bulk constituents. This means that deviation from the ideal mixture results from presence of the heteroclusters.

It has been shown that the germane Ph3GeH converts aryl and aliphatic acid fluorides directly to their corresponding aldehydes without over-reduction via the conversion of Ph3GeH to the germylium cation [Ph3Ge]+ by a catalytic amount of the tritylium salt [Ph3C][B(C6F5)4]. Here, no transition metal catalyst is required and there is no decarbonylation of the acid fluoride, which are advantages over existing methods. The fluorine atoms can also be abstracted from organofluorine compounds using this method.

Purpose: In phase I testing, alisertib tablets with irinotecan and temozolomide showed significant antitumor activity in patients with neuroblastoma. This study sought to confirm activity of this regimen; evaluate an alisertib oral solution; and evaluate biomarkers of clinical outcomes. Patients and Methods: We conducted a two-stage phase II trial of alisertib tablets (60 mg/m2/dose × 7 days), irinotecan (50 mg/m2/dose i.v. × 5 days), and temozolomide (100 mg/m2/dose orally × 5 days) in patients with relapsed or refractory neuroblastoma. The primary endpoint was best objective response. A separate cohort was treated with alisertib at 45 mg/m2 using oral solution instead of tablets. Exploratory analyses sought to identify predictors of toxicity, response, and progression-free survival (PFS) using pooled data from phase I, phase II, and oral solution cohorts. Results: Twenty and 12 eligible patients were treated in the phase II and oral solution cohorts, respectively. Hematologic toxicities were the most common adverse events. In phase II, partial responses were observed in 19 evaluable patients (21%). The estimated PFS at 1 year was 34%. In the oral solution cohort, 3 patients (25%) had first cycle dose-limiting toxicity (DLT). Alisertib oral solution at 45 mg/m2 had significantly higher median Cmax and exposure compared with tablets at 60 mg/m2. Higher alisertib trough concentration was associated with first cycle DLT, whereas MYCN amplification was associated with inferior PFS. Conclusions: This combination shows antitumor activity, particularly in patients with MYCN nonamplified tumors. Data on an alisertib oral solution expand the population able to be treated with this agent.

Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties of V1R during early embryonic development of the mouse spinal cord locomotor networks (E11.5–E16.5). We found that these interneurons are subdivided into several functional clusters from E11.5 and then display an unexpected transitory involution process during which they lose their ability to sustain tonic firing. We demonstrated that the essential factor controlling the diversity of the discharge pattern of embryonic V1R is the ratio of a persistent sodium conductance to a delayed rectifier potassium conductance. Taken together, our results reveal how a simple mechanism, based on the synergy of two voltage-dependent conductances that are ubiquitous in neurons, can produce functional diversity in embryonic V1R and control their early developmental trajectory.

Sugar beet (Beta vulgaris subsp. vulgaris) is the exclusive source of sugar in the form of sucrose in temperate climate zones. There, sugar beet is grown as an annual crop from spring to autumn because of the damaging effect of freezing temperatures to taproot tissue. Natural and breeded varieties display variance in the degree of tolerance to freezing temperatures and genotypes with elevated tolerance to freezing have been isolated. Here we compare initial responses to frost between genotypes with either low and high winter survival rates. The selected genotypes differed in the severity of frost injury. We combined transcriptomic and metabolite analyses of leaf- and taproot tissues from such genotypes to elucidate mechanisms of the early freezing response and to dissect genotype- and tissue-dependent responses. Freezing temperatures induced drastic downregulation of photosynthesis-related genes in leaves but upregulation of genes related to minor carbohydrate metabolism, particularly of genes involved in raffinose metabolism in both, leaf and taproot tissue. In agreement with this, it has been revealed that raffinose and the corresponding intermediates, inositol and galactinol, increased markedly in these tissues. We found that genotypes with improved tolerance to freezing, showed higher accumulation of raffinose in a defined interior region within the upper part of the taproot, the pith, representing the tissue most susceptible to freeze damages. This accumulation was accompanied by specific upregulation of raffinose synthesizing enzymes in taproots, suggesting a protective role for raffinose and its precursors for freezing damage in sugar beet.

Background AL amyloidosis (AL) is an incurable plasma cell (PC) disorder. The solely pathogenic mechanism in AL is deposition of immunoglobulin free light chains (FLC) organized in fibrils in target organs. Surprisingly, therapeutic strategies directly targeting FLC secretion are not available. SNARE proteins, which are the specific target of botulinum neurotoxin (BoNT), are involved in the docking and fusion of secretory vesicles. We hypothesized that certain BoNT serotypes may block FLC exocytosis, causing retention of FLC-loaded vesicles and triggering a terminal unfolded protein response (UPR). Methods Gene expression profiling in a cohort of 170 newly diagnosed multiple myeloma (MM) patients (IFM170) was used to interrogate SNAREs expression in malignant plasma cells. Western blotting (WB) was used to assess SNARE expression across MM and AL cell lines. We developed tetracycline inducible, lentiviral vectors expressing distinct BoNT serotypes (BoNT/A-F), T2A and GFP. Lentivirally transduced cells would express BoNT in a 1:1 stochiometric ratio with GFP, upon doxycycline (dox) administration, allowing for flow cytometry-based analysis. A vector comprising solely T2A and GFP was used as negative control. We transduced AL cell lines with Tet-On lentivirus expressing 7 distinct BoNTs and performed two sets of experiments. First, we performed time-course viability assays on polyclonally transduced cells and compared relative proportion of GFP+ cells over time. Then, we single-cell sorted transduced cells, triggered BoNT expression and assessed GFP kinetic and apoptosis via AnnexinV/DAPI flow cytometry at 24, 48 and 72 hours post dox. SNAREs cleavage following induction of BoNT expression was evaluated via WB in GFP+ clones. To assess if BoNT cytotoxicity correlated with cessation of FLC secretion, we performed a secretion assay in monoclones expressing distinct BoNTs. Results IFM170 GEP analysis showed VAMP2, VAMP3 and SNAP23 as the top expressed SNAREs. This was further confirmed in AL/MM cell lines. By using polyclonally transduced cells, we show that GFP+ cells are rapidly depleted over time after dox, across all serotypes, except BoNT/B, consistent with cytotoxic effect. Similarly, we observed rapid apoptosis in monoclones expressing any BoNT serotypes, except BoNT/B. We noted an association between SNAP23 and VAMP3 cleavage and BoNT toxicity, suggesting that dual targeting of SNAP23/VAMP3 may be necessary to mediate BoNT cytotoxicity. We next show that only BoNTs causing early cytotoxicity significantly inhibited FLC secretion. Cytotoxic BoNTs, activated PERK pathway with eIF2a phosphorylation (p-eIF2a); CHOP and GADD34 upregulation, presumably through FLC retention. Conclusions We show that cytotoxic BoNTs block FLC secretion, trigger a terminal UPR and induce apoptosis in AL and MM models. We provide proof of concept that targeting FLC secretion has a potential clinical translatability.

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Key Points MM cells suffer from proteotoxicity and depend on NRF1, the master regulator of proteasome stress response, for survival.KO of NRF1 or its activating protease DDI2 is cytotoxic in myeloma and overcomes de novo and acquired PI resistance., Visual Abstract, Multiple myeloma (MM) cells suffer from baseline proteotoxicity as the result of an imbalance between the load of misfolded proteins awaiting proteolysis and the capacity of the ubiquitin-proteasome system to degrade them. This intrinsic vulnerability is at the base of MM sensitivity to agents that perturb proteostasis, such as proteasome inhibitors (PIs), the mainstay of modern-day myeloma therapy. De novo and acquired PI resistance are important clinical limitations that adversely affect prognosis. The molecular mechanisms underpinning PI resistance are only partially understood, limiting the development of drugs that can overcome it. The transcription factor NRF1 is activated by the aspartic protease DNA damage inducible 1 homolog 2 (DDI2) upon proteasome insufficiency and governs proteasome biogenesis. In this article, we show that MM cells exhibit baseline NRF1 activation and are dependent upon DDI2 for survival. DDI2 knockout (KO) is cytotoxic for MM cells, both in vitro and in vivo. Protein structure-function studies show that DDI2 KO blocks NRF1 cleavage and nuclear translocation, causing impaired proteasome activity recovery upon irreversible proteasome inhibition and, thereby, increasing sensitivity to PIs. Add-back of wild-type, but not of catalytically dead DDI2, fully rescues these phenotypes. We propose that DDI2 is an unexplored promising molecular target in MM by disrupting the proteasome stress response and exacerbating proteotoxicity.

The primary objective of the Dynamic Albedo of Neutrons (DAN) experiment on board the Mars Science Laboratory (MSL) rover Curiosity is to assess the hydrogen content as the rover traverses the Martian surface. Because hydrogen is a light element, it is an efficient moderator for neutrons. The method used to estimate the hydrogen content by the DAN instrument is to measure the thermal neutron count rate emitted from the surface of the soil using a Pulsed Neutron Generator as an activation source coupled with a thermal neutron detector. However, boron has a high cross section for thermal neutron capture and can affect the thermal neutron flux measured by the DAN instrument. Recently, the MSL ChemCam instrument has shown high concentrations of B in the veins of the Murray formation and Yellowknife Bay at concentrations of 100 to 500 ppm. We show that the number of neutrons that are captured in the Martian soil increases with increasing B, resulting in reduced count rates observed by the DAN thermal neutron detector, which can lead to an overestimate of the hydrogen content.

Thirteen compounds were isolated from the methanolic extract of the leaves of Androcymbium palaestinum Baker (Colchicaceae). Of these, three were new, two were new natural products, and eight were known. The new isolated compounds were (+)-1-demethylandrocine (5), (−)-andropalaestine (8), and (+)-2-demethyl-β-lumicolchicone (10), while the new natural products were (+)-O-methylkreysigine-N-oxide (3) and (+)-O,O-dimethylautumnaline (9). Moreover, two known compounds are reported for the first time from this species, specifically (−)-colchicine (11) and (−)-3-demethyldemecolcine (13). The structures of the isolated compounds were elucidated using a series of spectroscopic and spectrometric techniques, principally HRESIMS, 1D-NMR (1H and 13C NMR) and 2D-NMR (COSY, edited-HSQC, and HMBC). ECD spectroscopy was used for assigning the absolute configurations of compounds 3, 5, and 10. The cytotoxic activities of the isolated compounds were evaluated using the MDA-MB-435 (melanoma), MDA-MB-231 (breast), and OVCAR3 (ovary) cancer cell lines. Compound 11 was the most potent against all tested cell lines, with IC50 values of 12, 95 and 23 nM, respectively.

The Hofmeister series is a qualitative ordering of ions according to their ability to precipitate proteins in aqueous solution and is extremely important to consider when trying to understand materials and biomolecular structure and function. Herein, we utilized optical devices (etalons) composed of poly(N-isopropylacrylamide) (pNIPAm)-co-10% acrylic acid (AAc) or pNIPAm-based microgels to investigate how various salts in the Hofmeister series influenced the microgel hydration state. Etalons were exposed to a series of salts solutions at different concentrations and the position of the peaks in the reflectance spectra monitored using reflectance spectroscopy. As expected, pNIPAm-co-10%AAc microgel-based etalons responded to the presence of ions, although in this case the response to cations deviated from the Hofmeister series. However, when using etalons prepared with pNIPAm-based microgels, the responses followed the Hofmeister series for both cation and anions. Finally, we observed that the sensitivity of etalons prepared with pNIPAm microgels was significantly higher than the response obtained from etalons composed of pNIPAm-co-10%AAc microgels. This was explained by considering the charge on the pNIPAm-co-10%AAc microgels that influences how osmotic and Hofmeister effects impacts hydration state.

During their first year of growth, overwintering biennial plants transport Suc through the phloem from photosynthetic source tissues to storage tissues. In their second year, they mobilize carbon from these storage tissues to fuel new growth and reproduction. However, both the mechanisms driving this shift and the link to reproductive growth remain unclear. During vegetative growth, biennial sugar beet (Beta vulgaris) maintains a steep Suc concentration gradient between the shoot (source) and the taproot (sink). To shift from vegetative to generative growth, they require a chilling phase known as vernalization. We studied sugar beet sink-source dynamics upon vernalization and showed that before flowering, the taproot underwent a reversal from a sink to a source of carbohydrates. This transition was induced by transcriptomic and functional reprogramming of sugar beet tissue, resulting in a reversal of flux direction in the phloem. In this transition, the vacuolar Suc importers and exporters TONOPLAST SUGAR TRANSPORTER2;1 and SUCROSE TRANSPORTER4 were oppositely regulated, leading to the mobilization of sugars from taproot storage vacuoles. Concomitant changes in the expression of floral regulator genes suggest that these processes are a prerequisite for bolting. Our data will help both to dissect the metabolic and developmental triggers for bolting and to identify potential targets for genome editing and breeding.

The paper presents the results of influence the light of different wavelengths and pulsed electric fields on the content of carotenoids. Seeds germination was carried out in a climatic chamber with phytotron system. The experiment was carried out under seven growing conditions differing in light-emitting diode (LED) wavelengths and using pulsed electric fields (PEFs) with different strength applied before sowing. Cultivation of the sprouts was carried out for seven days at relative humidity 80% and 20 &plusmn, 1 &deg, C. Different light wavelengths were used during cultivation: white light (380&ndash, 780 nm), UVA (340 nm), blue (440 nm), and red (630 nm). In addition, the pulsed electric field (PEF) with three values of strength equal to 1, 2.5 and 5 kV/cm, respectively, was applied to three series of sprouts before sowing. Sprouts treated with the PEF were grown under white light (380&ndash, 780 nm). The light exposure time for all experimental series of sprouts was 12 / 12 h (12 h light, 12 h dark for seven days). Lutein is the dominant carotenoid in germinating red clover seeds, the content of which varies from 743 mg/kg in sprouts grown in red light, 862 mg/kg in sprouts grown in UVA, to 888 mg/kg in sprouts grown in blue light. Blue light in the cultivation of red clover sprouts had the most beneficial effect on the increase of carotenoids content and amounted to 42% in &beta, carotene, 19% in lutein, and 14% in zeaxanthin. It confirms that modelling the content of carotenoids is possible using UVA and blue light (440 nm) during seed cultivation. An increase in the content of &beta, carotene and lutein in red clover sprouts was obtained in comparison to the test with white light without PEF pre-treatment, respectively by 8.5% and 6%. At the same time a 3.3% decrease in the content of zeaxanthin was observed. Therefore, it can be concluded that PEF pre-treatment may increase mainly the content of &beta, carotene.

We report here a low-cost electrochemical immunoarray with unprecedented sensitivity in the sub-zeptomole range with up to 5 log-decades dynamic range for accurate, multiplexed protein determinations. The microfluidic array features eight carbon sensors coated with a dense layer of 5 nm gold-nanoparticles derivatized with primary antibodies. Analyte proteins are captured by secondary antibody-poly-HPR (horseradish peroxidase) bioconjugates containing 400 HRP enzyme labels, with amplified amperometric peaks developed using H(2)O(2) activator and hydroquinone mediator. Prostate cancer biomarkers prostate specific antigen (PSA), vascular endothelial growth factor-D (VEGF-D), ETS-related gene protein (ERG), and insulin-like growth factor-1 (IGF-1) were measured simultaneously with sub-fg/mL LODs (0.08–0.22 zmol). These proteins were determined in serum of postprostatectomy cancer patients which had much lower levels than prostate cancer patients without surgery. This immunoassay protocol makes thousands of low-abundance proteins accessible to quantitative measurements down to zeptomole levels.

SUMMARYIn the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate action potentials. Accordingly, the neuroepithelial progenitors (NEPs) giving rise to all neurons and glial cells during development have been reported to remain electrically passive. Here, we investigated the physiological properties of NEPs in the mouse spinal cord at the onset of spontaneous neural activity (SNA) initiating motor behavior in embryos. Using patch-clamp recordings, we discovered that spinal NEPs exhibit spontaneous membrane depolarizations during episodes of SNA. These recurrent depolarizations exhibited a ventral-to-dorsal gradient with the highest amplitude located in the floor-plate – the ventral-most part of the neuroepithelium. Paired-recordings revealed that NEPs are extensively coupled via gap-junctions and form a single electrical syncytium. Although other NEPs were electrically passive, we discovered that floor-plate NEPs have the unique ability to generate large Na+/Ca++ action potentials. Unlike neurons, floor-plate action potentials relied primarily on the activation of voltage-gated T-type calcium channels (TTCCs). In situ hybridization showed that all 3 known subtypes of TTCCs are highly and predominantly expressed in the floor-plate. During SNA, we found that acetylcholine released by motoneurons recurrently trigger floor-plate action potentials by acting through nicotinic acetylcholine receptors. Finally, by expressing the genetically encoded calcium indicator GCaMP6f in the floor plate, we demonstrated that neuroepithelial action potentials are associated with calcium waves and propagate along the entire length of the spinal cord. By unraveling a novel physiological mechanism generating electrical signals which can propagate independently from neurons across a neural structure, our work significantly changes our understanding of the development, origin and extent of electrical signaling in the central nervous system.HIGHLIGHTSSpinal neuroepithelial progenitors (NEP) are depolarized during spontaneous neural activityNEPs form a single electrical syncytium connected by gap junctionsFloor-plate NEPs generate large Na+/Ca++ action potentials in response to acetylcholineNeuroepithelial action potentials propagate across the entire spinal cord

The onion is one of the most popular vegetables in the world, often used in the food industry. The purpose of this work was to determine the effect of osmotic dehydration of onions after storage in solutions containing various amounts of sucrose and sodium chloride on the course of osmoconcentration and the level of polyphenols in the dehydrated vegetables. The results could be useful to define the dehydration conditions under which a product retains the highest content of these health-promoting substances.Onions var. Robusta were used. The vegetables were stored for six months at 0deg;C (air relative humidity 75ndash;80%). They were cut into quarters just before dewatering. Samples of 20plusmn;1 g were dehydrated for five hours in a 40ndash;60deg;Bx sucrose solution and a 5ndash;15% NaCl solution (25deg;C); the weight ratio of the sample to the solution was 1:5. The contents of polyphenols and dry matter were determined.The use of a mixture of two osmotic agents (sucrose, sodium chloride) was more effective in the increase of dry matter content than using only sucrose. Nearly 49% dry matter content in onion was obtained by using a 60% solution (50% sucrose + 10% NaCl) for five hours. The greatest differences in the content of total polyphenols occurred during the first hour. After this time, retention amounted to 48ndash;90%, depending on the concentration of sucrose (40ndash;60%) and sodium chloride (5ndash;15%). The retention of diglycosides of quercetin (mainly quercetin-3,4rsquo;-diglucoside) was lower than that of monoglycosides (mainly quercetin-4rsquo;- -glucoside). Following dehydration in a solution containing 60% sucrose and 10% NaCl, after three hours, there was about one third of the initial amount of the above-mentioned compounds in onion.The increase in the concentration of the hypertonic solution, being a mixture of sucrose and sodium chloride, causes a reduction in the retention of total polyphenols in osmotically dehydrated onions. The smallest losses occur after applying a 40% sucrose solution with NaCl up to 10%.

The effect of elevated temperature (44 °C) and ultraviolet (UV) radiation on molecular structure of linoleic acid (LA) was studied by Attenuated Total Reflection Infrared (ATR-IR) spectroscopy. To obtain more detailed information on molecular mechanism of these changes we applied moving-window analysis and two-dimensional correlation spectroscopy (2DCOS). Analysis of the time-dependent ATR-IR spectra of LA before and after UV irradiation revealed the structural changes in molecules of LA. The extent of these changes was significantly higher after an application of UV radiation. During 24 h experiment temperature was constant, therefore the spectral changes result from relatively slow processes (and requiring more energy), e.g. cis/trans isomerization, disruption of the C=C double bonds and partial breaking of hydrogen bonds in the cyclic dimers. As a side effect of these structural changes one can observe variations in the orientation of the chains. It is of note that the methyl and methylene groups reveal slightly different behaviour.

During vegetative growth, biennial sugar beets maintain a steep gradient between the shoot (source) and the sucrose-storing taproot (sink). To shift from vegetative to generative growth, they require a chilling phase, called vernalization. Here, we studied sugar beet sink-source dynamics upon cold temperature-induced vernalization and revealed a pre-flowering taproot sink to source reversal. This transition is induced by transcriptomic and functional reprogramming of sugar beet tissue, resulting in a reversal of flux direction in long distance transport system, the phloem. As a key process for this transition, vacuolar sucrose importers and exporters, BvTST2;1 and BvSUT4, are oppositely regulated, leading to re-mobilization of sugars from taproot storage vacuoles. Concomitant changes in the expression of floral regulator genes suggest that the now deciphered processes are a prerequisite for bolting. Our data may thus serve dissecting metabolic and developmental triggers for bolting, which are potential targets for genome editing or breeding approaches.

Background. Osteoarthritis is an incurable, progressive, degenerative and debilitating joint disease, characterized by pain, stiffness and limitation of joint mobility. Treatment is limited to symptom management and includes pharmaco- and physiotherapy, rehabilitation and surgery. Objective. To evaluate safety and effectiveness of a selected hyaluronic acid injectable in the treatment of small joint osteoarthritis. Materials and methods. 324 patients (F: 190, M: 134) aged 19-84 completed the study. Each participant received three, weekly intra-articular hyaluronic acid injections (Suplasyn®, Bioniche Life Sciences Inc, Belleville, Ontario; 700 kDa, 7 ml/7 mg). Morning stiffness and pain intensity (at rest and movement-induced) before and after treatment as well as post-treatment improvement in joint mobility were assessed based on questionnaires filled out by patients and their physicians prior to treatment commencement and at its conclusion. Participants used a Numerical Rating Scale (range 0-10 points) to quantify assessments. Data was analysed with chi-square and Fisher’s exact tests and p = 0.05 was accepted as significant. Results. A significant (p

Near infrared (NIR) radiation has been widely used in medicine and biomedical engineering. In spite of numerous studies the molecular mechanism of NIR radiation on biological systems has not been established as yet. The objective of this work was examination of the effect of NIR irradiation on the skin components. Modifications of lipid organization after NIR exposure vs. temperature (from 20 to 90 °C) have been investigated using Attenuated Total Reflectance Infrared (ATR-IR) spectroscopy. This work is a continuation of our previous studies on the temperature effect on skin components [ 1 ]. After NIR exposure a temperature shift of the phase transition from the orthorhombic to hexagonal packing (≈40 °C) has been observed. In contrast, the second phase transition temperature (≈70 °C) is almost invariable. The phase transitions in lipids were correlated with modifications of the structure of water and proteins. To our knowledge, for the first time the temperatures of the phase transitions after NIR exposure were investigated.

Normal aging is associated with a number of smell impairments that are paralleled by age-dependent changes in the peripheral olfactory system, including decreases in olfactory sensory neurons (OSNs) and in the regenerative capacity of the epithelium. Thus, an age-dependent degradation of sensory input to the brain is one proposed mechanism for the loss of olfactory function in older populations. Here, we tested this hypothesis by performing in vivo optical neurophysiology in 6-, 12-, 18-, and 24-month-old mice. We visualized odor-evoked neurotransmitter release from populations of OSNs into olfactory bulb glomeruli, and found that these sensory inputs are actually quite stable during normal aging. Specifically, the magnitude and number of odor-evoked glomerular responses were comparable across all ages, and there was no effect of age on the sensitivity of OSN responses to odors or on the neural discriminability of different sensory maps. These results suggest that the brain's olfactory bulbs do not receive deteriorated input during aging and that local bulbar circuitry might adapt to maintain stable nerve input.

Crystals of {[Cu5(oba)4(bpmp)3(H2O)2]·10H2O}n (1, oba = oxybisbenzoate, bpmp = bis(4-pyridylmethyl)piperazine) were prepared by hydrothermal methods. A single-crystal structure determination showed the presence of [Cu5(oba)4(H2O)2]n ribbons with {Cu2(OCO)4} paddlewheel dimers connected to isolated divalent copper atoms and isolated monovalent copper atoms. These ribbon motifs are pillared into the full complicated 3D coordination polymer net of 1 by long-spanning bpmp tethers. Compound 1 presents the unique example of a self-penetrated 3,4,4-connected (83)2(6.8.104)(64.8.10) topology. Decameric water molecule clusters entrained within the net play an important stabilization role.

Four new homoisoflavonoids, 7-O-methyl-8-demethoxy-3′-hydroxy-3,9-dihydropunctatin (4), 6-hydroxy-8-demethoxy-4′-O-methyl-3,9-dihydropunctatin (8), 7,4′-O-dimethyl-8-demethoxy-3,3′-dihydroxy-3,9-dihydropunctatin (13), and 7-O-methyl-3-hyroxy-3,9-dihydropunctatin (14) were identified from a chloroform extract of the bulbs of Bellevalia flexuosa, along with 13 known analogues. The structures were determined by analysis of HRMS and NMR data, while ECD spectroscopy enabled the assignment of the absolute configurations of the new compounds 4, 8, 13 and 16. The cytotoxic activities of the isolated compounds (1–17) were evaluated using a panel of human cancer cell lines. Compounds 2 and 7 were the most potent against the MDA-MB-435 (melanoma) cancer cell line with IC50 values of 1.6 and 2.0 μM, respectively, and were essentially equipotent against the OVCAR3 (ovarian) cancer cell line with IC50 values of 9.5 and 10.8 μM, respectively. However, compound 7, with an IC50 value of 3.6 μM, was the most potent against the MDA-MB-231 (breast) cancer cell line. This research was supported, in part, by the Deanship of Research, Jordan University of Science and Technology , Irbid, Jordan (Grant No. 284/2017 ) and via program project grant P01 CA125066 from the National Cancer Institute / National Institutes of Health , Bethesda, MD, USA. Appendix A Scopus

Here we report ATR-IR spectroscopic study on the separation at a molecular level (microheterogeneity) and the degree of deviation of H2O/CH3OH and H2O/CD3OH mixtures from the ideal mixture. Of particular interest is the effect of isotopic substitution in methyl group on molecular structure and interactions in both mixtures. To obtain comprehensive information from the multivariate data we applied the excess molar absorptivity spectra together with two-dimensional correlation analysis (2DCOS) and chemometric methods. In addition, the experimental results were compared and discussed with the structures of various model clusters obtained from theoretical (DFT) calculations. Our results evidence the presence of separation at a molecular level and deviation from the ideal mixture for both mixtures. The experimental and theoretical results show that the maximum of these deviations appears at equimolar mixture. Both mixtures consist of three kinds of species: homoclusters of water and methanol and mixed clusters (heteroclusters). The heteroclusters exist in the whole range of mole fractions with the maximum close to the equimolar mixture. At this mixture composition near 55–60% of molecules are involved in heteroclusters. In contrast, the homoclusters of water occur in a limited range of mole fractions (XME

Background Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors Demographic, clinical, laboratory, and imaging features of participants. Outcomes Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations Relatively short follow-up of a clinical trial population. Conclusions Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.

We investigated near-infrared (7500–4000 cm−1) spectra of n-hexanol, cyclohexanol and phenol in CCl4 (0.2 M) by using anharmonic quantum calculations. These molecules represent three major kinds of alcohols; linear and cyclic aliphatic, and aromatic ones. Vibrational second-order perturbation theory (VPT2) was employed to calculate the first overtones and binary combination modes and to reproduce the experimental NIR spectra. The level of conformational flexibility of these three alcohols varies from one stable conformer of phenol through four conformers of cyclohexanol to few hundreds conformers in the case of n-hexanol. To take into account the most relevant conformational population of n-hexanol, a systematic conformational search was performed. Accurate reproduction of the experimental NIR spectra was achieved and detailed spectra-structure correlations were obtained for these three alcohols. VPT2 approach provides less reliable description of highly anharmonic modes, i.e. OH stretching. In the present work this limitation was manifested in erroneous results yielded by VPT2 for 2νOH mode of cyclohexanol. To study the anharmonicity of this mode we solved the corresponding time-independent Schrodinger equation based on a dense-grid probing of the relevant vibrational potential. These results allowed for significant improvement of the agreement between the calculated and experimental 2νOH band of cyclohexanol. Various important biomolecules include similar structural units to the systems investigated here. A detailed knowledge on spectral properties of these three types of alcohols is therefore essential for advancing our understanding of NIR spectroscopy of biomolecules.

In this work we report the studies of the effect of temperature on skin components, such as lipids, proteins and water. Modifications of lipids structure induced by increasing temperature (from 20 to 90°C) have been studied using ATR-IR (Attenuated Total Reflectance Infrared) spectroscopy, which is a powerful tool for characterization of the molecular structure and properties of tissues, such as skin. Due to the small depth of penetration (0.6-5.6μm), ATR-IR spectroscopy probes only the outermost layer of the skin, i.e. the stratum corneum (SC). The assignment of main spectral features of skin components allows for the determination of phase transitions from the temperature dependencies of band intensities [e.g. νas(CH2) and νs(CH2)]. The phase transitions were determined by using two methods: the first one was based on the first derivative of the Boltzmann function and the second one employed tangent lines of sigmoidal, aforementioned dependencies. The phase transitions in lipids were correlated with modifications of the structure of water and proteins.

Recently, we demonstrated the presence of microheterogeneity in binary mixtures of unlike alcohols. [ RSC Adv . 2016, 6, 37195–37202] The aim of this work was examination if this phenomenon occurs also in the mixture of very similar alcohols like CH 3 OH and CD 3 OH. Theoretical calculations suggest that the isotopic substitution in methyl group influences properties of the OH group. Hence, one can expect that this effect may lead to partial separation of CH 3 OH and CD 3 OH at a molecular level and it contributes to deviation from the ideal mixture. This work evidences that CH 3 OH/CD 3 OH mixture also deviates from the ideal one, but the extent of this deviation is much smaller as compared with the mixtures of other alcohols. It is of particular note that this deviation results mainly from the difference between the CH 3 and CD 3 groups, while the contribution from the OH groups is small. The structure of CH 3 OH/CD 3 OH mixture at a molecular level is similar to the structure of binary mixtures of other alcohols. The mixture is composed of the homoclusters of both alcohols and the mixed clusters. The homoclusters existing in the mixture are similar to those present in bulk alcohols. The highest population of the heteroclusters and the largest deviation from the ideal mixture were observed at equimolar mixture. Both the experimental and theoretical results reveal that in CH 3 OH/CD 3 OH mixture dominate the cyclic tetramers and larger clusters, while the population of the linear clusters is negligible. Though the extent and strength of hydrogen bonding in both alcohols are the same, the position and intensity of the 2ν(OH) band for CH 3 OH and CD 3 OH are different. We propose possible explanation of this observation.

Use of agricultural fertilizers as a means of increasing production has resulted in excessive nutrient loading to agricultural drainage ditches, contributing to the Gulf of Mexico hypoxic zone. Drainage ditches can have wetland characteristics and functionality, including the capacity to remediate nutrient loading, which can be promoted using management practices. The purpose of this study was to assess relationships between organic carbon (C) and nitrogen (N) contents of drainage ditch sediment and waters, and to evaluate the spatial scope in which organic C is potentially limiting N removal in drainage ditches throughout the Lower Mississippi Alluvial Valley (LMAV). Water and sediment samples were obtained from agricultural drainage ditches in Missouri, Arkansas, Mississippi, and Louisiana (n = 89). Nitrate (NO3−), nitrite (NO2−), ammonium (NH4+), and total N concentrations were determined in overlying and pore water, along with characterizing dissolved organic C aromaticity and molecular weight using absorbance analyses. A significant correlation was observed between sediment percentage N and percentage total organic C (r = 0.944, p