Preface

Data on the toxicity and selectivity of synthetic pyrethroids (SPs) to arthropod natural enemies and their host or prey are reviewed with emphasis on cotton, apple, alfalfa, cereal and vegetable inhabiting species. Generally, SPs are variably toxic and selective (in relation to their hosts or prey) to species within most families of natural enemies. Exceptions are low to moderate toxicity and favorable selectivity to most hemipteran predators, and high toxicity and unfavorable selectivity to virtually all phytoseiid mites in comparison to their prey. In North America, SPs are more favorably selective to cotton natural enemies over their prey or host than to apple inhabiting species. These differences may be due to intrinsic levels of susceptibility (preselection levels) between the types of natural enemies exploited on both crops in IPM programs (i.e. hemipteran species on cotton versus phytoseiid mites on apple) and/or to tolerances or resistances differences due to previous patterns of chemical use on these crops. Possible means of increasing selective use of SPs in future IPM systems based on ecological and physiological selectivity including the development of SP-resistant predators are discussed.     

Candidate neural locus for sex differences in reproductive decisions

Sexual selection and signal detection theories predict that females should be selective in their responses to mating signals in mate choice, while the response of males to signals in male competition should be less selective. The neural processes underlying this behavioural sex difference remain obscure. Differences in behavioural selectivity could result from differences in how sensitive sensory systems are to mating signals, distinct thresholds in motor areas regulating behaviour, or sex differences in selectivity at a gateway relaying sensory information to motor systems. We tested these hypotheses in frogs using the expression of egr-1 to quantify the neural responses of each sex to mating signals. We found that egr-1 expression in a midbrain auditory region was elevated in males in response to both conspecific and heterospecific calls, whereas in females, egr-1 induction occurred only in response to conspecific signals. This differential neural selectivity mirrored the sex differences in behavioural responsiveness to these stimuli. By contrast, egr-1 expression in lower brainstem auditory centres was not different in males and females. Our results support a model in which sex differences in behavioural selectivity arise from sex differences in the neural selectivity in midbrain areas relaying sensory information to the forebrain.     

Hydrophobic interaction chromatography selectivity changes among three stable proteins: conformation does not play a major role

Interesting retention and selectivity changes have been noted for a number of proteins in hydrophobic interaction chromatography (HIC). In this study, we investigated the degree to which conformational changes may be responsible for selectivity changes of stable proteins. Hydrogen-deuterium isotope exchange detected by mass spectrometry was used to investigate changes in solvent accessibility during adsorption on HIC media. Lysozyme was determined to exhibit EX2 hydrogen exchange kinetics both in solution and adsorbed to Butyl Sepharose 4 Fast Flow and Phenyl Sepharose 6 Fast Flow high sub surfaces. A small, but significant, increase in solvent accessibility was observed upon adsorption. Similar approaches were used to analyze solvent accessibility of three stable proteins with melting temperatures above 50 degrees C exhibiting significant selectivity changes on Butyl Sepharose and Toyopearl Butyl 650M. While all three proteins (lysozyme, chymotrypsinogen A, and ovalbumin) exhibited enhanced exchange while adsorbed, no differences in solvent accessibility on the different adsorbents were observed. More detailed studies of lysozyme showed no significant changes in labeling prior or during elution. These results demonstrate that HIC surfaces examined here do not dramatically alter the structure of these stable proteins and that differences in conformation are not responsible for the selectivity changes observed. Thus, other factors such as different preferred binding orientations or variations between the media pore structure, size, and/or surface chemistry must be responsible.     

Nonpeptide GPIIB/IIIA receptor antagonists. Part 21: C-6 flexibility and amide bond orientation are important factors in determining the affinity of compounds for activated or resting platelet receptors

Compound affinity for activated and resting GPIIb/IIIa receptors may differ, and comparison of those differences determines selectivity. Structural features that influence selectivity are discussed.     

The impact of plant secondary compounds on primate feeding behavior

The recent literature on plant secondary compounds and their influence on primate feeding behavior is reviewed. Many studies of nonhuman primates document the extreme selectivity that primates, particularly herbivorous species, demonstrate in their food choice. Until quite recently investigators interpreted this to mean that herbivorous primates were not food limited. This view has been challenged in the past 10 years by researchers concentrating on the primate–plant interaction. Chemical analyses have demonstrated that plant parts are of varying quality due to differences in nutrient and secondary compound content. The assumption that all leaves (or fruits, flowers, and insects) are potential foods of equal value to the primates eating them is refuted. The observed selectivity and preferences of primates for specific plant or insect species and parts are now viewed as strategies for dealing with the nutrient and secondary compound content variation in these foods.     

The role of electrostatic interaction in the molecular recognition of selective agonists to metabotropic glutamate receptors

The influence of electrostatic interactions in determining selectivity for individual subtypes of metabotropic glutamate receptors (mGluRs) is evaluated for a small set of agonists by using the program Delphi and the information thus obtained is compared with docking experiments carried out with AutoDock. The evaluation of the electrostatic component of the free energy of binding for L-Glu, L-AP4, or S-PPG to mGluR1, mGluR2, and mGluR4 subtypes allowed for the detection of subtle differences in the electronic properties of the three subtypes, differences that can account for the observed agonist selectivity.     

The Three Mycobacterium tuberculosis Antigen 85 Isoforms Have Unique Substrates and Activities Determined by Non-active Site Regions

The three isoforms of antigen 85 (A, B, and C) are the most abundant secreted mycobacterial proteins and catalyze transesterification reactions that synthesize mycolated arabinogalactan, trehalose monomycolate (TMM), and trehalose dimycolate (TDM), important constituents of the outermost layer of the cellular envelope of Mycobacterium tuberculosis. These three enzymes are nearly identical at the active site and have therefore been postulated to exist to evade host immunity. Distal to the active site is a second putative carbohydrate-binding site of lower homology. Mutagenesis of the three isoforms at this second site affected both substrate selectivity and overall catalytic activity in vitro. Using synthetic and natural substrates, we show that these three enzymes exhibit unique selectivity; antigen 85A more efficiently mycolates TMM to form TDM, whereas C (and to a lesser extent B) has a higher rate of activity using free trehalose to form TMM. This difference in substrate selectivity extends to the hexasaccharide fragment of cell wall arabinan. Mutation of secondary site residues from the most active isoform (C) into those present in A or B partially interconverts this substrate selectivity. These experiments in combination with molecular dynamics simulations reveal that differences in the N-terminal helix α9, the adjacent Pro²¹⁶–Phe²²⁸ loop, and helix α5 are the likely cause of changes in activity and substrate selectivity. These differences explain the existence of three isoforms and will allow for future work in developing inhibitors.     

Importance of hydration and dynamics on the selectivity of the KcsA and NaK channels

Fundamental concepts governing ion selectivity in narrow pores are reviewed and the microscopic factors responsible for the lack of selectivity of the NaK channel, which is structurally similar to the K+-selective KcsA channel, are elucidated on the basis of all-atom molecular dynamics free energy simulations. The results on NaK are contrasted and compared with previous studies of the KcsA channel. Analysis indicates that differences in hydration of the cation in the pore of NaK is at the origin of the lack of selectivity of NaK.     

Structural determinants of RXPA380, a potent and highly selective inhibitor of the angiotensin-converting enzyme C-domain

RXPA380 (Cbz-PhePsi[PO(2)CH]Pro-Trp-OH) was reported recently as the first highly selective inhibitor of the C-domain of somatic angiotensin-converting enzyme (ACE), able to differentiate the two active sites of somatic ACE by a selectivity factor of more than 3 orders of magnitude. The contribution of each RXPA380 residue toward this remarkable selectivity was evaluated by studying several analogues of RXPA380. This analysis revealed that both pseudo-proline and tryptophan residues in the P(1)' and P(2)' positions of RXPA380 play a critical role in the selectivity of this inhibitor for the C-domain. This selectivity is not due to a preference of the C-domain for inhibitors bearing pseudo-proline and tryptophan residues, but rather reflects the poor accommodation of these inhibitor residues by the N-domain. A model of RXPA380 in complex with the ACE C-domain, based on the crystal structure of germinal ACE, highlights residues that may contribute to RXPA380 selectivity. From this model, striking differences between the N- and C-domains of ACE are observed for residues defining the S(2)' pocket. Of the twelve residues that surround the tryptophan side chain of RXPA380 in the C-domain, five are different in the N-domain. These differences in the S(2)' composition between the N- and C-domains are suggested to contribute to RXPA380 selectivity. The structural insights provided by this study should enhance understanding of the factors controlling the selectivity of the two domains of somatic ACE and allow the design of new selective ACE inhibitors.     

Combined use of selective inhibitors and fluorogenic substrates to study the specificity of somatic wild-type angiotensin-converting enzyme

Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each bearing a functional active site. Studies on the selectivity of these ACE domains towards either substrates or inhibitors have mostly relied on the use of mutants or isolated domains of ACE. To determine directly the selectivity properties of each ACE domain, working with wild-type enzyme, we developed an approach based on the combined use of N-domain-selective and C-domain-selective ACE inhibitors and fluorogenic substrates. With this approach, marked differences in substrate selectivity were revealed between rat, mouse and human somatic ACE. In particular, the fluorogenic substrate Mca-Ala-Ser-Asp-Lys-DpaOH was shown to be a strict N-domain-selective substrate of mouse ACE, whereas with rat ACE it displayed marked C-domain selectivity. Similar differences in selectivity between these ACE species were also observed with a new fluorogenic substrate of ACE, Mca-Arg-Pro-Pro-Gly-Phe-Ser-Pro-DpaOH. In support of these results, changes in amino-acid composition in the binding site of these three ACE species were pinpointed. Together these data demonstrate that the substrate selectivity of the N-domain and C-domain depends on the ACE species. These results raise concerns about the interpretation of functional studies performed in animals using N-domain and C-domain substrate selectivity data derived only from human ACE.     

Structural studies of the pigeon cytosolic NADP(+)-dependent malic enzyme.

Malic enzymes are widely distributed in nature, and have important biological functions. They catalyze the oxidative decarboxylation of malate to produce pyruvate and CO(2) in the presence of divalent cations (Mg(2+), Mn(2+)). Most malic enzymes have a clear selectivity for the dinucleotide cofactor, being able to use either NAD(+) or NADP(+), but not both. Structural studies of the human mitochondrial NAD(+)-dependent malic enzyme established that malic enzymes belong to a new class of oxidative decarboxylases. Here we report the crystal structure of the pigeon cytosolic NADP(+)-dependent malic enzyme, in a closed form, in a quaternary complex with NADP(+), Mn(2+), and oxalate. This represents the first structural information on an NADP(+)-dependent malic enzyme. Despite the sequence conservation, there are large differences in several regions of the pigeon enzyme structure compared to the human enzyme. One region of such differences is at the binding site for the 2'-phosphate group of the NADP(+) cofactor, which helps define the cofactor selectivity of the enzymes. Specifically, the structural information suggests Lys362 may have an important role in the NADP(+) selectivity of the pigeon enzyme, confirming our earlier kinetic observations on the K362A mutant. Our structural studies also revealed differences in the organization of the tetramer between the pigeon and the human enzymes, although the pigeon enzyme still obeys 222 symmetry.     

Interactive effects of ocean acidification and rising sea temperatures alter predation rate and predator selectivity in reef fish communities

Ocean warming and acidification are serious threats to marine life. While each stressor alone has been studied in detail, their combined effects on the outcome of ecological interactions are poorly understood. We measured predation rates and predator selectivity of two closely related species of damselfish exposed to a predatory dottyback. We found temperature and CO₂ interacted synergistically on overall predation rate, but antagonistically on predator selectivity. Notably, elevated CO₂ or temperature alone reversed predator selectivity, but the interaction between the two stressors cancelled selectivity. Routine metabolic rates of the two prey showed strong species differences in tolerance to CO₂ and not temperature, but these differences did not correlate with recorded mortality. This highlights the difficulty of linking species‐level physiological tolerance to resulting ecological outcomes. This study is the first to document both synergistic and antagonistic effects of elevated CO₂ and temperature on a crucial ecological process like predator–prey dynamics.     

The M1 and pre-M1 segments contribute differently to ion selectivity in ASICs and ENaCs

The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological function. Members of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily of trimeric ion channels are typically sodium selective, but to a surprisingly variable degree. While acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium ratio ∼10:1), ENaCs show a remarkably high preference for sodium over potassium (>500:1). This discrepancy may be expected to originate from differences in the pore-lining second transmembrane segment (M2). However, these show a relatively high degree of sequence conservation between ASICs and ENaCs, and previous functional and structural studies could not unequivocally establish that differences in M2 alone can account for the disparate degrees of ion selectivity. By contrast, surprisingly little is known about the contributions of the first transmembrane segment (M1) and the preceding pre-M1 region. In this study, we used conventional and noncanonical amino acid–based mutagenesis in combination with a variety of electrophysiological approaches to show that the pre-M1 and M1 regions of mASIC1a channels are major determinants of ion selectivity. Mutational investigations of the corresponding regions in hENaC show that these regions contribute less to ion selectivity, despite affecting ion conductance. In conclusion, our work suggests that the remarkably different degrees of sodium selectivity in ASICs and ENaCs are achieved through different mechanisms. These results further highlight how M1 and pre-M1 are likely to differentially affect pore structure in these related channels.     

Altered complementary feeding strategies of the consumers <Emphasis Type="Italic">Hydrobia ulvae</Emphasis> and <Emphasis Type="Italic">Idotea emarginata</Emphasis> via passive selectivity

This study aimed to identify differences in selectivity, foraging behaviour and complementary feeding of two benthic consumers (the isopod Idotea emarginata and the snail Hydrobia ulvae) using traditional cell counting as an indicator for algal biomass reduction and stable isotope labelling to detect differences in assimilation and digestion. We hypothesized that even when active feeding preferences of food components are not apparent, passive selectivity via mechanisms such as food assimilation and digestion can be of relevance. Algal biomass was reduced to a similar degree by the grazers independently from grazer and prey combinations without any indication for an active choice of food components. However, the isotope labelling approach indicated that passive selectivity can alter complementary feeding strategies, as we detected shifts in feeding preferences in relation to food quantity and competition. Thus, stable isotope labelling of food components opens up new perspectives in community ecology, allowing assessment of such complex mechanisms as passive selectivity, complementary feeding and competition.     

Cation fluxes in excised and intact roots in relation to specific and varietal differences

Summary In this short survey differences between species and varieties in the four major mechanisms that affect selective uptake of potassium and sodium to the plant within the root are considered. These include influx selectivity, K⁺/Na⁺ exchange at the plasmalemma, and selectivity at the tonoplast as well as at the symplasm-xylem boundary. The affinity of various plants for potassium influx in system 1 is rather uniform although varietal differences in barley have been observed. Differences are much more pronounced for sodium influx, for which Helianthus showed rather high and Fagopyrum rather low affinity. There is substantial variation between species in the efficiency of K⁺/Na⁺ exchange at the plasmalemma of cortical root cells; the three cereals Hordeum, Triticum, and Secale were highly efficient while K⁺/Na⁺ exchange in Atriplex, Helianthus and Allium was poor, even if the cytoplasmic sodium content was accounted for. Apparently there was no direct relation between salt tolerance and K⁺/Na⁺ exchange. The observed differences in the efficiency of K⁺-dependent sodium extrusion or K⁺/Na⁺ exchange were not due to the use of excised roots, they were observed also when roots of whole seedlings were investigated. At the tonoplast a 11 exchange of vacuolar potassium for sodium has been observed in roots of Hordeum. By this exchange sodium ions are removed from the symplasm and potassium ions are recovered from vacuoles and thus made available for transport to the shoot. Indications for specific differences in this exchange have been observed; the exchange appears to be more efficient in Helianthus than in Hordeum roots. More comparative studies are needed here. At the boundary between symplasm and xylem vessels selectivity can be set up during xylem release of cations and there are reports that suggest a preference for sodium (Lycopersicum cheesemanii, Solanum pennellii, and Suaeda) and for varietal differences amongst tomatoes. Selectivity at this boundary, the plasmalemma of the xylem parenchyma cells was described in this paper by the selectivity ratio of transport that relates the rates of xylem transport to the cytoplasmic sodium and potassium concentrations. Based on this ratioAtriplex hortensis was shown to discriminate for sodium during xylem release while there was little selectivity in Hordeum and possibly some discrimination in favour of K⁺ in Allium roots. The data are shortly discussed in relation to salt tolerance and to the breeding of salt-tolerant crop varieties.     

Hydrolysis of nucleic acids by sepharose-micrococcal endonuclease

Initial reaction rates for the hydrolysis of nucleic acids with micrococcal endonuclease (EC 3.1.31.1) insolubilized on Sepharose are strongly influenced by diffusional limitations. Although the absolute values are low, they can be increased substantially by changing particle and pore size of the support, or enzyme concentration in the insoluble derivative. As a result of steric and diffusional limitations, the course of the reaction and selectivity to hydrolysis products for the insoluble derivatives are different to those of the native enzyme; the former produces mainly large and small fragments but few of intermediate size. Because of these differences in course and selectivity of the reaction, diffusional limitations become less important when high initial reaction rates are not required.     

Synaptic plasticity can produce and enhance direction selectivity

The discrimination of the direction of movement of sensory images is critical to the control of many animal behaviors. We propose a parsimonious model of motion processing that generates direction selective responses using short-term synaptic depression and can reproduce salient features of direction selectivity found in a population of neurons in the midbrain of the weakly electric fish Eigenmannia virescens. The model achieves direction selectivity with an elementary Reichardt motion detector: information from spatially separated receptive fields converges onto a neuron via dynamically different pathways. In the model, these differences arise from convergence of information through distinct synapses that either exhibit or do not exhibit short-term synaptic depression—short-term depression produces phase-advances relative to nondepressing synapses. Short-term depression is modeled using two state-variables, a fast process with a time constant on the order of tens to hundreds of milliseconds, and a slow process with a time constant on the order of seconds to tens of seconds. These processes correspond to naturally occurring time constants observed at synapses that exhibit short-term depression. Inclusion of the fast process is sufficient for the generation of temporal disparities that are necessary for direction selectivity in the elementary Reichardt circuit. The addition of the slow process can enhance direction selectivity over time for stimuli that are sustained for periods of seconds or more. Transient (i.e., short-duration) stimuli do not evoke the slow process and therefore do not elicit enhanced direction selectivity. The addition of a sustained global, synchronous oscillation in the gamma frequency range can, however, drive the slow process and enhance direction selectivity to transient stimuli. This enhancement effect does not, however, occur for all combinations of model parameters. The ratio of depressing and nondepressing synapses determines the effects of the addition of the global synchronous oscillation on direction selectivity. These ingredients, short-term depression, spatial convergence, and gamma-band oscillations, are ubiquitous in sensory systems and may be used in Reichardt-style circuits for the generation and enhancement of a variety of biologically relevant spatiotemporal computations.     

Oxamic acid analogues as LDH-C4-specific competitive inhibitors

We performed kinetic studies to determine whether oxamate analogues are selective inhibitors of LDH-C4, owing to their potential usefulness in fertility control and treatment of some cancers. These substances were shown to be competitive inhibitors of LDH isozymes and are able to discriminate among subtle differences that differentiate the active sites of LDH-A4, LDH-B4 and LDH-C4. N-Ethyl oxamate was the most potent inhibitor showing the highest affinity for LDH-C4. However, N-propyl oxamate was the most selective inhibitor showing a high degree of selectivity towards LDH-C4. Non-polar four carbon atoms chains, linear or branched, dramatically diminished the affinity and selectivity towards LDH-C4. N-Propyl oxamate significantly reduced ATP levels, capacitation and mouse sperm motility, in line with results shown by others, suggesting that LDH-C4 plays an essential role in mouse fertility.     

Physiological basis of differential response to salinity in rice cultivars

Growth analyses of rice Oryza sativa L. seedlings in salinized nutrient solution condition were conducted with 24 cultivars and lines after genetic purification. Cultivar differences in relative growth rate in salinized conditions were chiefly dependent on differences in shoot Na content. The shoot Na content was affected by Na selectivity in the root and by the leaf area ratio (LAR, leaf area per total dry weight). The contribution of LAR was equally important to that of root cultivar selectivity against Na uptake under a higher salinization condition where root selectivity against Na may be decreased due to reduced root activity. Cultivar differences in salt tolerance in highly salinized conditions were mainly attributed to differences in these two factors. A more convenient and efficient screening method for salt tolerance is proposed.