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M B Sokolowski

Publications and source records attributed to M B Sokolowski.

At least 19 recordsLinked to original sources

Lack of association between polymorphism of the human cyclic GMP-dependent protein kinase gene and obesity.

OBJECTIVE: To investigate whether genetic variation in the cyclic GMP-dependent protein kinase gene (PRKG1) is associated with obesity. METHODS: The study included 143 individuals from New York City area, NY, USA. The subjects were sampled on the basis of body mass index (BMI): obese (BMI ranging from 33.8 to 89.5 kg/m(2)), and nonobese (BMI ranging from 16.0 to 29.4 kg/m(2)). The association between C2276T polymorphism in PRKG1 gene and obesity was tested using linear regression analysis. RESULTS: BMI levels were predicted by linear regression models adjusted for demographic factors. An analysis was performed twice: in individuals of all ethnic backgrounds and in European-Americans only. In both cases, genotype did not have a significant effect. CONCLUSION: We found no evidence that the C2276T polymorphism in the PKRG1 gene is associated with obesity.

Adolescent↗

Turning behavior in Drosophila larvae: a role for the small scribbler transcript.

The Drosophila larva is extensively used for studies of neural development and function, yet the mechanisms underlying the appropriate development of its stereotypic motor behaviors remain largely unknown. We have previously shown that mutations in scribbler (sbb), a gene encoding two transcripts widely expressed in the nervous system, cause abnormally frequent episodes of turning in the third instar larva. Here we report that hypomorphic sbb mutant larvae display aberrant turning from the second instar stage onwards. We focus on the smaller of the two sbb transcripts and show that its pan-neural expression during early larval life, but not in later larval life, restores wild type turning behavior. To identify the classes of neurons in which this sbb transcript is involved, we carried out transgenic rescue experiments. Targeted expression of the small sbb transcript using the cha-GAL4 driver was sufficient to restore wild type turning behavior. In contrast, expression of this sbb transcript in motoneurons, sensory neurons or large numbers of unidentified interneurons was not sufficient. Our data suggest that the expression of the smaller sbb transcript may be needed in a subset of neurons for the maintenance of normal turning behavior in Drosophila larvae.

Age Factors↗

cGMP-dependent changes in phototaxis: a possible role for the foraging gene in honey bee division of labor.

Division of labor in honey bee colonies is influenced by the foraging gene (Amfor), which encodes a cGMP-dependent protein kinase (PKG). Amfor upregulation in the bee brain is associated with the age-related transition from working in the hive to foraging for food outside, and cGMP treatment (which increases PKG activity) causes precocious foraging. We present two lines of evidence in support of the hypothesis that Amfor affects division of labor by modulating phototaxis. We first show that a subset of worker bees involved in the removal of corpses from the hive had forager-like brain levels of Amfor brain expression despite being middle aged; age-matched food-handlers, who do not leave the hive to perform their job, had low levels of Amfor expression. This finding suggests that occupations that involve working outside the hive are associated with high levels of Amfor in brain. Secondly, foragers were much more positively phototactic than hive bees in a laboratory assay, and cGMP treatment caused a precocious onset of positive phototaxis. The cGMP effect was not due to a general increase in behavioral activity; cGMP treatment had no effect on locomotor activity under either constant darkness or a light:dark regime. The cGMP effect also was not due to changes in circadian rhythmicity; cGMP treatment had no effect on age at onset of locomotor circadian rhythmicity or the period of rhythmicity. The effects of Amfor on phototaxis are not related to peripheral processing; electroretinogram analysis revealed no effect of cGMP treatment on photoreceptor activity and no differences between untreated hive bees and foragers. The cAMP/PKA pathway does not appear to be playing a similar role to cGMP/PKG in the honey bee; cAMP treatment did not affect phototaxis and gene expression analysis revealed task-related differences only for the gene encoding the regulatory subunit, but not the catalytic subunit, of PKA. Our findings implicate one neural process associated with honey bee division of labor that can be affected by naturally occurring changes in the expression of AMFOR:

Aging↗

Influence of gene action across different time scales on behavior.

Genes can affect natural behavioral variation in different ways. Allelic variation causes alternative behavioral phenotypes, whereas changes in gene expression can influence the initiation of behavior at different ages. We show that the age-related transition by honey bees from hive work to foraging is associated with an increase in the expression of the foraging (for) gene, which encodes a guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG). cGMP treatment elevated PKG activity and caused foraging behavior. Previous research showed that allelic differences in PKG expression result in two Drosophila foraging variants. The same gene can thus exert different types of influence on a behavior.

Aging↗

Drosophila: genetics meets behaviour.

Genes are understandably crucial to physiology, morphology and biochemistry, but the idea of genes contributing to individual differences in behaviour once seemed outrageous. Nevertheless, some scientists have aspired to understand the relationship between genes and behaviour, and their research has become increasingly informative and productive over the past several decades. At the forefront of behavioural genetics research is the fruitfly Drosophila melanogaster, which has provided us with important insights into the molecular, cellular and evolutionary bases of behaviour.

Animals↗

Foraging behaviour in Drosophila larvae: mushroom body ablation.

Drosophila larvae and adults exhibit a naturally occurring genetically based behavioural polymorphism in locomotor activity while foraging. Larvae of the rover morph exhibit longer foraging trails than sitters and forage between food patches, while sitters have shorter foraging trails and forage within patches. This behaviour is influenced by levels of cGMP-dependent protein kinase (PGK) encoded by the foraging (for) gene. Rover larvae have higher expression levels and higher PGK activities than do sitters. Here we discuss the importance of the for gene for studies of the mechanistic and evolutionary significance of individual differences in behaviour. We also show how structure-function analysis can be used to investigate a role for mushroom bodies in larval behaviour both in the presence and in the absence of food. Hydroxyurea fed to newly hatched larvae prevents the development of all post-embryonically derived mushroom body (MB) neuropil. This method was used to ablate MBs in rover and sitter genetic variants of foraging to test whether these structures mediate expression of the foraging behavioural polymorphism. We found that locomotor activity levels during foraging of both the rover and sitter larval morphs were not significantly influenced by MB ablation. Alternative hypotheses that may explain how variation in foraging behaviour is generated are discussed.

Animals↗

Non-random mating in classical lekking grouse species: seasonal and diurnal trends.

This paper is the first to integrate both field and theoretical approaches to demonstrate that fertility benefits can be a direct benefit to females mating on the classical lek. Field data collected for male sharp-tailed grouse (Tympanuchus phasianellus), a classical lekking species, revealed potential fertility benefits for selective females. Adult males and individuals occupying centrally located territories on the lek were found to have significantly larger testes than juveniles and peripheral individuals. Further, using empirical data from previously published studies of classical lekking grouse species, time-series analysis was employed to illustrate that female mating patterns, seasonal and daily, were non-random. We are the first to show that these patterns coincide with times when male fertility is at its peak.

Animals↗

Abnormal turning behavior in Drosophila larvae. Identification and molecular analysis of scribbler (sbb).

Our genetic dissection of behavior has isolated scribbler (sbb), a vital gene that encodes a novel protein expressed in the embryonic and larval nervous systems and in the imaginal discs. Larvae with mutations in sbb exhibit abnormally high amounts of turning behavior in the absence of food. sbb is a large gene spanning >50 kb of genomic DNA with four major developmentally regulated transcripts. Transgenic rescue of scribbler behavior was demonstrated by targeting expression of a normal sbb transgene (sbb(+)) expressing one of the major transcripts to the nervous system. The vital function of sbb was restored by ubiquitous expression of this transgene throughout development.

Amino Acid Sequence↗

Isolation of larval behavioral mutants in Drosophila melanogaster.

Genetic loci that influence behavior are often difficult to identify and localize in part due to the quantitative nature of behavioral phenotypes. Previous studies had found an association between pupal lethality and altered larval behavior for mutants of several genes. To facilitate the identification and localization of new mutants that influence larval foraging (movement in the presence of food) and general locomotion (movement in the absence of food) behaviors we identified and then screened a collection of strains carrying pupal-lethal mutations for alterations in these larval behaviors. When the lethal mutation segregated with the behavioral alteration this permitted the mapping of the behavioral locus. Nine new loci on the second chromosome were found to affect larval behavior. Of these, seven loci affected foraging and two affected locomotion. Analyses of these new loci will lead to further understanding of the mechanistic bases of larval behavior.

Analysis of Variance↗

Neuronal polymorphism among natural alleles of a cGMP-dependent kinase gene, foraging, in Drosophila.

Natural variation in neuronal excitability and connectivity has not been extensively studied. In Drosophila melanogaster, a naturally maintained genetic polymorphism at a cGMP-dependent protein kinase (PKG) gene, foraging (for), is associated with alternative food search strategies among the allelic variants Rover (for(R); higher PKG activity) and sitter (for(s); lower PKG activity). We examined physiological and morphological variations in nervous systems of these allelic variants isolated from natural populations. Whole-cell current clamping revealed distinct excitability patterns, with spontaneous activities and excessive evoked firing in cultured sitter, but not Rover, neurons. Voltage-clamp examination demonstrated reduced voltage-dependent K(+) currents in sitter neurons. Focal recordings from synapses at the larval neuromuscular junction demonstrated spontaneous activity and supernumerary discharges with increased transmitter release after nerve stimulation. Immunolabeling showed more diffuse motor axon terminal projections with increased ectopic nerve entry points in sitter larval muscles. The differences between the two natural alleles was enhanced in laboratory-induced mutant alleles of the for gene. The pervasive effects of the for-PKG on neuronal excitability, synaptic transmission, and nerve connectivity illustrate the magnitude of neuronal variability in Drosophila that can be attributed to a single gene. These findings establish the consequences in cellular function for natural variation in an isoform of PKG and suggest a role for natural selection in maintaining variation in neuronal properties.

Action Potentials↗

The ideal free distribution in humans: an experimental test.

How the distribution of resources affects the spatial distribution of animals is a central concern of behavioral ecology. One influential model relating population dynamics to individual foraging behavior is that of ideal free distribution (Fretwell & Lucas, 1970). This model assumes foragers of equal competitive abilities, moving freely from one habitat to another, the choices made by each individual subject are supposed to equalize gains across habitats. The resulting distribution at the group level, or ideal free distribution, has been tested with various animal species. Here we report an experimental test with human subjects competing for money. The results approximate those predicted by the ideal free model, the degree of approximation being consistent with that obtained in other species. This similarity of results supports the application of behavioral ecology models to humanperformance.

Competitive Behavior↗

The foraging gene affects adult but not larval olfactory-related behavior in Drosophila melanogaster.

This study investigates the ability of larvae and adult rover and sitter Drosophila melanogaster to detect and migrate towards the source of a fly medium attractant using larval plate assays and an adult olfactory trap assay. Allelic variation at the foraging locus which encodes a cGMP-dependent protein kinase (PKG) did not affect larval olfactory response in the larval plate assays. In contrast, adult males of the sitter mutant for(s2) exhibited an olfactory trap response (OTR) which was significantly greater than that of males of the wild type forR strain from which for(s2) was derived and further genetic analysis showed that this was attributable to the for(s2) allele. The olfactory responses of fbrR and for(s2) flies to three odours (propionic acid, ethyl acetate and acetone) in a T-maze assay was normal indicating that they did not have general olfactory deficits. The finding that adult flies who differ in their PKG enzyme activities differ in foraging behaviours and olfactory trap responses to yeast odours suggests that PKG signalling pathways are involved in olfactory related responses to food.

Aging↗

Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila.

Naturally occuring polymorphisms in behavior are difficult to map genetically and thus are refractory to molecular characterization. An exception is the foraging gene (for), a gene that has two naturally occurring variants in Drosophila melanogaster food-search behavior: rover and sitter. Molecular mapping placed for mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and transgenic sitters expressing a dg2 complementary DNA from rover showed transformation of behavior to rover. Thus, PKG levels affected food-search behavior, and natural variation in PKG activity accounted for a behavioral polymorphism.

Animals↗

Evolution of foraging behavior in Drosophila by density-dependent selection.

One of the rare examples of a single major gene underlying a naturally occurring behavioral polymorphism is the foraging locus of Drosophila melanogaster. Larvae with the rover allele, forR, have significantly longer foraging path lengths on a yeast paste than do those homozygous for the sitter allele, fors. These variants do not differ in general activity in the absence of food. The evolutionary significance of this polymorphism is not as yet understood. Here we examine the effect of high and low animal rearing densities on the larval foraging path-length phenotype and show that density-dependent natural selection produces changes in this trait. In three unrelated base populations the long path (rover) phenotype was selected for under high-density rearing conditions, whereas the short path (sitter) phenotype was selected for under low-density conditions. Genetic crosses suggested that these changes resulted from alterations in the frequency of the fors allele in the low-density-selected lines. Further experiments showed that density-dependent selection during the larval stage rather than the adult stage of development was sufficient to explain these results. Density-dependent mechanisms may be sufficient to maintain variation in rover and sitter behavior in laboratory populations.

Animals↗

Larval behavior of Drosophila central complex mutants: interactions between no bridge, foraging, and Chaser.

The central complex (CC) is a prominent component of the adult insect brain. In Drosophila melanogaster, mutations which alter CC structure also impair adult locomotion. This has led to the suggestion that the CC functions as a higher organizer of adult locomotor patterns (Strauss and Heisenberg, 1993). In the present study, we describe altered larval behavior resulting from mutations in six CC structural genes. Differences from the control strain were found for larvae from each CC mutant strain in at least one of three assays. central body defect1 (cbd1), central complex deranged1 (ccd1), central brain deranged1 (ceb1) and central complex1 (cex1) larvae all had general defects in locomotion (on a non-nutritive agar surface). Both ellipsoid body open2 (ebo2) and no bridge1 (nob1) had larval foraging behavior defects (on a nutritive yeast surface). Only cex1 larvae required significantly longer time in a roll over assay of muscle tone. Genetic analysis suggested that nob1 interacts additively with two other genes influencing larval foraging behavior, foraging (for) and Chaser (Csr). for also had an influence on adult foraging, whereas here we found that Csr did not. We did not include adult foraging behavior tests of the CC mutants due to general locomotion defects in these flies (Strauss and Heisenberg, 1993).

Animals↗

The expression of additive and nonadditive genetic variation under stress.

Experimental lines of Drosophila melanogaster derived from a natural population, which had been isolated in the laboratory for approximately 70 generations, were crossed to determine if the expression of additive, dominance and epistatic genetic variation in development time and viability was associated with the environment. No association was found between the level of additive genetic effects and environmental value for either trait, but nonadditive genetic effects increased at both extremes of the environmental range for development time. The expression of high levels of dominance and epistatic genetic variation at environmental extremes may be a general expectation for some traits. The disruption of the epistatic gene complexes in the parental lines resulted in hybrid breakdown toward faster development and there was some indication of hybrid breakdown toward higher viability. A combination of genetic drift and natural selection had therefore resulted in different epistatic gene complexes being selected after approximately 70 generations from a common genetic base. After crossing, the hybrid populations were observed for 10 generations. Epistasis contributed on average 12 hr in development time. Fluctuating asymmetry in sternopleural bristle number also evolved in the hybrid populations, decreasing by > 18% in the first seven generations after hybridization.

Animals↗