What Are Lay Theories of Social Class?

Numerous studies have documented the effects of social class on psychological and behavioral variables. However, lay beliefs about how social class affects these dimensions have not been systematically tested. Studies 1 and 2 assessed lay beliefs about the association between social class and 8 variables (including psychological and behavioral tendencies and cognitive ability). Study 3 assessed lay beliefs about the Big five personality traits and social class, and study 4 reframed the 8 variables from study 1 in opposite terms and yielded similar results. Study 5 contained the variables framed as in both studies 1 and 4, and replicated those results suggesting that framing effects were not responsible for the effects observed. Interestingly, for the most part lay beliefs about social class did not differ as a function of participants’ own social class. In general people held relatively accurate and consistent stereotypes about the relationship between social class and well-being, health, intelligence, and neuroticism. In contrast lay beliefs regarding social class and reasoning styles, as well as relational, social, and emotional tendencies were less consistent and coherent. This work suggests that on the whole people’s beliefs about social class are not particularly accurate, and further that in some domains there are contradictory stereotypes about the consequences of social class.     

Thiadiazole derivatives as New Class of β-glucuronidase inhibitors

Thiadiazole derivatives 1–24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC₅₀ = 2.16 ± 0.01–58.06 ± 1.60 μM as compare to standard d-saccharic acid 1,4-lactone (IC₅₀ = 48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure–activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques ¹H, ¹³C NMR, and EIMS.     

Molecular Dynamics of Class A β-lactamases—Effects of Substrate Binding

The effects of substrate binding on class A β-lactamase dynamics were studied using molecular dynamics simulations of two model enzymes; 40 100-ns trajectories of the free and substrate-bound forms of TEM-1 (with benzylpenicillin) and PSE-4 (with carbenicillin) were recorded (totaling 4.0 μs). Substrates were parameterized with the CHARMM General Force Field. In both enzymes, the Ω loop exhibits a marked flexibility increase upon substrate binding, supporting the hypothesis of substrate gating. However, specific interactions that are formed or broken in the Ω loop upon binding differ between the two enzymes: dynamics are conserved, but not specific interactions. Substrate binding also has a global structuring effect on TEM-1, but not on PSE-4. Changes in TEM-1’s normal modes show long-range effects of substrate binding on enzyme dynamics. Hydrogen bonds observed in the active site are mostly preserved upon substrate binding, and new, transient interactions are also formed. Agreement between NMR relaxation parameters and our theoretical results highlights the dynamic duality of class A β-lactamases: enzymes that are highly structured on the ps-ns timescale, with important flexibility on the μs-ms timescale in regions such as the Ω loop.     

A Novel Class of Fungicides: α-Benzylidene-γ-valerolactones

Enzyme activities involved in the initial step of glycerol metabolism were determined in cells of methylotrophic yeasts grown on glycerol, methanol or glucose. In Candida boidinii (Kloeckera sp.) No. 2201, the activities of glycerol kinase and dihydroxyacetone kinase were detected in cells grown on glycerol and methanol, respectively. The activity of NAD⁺-linked glycerol dehydrogenase of Hansenula polymorpha dl-1 was induced by glycerol and methanol, while that of Hansenula ofunaensis was induced by glycerol. The enzymes of both strains were subject to catabolite repression by glucose.

The yeasts tested were divided into three groups as to the glycerol dissimilation patterns. Strains of the genera Candida, Saccharomyces, Pichia and Torulopsis had the phosphorylative pathway, in which glycerol is first phosphorylated. H. ofunaensis had the oxidative pathway, in which glycerol is first oxidized. H. polymorpha dl-1 had both the phosphorylative and oxidative pathways.     

Structure and evolution of the HLA Class II SXβ gene

The class II major histocompatibility complex antigens are cell-surface heterodimers consisting of an a and a chain. Cosmid cloning has shown that the three families of clas II antigens, DR, DQ, and DP, are encoded within the HLA-D region of chromosome 6 as a series of discrete gene clusters. The DP cluster contains two pairs of a and genes, one of which encodes the biochemically-defined DP antigen. In order to assess whether the other two genes, SXa and SX, are also expressed, potential coding regions have been subcloned and sequenced. The SX3 gene is shown to contain region closely homologous to all six exons of DP. A 1 bp deletion in the 2 exon, also observed for the SX4 allele, causes a translation frameshift, suggesting that SX is a pseudogene. However, all the other exons, as well as their splice sites and the putative promoter region, appear to be intact.     

Characterization of CamH from Methanosarcina thermophila,Founding Member of a Subclass of the γ Class of Carbonic Anhydrases

The homotrimeric enzyme Mt-Cam from Methanosarcina thermophila is the archetype of the γ class of carbonic anhydrases. A search of databases queried with Mt-Cam revealed that a majority of the homologs comprise a putative subclass (CamH) in which there is major conservation of all of the residues essential for the archetype Mt-Cam except Glu62 and an acidic loop containing the essential proton shuttle residue Glu84. The CamH homolog from M. thermophila (Mt-CamH) was overproduced in Escherichia coli and characterized to validate its activity and initiate an investigation of the CamH subclass. The Mt-CamH homotrimer purified from E. coli cultured with supplemental zinc (Zn-Mt-CamH) contained 0.71 zinc and 0.15 iron per monomer and had k_cat and k_cat/K_m values that were substantially lower than those for the zinc form of Mt-Cam (Zn-Mt-Cam). Mt-CamH purified from E. coli cultured with supplemental iron (Fe-Mt-CamH) was also a trimer containing 0.15 iron per monomer and only a trace amount of zinc and had an effective k_cat (k_cat^eff) value normalized for iron that was 6-fold less than that for the iron form of Mt-Cam, whereas the k_cat/K_m^eff was similar to that for Fe-Mt-Cam. Addition of 50 mM imidazole to the assay buffer increased the k_cat^eff of Fe-Mt-CamH more than 4-fold. Fe-Mt-CamH lost activity when it was exposed to air or 3% H₂O₂, which supports the hypothesis that Fe²⁺ has a role in the active site. The k_cat for Fe-Mt-CamH was dependent on the concentration of buffer in a way that indicates that it acts as a second substrate in a “ping-pong” mechanism accepting a proton. The k_cat/K_m was not dependent on the buffer, consistent with the mechanism for all carbonic anhydrases in which the interconversion of CO₂ and HCO₃⁻ is separate from intermolecular proton transfer.Carbonic anhydrases (CAs) are metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate (CO₂ + H₂O ⇆ HCO₃⁻ + H⁺) and are distributed among metabolically diverse species belonging to all three domains of life, reflecting the importance of these enzymes in biology (10, 26). Five classes (α, β, γ, δ, and ζ classes) of CAs that evolved independently and have no significant sequence identity have been identified. Our current understanding of the biochemistry and biological roles of CAs is based largely on several α and β class enzymes from mammals and plants. Two other CAs from members of the Eucarya domain, which belong to the δ and ζ classes and were isolated from a marine diatom, have been characterized (21). Although CAs are widely distributed in diverse prokaryotes (25), relatively few CAs belonging to the α and β classes from members of the Bacteria domain have been characterized. Remarkably, only two CAs from members of the Archaea domain, one each from the β and γ classes, have been characterized biochemically (35). Although the γ class is widely distributed in diverse species belonging to all three domains (26, 31), only the archetype γ class enzyme (Mt-Cam) from the anaerobic acetate-utilizing methane-producing species Methanosarcina thermophila in the Archaea domain has been characterized biochemically and shown to have CA activity (36). Mt-Cam belongs to a superfamily of proteins, comprised mainly of acyltransferases, that share a distinctive left-handed parallel β-helix fold predicted by a unique sequence motif (17, 19). Mt-Cam overproduced in Escherichia coli and purified aerobically contains zinc in the active site (2). However, overproduction in the closely related species Methanosarcina acetivorans yields an enzyme with 3-fold-greater CA activity and iron in the active site, establishing iron as the physiologically relevant metal (18).The kinetic mechanism of Mt-Cam (1, 36) resembles that of all classes of CAs studied despite structural differences. The overall reaction occurs in two mechanistically distinct half-reactions shown in equations 1 and 2 and in equations 3 and 4, where M is a metal, E is the enzyme, and B is buffer. (1) (2) (3) (4) The first half-reaction is a nucleophilic attack of metal-bound hydroxide on carbon dioxide, yielding bicarbonate, which is reflected in the steady-state parameter k_cat/K_m. The second half-reaction is the rate-determining proton transfer from metal-bound water to buffer, which is reflected in the steady-state parameter k_cat. The proton extracted from the metal-bound water is transferred to the buffer, which acts as the second substrate in a ping-pong mechanism.Kinetic analyses of single-amino-acid variants of Mt-Cam have identified Gln75, Asn73, and Asn202 as residues involved in a hydrogen bond network required for the first half-reaction and Glu62 and Glu84 as residues required for the second half-reaction (36). Also, analyses of single-amino-acid variants have identified Arg59, Asp61, and Asp76 as residues important for the integrity of the active site (31). The crystal structure identified a histidine motif (His81, His117, and His122) ligating the active site metal (17). Although Mt-Cam is the only γ class CA that has been characterized biochemically, homologs of Mt-Cam from Arabadopsis thaliana have also been investigated (20). Structural modeling and sequence analysis of the homologs have shown that there is conservation in Mt-Cam of the overall fold, metal ligand (Mt-Cam His81, His117, and His122), and residues important for catalysis (Mt-Cam Gln75 and Gln73) and active site structure (Mt-Cam Arg59, Asp61, and Asp76). However, Glu62 and Glu84 in Mt-Cam, which are required for the second half-reaction, are not conserved in the A. thaliana homologs, and CA activity was not detected in the proteins overproduced in E. coli. Furthermore, the proton shuttle residue (PSR) Glu84 in Cam is located on an acidic loop (30) that is not present in the A. thaliana homologs. A 2004 database search queried with one of the A. thaliana homologs retrieved sequences of putative γ class homologs from cyanobacteria, alpha- and gammaproteobacteria, plants, and green algae (20). With only one exception, all of the sequences showed conservation with the Mt-Cam residues essential for metal binding and catalysis except Glu62 and acidic loop residues that include Glu84. The crystal structure of an Mt-Cam homolog from the anaerobic archaeon Pyrococcus horikoshii that was overproduced in E. coli (14) has left-handed parallel β-helix fold and active site architecture similar to that of Mt-Cam (13) with bicarbonate bound to the active site zinc. However, the acidic loop and the PSR Glu84 of Mt-Cam are not conserved in the P. horikoshii enzyme, and CA activity was not examined. Interestingly, calcium was also shown to be present in the P. horikoshii structure. An Mt-Cam homolog from the marine alga Emiliania huxleyi was overproduced in E. coli and purified to homogeneity (27). The purified enzyme was not characterized, and CA activity was not examined, although 2-fold-greater CA activity was detected in extracts of E. coli expressing the gene. An alignment of the E. huxleyi homolog with Mt-Cam revealed the absence of residues essential for ligation of the active site metal (Mt-Cam His81, His117, and His122), residues important for activity (Mt-Cam Gln75, Gln73, and Glu62), and the acidic loop containing the PSR Glu84.Since only the archetype of the γ class CAs has been characterized biochemically, our overall understanding of the γ class is vague. Sequence analyses of putative homologs have suggested that there is substantial diversity similar to that in the α class (28). In particular, the sequence analyses indicated that many homologs lack the acidic loop and the essential PSR Glu84 of Mt-Cam, suggesting that these homologs belong to a subclass of the γ class. However, the absence of CA activity reported for the two purified proteins belonging to the putative subclass (14, 27) calls into question the catalytic activity, metal content, and other properties. Here we describe a more recent sequence analysis of the γ class and biochemical characterization of a representative of the putative subclass, Mt-CamH from M. thermophila, that was overproduced in E. coli and had substantial CA activity, although it has properties that distinguish it from Mt-Cam.     

Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus

Russian Journal of Bioorganic Chemistry - The paper reports the synthesis of a series of antisense oligonucleotides (aONs) directed against different segments of the influenza A virus genome (H1N1)...     

Conditions for Global Dynamic Stability of a Class of Resource-Bounded Model Ecosystems

This paper studies a class of dynamical systems that model multi-species ecosystems. These systems are ‘resource bounded’ in the sense that species compete to utilize an underlying limiting resource or substrate. This boundedness means that the relevant state space can be reduced to a simplex, with coordinates representing the proportions of substrate utilized by the various species. If the vector field is inward pointing on the boundary of the simplex, the state space is forward invariant under the system flow, a requirement that can be interpreted as the presence of non-zero exogenous recruitment. We consider conditions under which these model systems have a unique interior equilibrium that is globally asymptotically stable. The systems we consider generalize classical multi-species Lotka–Volterra systems, the behaviour of which is characterized by properties of the community (or interaction) matrix. However, the more general systems considered here are not characterized by a single matrix, but rather a family of matrices. We develop a set of ‘explicit conditions’ on the basis of a notion of ‘uniform diagonal dominance’ for such a family of matrices, that allows us to extract a set of sufficient conditions for global asymptotic stability based on properties of a single, derived matrix. Examples of these explicit conditions are discussed.     

“Reverse” Carbocyclic Fleximers: Synthesis of a New Class of Adenosine Deaminase Inhibitors

A series of flexible carbocyclic pyrimidine nucleosides has been designed and synthesized. In contrast to previously reported “fleximers” from our laboratory, these analogues have the connectivity of the heterocyclic base system “reversed”, where the pyrimidine ring is attached to the sugar moiety, rather than the five membered imidazole ring. As was previously seen with the ribose fleximers, their inherent flexibility should allow them to adjust to enzyme binding site mutations, as well as increase the affinity for atypical enzymes. Preliminary biological screening has revealed surprising inhibition of adenosine deaminase, despite their lack of resemblance to adenosine.     

A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins

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A New Class of Pyrethroidal Insecticides; α-Substituted Phenylacetic Acid Esters

A new nucleoside antibiotic, mildiomycin D, was isolated from the culture broth of Streptoverticillium rimofaciens B-98891 as a minor component. The molecular formula of the antibiotic purified by silica gel and ion exchange resin column chromatographies was determined to be C₁₉H₃₀N₈O₈ ? (2H₂O) from its physicochemical data. The ultraviolet and infrared spectra were very similar to those of mildiomycin, a major component. On the basis of ¹H and ¹³C-NMR spectra and acidic hydrolysates of the compound, the chemical structure of the antibiotic was determined as a deoxy compound at the C_8′ position in mildiomycin. Mildiomycin D showed weak activities against Gram-positive and negative bacteria, phytopathogenic fungi and some yeasts, and its activity against Rhodotorula rubura was about 40% that of mildiomycin.     

Tangled Up in Knots: Structures of Inactivated Forms of E. coli Class Ia Ribonucleotide Reductase

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Highlights? Two structures of inactivated RNRs show two concatenated α₄β₄ rings in the crystal ? Solution scattering shows rings interlock in the presence of crystallization solution ? Electron microscopy shows open and incomplete states of ring formation ? Mechanism of protein ring concatenation by ring opening and closing is proposed     

Class II α-mannosidase from Aspergillus fischeri: Energetics of catalysis and inhibition

Energetics of the catalysis of Class II α-mannosidase (E.C.3.2.1.24) from Aspergillus fischeri was studied. The enzyme showed K_cat/K_m for Man (α1-3) Man, Man (α1-2) Man and Man (α1-6) Man as 7488, 5376 and 3690 M^?1 min^?1, respectively. The activation energy, E_a was 15.14, 47.43 and 71.21 kJ/mol for α1-3, α1-2 and α1-6 linked mannobioses, respectively, reflecting the energy barrier in the hydrolysis of latter two substrates. The enzyme showed K_cat/K_m as 3.56 × 10⁵ and 4.61 × 10⁵ M^?1 min^?1 and E_a as 38.7 and 8.92 kJ/mol, towards pNPαMan and 4-MeUmbαMan, respectively. Binding of Swainsonine to the enzyme is stronger than that of 1-deoxymannojirimycin.     

Stochastic Models and Numerical Algorithms for a Class of Regulatory Gene Networks

Regulatory gene networks contain generic modules, like those involving feedback loops, which are essential for the regulation of many biological functions (Guido et al. in Nature 439:856–860, 2006). We consider a class of self-regulated genes which are the building blocks of many regulatory gene networks, and study the steady-state distribution of the associated Gillespie algorithm by providing efficient numerical algorithms. We also study a regulatory gene network of interest in gene therapy, using mean-field models with time delays. Convergence of the related time-nonhomogeneous Markov chain is established for a class of linear catalytic networks with feedback loops.     

The TMEM16 Protein Family: A New Class of Chloride Channels?

Cl⁻ channels play important roles in many physiological processes, including transepithelial ion absorption and secretion, smooth and skeletal muscle contraction, neuronal excitability, sensory perception, and cell volume regulation. The molecular identity of many types of Cl⁻ channels is still unknown. Recently, three research groups have arrived independently at the identification of TMEM16A (also known as anoctamin-1) as a membrane protein strongly related to the activity of Ca²⁺-activated Cl⁻ channels (CaCCs). Site-specific mutagenesis of TMEM16A alters the properties of the channels, thus suggesting that TMEM16A forms, at least in part, the CaCC. TMEM16A is a member of a family that includes nine other membrane proteins. All TMEM16 proteins have a similar structure, with eight putative transmembrane domains and cytosolic amino- and carboxy-termini. TMEM16B expression also evokes the appearance of CaCCs, but with biophysical characteristics (voltage dependence, unitary conductance) different from those associated to TMEM16A. The roles of the other TMEM16 proteins are still unknown. The study of TMEM16 proteins may lead to identification of novel molecular mechanisms underlying ion transport and channel gating by voltage and Ca²⁺.     

A Novel Class of 4′-Aza Analogues of 2′,3′-Dideoxynucleosides as Potential Anti-HIV Drugs

Abstract

The 1,3 dipolar cycloaddition approach represents the most valuable strategy for the preparation of isoxazolidine nucleosides. The latter posses more conformational degrees of freedom than the corresponding dideoxyribosides. Side reactions due to the presence of formaldehyde in the reaction media can be avoided by proper derivatization of the vinyl-nucleobase.     

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK _a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1–2591.4 μg/mL within the pH range 1.2–5.0) and low solubility at high pH (5.8–51.9 μg/mL within the pH range 6.5–7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8–98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2–5.0) and relatively low (15.9–86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5–7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.     

The Series Solution for a Class of Nonstationary Biological Population Systems and Their Stability

1IntroductionInaStableenjoinment,thegeneral~populationSystemcanbeexpr~asfollows(see[1,21)In[2,3],wedi~theP~ofationforaStatiomppopulationsyStem,theanduniquenessOfthesolutionforanonStatio~populationsystemwereP~.InthiSPaper,wediscusstheseriessolutionOf~tO~adulationSyStem,wedefinethecriticsproliferationrate,anddiscussthestabilityOftheSySt~.InSyStem(1),p(r,t)iscalledpopulationdenSi.tyfUnCtionOfagerandtimet,p,(r)isaninitialdistribution,8(t)istheprDliferationrate,p(r)isanincreasingfUnction(…