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Studies on the genetic determinants of influenza virus pathogenicity for mice with the use of reassortants between mouse-adapted and non-adapted variants of the same virus strain.

The original influenza virus strain A/USSR/90/77 (H 1 N 1) and its mouse-adapted variant, differing in their reactivity with anti-hemagglutinin monoclonal antibodies HC 22 and HC 124, were crossed in MDCK cells and in chicken embryos, and 21 clones were isolated by non-selective random cloning. In all the clones the virulence for mice was found to be linked to the antigenic specificity of hemagglutinin (HA). An independent marker, formation of filamentous forms, was reassorted with an expected frequency. In the crosses between UV-irradiated mouse-adapted variant and live non-adapted strain, with selection of clones by a mixture of monoclonal antibodies discriminating between HA of the two variants, virulence also was linked to HA gene. On the contrary, in the experiments with A/Aichi/2/68 (H 3 N 2) strain and its mouse-adapted highly virulent variant these two characteristics--virulence and HA antigenic specificity--could be dissociated. A pathogenic clone having HA of the non-adapted strain was readily obtained; its virulence, however, was weaker than that of the mouse-adapted parent. In the inter-subtypic crosses between A/USSR/90/77 and A/Aichi/2/68 the transfer of the HA gene of the mouse-adapted A/Aichi/2/68 did not confer virulence to the reassortant. The results are discussed in terms of the genetic basis of virulence acquired in the course of influenza virus adaptation to a new host.

Animals↗

TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta.

Lipopolysaccharide (LPS) is an agonist for Toll-like receptor (TLR) 4 and expresses many genes including NF-kappaB- and interferon regulatory factor (IRF)-3/IFN-inducible genes in macrophages and dendritic cells (DCs). TICAM-1/TRIF was identified as an adapter that facilitates activation of IRF-3 followed by expression of interferon (IFN)-beta genes in TLR3 signaling, but TICAM-1 does not directly bind TLR4. Although MyD88 and Mal/TIRAP adapters functions downstream of TLR4, DC maturation and IFN-beta induction are independent of MyD88 and Mal/TIRAP. In this investigation, we report the identification of a novel adapter, TICAM-2, that physically bridges TLR4 and TICAM-1 and functionally transmits LPS-TLR4 signaling to TICAM-1, which in turn activates IRF-3. In its structural features, TICAM-2 resembled Mal/TIRAP, an adapter that links TLR2/4 and MyD88. However, TICAM-2 per se exhibited minimal ability to activate NF-kappaB and the IFN-beta promoter. Hence, in LPS signaling TLR4 recruits two types of adapters, TIRAP and TICAM-2, to its cytoplasmic domain that are indirectly connected to two effective adapters, MyD88 and TICAM-1, respectively. We conclude that for LPS-TLR4-mediated activation of IFN-beta, the adapter complex of TICAM-2 and TICAM-1 plays a crucial role. This results in the construction of MyD88-dependent and -independent pathways separately downstream of the two distinct adapters.

Adaptor Proteins, Signal Transducing↗

Adaptation and recovery from adaptation in single fiber responses of the cat auditory nerve.

This study examined the time course of adaptation and recovery from adaptation of single auditory-nerve fiber responses. The conditions studied were: (1) adaptation response using low level, 800 Hz or characteristic frequency (CF) stimuli; and (2) onset recovery and whole tone response recovery of a probe tone following a masker of equal frequency with variable silent intervals between the masker offset and probe onset. Single unit responses to 290 ms long, 800 Hz or CF tones presented at 10-30 dB SL were recorded from the auditory nerve of the cat. Adaptation properties were determined and fit to the equation: A(tp) = Yre(-tp/tau Rr) + Yse(-tp/tau Rs) + Ass. Recovery from adaptation was determined by recording the response of a probe tone following a 100-ms masker tone equal in frequency to the probe, and with amplitudes ranging from 20- to 30-dB relative to the probe amplitude. Both the onset recovery and the whole tone recovery were determined for the single unit responses. The onset data were analyzed and fit to either the equation: A (delta xt,tp) = Ass - Yre(-tp/tau Rr) - Yse(- delta t/tau Rs) or A (delta t,tp) = Ass - Yre(- delta t/tau R). The whole tone response showed two distinctive time patterns that could be fit to either an adaptation equation or to the two-time-constant recovery equation, depending on the relative amplitude of the masker and the length of the silent interval between masker offset and probe onset. The results of this study indicate that single fiber time constants are comparable to those measured in previous studies using the auditory-nerve neurophonic (ANN). Likewise, the pattern of recovery of the whole tone response for single fiber responses is comparable to the ANN. Possible sites and mechanisms for adaptation and recovery from adaptation taking into account recent data from electrical stimulation studies and receptor channel morphology and kinetics are discussed.

Animals↗

Efficacy of prism adaptation in the surgical management of acquired esotropia. Prism Adaptation Study Research Group.

Prism adaptation, the preoperative use of prisms in acquired esotropia to determine the maximum angle of strabismus and to estimate fusional potential, has been suggested as a method of improving the results of initial surgery and minimizing the rate of reoperation. We performed a prospective, randomized, multicenter clinical trial of the effectiveness of prism adaptation. Two levels of randomization were used. Sixty percent of the patients underwent prism adaptation and 40% did not. Of those who responded to prisms with motor stability and sensory fusion, half underwent a conventional amount of surgery and half underwent augmented surgery based on the prism-adapted angle of deviation. Success rates were highest (54 [89%] of 61 patients) in prism adaptation responders who underwent augmented surgery and lowest (92 [72%] of 127 patients) in patients who did not undergo prism adaptation. Prism responders had better results with augmented surgery than with conventional surgery (54 [89%] of 61 patients vs 53 [79%] of 67 patients, P = .23). Our results indicated a significant beneficial overall effect of prism adaptation in patients with acquired esotropia (success rates, 83% vs 72%, P = .04). Although the process requires some additional time and effort, it appears to result in a higher rate of satisfactory alignment.

Adaptation, Ocular↗

A motion aftereffect seen more strongly by the non-adapted eye: evidence of multistage adaptation in visual motion processing.

We found that the motion aftereffect measured using a directionally ambiguous counterphase grating (flicker MAE) can be stronger when it is measured for the non-adapted eye than when measured for the adapted eye. The monocularly viewed adaptation stimulus was the movement of a missing-fundamental grating (2f+3f motion), for which the movement of the higher-order spatial structure was dominantly perceived, while the first-order structure was physically moving in the opposite direction. For observers who perceived the MAE consistently in the direction opposite to the movement of the higher-order structures, the MAE was larger for the non-adapted eye than for the adapted eye. This finding of 'over-100% transfer' invalidates the standard view that the IOT is a direct measure of the binocularity of the adapted neurones. In addition, the finding provides convincing support for the hypothesis that the flicker MAE reflects adaptation at multiple processing stages

Adaptation, Physiological↗

Cytogenetic adaptive response in cultured human lymphocytes: dependence on the time of exposure to adapting and challenging doses of gamma-rays.

Human lymphocytes from 16 healthy donors were exposed in vitro to an adapting dose of gamma-rays (0.05 Gy) at G0, or G1, or G1/S stage of the cell cycle and subsequently to a challenging dose of gamma-rays at G1, or G1/S, or S (1 Gy), or G2 (0.5 Gy) stage. Frequencies and distributions of the induced chromosome aberrations were analyzed in first-division metaphases. The data averaged over the donors revealed the protective action of the adapting exposure under the irradiation schemes with the challenging dose delivered at S or G2 stage. The majority of aberrations induced at these stages belonged to the chromatid type, and their yield was significantly higher in G2-exposed cells than in S-exposed cells. However, the relative reduction of the challenging dose effect (about 34%) in the adapted cells did not depend on the magnitude of this effect, and its value remained the same (within the experimental error) if aberrations were subdivided into chromosome and chromatid types or grouped as total deletions and total fragments. The adaptive response was not revealed under the schemes with the challenging dose delivered at G1 or G1/S stage. Analysis of the individual results showed that, in one and the same donor, the adaptive response could be observed under one irradiation scheme and not observed under other schemes, the most effective schemes being those with the challenging dose delivered at G2 stage. Four donors, however, did not show the adaptive response even under such schemes. Data on aberration distributions suggested that different repair processes, rather than a unique one, may underlie the adaptive response.

Adaptation, Physiological↗

Correlation of Na+,K+-ATPase content and plasma membrane surface area in adapted and de-adapted salt glands of ducklings.

During salt-water adaptation, an increase occurs in Na+,K+-ATPase content and surface area of the basolateral plasma membrane of the principal cell of the duck salt gland. To determine the degree to which these changes are correlated, accepted morphometric methods were used to determine numerical cell densities and plasma membrane surface densities of peripheral and principal cells. After adaptation, the plasma membrane surface area per principal cell was five times greater than in controls. Following de-adaptation, the plasma membrane content in principal cells returned to 1.9 times control levels. Two other cell constituents, mitochondria and lipid droplets, displayed similar quantitative changes. Na+,K+-ATPase content increased about fourfold with adaptation and decreased to near control levels with de-adaptation. Thus, changes in Na+,K+-ATPase content and basolateral plasma membrane surface area in adapting and de-adapting secretory epithelia of the salt gland occur nearly in parallel. These quantitative data enable Na+,K+-ATPase synthesis and degradation to be investigated in relation to membrane biogenesis.

4-Nitrophenylphosphatase↗

The population ecology of contemporary adaptations: what empirical studies reveal about the conditions that promote adaptive evolution.

Under what conditions might organisms be capable of rapid adaptive evolution? We reviewed published studies documenting contemporary adaptations in natural populations and looked for general patterns in the population ecological causes. We found that studies of contemporary adaptation fall into two general settings: (1) colonization of new environments that established newly adapted populations, and (2) local adaptations within the context of a heterogeneous environments and metapopulation structure. Local ecological processes associated with colonizations and introductions included exposure to: (1) a novel host or food resource; (2) a new biophysical environment; (3) a new predator community; and (4) a new coexisting competitor. The new environments that were colonized often had depauperate communities, sometimes because of anthropogenic disturbance. Local adaptation in heterogeneous environments was also often associated with recent anthropogenic changes, such as insecticide and herbicide resistance, or industrial melanism. A common feature of many examples is the combination of directional selection with at least a short-term opportunity for population growth. We suggest that such opportunities for population growth may be a key factor that promotes rapid evolution, since directional selection might otherwise be expected to cause population decline and create the potential for local extinction, which is an ever-present alternative to local adaptation. We also address the large discrepancy between the rate of evolution observed in contemporary studies and the apparent rate of evolution seen in the fossil record.

Adaptation, Biological↗

Photoconversion from the light-adapted to the dark-adapted state of bacteriorhodopsin.

Dark and light adaptation of bacteriorhodopsin in purple membrane multilayers at less than 100% relative humidity differs from that seen in suspensions. Equilibrium between the two bacteriorhodopsin isomers (bR cis 550 and bR trans 570) in the light-adapted state becomes dependent on the wavelength of actinic light. Excitation at the red edge of the visible absorption band causes dark adaptation in a light-adapted sample. Using polarized actinic and measuring light, we show that acceleration of the dark adaptation through heating by actinic light cannot explain this observation. A light-driven bR trans 570 to bR cis 550 reaction that competes with the well-known 13 cis-to-all-trans light adaptation reaction must exist under our experimental conditions. Trans-to-cis conversion is a one-photon process distinct from the two photon process observed by others in purple membrane suspensions (Sperling, W., C. N. Rafferty, K. D. Kohl, and N. A. Dencher, 1978, FEBS (Fed. Eur. Biochem. Soc.) Lett. 97:129-132). Its quantum efficiency increases monotonously on reducing the hydration level, and is paralleled by an increase in the lifetime of the M410 intermediate of the trans photocycle. We suggest that at this point a branch leads from the all-trans into the 13-cis photocycle. It is probably the same reaction that causes the reduced light adaptation in monomeric bacteriorhodopsin (Casadio, R., H. Gutowitz, P. Mowery, M. Taylor, and W. Stoeckenius, 1980, Biochim. Biophys. Acta. 590:13-23; Casadio, R., and W. Stoeckenius, 1980, Biochemistry. 19:3374-3381).

Bacteriorhodopsins↗

Base compositions of genes encoding alpha-actin and lactate dehydrogenase-A from differently adapted vertebrates show no temperature-adaptive variation in G + C content.

There is a long-standing debate in molecular evolution concerning the putative importance of GC content in adapting the thermal stabilities of DNA and RNA. Most studies of this relationship have examined broad-scale compositional patterns, for example, total GC percentages in genomes and occurrence of GC-rich isochores. Few studies have systematically examined the GC contents of individual orthologous genes from differently thermally adapted species. When this has been done, the emphasis has been on comparing large numbers of genes in only a few species. We have approached the GC-adaptation temperature hypothesis in a different manner by examining patterns of base composition of genes encoding lactate dehydrogenase-A (ldh-a) and alpha-actin (alpha-actin) from 51 species of vertebrates whose adaptation temperatures ranged from -1.86 degrees C (Antarctic fishes) to approximately 45 degrees C (desert reptile). No significant positive correlation was found between any index of GC content (GC content of the entire sequence, GC content of the third codon position [GC(3)], and GC content at fourfold degenerate sites [GC(4)]) and any index of adaptation temperature (maximal, mean, or minimal body temperature). For alpha-actin, slopes of regression lines for all comparisons did not differ significantly from zero. For ldh-a, negative correlations between adaptation temperature and total GC content, GC(3), and GC(4) were observed but were shown to be due entirely to phylogenetic influences (as revealed by independent contrast analyses). This comparison of GC content across a wide range of ectothermic ("cold-blooded") and endothermic ("warm-blooded") vertebrates revealed that frogs of the genus Xenopus, which have commonly been used as a representative cold-blooded species, in fact are outliers among ectotherms for the alpha-actin analyses, raising concern about the appropriateness of choosing these amphibians as representative of ectothermic vertebrates in general. Our study indicates that, whereas GC contents of isochores may show variation among different classes of vertebrates, there is no consistent relationship between adaptation temperature and the percentage of thermal stability-enhancing G + C base pairs in protein-coding genes.

Actins↗

Adapting to supernormal auditory localization cues. II. Constraints on adaptation of mean response.

A series of experiments was performed in which subjects were trained to interpret auditory localization cues arising from locations different from their normal spatial positions. The exact pattern of mean response to these alterations (as a function of time) was examined in order to begin to develop a quantitative model of adaptation. Mean responses were roughly proportional to the normal position associated with the localization cues presented. As subjects adapted, the best-fit slope (relating mean response and normal position) changed roughly exponentially with time. The exponential rate and adaptation asymptote were found for each subject in each experiment, as well as the rate and asymptote of readaptation to normal cues. The rate of adaptation does not show any statistical dependence on experimental conditions; however, the asymptote of the best-fit slope varied with the strength of the transformation used in each experiment. This result is consistent with the hypothesis that subjects cannot adapt to a nonlinear transformation of auditory localization cues, but instead adapt to a linear approximation of the transformation. Over time, performance changes exponentially towards the best-fit linear approximation for the transformation used in a particular experiment, and the rate of this adaptation does not depend upon the transformation employed.

Auditory Perception↗

Background light adaptation of the retinal neuronal adaptive system. I. Effect of background light intensity.

The behaviour of the neuronal adaptive retinal mechanisms to environmental light exposures was studied by measuring the oscillatory potentials (OPs) of the electroretinogram. Dark adapted rats were exposed to four levels of background light (BG), starting at a 'low scotopic' level of 1.43x 10(6) cd/m2, increased by steps of two log units, through 'high scotopic' -, 'low mesopic' - and finally the 'high mesopic' BG of 1.43x 10(0) cd/m2. The summed oscillatory response significantly increased as the BG intensity was raised, except at the 'high mesopic' level. The amplitudes of the a- and b-waves reduced as the BG light increased above the 'high scotopic' level. Each OP responded individually to the different BGs. O1 and O2, significantly enhanced at the 'low scotopic' BG. The amplitudes of the three later OPs increased significantly at the 'low mesopic' BG. The adaptational behaviour of the retinal oscillatory response to BG illumination was different to that of the a- and b- waves. The results indicate that the adaptational neuronal system, as reflected by the OPs, seems to be relatively robust and is separate from the slower photochemical adaptive process in the distal retina. The tentative corollary suggests the oscillatory system to play a vision-preserving role, possibly as an alert against undue depletion of the slowly regenerating visual pigment. The enhancement of the oscillatory response at the 'mesopic' illumination levels indicate both scotopic and photopic processes to contribute to neuronal adaptive activity of the retina.

Adaptation, Ocular↗

Relation of brightness to threshold for light-adapted and dark-adapted rods and cones: effects of retinal eccentricity and target size.

'Equal-brightness' functions of retinal eccentricity and target diameter were measured by a matching procedure, and compared with the corresponding threshold functions for four different adaptation conditions: light-adapted cones (LAC), dark-adapted cones (DAC), light-adapted rods (LAR) and dark-adapted rods (DAR). The separation between log brightness matches and log thresholds decreased with eccentricity and increased with target size for all adaptation conditions, but overall separation was substantially greater for the DAR condition than for the other three. A two-channel model of achromatic brightness is proposed to explain the results. The model assumes 'strong' and 'weak' channels, which contribute unequally to brightness. These channels are tentatively identified with tonic and phasic classes of retinal ganglion cells.

Adaptation, Ocular↗

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗

Adaptation and recovery from adaptation of the auditory nerve neurophonic (ANN) using long duration tones.

The time course of the interaction between adaptation and the recovery from adaptation of the auditory nerve neurophonic (ANN) responses was examined. The interaction between the process of recovery and the adaptation process of long probe tones which follow a masker, the so called whole tone recovery, was determined for the ANN response for different silent intervals between masker offset and probe onset. The auditory nerve neurophonic (ANN) reflects the ensemble response of phase-locked firing in single auditory nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation of these coherent, time-locked responses can be studied. Recovery from adaptation was determined by recording the response of a 290 ms duration probe tone following a 100 ms masker tone, equal in frequency to the probe, ranging from -5 to 20 dB relative to the probe amplitude. Two different time patterns of the whole tone recovery were observed. If short silent intervals and/or loud maskers were used, the time course of the probe tone can be described as an exponential increase in amplitude toward a steady state expressed by the equation: A(tp) = Ass-Yr e(-tp/tau Rr)-Ys e(-tp/tau Rs) ('ascending exponential'). For longer silent intervals and/or fainter maskers, the time course of the probe tone can be described by an exponential decrease expressed by the equation: A(tp) = Yr e(-tp/tau Rr) +Ys e(-tp/tau Rs) +A(ss) ('declining exponential').

Acoustic Stimulation↗

Microtubule assembly in cold-adapted organisms: functional properties and structural adaptations of tubulins from antarctic fishes.

Fishes native to the coastal waters of the Antarctic have adapted to habitat and body temperatures in the range -1.8 to +2 degrees C. Their cytoplasmic microtubules, unlike those of mammals and temperate poikilotherms, have evolved to assemble efficiently at these low temperatures. To learn about the underlying molecular adaptations, my laboratory is studying microtubule proteins [tubulin alpha beta dimers and microtubule-associated proteins (MAPs)] and tubulin genes from several Antarctic fishes, including the rockcods Notothenia coriiceps and Gobionotothen gibberifrons. We find that the assembly-enhancing adaptations of the fish microtubule proteins are intrinsic to the tubulin subunits themselves. Furthermore, microtubule formation by Antarctic fish tubulins is strongly entropy driven, due in part to an increased reliance, relative to tubulins from other species, on hydrophobic interactions. Based on analyses of tubulin polypeptides and cDNAs, we suggest that the structural adaptations of Antarctic fish tubulins most likely involve alterations in the primary sequences of tubulin isotypes. With respect to neural beta tubulins from other vertebrates, for example, the class II beta-tubulin isotype of N. coriiceps brain contains seven unique amino acid substitutions and one novel insertion in its 446-residue primary sequence. Most of these changes are located in a structural domain that forms contacts between tubulin dimers during microtubule assembly and would be expected to enhance polypeptide flexibility, thereby facilitating addition of tubulin to microtubule ends. The acidic carboxy-terminal tails of the alpha and beta tubulins, by contrast, appear not to be sites of cold adaptation of polymerization. We have also found that brain and egg tubulins from Antarctic fishes differ strikingly in their polymerization efficiencies, which demonstrates, in agreement with the multitubulin hypothesis, that tissue-specific tubulin isoforms can possess distinct functional properties. Thus, study of microtubule proteins from organisms, such as the Antarctic fishes, that have adapted to extreme thermal regimes should contribute significantly to an understanding of the quaternary interactions that control microtubule assembly in all eukaryotes.

Adaptation, Physiological↗

Phosphate analogs block adaptation in hair cells by inhibiting adaptation-motor force production.

To ensure optimal sensitivity for mechanoelectrical transduction, hair cells adapt to prolonged stimuli using active motors. Adaptation motors are thought to employ myosin molecules as their force-producing components. We find that beryllium fluoride, vanadate, and sulfate, phosphate analogs that inhibit the ATPase activity of myosin, inhibit adaptation by abolishing motor force production. Phosphate analogs interact with a 120-kDa bundle protein, most likely myosin 1 beta, in a manner that coincides with their effects on adaptation. Features of transduction following inhibition of motor force production suggest that the gating and extent springs of the hair cell orient in parallel at rest and that the negative limit of adaptation arises when force in the stretched extent spring matches the force output of the adaptation motor.

Adaptation, Physiological↗

SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification.

Adaptive point mutation and amplification are induced responses to environmental stress, promoting genetic changes that can enhance survival. A specialized adaptive mutation mechanism has been documented in one Escherichia coli assay, but its enzymatic basis remained unclear. We report that the SOS-inducible, error-prone DNA polymerase (pol) IV, encoded by dinB, is required for adaptive point mutation in the E. coli lac operon. A nonpolar dinB mutation reduces adaptive mutation frequencies by 85% but does not affect adaptive amplification, growth-dependent mutation, or survival after oxidative or UV damage. We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change.

Adaptation, Physiological↗