Single Functional Group Research Articles

Attempted “Rescue” of Glutamic Acid by Arginine in a Transmembrane Helix

Membrane proteins are vital for biological function and are complex to study, as they must be investigated in lipid membranes. While studies of small proteins or model peptides in lipid membranes have begun to reveal some of the important lipid interactions of single residues or individual functional groups, the combined effects or interactions of even pairs of protein or peptide side chains still are not well understood. The goal of this research is to understand the combined effects of a glutamic acid and an arginine spaced two residues apart - giving 200° radial separation - within a hydrophobic transmembrane alpha-helix. To this end, we incorporated E16 and R14 the transmembrane helix of acetyl-GGALW5(LA)6LW19LAGA-amide (GWALP23) and labeled selected core alanines with deuterium for detection using 2H NMR spectroscopy. The singly substituted R14-GWALP23 shows remarkably narrow 2H NMR resonances (J Am Chem Soc 132, 5803), whereas the singly substituted E16-GWALP23 shows very broad spectra (BBA 1859, 484). Initial results for the doubly substituted R14,E16-GWALP23 show multiple populations of states for the helix in DOPC bilayers, which is very different from the effects of either residue alone. There is furthermore early indication that a major preferred helix orientation emerges when the pH is lowered from 6 to 3 in DOPC. Ongoing experiments are addressing the multi-state behavior and the pH dependence of the properties of the R14,E16-GWALP23 helix in DOPC membranes. Additional experiments will address the behavior of this helix in DLPC, DMPC and DEiPC bilayer membranes.

The effects of anthracycline drugs on the conformational distribution of mouse P-glycoprotein explains their transport rate differences

P-glycoprotein (Pgp) is an ATP-dependent efflux transporter and plays a major role in anti-cancer drug resistance by pumping a chemically diverse range of cytotoxic drugs from cancerous tumors. Despite numerous studies with the transporter, the molecular features that drive anti-cancer drug efflux are not well understood. Even subtle differences in the anti-cancer drug molecular structure can lead to dramatic differences in their transport rates. To unmask these structural differences, this study focused on two closely-related anthracycline drugs, daunorubicin (DNR), and doxorubicin (DOX), with mouse Pgp. While only differing by a single hydroxyl functional group, DNR has a 4 to 5-fold higher transport rate than DOX. They both non-competitively inhibited Pgp-mediated ATP hydrolysis below basal levels. The Km of Pgp-mediated ATP hydrolysis extracted from the kinetics curves was lower for DOX than DNR. However, the dissociation constants (KDs) for these drugs determined by fluorescence quenching were virtually identical. Acrylamide quenching of Pgp tryptophan fluorescence to probe the tertiary structure of Pgp suggested that DNR shifts Pgp to a “closed” conformation, while DOX shifts Pgp to an “intermediate” conformation. The effects of these drugs on the Pgp conformational distributions in a lipid bilayer were also examined by atomic force microscopy (AFM). Analysis of AFM images revealed that DNR and DOX cause distinct and significant shifts in the conformational distribution of Pgp. The results were combined to build a conformational distribution model for anthracycline transport by Pgp.

Thermodynamic Study of Ion-Driven Aggregation of Cellulose Nanocrystals

The thermodynamics of interactions between cations of the second group of the periodic table and differently negatively charged cellulose nanocrystals was investigated using isothermal titration calorimetry (ITC). The interaction of cations with the negatively charged CNCs was found to be endothermic and driven by an increase in entropy upon adsorption of the ions, due to an increase in degrees of freedom gained by the surface bound water upon ion adsorption. The effect was pH-dependent, showing an increase in enthalpy for cellulose suspensions at near-neutral pH (6.5) when compared to acidic pH (2). Sulfated cellulose nanoparticles were found to readily interact with divalent ions at both pH levels. The adsorption on carboxylate nanocrystals was found to be pH dependent, showing that the carboxylic group needs to be in the deprotonated form to interact with divalent ions. For the combined system (sulfate and carboxylate present at the same time), at neutral pH, the adsorption enthalpy was higher than the value obtained from cellulose nanocrystals containing a single functional group, while the association constant was higher due to an increased favorable entropic contribution. The higher entropic contribution indicates a more restricted surface-bound water layer when multiple functionalities are present. The stoichiometric number n was nearly constant for all systems, showing that the adsorption depends almost completely on the ion valency and on the amount of ionic groups on the CNC surface, independent of the type of functional group on the CNC surface as long as it is deprotonated. In addition, we showed that the reduction in Gibbs free energy drives the ionotropic gelation of nanocellulose suspensions, and we show that ITC is able to detect gel formation at the same time as determining the critical association concentration.

Revealing the Structural Complex of Adsorption and Assembly of Benzoic Acids at Electrode–Electrolyte Interfaces Using Electrochemical Scanning Tunneling Microscopy

Self-assembly of benzenecarboxylic acids on well-defined noble metals has been intensively investigated using surface-sensitive techniques. However, most studies were focused on the formation of nanostructures via benzenetricarboxylic and benzenedicarboxylic acids, which are composed of multiple carboxylic acid functional groups in either the meta or para positions of the benzene ring, allowing the formation of long-range ordered molecular arrays through −COOH-mediated intermolecular hydrogen bonds. Two-dimensional nanostructures of benzoic acid molecules that are composed of a single carboxylic acid functional group on the phenyl ring at metal–electrolyte interfaces were rarely reported using scanning tunneling microscopy (STM) because there is only one carboxylic acid functional group for each benzoic acid available to form intermolecular hydrogen bonds, making it difficult to construct long-range ordered nanoarchitectures. In this work, we employed electrochemical scanning tunneling microscopy (EC-STM)...

Host Genome Variation is Associated with Neurocognitive Outcome in Survivors of Pediatric Medulloblastoma

Host genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology, are limited. Here, we evaluated variation in host genome of long-term survivors of medulloblastoma and its association with neurocognitive outcome. Whole-genome sequencing was conducted on peripheral blood of long-term survivors of pediatric medulloblastoma who also completed neuropsychological testing. Cognitively impaired and less impaired survivors did not differ in exposure to chemoradiation therapy or age at treatment. Unsupervised consensus clustering yielded two distinct variant clusters that were significantly associated with neurocognitive outcome. Interestingly, 34 of the 36 significant variants were found in noncoding DNA regions with unknown regulatory function. A separate unsupervised cluster analysis of variants within DNA repair genes identified discrete variant groups that were not associated with neurocognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. These findings are supportive of the presence of a genetic diathesis for treatment-related neurocognitive morbidity in medulloblastoma that may be driven by variation in noncoding regulatory elements.

Interaction mechanism between copolymer inhibitor and β-dicalcium silicate surface based on molecular dynamics simulation

Copolymer inhibitor with multifunctional groups has a good effect on inhibiting the secondary reaction in the clinker leaching process for alumina production, but the inhibition mechanism of the copolymer is not clear yet. In this paper, molecular dynamics simulation was used to study the adsorption process of the copolymer inhibitor with multifunctional groups, such as acrylic acid-vinyl alcohol copolymer (PAV) and acrylic acid-hydroxypropyl acrylate copolymer (PAH), on the β-dicalcium silicate (C2S) crystal surface, and reveal its inhibiting mechanism. Meanwhile, the polyacrylic acid (PAA) with only the carboxyl group also is simulated for comparing the inhibition effect with copolymer inhibitors. The results show that the binding energy between copolymer (PAV, PAH) and β-C2S is greater than that of PAA with a single functional group. The order of binding energy is as follows: PAH > PAV > PAA. In aqueous solution, the water molecule can restrict the degree of deformation of polymers, increase the distance between polymers and β-C2S and then lead to weakening of the adsorption of polymers on the crystal surface. The comprehensive and coordination effect of carboxyl and hydroxyl functional groups in PAV and PAH can strengthen the adsorption of copolymers on the β-C2S surface. The different spatial distribution of multifunctional groups in the molecular structure has a different influence on the adsorption of the copolymer. The results can provide a theoretical basis for researching new and highly effective copolymer inhibitors with multifunctional groups. Compared the adsorption state: The comprehensive and coordinate action of carboxyl and hydroxyl groups of the inhibitor with multifunctional groups make the inhibitor have a stronger adsorption ability on the surface of β-C2S than that with a single functional group. The results obtained in this paper can provide a theoretical basis for the research and development of new and highly effective polymeric inhibitors with multifunctional groups. Highlights The interaction between copolymer and β-C2S was investigated by MD simulation. The binding energy order between polymers and β-C2S is PAH > PAV > PAA. The presence of water molecules can weaken the adsorption of the copolymer on the surface of β-C2S. The comprehensive and coordinate action of carboxyl and hydroxyl groups of the inhibitor with multifunctional groups make the inhibitor have a stronger adsorption ability on the surface of β-C2S than that with a single functional group.

Palladium catalyzed domino C-H activation strategy: An access to 9- fluorenones

Palladium catalyzed domino C-H functionalization reaction of arylaldehyde with dihaloarene has been developed to access 9-flourenone molecules. Bidentate ligand assisted strategy, single step reaction, high yield and excellent functional group tolerance make this method concise and effective for the synthesis of 9-flourenone. In addition, proposed method has been successfully employed to synthesise Tilorone in gram scale.

Interfacial modulus and surfactant coated surfaces

The Interfacial Modulus () describes the ease at which a functional group within a solid’s outer layer can move from a buried position to a more protruding orientation or vice versa. is typically sensitive to the out-most layer of the solid’s molecules. It can be measured using a Centrifugal Adhesion Balance (CAB) configuration that is aligned for drop sliding at zero normal force. Currently, however, there is no way of measuring independently of CAB experiments. In a desire to find independent means for evaluating the interfacial modulus, we present here an alternative way to estimate through Surface Force Apparatus estimates of the force associated with single functional groups within such a layer.

Aboveground facilitation and not complementary resource use cause overyielding among grasses in Tibetan alpine ecosystems

Although plant-plant interactions and their effects on ecological functioning have been examined in communities composed of different functional groups, they have rarely been studied in communities that contained a single functional group. We established a five-year experiment using three grass species with different nutrient addition and mowing treatments to explore overyielding and species interactions. We found strong overyielding caused by trait-independent complementarity effects. Nutrient addition increased overyielding via increasing trait-independent complementarity effects whereas mowing eliminated overyielding. One possible mechanism underlying the responses observed is the changes of positive aboveground species interactions. This result is consistent with the considerable literature identifying facilitation in alpine ecosystems by which coexisting plant species improve the microclimate and thereby promote the performance of all species. Complimentary resource use and selection effect have been demonstrated frequently as the mechanisms driving overyielding in grasslands. However, as we identify here, and positive interactions may be especially important in driving overyielding and positive interactions may be especially important in stressful environments such as alpine grasslands.

A comprehensive analysis about thermal conductivity of multi-layer graphene with N-doping, -CH3 group, and single vacancy

Graphene has received great attention due to its fascinating thermal properties. The inevitable defects in graphene, such as single vacancy, doping, and functional group, greatly affect the thermal conductivity. The sole effect of these defects on the thermal conductivity has been widely studied, while the mechanisms of the coupling effects are still open. We studied the combined effect of defects with N-doping, the -CH3 group, and single vacancy on the thermal conductivity of multi-layer graphene at various temperatures using equilibrium molecular dynamics with the Green-Kubo theory. The Taguchi orthogonal algorithm is used to evaluate the sensitivity of N-doping, the -CH3 group, and single vacancy. Sole factor analysis shows that the effect of single vacancy on thermal conductivity is always the strongest at 300 K, 700 K, and 1500 K. However, for the graphene with three defects, the single vacancy defect only plays a significant role in the thermal conductivity modification at 300 K and 700 K, while the -CH3 group dominates the thermal conductivity reduction at 1500 K. The phonon dispersion is calculated using a spectral energy density approach to explain such a temperature dependence. The combined effect of the three defects further decreases the thermal conductivity compared to any sole defect at both 300 K and 700 K. The weaker single vacancy effect is due to the stronger Umklapp scattering at 1500 K, at which the combined effect seriously covers almost all the energy gaps in the phonon dispersion relation, significantly reducing the phonon lifetimes. Therefore, the temperature dependence only appears on the multi-layer graphene with combined defects.

Floral resource partitioning by individuals within generalised hoverfly pollination networks revealed by DNA metabarcoding

Pollination is a key ecosystem service for agriculture and wider ecosystem function. However, most pollination studies focus on Hymenoptera, with hoverflies (Syrphidae) frequently treated as a single functional group. We tested this assumption by investigating pollen carried by eleven species of hoverfly in five genera, Cheilosia, Eristalis, Rhingia, Sericomyia and Volucella, using DNA metabarcoding. Hoverflies carried pollen from 59 plant taxa, suggesting they visit a wider number of plant species than previously appreciated. Most pollen recorded came from plant taxa frequently found at our study sites, predominantly Apiaceae, Cardueae, Calluna vulgaris, Rubus fruticosus agg., and Succisa pratensis, with hoverflies transporting pollen from 40% of entomophilous plant species present. Overall pollen transport network structures were generalised, similar to other pollination networks elsewhere. All hoverfly species were also generalised with few exclusive plant/hoverfly interactions. However, using the Jaccard Index, we found significant differences in the relative composition of pollen loads between hoverfly genera, except for Volucella, demonstrating some degree of functional complementarity. Eristalis and Sericomyia species had significant differences in relative pollen load composition compared to congeners. Our results demonstrate the range of pollens transported by hoverflies and the potential pollination function undertaken within this ecologically and morphologically diverse guild.

Functional specialization and phenotypic generalization in the pollination system of an epiphytic cactus

ABSTRACT Plant-pollinator interactions range from obligatory specialists to facultative generalists, and floral morphology and pollination system may not match completely. The floral biology, reproductive system and floral visitors of a species of the tribe Rhipsalideae were investigated with a focus on the consistency between the pollination system and the floral phenotype. Rhipsalis neves-armondii is an obligate xenogamous species, due to self-sterility. Its flowers are white, small and diurnal, and radially symmetrical. These features, along with their small amount of nectar, characterize the flowers as phenotypic generalists. The most frequent pollinators were a solitary oligolectic species of Andrenidae (Rhophitulus solani), two species of Meliponinae (Trigona spinipes and T. braueri) and Apis mellifera. Despite the generalist floral phenotype, the pollination system is functionally specialized, since only small bees performed effective visits. Flowers of R. neves-armondii may represent a case of cryptic floral specialization in which attributes other than morphology act as filters, restricting them to a single functional group of pollinators. Moreover, the four most frequent species of pollinators cover a spectrum ranging from solitary oligolectic to social polylectic bees, including an exotic species. These results illustrate the distinct dimensions of specialization-generalization that may occur in the pollination process of a single species.

Curing reaction mechanism and heat resistance properties of hexa‐(4‐carboxyl‐phenoxy)‐cyclotriphosphazene/bisphenol A aniline benzoxazine blends

ABSTRACTA blend system of hexa‐(4‐carboxyl‐phenoxy)‐cyclotriphosphazene (HCPCP) and bisphenol A aniline benzoxazine (BA‐a) was prepared, and its curing reaction mechanism and heat resistance properties were studied. The curing reaction mechanism of the blend was explored by differential scanning calorimetry, Fourier transform infrared spectroscopy, and modeling software using model compounds Ar‐COOH and hexachlorocyclotriphosphazene (HCCP). The heat resistance properties of the cured blends were studied by thermogravimetric analysis and dynamic mechanical analysis. The polymerization of benzoxazine was catalyzed by HCPCP through phosphazene ring and acid groups, and phosphazene played a predominant role. Compared with the materials with a single functional group (Ar‐COOH and HCCP), HCPCP containing two functional groups (phosphazene ring and acid) exhibited weaker catalytic effects, mainly due to the high molecular weight of HCPCP obstructing movement and causing steric hindrance. In addition, HCPCP had a positive effect on the thermal stability of polybenzoxazine from 250 to 400 °C. When the HCPCP content reached 3%, the cured blend had the highest glass‐transition temperature (222.2 °C), which is higher by 20 °C than that of cured benzoxazine. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46389.

Atomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release

Termination of protein synthesis is triggered by the recognition of a stop codon at the ribosomal A site and is mediated by class I release factors (RFs). Whereas in bacteria, RF1 and RF2 promote termination at UAA/UAG and UAA/UGA stop codons, respectively, eukaryotes only depend on one RF (eRF1) to initiate peptide release at all three stop codons. Based on several structural as well as biochemical studies, interactions between mRNA, tRNA, and rRNA have been proposed to be required for stop codon recognition. In this study, the influence of these interactions was investigated by using chemically modified stop codons. Single functional groups within stop codon nucleotides were substituted to weaken or completely eliminate specific interactions between the respective mRNA and RFs. Our findings provide detailed insight into the recognition mode of bacterial and eukaryotic RFs, thereby revealing the chemical groups of nucleotides that define the identity of stop codons and provide the means to discriminate against noncognate stop codons or UGG sense codons.

Surface Complexation Modeling of Fluoride Adsorption by Soil and the Role of Dissolved Aluminum on Adsorption

Core Ideas A surface complexation model for F− adsorption on soil was developed. Dissolved Al and Al–F complex adsorption added to the model better explained F− adsorption. The model can be extended to study the effect of existing co‐anions or humic substances. The adsorption processes of F− on a natural soil as a function of varying pH and F− concentration were evaluated by applying a surface complexation model (SCM) based on a single surface functional group with monodentate binding sites. A granitic soil from Tsukuba, Japan, was chosen as an example, and the SCM was developed to explain the pH dependency of F− sorption isotherms on the soil. Four possible surface complexation reactions were postulated with and without including dissolved Al. Optimized constants for F− surface complexation, and those for protonation and deprotonation, were used for the simulations. The SCM including dissolved Al and the adsorption of Al–F complex can simulate the experimental results, the decreasing trend of F− adsorption with the increase in pH, quite successfully. Also, including dissolved Al and the adsorption of Al–F complex to the model explained the change in solution pH after F− adsorption. Therefore, incorporation of dissolved Al and Al–F complex in model calculations of a soil–F system is an important improvement to predict F− concentrations of soil solutions.

A removable functional group strategy for regiodivergent Wittig rearrangement products.

[1,2] and [2,3] Wittig rearrangements are competing reaction pathways, often leading to uncontrollable product distribution. We employ a single removable functional group to fulfill the dual role of attaining a reversible [2,3] and stabilizing radical intermediate for the [1,2] path to obtain both the Wittig products selectively for a broad range of substrates.

Study on environment-frientdly UV-led ceramic ink transfer film

UV polyurethane acrylate (PUA-1) oligomer was synthesized and used to prepare the UV-LED ceramic ink transfer film. The effects of active thinner (or active monomer), photosensitizer type, photo-sen-sitizer percentage, photosensitizer consumption, etc. on the ceramic ink transfer film performance was studied. The results showed that the prepared PUA prepolymer, single functional group thinner, and the UV-LED curing system consisting of 2,4,6-Trimethyl Benzoyl Diphenyl Phosphine Oxide (TPO), 2,4-Diethyl-9H-Thioxanthen-9-one(DETX) and Reactive Amine (P115) could meet the technical requirements of transfer film.

Translational model to predict pulmonary pharmacokinetics and efficacy in man for inhaled bronchodilators.

Translational pharmacokinetic (PK) models are needed to describe and predict drug concentration‐time profiles in lung tissue at the site of action to enable animal‐to‐man translation and prediction of efficacy in humans for inhaled medicines. Current pulmonary PK models are generally descriptive rather than predictive, drug/compound specific, and fail to show successful cross‐species translation. The objective of this work was to develop a robust compartmental modeling approach that captures key features of lung and systemic PK after pulmonary administration of a set of 12 soluble drugs containing single basic, dibasic, or cationic functional groups. The model is shown to allow translation between animal species and predicts drug concentrations in human lungs that correlate with the forced expiratory volume for different classes of bronchodilators. Thus, the pulmonary modeling approach has potential to be a key component in the prediction of human PK, efficacy, and safety for future inhaled medicines.

Community structure of rare methanogenic archaea: insight from a single functional group.

The rare biosphere, the low abundant microbial populations, is suggested to be a conserved way of microbial life. Here we conducted a molecular survey of rare methanogenic archaea in the environment targeting the mcrA gene in order to test if general concepts associated with the structure of the rare bacterial biosphere also apply to single functional groups. Similar to what is known about rare bacterial communities, the contribution of rare methanogens to the alpha diversity is much larger than to Bray-Curtis measures. Moreover, a similar core group of methanogens harbored by the abundant and rare communities suggests similar sources and environmental controls of both groups. Among the communities of different levels of rarity, the conditionally rare methanogenic taxa largely account for the overall community dynamics of the rare biosphere and likely enter the dominant community under favorable environmental conditions. In addition, we observed a positive correlation between the alpha diversity and the production of methane when the rare taxa were taken into account. This supports the concept that increasing microbial biodiversity enhances ecological function. The composition and environmental associations of the rare methanogenic biosphere allow us to conclude that rarity is a conserved way also for single functional groups.

Epifaunal community composition in five macroalgal species – What are the consequences if some algal species are lost?

Anthropogenic disturbances such as eutrophication and climate change are affecting the distribution and coverage of macroalgae in coastal areas worldwide. How these changes will affect the littoral food webs is challenging to predict as we still lack basic knowledge of epifaunal communities in different macroalgal species. The aim of this study was therefore to compare the epifauna in five common macroalgal species in the northern Baltic Sea. Samples of macroalgae and the associated epifauna were collected in mesh bags at 2 m depth in July–August 2014. The epifaunal abundance data were analyzed with univariate and multivariate methods. The results revealed significant differences in the epifaunal composition among the studied macroalgal species. Ceramium tenuicorne hosted the significantly highest and Fucus vesiculosus the lowest abundance of epifauna per algal dry weight. When comparing the relative epifaunal abundances in percentage, we found that different epifaunal taxa representing different functional groups dominated Pylaiella littoralis (Chironomidae, deposit feeder), Cladophora rupestris (Gammarus spp., herbivorous/omnivorous) and Furcellaria lumbricalis (Mytilus trossulus, suspension feeder). However, most of the epifaunal taxa were found in all algal species studied. We conclude that the loss or decline of specific macroalgal species will affect the ecosystem functions and energy flows to the higher trophic levels, but that none of the studied algal species seems to be crucial for the existence of single taxa or functional group of epifauna.