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Determination of the environmental sensitivity of selection lines by the selection environment.

The parents chosen to continue 10 independent selection lines of Schizophyllum commune over eight successive generations of selection, along with unselected controls, have been retrospectively examined for their response to growth at 15 degrees, 20 degrees, 25 degrees, 30 degrees and 35 degrees C. The regression of rate of growth on temperature was essentially linear over the range 15 degrees to 30 degrees C for all lines in all generations as was also the regression of rate of growth on various biological assessments of the environments over the whole temperature range. Either regression, therefore, provided linear regression coefficients which adequately accounted for the relative sensitivities of the lines to temperature in each generation of selection. These measures of environmental sensitivity confirmed our earlier report that selection for high mean performance in a good environment or for low mean performance in a poor environment leads to selections that are more sensitive to environmental variation than selections for high mean performance in a poor environment or for low mean performance in a good environment. These differences in sensitivity emerge as correlated responses during selection and the magnitude of these correlated responses is higher in the good environment than in the poor environment irrespective of the direction of selection. The environmental sensitivity of selection lines can be modified in either direction as required by either selecting for sensitivity simultaneously with the selection for mean performance or by selecting for mean performance in an above or below average environment. The quality of environments in which artificial selection is usually carried out is likely to have led to high selections with maximum environmental sensitivity and low selections with minimum sensitivity.

Environment

The inversion In(2L)t impacts complex, environmentally sensitive behaviors in Drosophila melanogaster.

Genetic variation in behavioral traits allows organisms to respond and adapt to environmental challenges. Genetic variation in behavior is often affected by many genes and thus has a complex genetic basis. Inversions, the reorientation of genes along the chromosome, tightly link genetic variants together because they suppress recombination. Therefore, inversions are believed to have a major impact on phenotypic variation because they combine the effects of multiple genes, which can pleiotropically alter multiple aspects of behavior. This study investigates how the inversion In(2L)t, found in Drosophila melanogaster populations around the world, impacts different aspects of behavior in an environment-sensitive manner. We test the activity, foraging, and startle-induced behavior of flies with different In(2L)t genotypes across sex and temperatures. We observe that Drosophila homozygous for In(2L)t sleep less frequently, spend more time away from a food source, and have a longer duration of startle response. Additionally, the impacts of In(2L)t on aspects of behavior can be sex-specific and are largely consistent across temperatures. Taken together, our research demonstrates that inversions can regulate aspects of behavior, and suggests hypotheses explaining the distribution of In(2L)t across space and time.

Behavior

Lanthanide ion probes of structure in biology. Environmentally sensitive fine structure in laser-induced terbium(III) luminescence.

The 488 nm line of the CW argon ion laser provides a convenient visible source for the direct excitation of the emissive 5D4 state of the Tb(III) ion. Room temperature emission spectra of Tb(III) in a variety of environments have been examined under relatively high resolution. The samples studied include structurally well-characterized crystalline solids, model chelate complexes in solution and Tb(III) bound to the enzyme thermolysin and the protein parvalbumin. The fine structure in the emissions is caused by ligand field splittings of both ground and excited state J manifolds. These spectra provide signatures sensitive to the immediate coordination environment of the Tb(III) ion. Solid state/solution state structural comparisons are made. The emission fine structure reveal differences between the EF side calcium-binding sites of parvalbumin and the calcium site 1 of thermolysin.

Calcium

Sensitivity of environmental microorganisms to antimicrobial agents.

The sensitivity of different microorganisms, considered as typical representatives of the microflora of soil and water, was established to evaluate the influence of the nonmedical use of antimicrobial agents on bacterial ecology. Only seven strains, six chemoorganotrophs and one chemolithotroph, could be considered as relatively sensitive to the 21 antimicrobial compounds tested. The other 29 microorganisms may be regarded as resistant to most antimicrobial agents. Streptomyces were sensitive to high concentrations of active substances. Broad-spectrum antibiotics showed an effect on environmental bacteria similar to that on human pathogens. Cephalothin stimulated the growth of a Chlorella sp. From these experiments, it appears that spilled antimicrobial agents have little chance of causing an alteration in the microbial ecology.

Anti-Bacterial Agents

Use of a distant reporter group as evidence for a conformational change in a sensory receptor.

A highly sensitive method for demonstrating ligand-induced conformational changes in protein molecules in solution is described. The method utilizes an environmentally sensitive reporter group that is known to be distant from the active site. In the present application a conformational change is demonstrated in the galactose receptor of Salmonella typhimurium, involved in bacterial sensing and transport, by means of an extrinsic fluorophore, 5-iodoacetamidofluorescein, attached at a single methionine residue, and the intrinsic tryptophan fluorophore. Binding of the ligand galactose perturbs the microenvironment of both the fluorescein and tryptophan, as shown by both spectral and potassium iodide quenching changes. The distance between the two dyes is established by fluorescence energy transfer methods to be 41 +/- 10A. Since only one molecule of galactose binds per molecule of receptor and since the galactose molecule is only about 5 A in length, changes at one of these sites reflect the result of an indirect effect. Hence, there must be a ligand-induced conformational change that is propagated a minimum of 30 A through the receptor molecule.

Bacterial Proteins

Fate of arsenicals in different environmental substrates.

The current knowledge of arsenic (As) transformations in the environment, as well as some gaps in this knowledge, are reviewed. These transformations involve As chemical and biochemical transformations in air, waters, sediments, and soils. Arsenic moves in a dispersive manner through air and water and is in physical and chemical equilibrium in many substrates. It is oxidized, reduced, methylated, volatilized, incorporated into biotic tissues, excreted, adsorbed, and desorbed. Oceanic sediments become the eventual sink for As. The rates of As movement and transformation vary with environmental conditions. Besides inorganic As, various methylated arsenicals are found naturally at environmentally sensitive equilibrium concentrations, which are probably maintained biotically. An As-transformation model has been constructed from rate constants derived from field observations. The environmental factors affecting these rate constants are discussed.

Air Pollutants

Genetic Susceptibility to the Environment Moderates the Impact of Childhood Experiences on Psychotic, Depressive, and Anxiety Dimensions.

BACKGROUND AND HYPOTHESIS: Gene-by-environment (GxE) studies in psychosis have exclusively focused on negative exposures. However, evidence supports the resilience-enhancing effect of positive factors on psychosis outcome. The Differential Susceptibility (DS) model proposes that common genetic variants may confer not only disproportionate responsiveness to negative environments, but also greater sensitivity to positive, resilience-enhancing conditions. This study is the first to apply the DS model to the expression of subclinical psychosis, employing polygenic risk scores of environmental sensitivity (PRS-ES). PRS-ES were hypothesized to moderate, in a DS manner, associations between childhood adversity and psychosis, affective, and anxiety dimensions in young adults. An exploratory goal examined whether PRS for psychotic-like experiences (PRS-PLE) also showed DS patterns. STUDY DESIGN: PRS, schizotypy, PLE, depression, anxiety, and childhood adversity ratings were obtained for 197 nonclinical young adults. LEGIT software for testing competitive-confirmatory GxE models was employed. STUDY RESULTS: Results largely supported DS: Individuals high on PRS-ES showed increased subclinical psychosis, depression, and anxiety if they had experienced elevated childhood adversity, and lower symptoms if exposed to low levels of adversity as compared with those with low PRS-ES. Similarly, PRS-PLE moderated the effect of adversity on PLE, positive schizotypy, and depression following the DS model, but only PRS-ES moderation on PLE survived statistical correction. CONCLUSIONS: Our results suggest that genetic DS to the environment is relevant to psychosis, depression, and anxiety. Current debates on reconceptualization of genetic "risk" and resilience may benefit from this insight that support optimistic views on preventative efforts for early detection and intervention.

Humans

Genetic Differences in Reactivity to the Environment Impact Psychotic-Like and Affective Reactivity in Daily Life.

BACKGROUND AND HYPOTHESIS: Consistent with diathesis-stress models, psychosis research has focused on genetic moderation of adverse environmental exposures. In contrast, the Differential Susceptibility (DS) model suggests that the same genetic variants that increase risk-inducing effects of adverse experiences also enhance beneficial effects from positive experiences. This study examined whether individuals with high genetic susceptibility to the environment showed differential psychotic-like and affective reactivity in response to positive and negative events in daily life. STUDY DESIGN: Experience sampling methodology assessed context (positive and stressful) and momentary levels of paranoia, psychotic-like experiences (PLE), and positive (PA) and negative affect (NA) in 217 non-clinical adults oversampled for schizotypy. Linear mixed models examined whether Polygenic Risk Scores of Environmental Sensitivity (PRS-ES) moderated the impact of current context on subsequent experiences. STUDY RESULTS: PRS-ES moderated positive, but not stressful, context on subsequent levels of momentary paranoia, NA, and PA, but not PLE. Genetic and environmental (G × E) interactions indicated diathesis-stress at lower thresholds of PRS-ES, but a DS model at the highest threshold of the PRS-ES. Participants with elevated PRS-ES showed increased paranoia and NA and decreased PA in subsequent assessments when reporting low levels of positive situations, but also decreased paranoia and NA and increased PA when rating contexts as positive. CONCLUSIONS: Findings support the influence of genetic sensitivity to the environment on psychotic-like and affective reactivity in daily life, particularly in response to positive contexts. This highlights the transdiagnostic protective role of positive experiences and informs ecological momentary interventions.

Humans

Land use and transportation issues in environmental control.

Analyses have been made of the effects of environmental controls and planning at regional, subarea, and project levels. The results obtained at the regional level are reviewed for a proposed highway development around Baltimore, Md. The findings for both short-term and long-term effects of alternative transport policies are summarized in respect of population and employment, economic indicators, traffic and travel, air quality, water and solid waste, noise, and environmentally sensitive areas. Problems at subarea and project levels are briefly considered.

Air Pollution

The spectroscopic properties of the lipodepsipeptide, syringomycin E.

The spectroscopic properties of syringomycin E, an antibiotic lipodepsinonapeptide associated with pathological states in plants, have been investigated by uv absorbance and CD spectroscopies, and by the synthesis of relevant model compounds. Initial studies [E. Vaillo, A. Ballio, P. L. Luisi, and R. M. Thomas (1990) in Peptides 1990, Giralt, E. & Andreu, D., Eds., Escom Scientific, Leiden, Netherlands] suggested that a significant contribution to the spectra was due to the presence of a zdehydroaminobutyric acid residue in the amino acid sequence. The model peptides N-Boc-L-Phe-delta zAbu-OMe and its analogue, N-Boc-L-Phe-L-Thr-OMe, lacking the unsaturated bond, were synthesized using standard solution chemistry, and a detailed investigation was made in which the spectra of the models and that of syringotoxin (an antibiotic closely related to syringomycin E but without a Phe residue) were compared with those of syringomycin E under a variety of solvent conditions. The uv absorbance spectra of both N-Boc-L-Phe-delta zAbu-OMe and syringomycin E clearly showed the presence of the unsaturated residue while the CD spectra were complex, environmentally sensitive, and contained contributions from both the delta zAbu and Phe residues. In the course of these studies extinction coefficients were obtained for syringomycin E and its dipeptide model. The origins of the uv and CD spectra are discussed in detail, and a comparison is made with the spectra of other, similar lipopeptide antibiotics. Finally, a structural model for syringomycin is proposed in which the changes induced in the spectrum by alterations in the solvent environment are accommodated.

Amino Acid Sequence

Comment on the carbon-hydrogen stretching region of vibrational Raman spectra of phospholipids.

The broad, environmentally sensitive 2935-2910 cm-1 feature in the vibrational Raman spectra of phospholipids originates primarily from methylene symmetric carbon-hydrogen (C-H) stretching modes. For ordered acyl chains exhibiting local C2h symmetry at low temperatures, the infrared active methylene C-H asymmetric stretching modes become increasingly apparent at higher temperatures in the Raman spectrum as intramolecular chain disorder (trans-gauche isomerization) leads to a loss of chain symmetry. The 2935 cm-1 shoulder, assigned to the acyl chain methyl group C-H symmetric stretching vibration, is difficult to distinguish as a separate spectral transition in the chain disordered state. An ordering of lipid fluidity for several phospholipids is presented in terms of the intensities of features in the 3000-2800 cm-1 region with particular emphasis upon the 2935-2910 cm-1 contour.

Phospholipids

Synthesis and spectral properties of a hydrophobic fluorescent probe: 6-propionyl-2-(dimethylamino)naphthalene.

Environmentally sensitive fluorescent probes involve two groups, an electron donor and an electron acceptor, attached to an aromatic ring system, and maximal effects may be expected when these groups are as far apart as feasible. The syntheisis, characterization, and spectroscopic properties of 6-propionyl-2-(dimethylamino)naphthalene (PRODAN), a compound that fulfills these conditions, are described. The maximum of emission is at 401 nm in cyclohexane solution and at 531 nm in water solution, indicating an increase of dipole moment of approximately 20 D units on excitation to the lowest singlet state. The effect of temperature upon the spectral distribution and the bandwidth of fluorescence of PRODAN in 1:1 complexes with albumin shows the existence of a dynamic relaxation process of the protein surroundings within th 2-4 ns of the fluorescence lifetime.

2-Naphthylamine

Circular dichroism-inhibitor titrations of arsanilazotyrosine-248 carboxypeptidase A.

Coupling of carboxypeptidase with diazotized arsanilic acid specifically modifies a single tyrosyl residue. Yet, owing to the fact that the resultant azoTyr-248 can form an intramolecular chelate with zinc, two different circular dichroism probes result: azoTyr-248 itself and the azoTyr-248-Zn chelate. Both are environmentally sensitive and, characteristically, each can signal the same or different perturbations, as is apparent from circular dichroic spectra. This dual probe function greatly magnifies the scope of these chromophores in mapping the topography of the active center with respect to sites of interaction of inhibitors (or substrates). Titration of the azoenzyme with a series of synthetic, competitive inhibitors, e.g., L-benzylsuccinate, L-phenyllactate, and L-Phe, and with the pseudosubstrate, Gly-L-Tyr, in turn generates characteristic circular dichroic spectra. Their analysis yields a single binding constant for each of these agents, one molecule of each binding to the active center. Mixed inhibitions, as seen with beta-phenylpropionate and phenylacetate, resolved previously into competitive and noncompetitive components, are characterized by different spectral effects. Two molecules of these agents bind to the enzyme, consistent with both thermodynamic and enzymatic studies. The interactions leading to competitive and noncompetitive inhibition, respectively, can be recognized and assigned, based on the manner in which the extrema at 340 and 420 nm, reflecting azoTyr-248, and the negative 510-nm circular dichroism band, typical of its chelate with zinc, are affected and on the pH dependence of spectral and kinetic data. Certai4 noncompetitive inhibitors and modifiers induce yet other spectral features. Each probe is very sensitive to changes in its particular active center environment, though both can be relatively insensitive to inhibitors interacting at a distance from the active center.

Arsenic

Patterns of elevated free calcium and calmodulin activation in living cells.

The temporal and spatial dynamics of intracellular signals and protein effectors are being defined as a result of imaging using fluorescent reagents within living cells. We have described a new class of fluorescent analogues termed optical biosensors, which sense chemical or molecular events through their effects on protein transducers. One example of this new class of indicators is MeroCaM, an environmentally sensitive fluorophore which when it is attached to calmodulin reflects the activation of calmodulin by calcium in vitro. We report here that the rise in free calcium and MeroCaM activation occur in the same period during serum stimulation of quiescent fibroblasts. MeroCaM activation also correlates with the spatial pattern of increased free calcium and the contraction of transverse fibres during wound healing. Finally, migrating fibroblasts in the later stages of wound-healing exhibit an increasing gradient of free calcium and MeroCaM activation from the front to the rear.

3T3 Cells

A reporter group delivery system with both absolute and selective specificity for thiol groups and an improved fluorescent probe containing the 7-nitrobenzo-2-oxa-1,3-diazole moiety.

1. 4-(N-2-Aminoethyl2'-pyridyl disulphide)-7-nitrobenzo-2-oxa-1,3-diazole (compound I) was synthesized and evaluated as a fluorescent labelling reagent for thiol groups. 2. The design of compound (I) as one example of a general type of reporter group delivery reagent (2-pyridyl-S-S-X, where X contains an environmentally sensitive spectroscopic probe) is discussed. 3. The electronic absorption spectrum of compound (I) was determined over a wide range of pH and the spectral changes that accompany its reaction with low-molecular-weight thiols, e.g. L-cysteine, and with papain (EC 3.4.22.2) and bovine serum albumin are discussed. 4. A new value of epsilon343 for 2-thiopyridone (Py-2-SH) was determined as 8.08 X 10(3) +/- 0.08 X 10(3)M-1-cm-1. 5. Spectral analysis of the reactions of compound (I) with L-cysteine and with papain (in the pH range 3.5-8.0) showed that even under equimolar conditions the reaction (thiol-disulphide interchange to release Py-2-SH) is essentially stoicheimoetric and probably proceeds by specific attack at the sulphur atom distal from the pyridyl ring of compound (I). 6. The fluorescence-emission spectra of compound (I) and of the products of its reaction with papain and with ficin (EC 3.4.22.3) were determined. Compound (I) is highly fluorescent in aqueous solution. Excitation within the intense visible absorption band (lambda max. 481 nm, epsilon max. 2.52 X 10(4)M-1-cm-1) provides green fluorescence with an emission maximum at 540 nm. Both papain and ficin labelled by reaction with compound (I) are characterized by fluorescence-emission maxima (535 nm and 530 nm respectively) of even higher intensity. The fluorescence emission of the product of the reaction of papain with compound (I) was shown to be 25 times more intense than that of the product of the reaction of papain with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride). 7. The second-order rate constants (k2) for the reactions of compound (I) and of Nbd chloride with GSH, papain, albumin, ficin, 2-benzimidazolylmethanethiol and 2-benzimidazolylethanethiol were determined at 25.0 degrees C and various pH values. At pH4 the values of k2(compound I)/k2(Nbd chloride) are: GSH, 288; albumin, 36; papain 3 X 10(3); ficin, 3 X 10(4). 8. The pH-k2 profiles for the reactions of compound (I) and of Nbd chloride with the two 2-benzimidazolylalkanethiols were determined. Of the four profiles only that for the reaction of compound (I) with 2-benzimidazolylmethanethiol is characterized by a striking rate maximum in acidic media.

Benzimidazoles