Molecular‐Dynamics Simulation of Dioxygen Egress from 12/15‐Lipoxygenase?Arachidonic Acid Complex

Extensive random‐acceleration molecular‐dynamics (RAMD) simulations of the egress of dioxygen (O₂) from a model of rabbit 12/15‐lipoxygenase? arachidonic acid complex disclosed several exit portals in addition to those previously described from implicit ligand sampling calculations and limited MD simulations.     

Single‐Atom to Single‐Atom Grafting of Pt1 onto Fe?N4 Center: Pt1@Fe?N?C Multifunctional Electrocatalyst with Significantly Enhanced Properties

Nonprecious metal catalysts (NPMCs) Fe? N? C are promising alternatives to noble metal Pt as the oxygen reduction reaction (ORR) catalysts for proton‐exchange‐membrane fuel cells. Herein, a new modulation strategy is reported to the active moiety Fe? N₄ via a precise “single‐atom to single‐atom” grafting of a Pt atom onto the Fe center through a bridging oxygen molecule, creating a new active moiety of Pt₁? O₂? Fe₁? N₄. The modulated Fe? N? C exhibits remarkably improved ORR stabilities in acidic media. Moreover, it shows unexpectedly high catalytic activities toward oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), with overpotentials of 310 mV for OER in alkaline solution and 60 mV for HER in acidic media at a current density of 10 mA cm^?2, outperforming the benchmark RuO₂ and comparable with Pt/C(20%), respectively. The enhanced multifunctional electrocatalytic properties are associated with the newly constructed active moiety Pt₁? O₂? Fe₁? N₄, which protects Fe sites from harmful species. Density functional theory calculations reveal the synergy in the new active moiety, which promotes the proton adsorption and reduction kinetics. In addition, the grafted Pt₁? O₂? dangling bonds may boost the OER activity. This study paves a new way to improve and extend NPMCs electrocatalytic properties through a precisely single‐atom to single‐atom grafting strategy.     

GC (Guanine‐Cytosine)‐Selective DNA‐Binding and Antitumor Activity of a Quercetin?Manganese(II) Complex

The DNA binding and cleavage properties of quercetin? manganese(II) complexes have been studied, but little attention has been devoted to the relationship between the antitumor activity of these complexes and the DNA‐binding properties. Here, the DNA binding properties of the quercetin? manganese(II) complex [Mn(Que)₂(H₂O)₂] were studied using UV/VIS and fluorescence spectroscopy and viscosity measurements. The results indicate that the complex was preferentially bound to DNA in the GC (guanine? cytosine)‐rich regions via an intercalative mode. Furthermore, the cytotoxicity experiments confirmed its apoptosis‐inducing activity. We also demonstrated that the levels of survivin protein expression in HepG2 cells decreased and that the relative activity of caspase‐3 significantly increased after treatment with the complex. Hence, our results suggest that the antitumor activity of the [Mn(Que)₂(H₂O)₂] complex might be related to its intercalation into DNA and its DNA‐binding selectivity.     

The Creation of Proton Hopping from a Drug?Receptor Encounter

We extend recent modeling studies of proton hopping, used to describe the functioning of membrane channels and axon nerve conduction, to offer an explanation of the initiation of the nerve impulse at an effector? ligand encounter. This encounter is proposed to create a hydronium ion in the vicinity of the effector and ligand, which leads to a continuous flow of protons, called proton hopping, through water adjacent to this encounter. This proton hopping is proposed to be the message carried from the encounter to the axon of a particular nerve system associated with that particular effector? ligand system.     

Synthesis,Characterization, and DNA‐Binding and ‐Cleavage Properties of Dinuclear CuII?Salophen/Salen Complexes

Dinuclear Cu^II complexes, [Cu₂(salophen)₂] ( 1 ) and [Cu₂(salen)₂] ( 2 ), with Schiff bases derived from salicylaldehyde and o‐phenylenediamine (ophen) or ethylenediamine (en) were synthesized and characterized. They exhibit square‐planar geometry with CuN₂O₂ coordination, where the dianionic Schiff base acts as a tetradentate N₂O₂ donor ligand. Calf thymus (CT)‐DNA Binding studies revealed that the complexes possess good binding propensities (K_b=3.13×10⁵ for 1 and K_b=2.99×10⁵ M ⁻¹ for 2 ). They show good DNA‐cleavage abilities under oxidative and hydrolytic conditions. Complex 1 binds and cleaves DNA more efficiently as compared to 2 due to the presence of an extended aromatic phenyl ring which might be involved in an additional stacking interaction with DNA bases. From the kinetic experiments, hydrolytic DNA‐cleavage rate constants were determined as 1.54 for 1 and 0.72 h⁻¹ for 2 . The nuclease activities of 1 and 2 are significant, giving rise to (2.03–2.88)×10⁷‐fold rate enhancement compared to non‐catalyzed DNA cleavage.     

Proteasomal dysfunction induced by 4‐hydroxy‐2,3‐trans‐nonenal,an end‐product of lipid peroxidation: a mechanism contributing to neurodegeneration?

4-Hydroxy-2,3-trans-nonenal (HNE) is a neurotoxic unsaturated aldehyde end-product of lipid peroxidation. The addition of HNE to NT-2 and SK-N-MC cell lines induces apoptosis and we now investigated the time-course of events occurring prior to apoptosis. Treatment of both NT-2 and SK-N-MC cell lines with HNE led to HNE association with the proteasome, increased levels of protein carbonyls and ubiquitinated proteins, and decreased proteasomal function. There was also decreased metabolic activity, cytochrome c release and activation of caspase 3, followed by apoptotic changes including chromatin condensation, cell shrinkage and DNA fragmentation and laddering. Overexpression of mutant superoxide dismutase 1 proteins associated with amyotrophic lateral sclerosis decreased proteasomal activities in the absence of HNE and accelerated the apoptosis induced by HNE. By contrast, overexpression of wild-type superoxide dismutase 1 did not affect basal levels of proteasomal activity. The data suggest that accumulation of ubiquitinated proteins and impairment of proteasomal function are important events in HNE toxicity. We propose that the proteasomal system is a significant target of HNE neurotoxicity in a wide range of neurodegenerative diseases, especially if abnormal proteins are being expressed.     

In Situ Revealing the Electroactivity of P?O and P?C Bonds in Hard Carbon for High‐Capacity and Long‐Life Li/K‐Ion Batteries

The low capacity and unsatisfactory rate capability of hard carbon still restricts its practical application for Li/K‐ion batteries. Herein, a low‐cost and large‐scale method is developed to fabricate phosphorus‐doped hard carbon (PHC‐700) by crosslinking phosphoric acid and epoxy resin and followed by annealing at 700 °C. H₃PO₄ acts not only as a crosslinker to solidify epoxy resin for promoting the degree of graphitization and lowering the specific surface area, but also as phosphorus source for forming P? C and P? O bonds, thus providing more active sites for Li/K storage. As a result, the PHC‐700 electrode delivers a highly reversible capacity of 1294.8 mA h g^?1 at 0.1 A g^?1 and a capacity of 214 mA h g^?1 after 10 000 cycles at 10 A g^?1. As for potassium‐ion batteries, PHC‐700 exhibits a reversible capacity of 381.9 mA h g^?1 at 0.1 A g^?1 and a capacity of 260 mA h g^?1 after 1000 cycles at 0.2 A g^?1. In situ Raman and in situ NMR measurements reveal that the P‐containing bonds can enhance the adsorption to alkali metal ions, and the P? C bond can participate in electrochemical redox reaction by forming Li_x PC_y . Additionally, P‐doped hard carbon shows better structural/interfacial stability for improved long‐term cycling stability.     

Molecular simulations reveal a new entry site in quercetin 2,3‐dioxygenase. A pathway for dioxygen?

Molecular dynamics simulations performed on quercetin 2,3-dioxygenase have shown the existence of a channel linking the bulk solvent and the cavity of the enzyme. Although much is known about the the oxygenolysis reaction catalyzed by this enzyme, the way dioxygen enters the active site has not been firmly established. The size, orientation and hydrophobic character of this channel suggests that it could provide an entrance for molecular dioxygen into the cavity. Free energy calculations show that such a process is likely to occur.     

Correlation between sugar pucker and the orientation around the C3′?O3′ bond (Φ′) in 3′-mononucleotides

Classical potential functions (CPF) calculations on 3′-mononucleotides, the building blocks of nucleic acids, predict a correlation between the sugar ring pucker and the torsion angle Φ′ around the C3′? O3′ bond. In ribonucleotides, the value of Φ′ depends on the sugar pucker, viz. the C2′-endo sugar pucker is associated with Φ′ = 210° and 270°, while the C3′-endo sugar pucker favors only Φ′ = 210°. On the other hand, in deoxyribonucleotides, both sugar puckers show a preference for Φ′ = 180°. These theoretical predictions are fully corroborated by the results obtained from x-ray and nmr studies on mono-, di-, and polynucleotides.     

The α‐sheet: A missing‐in‐action secondary structure?

The α-sheet has been speculated to play a role as a toxic conformer in amyloid diseases. However, except for relatively short fragments, its detection has remained elusive. Here, we present molecular dynamics simulations that support the existence of the α-sheet as a stable, metastable, or long-lived secondary structure in polyglutamine and, to a lesser extent, in polyasparagine aggregates.     

Does a polymorphic species have a ‘polymorphic’ diet? A case study from a lacertid lizard

Lizards are ideal for studying colour polymorphism, because some species are polymorphic and the morphs often have different ecological or reproductive strategies. We studied the feeding habits of six polymorphic populations of Podarcis muralis to test whether morphs differed in their diet. Some taxa were selected in a similar way by all morphs, but selection on other taxa varied and was characteristic of each morph. Diet was most different for the red and yellow morphs. Two hypotheses could explain these differences: active segregation in the trophic niche or active segregation in space dependent on spatial heterogeneity in prey availability. The former is improbable because P. muralis is considered an opportunistic feeder, whereas the latter could occur if the morphs adopted alternative territorial strategies with consequent spatial segregation.     

How Accurate are Recalls of Self‐Weighing Frequency? Data from a 24‐Month Randomized Trial

Introduction

Self‐weighing is an important component of self‐monitoring during weight loss. However, methods of measuring self‐weighing frequency need to be validated. This analysis compared self‐reported and objective weighing frequency.

Methods

Data came from a 24‐month randomized controlled trial. Participants received 12 months of a behavioral weight‐loss program and were randomly assigned to (1) daily self‐weighing, (2) weekly weighing, or (3) no weighing (excluded from analysis). Objective weighing frequency was measured by Wi‐Fi enabled scales, and self‐reported weighing frequency was assessed every 6 months by questionnaire. Objective weights were categorized to match the scale of the self‐report measure.

Results

At 12 months, there was 80.8% agreement between self‐reported and objective weighing frequency (weighted kappa = 0.67; P < 0.001). At 24 months, agreement decreased to 48.5% (kappa = 0.27; P < 0.001). At both time points in which disagreements occurred, self‐reported frequencies were generally greater than objectively assessed weighing. Both self‐reported and objectively assessed weighing frequency was associated with weight loss at 12 and 24 months (P < 0.001).

Conclusions

Self‐reported weighing frequency is modestly correlated with objective weighing frequency; however, both are associated with weight change over time. Objective assessment of weighing frequency should be used to avoid overestimating actual frequency.

     

Towards Squalamine Mimics: Synthesis and Antibacterial Activities of Head‐to‐Tail Dimeric Sterol?Polyamine Conjugates

Four dimeric sterol? polyamine conjugates have been synthesized from the homo‐ and hetero‐connection of monomeric sterol? polyamine analogs in a head‐to‐tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram‐positive bacteria, whereas their corresponding activities against Gram‐negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid‐containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid‐derived analogs. This is in contrast to the finding that a monomeric deoxycholic acid‐spermine conjugate was more active than the corresponding cholic acid‐derived analog.     

A gene for speed? The evolution and function of α‐actinin‐3

The alpha-actinins are an ancient family of actin-binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. alpha-actinin-3 is the most-highly specialised of the four mammalian alpha-actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion ( approximately 18%) of the human population is totally deficient in alpha-actinin-3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other alpha-actinin family members. The alpha-actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution.     

‘O sibling,where art thou?’‐ a review of avian sibling recognition with respect to the mammalian literature

Avian literature on sibling recognition is rare compared to that developed by mammalian researchers. We compare avian and mammalian research on sibling recognition to identify why avian work is rare, how approaches differ and what avian and mammalian researchers can learn from each other. Three factors: (1) biological differences between birds and mammals, (2) conceptual biases and (3) practical constraints, appear to influence our current understanding. Avian research focuses on colonial species because sibling recognition is considered adaptive where 'mixing potential' of dependent young is high; research on a wider range of species, breeding systems and ecological conditions is now needed. Studies of acoustic recognition cues dominate avian literature; other types of cues (e.g. visual, olfactory) deserve further attention. The effect of gender on avian sibling recognition has yet to be investigated; mammalian work shows that gender can have important influences. Most importantly, many researchers assume that birds recognise siblings through 'direct familiarisation' (commonly known as associative learning or familiarity); future experiments should also incorporate tests for 'indirect familiarisation' (commonly known as phenotype matching). If direct familiarisation proves crucial, avian research should investigate how periods of separation influence sibling discrimination. Mammalian researchers typically interpret sibling recognition in broad functional terms (nepotism, optimal outbreeding); some avian researchers more successfully identify specific and testable adaptive explanations, with greater relevance to natural contexts. We end by reporting exciting discoveries from recent studies of avian sibling recognition that inspire further interest in this topic.     

Centenarians – a useful model for healthy aging? A 29‐year follow‐up of hospitalizations among 40 000 Danes born in 1905

Centenarians surpass the current human life expectancy with about 20–25 years. However, whether centenarians represent healthy aging still remains an open question. Previous studies have been hampered by a number of methodological shortcomings such as a cross-sectional design and lack of an appropriate control group. In a longitudinal population-based cohort, it was examined whether the centenarian phenotype may be a useful model for healthy aging. The study was based on a complete follow up of 39 945 individuals alive in the Danish 1905 birth cohort on January 1, 1977 identified through the Danish Civil Registration System (DCRS). Data from the Danish Demographic Database and The Danish National Patient Register (in existence since 1977) were used. The 1905 cohort was followed up from 1977 through 2004 with respect to hospitalizations and number of hospital days. Survival status was available until December 2006. Danish centenarians from the 1905 cohort were hospitalized substantially less than their shorter-lived contemporaries at the same point in time during the years 1977 through 2004. For example, at age 71–74, the proportion of nonhospitalized centenarians was 80.5% compared with 68.4% among individuals who died in their early 80s. This trend was evident in both sexes. As a result of their lower hospitalization rates and length of stay in hospital compared with their contemporaries, who died at younger ages, Danish centenarians represent healthy agers. Centenarians constitute a useful study population in the search for fixed traits associated with exceptional longevity, such as genotype.     

Revisiting “what do tadpoles really eat?” A 10‐year perspective

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Can we disentangle predator–prey interactions from species distributions at a macro‐scale? A case study with a raptor species

There is a debate on whether an influence of biotic interactions on species distributions can be reflected at macro‐scale levels. Whereas the influence of biotic interactions on spatial arrangements is beginning to be studied at local scales, similar studies at macro‐scale levels are scarce. There is no example disentangling, from other similarities with related species, the influence of predator–prey interactions on species distributions at macro‐scale levels. In this study we aimed to disentangle predator–prey interactions from species distribution data following an experimental approach including a factorial design. As a case of study we selected the short‐toed eagle because of its known specialization on certain prey reptiles. We used presence–absence data at a 100 km2 spatial resolution to extract the explanatory capacity of different environmental predictors (five abiotic and two biotic predictors) on the short‐toed eagle species distribution in peninsular Spain. Abiotic predictors were relevant climatic and topographic variables, and relevant biotic predictors were prey richness and forest density. In addition to the short‐toed eagle, we also obtained the predictor's explanatory capacities for 1) species of the same family Accipitridae (as a reference), 2) for other birds of different families (as controls) and 3) artificial species with randomly selected presences (as null models). We run 650 models to test for similarities of the short‐toed eagle, controls and null models with reference species, assessed by regressions of explanatory capacities. We found higher similarities between the short‐toed eagle and other species of the family Accipitridae than for the other two groups. Once corrected by the family effect, our analyses revealed a signal of predator–prey interaction embedded in species distribution data. This result was corroborated with additional analyses testing for differences in the concordance between the distributions of different bird categories and the distributions of either prey or non‐prey species of the short‐toed eagle. Our analyses were useful to disentangle a signal of predator–prey interactions from species distribution data at a macro‐scale. This study highlights the importance of disentangling specific features from the variation shared with a given taxonomic level.     

Extraordinary Thermal Stability of an Oligodeoxynucleotide Octamer Constructed from Alternating 7‐Deaza‐7‐iodo guanine and 5‐Iodocytosine Base Pairs – DNA Duplex Stabilization by Halogen Bonds?

A reinvestigation of the published X‐ray crystal‐structure analyses of 7‐halogenated (Br, I) 8‐aza‐7‐deaza‐2′‐deoxyguanosines Br⁷c⁷z⁸G_d; 1a and I⁷c⁷z⁸G_d, 1b , as well as of the structurally related 7‐deaza‐7‐iodo‐2′‐deoxy‐β‐D ‐ribofuranosyladenine (β‐I⁷c⁷A_d; 2 = 6e in Table 1) and its α‐D ‐anomer (α‐I⁷c⁷A_d; 3 ) clearly revealed the existence of halogen bonds between corresponding halogen substituents and the adjacent N(3)‐atoms of neighboring nucleoside molecules within the single crystals. These halogen bonds can be rationalized by the presence of a region of positive electrostatic potential, the σ‐hole, on the outermost portion the halogen's surface, while the three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of the halogen substituent. The N(3) atoms of the halogenated nucleosides carry a partial negative charge. This novel type of bonding between nucleosides was tentatively used to explain the extraordinary high stability of oligodeoxynucleotides constructed from halogenated nucleotide building blocks.