Sequential nearest-neighbor effects on computed <Superscript>13</Superscript>C<Superscript>α</Superscript> chemical shifts

To evaluate sequential nearest-neighbor effects on quantum-chemical calculations of ¹³C^α chemical shifts, we selected the structure of the nucleic acid binding (NAB) protein from the SARS coronavirus determined by NMR in solution (PDB id 2K87). NAB is a 116-residue α/β protein, which contains 9 prolines and has 50% of its residues located in loops and turns. Overall, the results presented here show that sizeable nearest-neighbor effects are seen only for residues preceding proline, where Pro introduces an overestimation, on average, of 1.73 ppm in the computed ¹³C^α chemical shifts. A new ensemble of 20 conformers representing the NMR structure of the NAB, which was calculated with an input containing backbone torsion angle constraints derived from the theoretical ¹³C^α chemical shifts as supplementary data to the NOE distance constraints, exhibits very similar topology and comparable agreement with the NOE constraints as the published NMR structure. However, the two structures differ in the patterns of differences between observed and computed ¹³C^α chemical shifts, Δ _ca,i , for the individual residues along the sequence. This indicates that the Δ _ca,i -values for the NAB protein are primarily a consequence of the limited sampling by the bundles of 20 conformers used, as in common practice, to represent the two NMR structures, rather than of local flaws in the structures.     

δ<Superscript>15</Superscript>N constraints on long-term nitrogen balances in temperate forests

Biogeochemical theory emphasizes nitrogen (N) limitation and the many factors that can restrict N accumulation in temperate forests, yet lacks a working model of conditions that can promote naturally high N accumulation. We used a dynamic simulation model of ecosystem N and δ¹⁵N to evaluate which combination of N input and loss pathways could produce a range of high ecosystem N contents characteristic of forests in the Oregon Coast Range. Total ecosystem N at nine study sites ranged from 8,788 to 22,667 kg ha⁻¹ and carbon (C) ranged from 188 to 460 Mg ha⁻¹, with highest values near the coast. Ecosystem δ¹⁵N displayed a curvilinear relationship with ecosystem N content, and largely reflected mineral soil, which accounted for 96–98% of total ecosystem N. Model simulations of ecosystem N balances parameterized with field rates of N leaching required long-term average N inputs that exceed atmospheric deposition and asymbiotic and epiphytic N₂-fixation, and that were consistent with cycles of post-fire N₂-fixation by early-successional red alder. Soil water δ¹⁵NO₃ ⁻ patterns suggested a shift in relative N losses from denitrification to nitrate leaching as N accumulated, and simulations identified nitrate leaching as the primary N loss pathway that constrains maximum N accumulation. Whereas current theory emphasizes constraints on biological N₂-fixation and disturbance-mediated N losses as factors that limit N accumulation in temperate forests, our results suggest that wildfire can foster substantial long-term N accumulation in ecosystems that are colonized by symbiotic N₂-fixing vegetation.     

Reactive oxygen and nitrogen species’ effect on <Emphasis Type="Italic">lux</Emphasis>-biosensors based on <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Salmonella typhimurium</Emphasis>

The effect of reactive oxygen and nitrogen species on lux-biosensors based on the Escherichia coli K12 MG1655 and Salmonella typhimurium LT2 host strains was investigated. The bioactivity of exogenous free radicals to the constitutively luminescent E. coli strain with plasmid pXen7 decreased in the order H₂O₂ > OCl^– > NO^? > RОO^? > ONOO^–> O₂^?- while the bioluminescence of S. typhimurium strain transformed with this plasmid decreased in the order NO^? > H₂O₂ > ONOO^– > RОO^? > OCl^– > O₂^?- The cross-reactivity of induced lux-biosensors to reactive oxygen and nitrogen species, the threshold sensitivity and the luminescence amplitude dependences from the plasmid specificity and the host strain were indicated. The biosensors with plasmid pSoxS′::lux possessed a wider range of sensitivity, including H₂O₂ and OCl^–, along with O₂^?- and NO^?. Among the used reactive oxygen and nitrogen species, H₂O₂ showed the highest induction activity concerning to the plasmids pKatG′::lux, pSoxS′::lux and pRecA′::lux. The inducible lux-biosensors based on S. typhimurium host strain possessed a higher sensitivity to the reactive oxygen and nitrogen species in comparison with the E. coli lux-biosensors.     

A theoretical study on the reaction mechanism of O<Subscript>2</Subscript> with C<Subscript>4</Subscript>H<Subscript>9</Subscript>• radical

Ab initio calculations have been performed using the complete basis set model (CBS-QB3) to study the reaction mechanism of butane radical (C₄H₉•) with oxygen (O₂). On the calculated potential energy surface, the addition of O₂ to C₄H₉• forms three intermediates barrierlessly, which can undergo subsequent isomerization or decomposition reaction leading to various products: HOO• + C₄H₈, C₂H₅• + CH₂CHOOH, OH• + C₃H₇CHO, OH• + cycle-C₄H₈O, CH₃• + CH₃CHCHOOH, CH₂OOH• + C₃H₆. Five pathways are supposed in this study. After taking into account the reaction barrier and enthalpy, the most possible reaction pathway is C₄H₉• + O₂ → IM1 → TS5 → IM3 → TS6 → IM4 → TS7 → OH• + cycle-C₄H₈O.     

Effects of Prostaglandins F<Subscript>2α</Subscript>, E<Subscript>2</Subscript> and E<Subscript>1</Subscript> on Fertility in Mice

PROSTAGLANDIN (PG) F_2αhas antifertility effects in many species^1–3 but there are conflicting suggestions as to its mechanism of action. For example, it may cause the degeneration of the corpus luteum by decreasing blood flow in the uteroovarian vein⁴; alternatively, its action may be due to a hypersecretion of luteinizing hormone (LH) by the pituitary^3,5. I have investigated the effects of PGF_2α, E₂ and E₁ on pregnancy in mice and examined the mechanism of action of PGF_2α.     

<Emphasis Type="Italic">In Vitro</Emphasis> effect of C<Subscript>2</Subscript>–C<Subscript>18</Subscript> fatty acids on salmonellas

The susceptibility of Salmonella spp. to 15 fatty acids was determined in vitro in cultures grown on glucose. Antimicrobial activity was expressed as IC50 (a concentration at which only 50% of the initial glucose in cultures was utilized). Caprylic acid was the only acid inhibiting glucose utilization. In cultures of S. enteritidis, S. infantis and S. typhimurium, IC50 of caprylic acid ranged from 0.75 to 1.17 mg/mL. A moderate adaptation effect was observed as these values increased 1.5-1.8 times when bacteria were subcultured 10 times in media containing a low concentration of caprylic acid (1/3 IC50). No effect of calcium ions added in excess on antimicrobial activity of caprylic acid was observed. Incubation of salmonellas with caprylic acid (1 mg/mL; 30 min) at pH 5.2-5.3 led to a reduction in the concentration of viable cells below the detection limit; 2-6% of Salmonella cells survived at pH 6.3-6.6.     

Does COMT genotype influence the effects of d‐amphetamine on executive functioning?

In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N‐Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol‐O‐methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d‐amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double‐blind conditions and completed WCST and N‐back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.     

Phororhacoidea or Phorusrhacoidea? A note on the nomenclature of the “terror birds”

The Phorusrhacidae, a group of large terrestrial carnivorous birds mostly known from the Cenozoic of South America, are often placed in a superfamily, for which the taxon name Phororhacoidea Patterson, 1941 is frequently used. However, according to the International Code of Zoological Nomenclature, Phororhacoidea is not valid. The proper taxon name at the superfamily level is Phorusrhacoidea Ameghino, 1889.     

Effects of Spontaneous Bilayer Curvature on Influenza Virus–mediated Fusion Pores

Cells expressing the hemagglutinin protein of influenza virus were fused to planar bilayer membranes containing the fluorescent lipid probes octadecylrhodamine (R18) or indocarbocyanine (DiI) to investigate whether spontaneous curvature of each monolayer of a target membrane affects the growth of fusion pores. R18 and DiI lowered the transition temperatures for formation of an inverted hexagonal phase, indicating that these probes facilitate the formation of negative curvature structures. The probes are known to translocate from one monolayer of a bilayer membrane to the other in a voltage-dependent manner. The spontaneous curvature of the cis monolayer (facing the cells) or the trans monolayer could therefore be made more negative through control of the polarity of voltage across the planar membrane. Electrical admittance measurements showed that the open times of flickering fusion pores were shorter when probes were in trans monolayers and longer when in cis monolayers compared with times when probe was symmetrically distributed. Open times were the same for probe symmetrically distributed as when probes were not present. Thus, open times were a function of the asymmetry of the spontaneous curvature between the trans and cis monolayers. Enriching the cis monolayer with a negative curvature probe reduced the probability that a small pore would fully enlarge, whereas enriching the trans monolayer promoted enlargement. Lysophosphatidylcholine has positive spontaneous curvature and does not translocate. When lysophosphatidylcholine was placed in trans leaflets of planar membranes, closing of fusion pores was rare. The effects of the negative and positive spontaneous curvature probes do not support the hypothesis that a flickering pore closes from an open state within a hemifusion diaphragm (essentially a “flat” structure). Rather, such effects support the hypothesis that the membrane surrounding the open pore forms a three-dimensional hourglass shape from which the pore flickers shut.     

<Emphasis Type="Italic">Darkness’s</Emphasis> Descent on the American Anthropological Association

In September 2000, the self-styled “anthropological journalist” Patrick Tierney began to make public his work claiming that the Yanomamö people of South America had been actively—indeed brutally—harmed by the sociobiological anthropologist Napoleon Chagnon and the geneticist-physician James Neel. Following a florid summary of Tierney’s claims by the anthropologists Terence Turner and Leslie Sponsel, the American Anthropological Association (AAA) saw fit to take Tierney’s claims seriously by conducting a major investigation into the matter. This paper focuses on the AAA’s problematic actions in this case but also provides previously unpublished information on Tierney’s falsehoods. The work presented is based on a year of research by a historian of medicine and science. The author intends the work to function as a cautionary tale to scholarly associations, which have the challenging duty of protecting scholarship and scholars from baseless and sensationalistic charges in the era of the Internet and twenty-four-hour news cycles.     

Stabilizing effect of <Emphasis Type="Italic">Azospirillum</Emphasis> lectins on β-glucosidase activity

Lectins from the surface of Azospirillum brasilense Sp7 and Azospirillum brasilense Sp7.2.3 (a mutant with impaired lectin activity) were shown to induce a stabilizing effect on the activity of almond β-glucosidase under conditions of thermoinactivation and proteolytic enzyme treatment. Differences were revealed in the influence of lectins with various antigenic properties. Our results indicate that the effects of lectins on the catalytic activity of the enzyme are mainly associated with conformational changes in lectin molecules during mutagenesis, but not with carbohydrate specificity (general property). These data should be taken into account in evaluating the role of lectins in the formation of nitrogen-fixing associations.     

Evaluation of <Superscript>15</Superscript>N-detected H–N correlation experiments on increasingly large RNAs

Recently, ¹⁵N-detected multidimensional NMR experiments have been introduced for the investigation of proteins. Utilization of the slow transverse relaxation of nitrogen nuclei in a ¹⁵N-TROSY experiment allowed recording of high quality spectra for high molecular weight proteins, even in the absence of deuteration. Here, we demonstrate the applicability of three ¹⁵N-detected H–N correlation experiments (TROSY, BEST-TROSY and HSQC) to RNA. With the newly established ¹⁵N-detected BEST-TROSY experiment, which proves to be the most sensitive ¹⁵N-detected H–N correlation experiment, spectra for five RNA molecules ranging in size from 5 to 100 kDa were recorded. These spectra yielded high resolution in the ¹⁵N-dimension even for larger RNAs since the increase in line width with molecular weight is more pronounced in the ¹H- than in the ¹⁵N-dimension. Further, we could experimentally validate the difference in relaxation behavior of imino groups in AU and GC base pairs. Additionally, we showed that ¹⁵N-detected experiments theoretically should benefit from sensitivity and resolution advantages at higher static fields but that the latter is obscured by exchange dynamics within the RNAs.     

The Effects of FeCl<Subscript>3</Subscript> and Fe–EDTA on the Development of Psoriasis

The effects of FeCl₃ and Fe–EDTA on the development of psoriasis were studied in the mouse model of vaginal epithelium and tail epidermis. The mitoses of vaginal epithelial cell in female mice of their estrogenic stage and the formation of granular cell layers in male mouse tail scale were observed. Mice were randomly divided into eight groups and treated with normal saline, methotrexate, and different doses of two iron forms, FeCl₃ and Fe–EDTA, respectively, for 10 days. To explore the influence of FeCl₃ and Fe–EDTA on the excretion of Cu, Fe, Zn, Ca, Mg, Mn, and Se, the concentration of those elements in liver and kidney was analyzed by atomic absorption spectrometry. The different doses of FeCl₃ or Fe–EDTA could obviously inhibit the mitoses of vaginal epithelial cell (p< 0.05) and promote the formation of granular cell layers in mice tail scale (p < 0.05). No statistically significant results were found between the groups of FeCl₃ and Fe–EDTA, and between experimental groups and methotrexate group acted as the positive control (p>0.05). Compared with the negative group, the concentrations of Cu, Fe, Zn, Ca, Mg, Mn, and Se in liver and kidney of experimental groups and positive control group were not significantly changed (p > 0.05). FeCl₃ and Fe–EDTA are as effective as methotrexate on inhibiting hyperplasia of epidermal cells and increasing the formation of granular cell layers, and the concentrations of Cu, Fe, Zn, Ca, Mg, Mn, and Se in liver and kidney of experimental groups and positive control group were not significantly changed compared with the negative group, possibly retarding the development of psoriasis.     

SYNE1-QK1 SNPs,G × G and G × E interactions on the risk of hyperlipidaemia

This study aimed to assess the relationship of 3 spectrin repeat containing nuclear envelope protein 1 (SYNE1) and 4 KH domain containing RNA binding (QK1) single nucleotide polymorphisms (SNPs), their haplotypes, gene-gene (G × G), gene-environment (G × E) interactions and hypercholesterolaemia (HCH) and hypertriglyceridaemia (HTG) in the Chinese Maonan minority. The genetic make-up of the SYNE1-QK1 SNPs in 1932 unrelated subjects (normal, 641; HCH, 649; and HTG, 642) was obtained by next-generation sequencing technologies. The genotypic frequencies of following SNPs were suggestively distinctive between the control and HCH groups (rs2623963, rs7745725, rs9459317, rs16897566), or between the control and HTG groups (rs2623963, rs1358317, rs7745725, rs1923608, rs16897566 SNPs; P < .05, respectively). Multiple-locus linkage disequilibrium analysis indicated that the identified SNPs were not inherited independently. Several haplotypes and gene-gene interaction haplotypes among the detected SNPs may be related with an increased morbidity of HCH (C-G-A, C-G-G and C-G-G-T-C-A-T) and HTG (C-G-G, G-T-G-C, C-G-G-G-T-G-C and C-G-G-T-C-A-T), whereas others may be related with an decreased risk of HCH (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T) and HTG (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T). The association evaluation based on haplotypes and gene-gene interactions could improve the power of detecting the risk of dyslipidaemia than anyone of SNP alone. There was significant three-locus model involving SNP-SNP, haplotype-haplotype/environment and G × G interactions (P < .05-0.001) that were detected by GMDR in HCH and HTG groups. Different interactions between genetic and environmental factors would produce different redundancy or synergy effects on the morbidity of HCH and/or HTG.     

R-Ras regulates β<Subscript>1</Subscript>-integrin trafficking via effects on membrane ruffling and endocytosis

Background  

Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to the leading edge of migrating cells, and regulates membrane protrusion. The exact mechanisms by which R-Ras regulates integrin function are not fully known. Nor is much known about the spatiotemporal relationship between these two molecules, an understanding of which may provide insight into R-Ras regulation of integrins.     

Different effects of SNP and GSNO on mitochondrial O<Stack><Subscript>2</Subscript><Superscript>.−</Superscript></Stack>/H<Subscript>2</Subscript>O<Subscript>2</Subscript> production

Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) differently affect mitochondrial H₂O₂ release at Complex-I. mM SNP increases while GSNO decreases the release induced by succinate alone or added on top of NAD-linked substrates. Stimulation likely depends on Nitric Oxide ( ^. NO) (released by SNP but not by GSNO) inhibiting cytochrome oxidase and mitochondrial respiration. Preincubations with SNP or high GSNO (10 mM plus DTE to increases its ^. NO release) induces an inhibition of the succinate dependent H₂O₂ production consistent with a ^. NO dependent covalent modification. However maximal inhibition of the succinate dependent H₂O₂ release is obtained in the presence of low GSNO (20–100 μM), but not with SNP. This inhibition appears independent of ^. NO release since μM GSNO does not affect mitochondrial respiration, or the H₂O₂ detection systems and its effect is very rapid. Inhibition may be partly due to an increased removal of O₂^.− since GSNO chemically competes with NBT and cytochrome C in O₂^.− detection.     

Oxygen supply in <Emphasis Type="Italic">Bacillus thuringiensis</Emphasis> fermentations: bringing new insights on their impact on sporulation and δ-endotoxin production

The growth kinetics, sporulation, and toxicity of Bacillus thuringiensis var. israelensis were evaluated through the analysis of batch cultures with different dissolved oxygen (DO) profiles. Firstly, DO was maintained constant at 5%, 20%, or 50% throughout fermentation in order to identify the most suitable one to improve the main process parameters. Higher biomass concentration, cell productivity, and cell yield based on glucose were obtained with 50% DO. The higher aeration level also resulted in higher spore counts and markedly improved the toxic activity of the fermentation broth, which was 9-fold greater than that obtained with 5% DO (LC₅₀ of 39 and 329 mg/L, respectively). Subsequently, using a two-stage oxygen supply strategy, DO was kept at 50% during the vegetative and transition phases until the maximum cell concentration was achieved. Then, DO was changed to 0%, 5%, 20%, or 100% throughout sporulation and cell lysis phases. The interruption of oxygen supply strongly reduced the spore production and thoroughly repressed the toxin synthesis. On the contrary, when DO was raised to 100% of saturation, toxic activity increased approximately four times (LC₅₀ of 8.2 mg/L) in comparison with the mean values reached with lower DO levels, even though spore counts were lower than that from the 50% DO assay. When pure oxygen was used instead of normal air, it was possible to obtain 70% of the total biomass concentration achieved in the air assays; however, cultures did not sporulate and the toxin synthesis was consequently suppressed.     

An optical material for the detection of trace S<Subscript>2</Subscript>O<Subscript>3</Subscript><Superscript>2−</Superscript> in milk based on a copper complex

A novel S₂O₃ ^2? luminescent sensor (Cu²⁺-p-CPIP) was developed and the presence of S₂O₃ ^2? caused an obvious fluorescence enhancement at 420 nm upon excitation at 330 nm, which could be distinguished with the naked eye under a UV lamp. Remarkably, the compound exhibited excellent selective and sensitive response to S₂O₃ ^2? over other common anions with a micromolar limit of detection (0.442 μM) in DMSO/H₂O (v/v, 1:1) buffer. The absorbance intensity and the color of Cu²⁺-p -CPIP solution changed gradually with the increase of S₂O₃ ^2? concentration. The proposed method was applied to the determination of S₂O₃ ^2? in milk samples and the recoveries were 97.5–105%. The preparation of Cu²⁺-p -CPIP exhibited the quick, simple and facile advantages. The results showed that Cu²⁺-p -CPIP can be a good candidate for simple, rapid and sensitive colorimetric detection of S₂O₃ ^2? in aqueous solution.