Is the prediction of pKa values by constant-pH molecular dynamics being hindered by inherited problems?

In this study, we investigate two factors that can hinder the performance of constant-pH molecular dynamics methods in predicting protein pK(a) values, using hen egg white lysozyme as a test system. The first factor is related to the molecular definition and pK(a) value of model compounds in the Poisson-Boltzmann framework. We address this by defining the model compound as a molecular fragment with an associated pK(a) value that is calibrated against experimental data, which results in a decrease of 0.12 units in pK(a) errors. The second addressed factor is the possibility that detrimental structural distortions are being introduced in the simulations by the underlying molecular mechanics force field. This issue is investigated by analyzing how the gradual structural rearrangements affect the predicted pK(a) values. The two GROMOS force fields studied here (43A1 and 53A6) yield good pK(a) predictions, although a time-dependent performance is observed: 43A1 performs better after a few nanoseconds of structural reorganization (pK(a) errors of ~0.45), while 53A6 gives the best prediction right at the first nanosecond (pK(a) errors of 0.42). These results suggest that the good performance of constant-pH molecular dynamics methods could be further improved if these force field limitations were overcome.     

How natural is a nature reserve?: an ideological study of British nature conservation landscapes

Areas set apart for nature conservation in Britain are broadly categorised according to their cultural purpose, and names are assigned to these in this paper. Nature reserves may be similar to zoos and botanic gardens in aiming to maintain the diversity of species and if so are termed biodiversity reserves. This tradition understands nature as a static collection of entities apart from humans. Maintaining traditional management at a site is arguably a good way to sustain species, it also retains old ways in which humans and nature were integrated in the life of the nation and so are called historic countryside parks. There is growing interest in wilderness areas, where nature is seen as primarily processes protected from human interference. Despite the strength of each of these, they suffer from attempting to restrict nature to a ghetto, a process that is economically and environmentally costly. Companion places are places which set sustainable examples of integrating human life and economic activity with maintaining biodiversity and offering an opportunity to encounter wild processes at the heart of life. The language of these four types, or vectors, of nature reserves is offered to help the discussion of our place in nature.     

The cultural nature of risk: Can there be an anthropology of uncertainty?

In risk research, culture has been used mainly as a 'black box' of unknowns into which 'irregularities' of risk perceptions that could not be otherwise accounted for can be referred. In social anthropology it has been taken for granted that what is to be considered a 'risk' depends entirely on cultural settings and assumptions; risks are culturally defined and selected. This article takes a critical stance towards any such simplistic ideas about risk and culture. Culture is approached from a perspective of cognitive theory and is hence understood as shared schemata that define categories, relationships and contexts, making it possible to process meanings and order information. It is argued that if we are to succeed in investigating risk contextually, without ending up in a relativistic muddle which merely acknowledges myriads of diverse risk perceptions, it is necessary to problematize the assumed simplistic cultural nature of risk.     

The nature of chiral recognition: Is it a three-point interaction?

Evolution of the initial “three-point attachment model” resulted in the understanding that an interaction in at least three configuration-dependent points is needed for a chiral selector to recognize entantiomers. Thermodynamic enantioselectivity of this interaction can result in chiral discrimination of the enantiomers, with the exception of a temperature range where enthalpic and entropic contributions to the free energy of discrimination balance each other. Similarly, a three-point interaction is needed for a chiral inductor to modify enantiospecifically a prochiral molecule. The difference between a theoretical interaction point and real interaction sites in chemical molecules is emphasized. The role of conformational rigidity of chiral species is discussed in relation to the dependence of spatial arrangement of three active points on the configuration of the species. Chirality 9:99–102, 1997. © 1997 Wiley-Liss, Inc.     

Are human beings part of the rest of nature?

Unified explanations seek to situate the traits of human beings in a causal framework that also explains the trait values found in nonhuman species. Disunified explanations claim that the traits of human beings are due to causal processes not at work in the rest of nature. This paper outlines a methodology for testing hypotheses of these two types. Implications are drawn concerning evolutionary psychology, adaptationism, and anti-adaptationism. This revised version was published online in July 2006 with corrections to the Cover Date.     

Enhancement of α-cyclodextrin product specificity by enriching histidines of α-cyclodextrin glucanotransferase at remote subsite −6

The industrial use of α-cyclodextrins (α-CDs) has increased because their solubility is higher than those of β-CDs. However, improving the product specificity of α-cyclodextrin glucanotransferases (CGTases) remains unresolved. In this study, three mutants (Y167-deletion, Y167HH, and Y167HHH) were constructed at subsite −6 of α-CGTase to investigate the contribution of amino acid residue 167 to the cyclization ability of α-CD by comparing it with Tyr167His mutant α-CGTase (previously constructed based on the wild-type gene of Bacillus sp. 602-1). As expected, the α:β ratio improved with increasing number of histidine along with residue 167. The Y167HHH mutant had the highest α:β ratio of 13.2 and almost produced single type α-CDs. The Y167HHH mutant enzyme was subsequently purified to homogeneity. The enzymatic properties and the optimal condition of Y167HHH mutant in converting raw starch were also investigated. This study discusses product specificity improvement by inserting specific amino acid residues in the active groove. The results indicate that the histidine-rich mutant α-CGTase possessed better potential in producing α-CDs in an industrial scale.     

The nature of predation: prey dependent, ratio dependent or neither?

To describe a predator-prey relationship, it is necessary to specify the rate of prey consumption by an average predator. This functional response largely determines dynamic stability, responses to environmental influences and the nature of indirect effects in the food web containing the predator-prey pair. Nevertheless, measurements of functional responses in nature are quite rare. Recently, much work has been devoted to comparing two idealized forms of the functional response: prey dependent and ratio dependent. Although we agree that predator abundance often affects the consumption rate of individual predators, this phenomenon requires more attention. Disagreement remains over which of the two idealized responses serves as a better starting point in building models when data on predator dependence are absent.     

One mechanostat or many? Modifications of the site-specific response of bone to mechanical loading by nature and nurture

The concept of the mechanostat was not new in 1983, when Harold Frost coined the term to describe a mechanism by which bone responded to habitual exercise and changes in loading with structurally appropriate alterations in bone architecture. However, the word "mechanostat" has a meaning that is immediately apparent, and its adoption has led to a much wider appreciation of the process of functional adaptation by other scientists than those whose primary research focus is in the biology of adaptation. One problem exists though: it is widely thought that in a single individual, there is a setting for the mechanostat, just as a single thermostat might set the temperature for a whole house, and this is reflected in the idea that bones throughout the skeleton require a specific strain magnitude for maintenance. Increases in loading above that threshold are expected to induce bone formation and a stiffer structure that then experiences again the habitual strain magnitude. Reductions in strain magnitude supposedly induce resorption to reduce tissue mass and architectural properties so that the lower loading restores habitual strain magnitude. That widely held belief of a single unifying number of strain is fundamentally flawed. The purpose of this article is to explain the real basis of the mechanostat; that the skeleton responds to a complex strain stimulus, made up of numerous different parameters, of which peak magnitude is only one, and that the strain stimulus is different in different parts of the skeleton, so there is no universal number to describe a tissue strain magnitude that underlies the mechanostat's setting. Furthermore, males and females have different responses to loading, and those responses change in response to many factors including genetic constitution, age, concomitant disease, nutrient availability, and exposure to drugs or biochemicals. In summary then, there is not a single mechanostat controlling the skeleton of each of us. At a fundamental tissue level, small functional units of bone each have their own multifactorial threshold target strain stimuli for a given set of dynamic modifying influences. Understanding the biology behind the way that each of these mechanostats functions independently is likely to have pervasive consequences on our ability to control bone mass by manipulation of loading, either directly through different exercise regimens, or in a targeted manner using tailored site and individual specific pharmaceuticals.     

Retention–property relationships of anticonvulsant drugs by biopartitioning micellar chromatography

Epilepsy may be considered as a group of disorders with only one thing in common: the fact that recurrent anomalous electrochemical phenomena appear in the central nervous system. Different classes of drugs are included under the generic term of anticonvulsant drugs. All of them work by decreasing discharge propagation in different ways. Biopartitioning micellar chromatography (BMC) is a mode of reversed-phase liquid chromatography, which can be used as an in vitro system to model the biopartitioning process of drugs when there are no active processes. In this paper, relationships between the BMC retention data of anticonvulsant drugs, their pharmacokinetics (oral absorption, protein binding, volume of distribution, clearance, and renal elimination) and their therapeutic parameters (therapeutic, toxic and comatose-fatal concentration, and LD₅₀) are studied and the predictive ability of models is evaluated.     

Simplicity or complexity? Important aspects of high nature value grassland management in nature conservation

Biodiversity and Conservation - Local, adaptive traditional grassland management systems have played a fundamental role in the creation, maintenance and conservation of high nature value (HNV)...     

Atelinae phylogenetic relationships: The trichotomy revived?

This research examines phylogenetic relationships between members of the Atelinae subfamily (Alouatta, Ateles, Brachyteles, and Lagothrix), based on analysis of three genetic regions. Two loci, cytochrome c oxidase subunit II (COII) and the hypervariable I portion of the control region, are part of the mitochondrial genome. The other is a single-copy nuclear gene, Aldolase A Intron V. Analysis of these genetic regions provides support for tribe Alouattini containing the Alouatta species, while tribe Atelini contains the other three genera. However, these three genetic regions produce conflicting results for relationships among tribe Atelini members. Previous genetic studies supported grouping Brachyteles with Lagothrix, leaving Ateles in a separate subclade. The present data sets vary based on the genetic region analyzed and method of analysis suggesting all possible cladistic relationships. These results are more consistent with investigations of morphology and behavior among these primates. The primary cause of discrepancy between this study and previous genetic studies is postulated to reside in increased sampling in the present study of genetic variation among members of the Atelinae, specifically Ateles. The present study utilized samples of Ateles from all postulated species for this genetically variable primate, while previous studies used only one or two species of Ateles. This paper demonstrates that shifting relationships are produced when different species of Ateles are used to reconstruct phylogenies. This research concludes that a trichotomy should still be supported between members of tribe Atelini until further analyses, which include additional Atelinae haplotypes are conducted.     

Can we determine if the linear nature of quantum mechanics is violated by the perceptual process?

It now appears feasible to be able to subject to experimental test Ghirardi's proposal concerning utilizing superposed photon states to check reduction mechanisms in perceptual processes which may be governed by nonlinear evolution laws. This can be accomplished with existing techniques involving superposed single photon states and living retinal tissue mounted on microelectrode arrays.     

The nature of natural: defining natural character for the New?Zealand context

New?Zealand has a long-standing statutory policy goal to preserve the natural character of the coastal environment and various freshwater environments and their margins. In the absence of an authoritative definition, it has not been possible to develop a method to measure natural character and its change, nor the outcomes of the long-standing national policy goal. Here we develop a definition of natural character that is relevant and useful in the New?Zealand environmental, cultural and legal/policy context. Literature-derived interpretations of natural character and equivalent concepts are evaluated as to their potential suitability for developing a biophysical definition of natural character. Using a set of carefully designed criteria a subset of interpretations are condensed into a definition of natural character. The application of this definition is qualified following consideration of the literature addressing human perception and experiences of natural character. Appropriate reference conditions and baselines for evaluating natural character in different contexts are discussed.     

Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic effect?

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit severe ventricular arrhythmias. The aims of our study were to compare the effects of total left anterior descending coronary artery (LAD) occlusion to intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into LAD for 30 min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial monophasic action potential (MAP) recordings were performed to detect electrophysiologic changes and ischemia Blood samples for lactate measurements were collected from the coronary sinus (CS) and from the femoral artery. Infrared imaging was applied to follow epimyocardial heat emission changes. At the end of the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled by a significant epimyocardial temperature decrease in group C (deltaT30MIN: -0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in the reperfusion period in group A. Ventricular premature contractions and non-sustained ventricular tachycardic episodes appeared in group B, whereas six dogs died of VF in group C. Significant CS lactate level elevation indicating ischemia was observed only in group A from the 30th min occlusion throughout the reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l, p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes were observed only in group A. Although ET-1 reduced CBF significantly in groups B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced major ventricular arrhythmias appeared before signs of myocardial ischemia developed, though reduced CBF presumably contributed to sustaining the arrhythmias.     

Connecting human–nature relationships to environmental behaviors that minimize the spread of aquatic invasive species

Management of aquatic invasive species (AIS) is widely recognized as a global conservation concern driven by myriad factors, particularly individual behaviors. A burgeoning literature focused on the human dimensions of AIS has begun to provide insight into the complexities of behavior change; however, most studies are bound to specific geographic locales and have prevented resource management agencies from making regionally valid statements about the anthropogenic factors contributing to biological invasions. We examined stakeholders’ awareness and knowledge of AIS transmission in an evaluation of educational outreach campaign logos and illustrated how human–nature relationships were related to behaviors relevant to AIS reduction at two case study sites. Drawing from a thematic analysis of data from semi-structured interviews with organisms-in-trade hobbyists and recreational water users in the state of Illinois, we observed high awareness of environmental impacts and modes of transmission by the two groups. Both awareness advanced through AIS outreach and a diversity of human–nature relationships were helpful for understanding reported environmental behaviors. Specifically, stakeholders’ views of their relationships with nature affected decisions to engage in activities that contributed to social-ecological change. Results also revealed preferences for national rather than state-level outreach campaign logos, which carry implications for designing communication strategies that will minimize the likelihood of biological invasions in freshwater ecosystems.     

Dentition of eight species of Mediterranean Sea Gobiidae: do dentition characters of gobies reflect phylogenetic relationships?

Oral and pharyngeal dentition was analysed in eight Mediterranean species of five different genera using scanning electron microscopy (SEM). Number, position, shape and size of teeth in the jaws and the pharyngeal tooth plates were used as a basis for comparison among taxa. Three different groups could be established based on the dental morphology among the species investigated and homoplasy due to feeding ecology cannot be considered the reason for similarity among them. The established groups are suggested to reflect phylogenetic relationships and correspond with the scarce published data on the topic.