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PubMed1989

In vitro chemosensitivity testing and its clinical application in human gliomas.

Several in vitro chemosensitivity assays have been developed for predicting clinical response to chemotherapeutic and biologic agents, alone and in combinations. The most widely accepted assay is the colony forming assay (CFA) which assesses the clonogenic capability of stem cells. Other methods include growth inhibition assays by evaluating cell number; thymidine incorporation; or amino acid uptake. More recently an automatic colorimetric technique utilizing crystal violet dye or a tetrazolium (MTT) vital dye has been developed for more rapid assessment of cytotoxic or growth inhibitory activity in vitro. Several reports have compared the results of in vitro tests with patients' clinical response. Two major problems affect the predictive value of in vitro chemosensitivity tests. The foremost is cellular heterogeneity which exists within a single tumor as well as between tumors. Artificial selective pressure inherent to tissue culture system is the other problem. In general, in vitro tests predict clinical resistance more consistently than clinical sensitivity. However, chemosensitivity assays remain useful in screening new agents and preclinical modeling of clinical trials.

Amino Acids↗
PubMedDate not supplied

Metastatic instability of murine tumor metastases: dependence on tumor type.

Fifteen metastatic lines derived in vivo from three syngeneic murine tumors, the sarcomas SA-NH and SA-4020 and the hepatic carcinoma HCA-I, were assessed for their stability of metastasis formation upon isotransplantation for several successive generations in syngeneic animals. Change in the metastatic phenotype was actively encouraged by a new procedure, the artificial selection for increased or decreased metastasis formation. Metastatic instability was dependent on tumor type, with five of six lines of tumor SA-NH, one of four lines of tumor SA-4020, and possibly one of five lines of HCA-I changing in lung metastasis formation. The instability of lung metastasis formation was also assessed by analyzing changes in the variance of the lines. Concomitant with a change in metastatic potential for lung metastasis, we observed a similar change for abdominal lymph node metastasis. We also report the selection of a less metastatic line. The variance of lung metastasis increased significantly only in the SA-NH lines. The instability of metastasis formation was attributed to genetic instability of metastatic cell lines.

Animals↗
PubMed1997

Hereditarian scientific fallacies.

Some have recently declared that a hereditarian or more balanced approach has triumphed over environmentalism as an explanatory tool for variation in the cognitive ability and behaviour of humans. However, the entire debate is constrained by several fallacies described here. Heritability of a trait, does not predict the effect of environmental or genetic changes on the trait (Fallacy #1), so knowing heritability does not assist in writing prescriptions for societal ills or budget cuts. Heritability estimates themselves are inaccurate, given the potential for gene-environment covariance and interaction, as well as other non-additive effects on behavior or cognitive ability (Fallacy #2). The 'revolution in molecular genetics' has provided more effective tools for describing the genome, but doesn't permit separation of gene and environmental effects on traits (Fallacy #3). If we were able to measure heritability accurately, it would give us absolutely no indication of whether or not group differences are genetically based (Fallacy #4). Finally, any proposed models of the evolutionary divergence of human groups must more adequately answer the basic questions of such a study, and are not supported by high heritability in present populations (Fallacy #5). Humans are not and should never be exposed to artificial selection and crossing experiments, so behavior geneticists will continue to be very limited in their ability to partition the effects of genes, the environment, and their covariance and interaction on human behavior and cognitive ability.

Biological Evolution↗
PubMed1996

Genetic variation in "first" male effects on egg laying and remating by female Drosophila melanogaster.

Male Drosophila melanogaster from lines artificially selected to have divergent life histories were tested to determine if they differed in their effects on female reproductive behavior. During the first 5 days after mating, males from short-generation populations caused females to lay eggs at a faster rate than did males from long-generation populations. This faster oviposition rate resulted in greater numbers of adult progeny produced by short-generation males. During the period 6-21 days after mating, long-generation males fathered more adult progeny. Females that were first mated to short-generation males were more likely to remate than were females first mated to long-generation males. Rematings were interrupted in order to prevent transfer of second-male accessory fluid and sperm. Females that were first mated to long-generation males produced more progeny after interrupted matings than did females that were first mated to short-generation males.

Animals↗
PubMed2005

Riboswitches: natural SELEXion.

Advances in our knowledge of the structure and chemistry of RNA have been harnessed in the process known as SELEX to develop artificial RNA-based molecules that can act as enzymes and ligand binders performing a wide variety of functions. The discovery of riboswitches, natural RNA aptamers involved in genetic regulation, offers a basis of comparison between the artificial selection and the natural selection of structured RNAs for small-molecule recognition. The guanine riboswitch structural determination allows us to draw conclusions regarding the apparent increased complexity of the riboswitch aptamers compared to their in-vitro-selected cousins.

Aptamers, Nucleotide↗
PubMed2005

Evidence of the domestication history of flax (Linum usitatissimum L.) from genetic diversity of the sad2 locus.

A phylogenetic analysis was conducted on 34 alleles of 2.5 kb sized stearoyl-ACP desaturase II (sad2), obtained from 30 accessions of cultivated and pale flax (Linum spp.), to elucidate the history of flax domestication. The analysis supports a single domestication origin for extant cultivated flax. The phylogenetic evidence indicates that flax was first domesticated for oil, rather than fibre. The genetic diversity of the sad2 locus in cultivated flax is low when compared to that of the pale flax assayed. An absolute archaeological date could be applied to the synonymous substitution rate of sad2 in cultivated flax, yielding a high estimate of 1.60-1.71x10(-7) substitutions/site/year. The occurrence of nonsynonymous substitutions at conserved positions of the third exon in alleles from cultivated flax suggests that the locus may have been subjected to an artificial selection pressure. The elevated synonymous substitution rate is also compatible with a population expansion of flax since domestication, followed by a population decline in historic times. These findings provide new insight into flax domestication and are significant for the continuous exploration of the flax germplasm for utilization.

Crops, Agricultural↗
PubMed1999

Quantitative trait loci for growth traits in C57BL/6J x DBA/2J mice.

Quantitative trait loci (QTLs) for body weight and tail length are mapped in an F2 population of 927 C57BL/6J x DBA/2J mice. We test the concordance between the locations of the mapped QTLs with those detected by changes of marker frequency under artificial selection in a previous experiment with the same base population. The directions of effects of the QTLs are generally in agreement, and in many cases significant QTLs are found in similar map positions, but there are also discrepancies between the two experiments. There are indications of age-specific QTL effects on growth. For body weight traits, the genetic variation in the F2 appears to result from many loci with relatively small effects. For tail length at 10 weeks, however, a single QTL on Chromosome (Chr) 1 with a peak LOD score of approximately 33 contributes most of the genetic variation detected, changes the trait value by about 6%, and explains about 20% of the phenotypic variance of the trait.

Animals↗
PubMed1998

The effect of genotype on response thresholds to sucrose and foraging behavior of honey bees (Apis mellifera L.).

Honey bee foragers were tested for their proboscis extension response (PER) to water and varying solutions of sucrose. Returning pollen and nectar foragers were collected at the entrance of a colony and were assayed in the laboratory. Pollen foragers had a significantly higher probability of responding to water and to lower concentrations of sucrose. Bees derived from artificially selected high- and low-pollen-hoarding strains were also tested using the proboscis extension assay. Returning foragers were captured and tested for PERs0 to 30% sucrose. Results demonstrated a genotypic effect on PERs of returnining foragers. The PERs of departing high- and low-strain foragers were consistent with those of returning foragers. The PERs were related to nectar and water reward perception of foragers. High strain bees were more likely to return with loads of water and lower concentrations of sucrose than foragers from low pollen strain. Low-strain bees were more likely to return empty. We identified a previously mapped genomic region that contains a variable quantitative trait locus that appears to influence sucrose response thresholds. These studies demonstrate a gene-brain-behavior pathway that can be altered as a consequence of colony-level selection for quantities of stored food.

Animals↗
PubMed1999

The effect of genotype, age, sex, and caste on response thresholds to sucrose and foraging behavior of honey bees (Apis mellifera L.).

Bees derived from artificially selected high- and low-pollen-hoarding strains were tested for their proboscis extension reflex response to water and varying sucrose concentrations. High-strain bees had a lower response threshold to sucrose than low-strain bees among pre-foragers, foragers, queens and drones. Pre-foraging low-strain workers showed ontogenetic changes in their response threshold to sucrose which was inversely related to age. High-strain foragers were more likely to return with loads of water compared to low-strain foragers. Whereas low-strain foragers were more likely to return with loads of nectar. Low-strain nectar foragers collected nectar with significantly higher sucrose concentrations than did the high-strain nectar foragers. Alternatively, low-strain foragers were more likely to return empty compared to high-strain foragers. These studies demonstrate how a genotypically varied sensory-physiological process, the perception of sucrose, are associated with a division of labor for foraging.

Aging↗
PubMed2001

Modulation of sucrose response thresholds in honey bees (Apis mellifera L.): influence of genotype, feeding, and foraging experience.

The perception of sugar is important to honey bees for making foraging decisions. We measured bees' perception by determining what concentration of sucrose touched to the antennae elicited the proboscis extension response (response threshold). A low response threshold (extension at low concentration) suggests a high perceptual value of sucrose. and vice versa. Perception of sucrose solutions differed between two artificially selected genotypic strains and was modulated by the bees' recent feeding experiences. Bees offered 10%, 30%, or 50% sucrose solutions in small cages overnight, and in large flight-cages or free-flying in the field for several days, had subsequent response thresholds positively correlated to the concentration offered. Empty bees, whether they were nectar, water or pollen foragers, dancers or non-dancers, had a significantly lower threshold than loaded bees. Crop volume affected response thresholds directly and independently of sucrose concentration. We interpret these findings as multiple mechanisms that operate in different time scales, modulating perception of sucrose. Changes occurred in the time scale of evolutionary processes as demonstrated by genotypic differences. Changes with foraging experience occur in hours or minutes while effects of crop filling are instantaneous.

Adaptation, Physiological↗
PubMed1997

Use of random amplified polymorphic DNA-polymerase chain reaction for the definition of genetic markers for species and strains of porcine Oesophagostomum.

Nodular worms are common parasites of pigs, and research has recently started to focus on the biology of these nematodes. However, the methods for delineation of species at immature developmental stages and for differentiation of various lines of the same species remain limited. For differentiation of porcine Oesophagostomum species and strains by genomic fingerprinting, random amplified polymorphic DNA-polymerase chain reaction was performed on DNA derived from 20 larval batches of anthelmintic-susceptible and resistant strains and isolates of these nematodes and 2 ruminant Oesophagostomum spp. Polymorphic DNA markers could be amplified with 9 of the 33 primers tested. In all, 13 markers were species-specific and 6 markers could differentiate between strains or groups of strains. With a combination of the latter, artificially selected anthelmintic-resistant strains and the susceptible mother strain of O. dentatum could be delineated. When single adult worms were compared, considerable variations between strains of the same species and between individuals from the same strain could be detected. The differentiation of Oesophagostomum strains and species at all parasitic stages on the basis of genetic markers could greatly facilitate studies on the biology of these parasites.

Animals↗
PubMed2006

Phenotypic plasticity of reproductive traits in response to food availability and photoperiod in white-footed mice (Peromyscus leucopus).

Although most temperate-zone mammals are seasonal breeders, many populations display variation in winter reproductive phenotype. For most mammals, the primary environmental cues regulating reproductive status are food availability and photoperiod, and these two factors can interact in their effect. Low food availability is primarily thought to suppress reproduction by reducing body mass and thereby forcing energy allocations to survival alone. However, because most small mammals rely on an increase in food intake rather than stored nutrients for reproduction, we hypothesized that food availability could act as a signal for low resource availability and affect reproduction even when body condition was not affected. We tested the prediction that restricted food access, without reduced body mass, could alter reproductive responses to short photoperiod. We used genetically distinct lines of white-footed mice (Peromyscus leucopus) derived from a wild population with genetic variation in the neuroendocrine pathway that regulates reproduction in response to environmental cues. The lines were created by artificial selection on gonad size in short photoperiods. Individuals from one line strongly suppress gonadal development in response to short photoperiods, while individuals from the other line suppress gonadal development weakly or not at all. Unresponsive individuals from the selected and an unselected control line were exposed to an intermittent food access protocol that did not affect body mass and only slightly reduced total food intake. We found that restricting food access caused reproductive suppression in short photoperiods but not long photoperiods, with no decrease in body mass. These results provide evidence for an interaction between food and photoperiod that is not dependent upon body condition or energy balance. The results also demonstrate plasticity in the reproductive response to photoperiod of otherwise reproductively nonphotoperiodic white-footed mice.

Analysis of Variance↗
PubMed2026

Seed shattering habit in millets and the secrets of the abscission layer - a comprehensive review.

Though seed shattering continues to be a significant barrier affecting yield stability and harvesting efficiency in millets and other grasses, millets are increasingly acknowledged as climate-resilient, nutrient-rich 2007cereal crops with the potential to strengthen global nutritional and food security under the combined pressures of climate change, population growth, and limited natural resources. Since strong artificial selection favoured non-shattering phenotypes during domestication, seed shattering, an adaptive trait in wild species that promotes seed dispersal through the formation and activation of specialised abscission layers, became a distinguishing feature of cultivated cereals. With a focus on the morphological, physiological, hormonal, and genetic modulation of the abscission zone, this article summarizes the state of the art regarding seed shattering in millets. Abscission layer morphology, location, and lignification vary greatly among grasses, from well-defined lignified zones in rice and sorghum to non-lignified and anatomically subtle zones in Setaria and Panicum species. Cell wall-modifying enzymes like polygalacturonases, cellulases, expansins, and pectin methylesterases that mediate middle lamella degradation are modulated by coordinated hormonal signalling involving auxin, ethylene, and abscisic acid, which controls the timing and progression of cell separation at the physiological level. Domestication-related genes, including SH1, qSH1, SH4, and LES1, demonstrate convergent evolutionary mechanisms controlling abscission layer development in a variety of grass lineages at the molecular level. Understanding these regulatory networks has been greatly enhanced by recent developments in transcriptomics, functional genomics, and genome sequencing in both model species and underused millets. The role of millets as climate-smart cereals for sustainable future agriculture is reinforced by the integration of anatomical, physiological, and genetic insights, which offer a solid basis for targeted breeding and genome-editing strategies intended to improve seed retention, enhance yield stability, and increase harvest efficiency.

Abscission Layer↗
PubMed2003

Genetic animal models of anxiety.

The focus of this review is on progress achieved in identifying specific genes conferring risk for anxiety disorders through the use of genetic animal models. We discuss gene-finding studies as well as those manipulating a candidate gene. Both human and animal studies thus far support the genetic complexity of anxiety. Clinical manifestations of these diseases are likely related to multiple genes. While different anxiety disorders and anxiety-related traits all appear to be genetically influenced, it has been difficult to ascertain genetic influences in common. Mouse studies have provisionally mapped several loci harboring genes that affect anxiety-related behavior. The growing array of mutant mice is providing valuable information about how genes and environment interact to affect anxious behavior via multiple neuropharmacological pathways. Classical genetic methods such as artificial selection of rodents for high or low anxiety are being employed. Expression array technologies have as yet not been employed, but can be expected to implicate novel candidates and neurobiological pathways.

Animals↗
PubMed2005

Parallel genotypic adaptation: when evolution repeats itself.

Until recently, parallel genotypic adaptation was considered unlikely because phenotypic differences were thought to be controlled by many genes. There is increasing evidence, however, that phenotypic variation sometimes has a simple genetic basis and that parallel adaptation at the genotypic level may be more frequent than previously believed. Here, we review evidence for parallel genotypic adaptation derived from a survey of the experimental evolution, phylogenetic, and quantitative genetic literature. The most convincing evidence of parallel genotypic adaptation comes from artificial selection experiments involving microbial populations. In some experiments, up to half of the nucleotide substitutions found in independent lineages under uniform selection are the same. Phylogenetic studies provide a means for studying parallel genotypic adaptation in non-experimental systems, but conclusive evidence may be difficult to obtain because homoplasy can arise for other reasons. Nonetheless, phylogenetic approaches have provided evidence of parallel genotypic adaptation across all taxonomic levels, not just microbes. Quantitative genetic approaches also suggest parallel genotypic evolution across both closely and distantly related taxa, but it is important to note that this approach cannot distinguish between parallel changes at homologous loci versus convergent changes at closely linked non-homologous loci. The finding that parallel genotypic adaptation appears to be frequent and occurs at all taxonomic levels has important implications for phylogenetic and evolutionary studies. With respect to phylogenetic analyses, parallel genotypic changes, if common, may result in faulty estimates of phylogenetic relationships. From an evolutionary perspective, the occurrence of parallel genotypic adaptation provides increasing support for determinism in evolution and may provide a partial explanation for how species with low levels of gene flow are held together.

Adaptation, Biological↗
PubMed2006

Genome-wide investigation on the genetic variations of rice disease resistance genes.

Exploitation of plant disease resistance (R) gene in breeding programs has been proven to be the most efficient strategy for coping with the threat of pathogens. An understanding of R-gene variation is the basis for this strategy. Here we report a genome-wide investigation on the variation of NBS-LRR-encoding genes, the common type of R genes, between two sequenced rice genomes, Oryza sativa L. var. Nipponbare and 93-11. We show that the allelic nucleotide diversity in 65.0% of 397 least-divergent pairs is not high (0.344% on average), while the remaining 35% display a greater diversity (5.4% on average). The majority of conserved R genes is single-copy and/or located as a singleton. The clustered, particularly the complex-clustered, R-genes contribute greatly to the rich genetic variation. Surprisingly only 11.2% of R-genes have remarkably high ratios of non-synonymous to synonymous rates, which is much less than the 17.4% observed between Arabidopsis genomes. Noticeable "artificially selective sweeping" could be detected in a large proportion of the conserved R-genes, a scenario described in the "arms race" co-evolutionary model. Based on our study, a variation pattern of R-genes is proposed and confirmed by the analysis of R-genes from other rice lines, indicating that the observed variation pattern may be common in all rice lines.

Genes, Plant↗
PubMed1993

Effects of bilateral hemispherectomy on genetically variable stimulus preferences and imprinting in quail chicks.

Bilateral ablation of the telencephalon on the 1st posthatch day prevented learning from imprinting to colored stimuli in Japanese quail chicks C. coturnix japonica, but it spared their artificially selected approach preferences for particular colors and patterns. Post-imprinting decerebration on the 3rd posthatch day erased the imprinted memory, but did not revert the chicks' approach choices to the colors of their genetically distinct initial preferences. The genetically determined and the acquired preferences were both lost in the latter birds, regardless whether they were imprinted to the initially preferred or the initially nonpreferred stimuli before decerebration. Discussion focuses on implications of the data for modeling specific interactions between and the interrelated neural representation of genetic and environmental influences in early behavioral development.

Animals↗
PubMed1985

Determination of approximate size of maxillary anterior denture teeth when mandibular anterior teeth are present. Part III: Relationship of maxillary to mandibular central incisor widths.

The average width of a natural maxillary central incisor is 8.92 mm. This value is determined from the results of three studies of natural dentitions. The average width of a mandibular central incisor is 5.5 mm. The average ratio produced by dividing the average maxillary central incisor width by the average mandibular incisor width is 1.62. The factor of 1.5 times the width of a mandibular central incisor produces a maxillary central incisor width that is too narrow. The width of a mandibular central incisor plus half the width of the mandibular lateral incisor also produces a maxillary central incisor width that is too narrow. There may be a tendency to undersize the maxillary prosthetic dentition. The ratio of 1.62 can be used to select the appropriate width for a missing maxillary central incisor when given the width of the mandibular central incisor. This ratio of 1.62 is also valuable to verify the dimension of a selected artificial maxillary central incisor when the patient complains that the tooth is too large. If substitutions or adjustments are made in the mold, the desired canine-to-canine measurement produced by the ratio range of 1.3 to 1.38 reported in Parts I and II of this study should be maintained.

Female↗