Unilateral clefts: a new defect of the rat secondary palate

As shown in a previous study [Schüpbach et al, 1984], different types of total and partial clefts of the secondary palate can be produced through amniocentesis performed in Sprague-Dawley rats at day 16.2 of gestation. Among these were a small number of unilateral clefts that were examined in the scanning electron microscope and in Epon sections. The 410 treated amnions yielded a total of 395 viable fetuses. Total clefts occurred in 48.9% of viable fetuses examined at day 17.8 and in 21.8% of those examined at days 19.3. Partial clefts were observed in 14.1% and 18.5% of viable fetuses examined at days 17.8 and 19.3, respectively. Unilateral clefts were observed in 3.8-10.2% of the partial clefts and in 0.5-1.8% of all viable fetuses. The eight animals with unilateral clefting included fetuses with a total unilateral cleft in the anterior hard palate. Morphological observations suggested that under conditions of delayed palatal closure total unilateral clefts may be the result of initial elevation of one, and delayed elevation of the other, shelf and partial unilateral clefts probably represent the result of an incomplete retrograde closure.     

Selection analysis on the rapid evolution of a secondary sexual trait

Evolutionary analyses of population translocations (experimental or accidental) have been important in demonstrating speed of evolution because they subject organisms to abrupt environmental changes that create an episode of selection. However, the strength of selection in such studies is rarely measured, limiting our understanding of the evolutionary process. This contrasts with long-term, mark–recapture studies of unmanipulated populations that measure selection directly, yet rarely reveal evolutionary change. Here, we present a study of experimental evolution of male colour in Trinidadian guppies where we tracked both evolutionary change and individual-based measures of selection. Guppies were translocated from a predator-rich to a low-predation environment within the same stream system. We used a combination of common garden experiments and monthly sampling of individuals to measure the phenotypic and genetic divergence of male coloration between ancestral and derived fish. Results show rapid evolutionary increases in orange coloration in both populations (1 year or three generations), replicating the results of previous studies. Unlike previous studies, we linked this evolution to an individual-based analysis of selection. By quantifying individual reproductive success and survival, we show, for the first time, that males with more orange and black pigment have higher reproductive success, but males with more black pigment also have higher risk of mortality. The net effect of selection is thus an advantage of orange but not black coloration, as reflected in the evolutionary response. This highlights the importance of considering all components of fitness when understanding the evolution of sexually selected traits in the wild.     

Maternal immune factors and the evolution of secondary sexual characters

Secondary sexual characters have been hypothesized to revealthe ability of males to resist debilitating parasites. Althoughsuch reliable signaling of parasite resistance may be maintainedby parasite–host coevolution, maternal effects potentiallyprovide a previously neglected factor that could affect thelevel of genetic variation in resistance to parasites. Thatcould be the case because maternal effects have an entirelyenvironmental basis, or because they can maintain considerableamounts of genetic variation through epistatic effects, evenin the presence of strong directional selection. Maternal effectshave been shown to occur as maternal allocation of immune factorsto offspring, and such allocation may depend on the mating prospectsof sons, causing mothers to differentially allocate maternaleffects to eggs in species subject to intense sexual selection.Here we show that a maternal effect through innate antibacterialimmune defense, lysozyme, which is transferred from the motherto the egg in birds, is positively associated with the evolutionof secondary sexual characters. Previous studies have shownthat females differentially allocate lysozyme to their eggswhen mated to attractive males, and elevated levels of lysozymeare associated with reduced hatching failure and superior healthamong neonates and adults. In this study, comparative analysesof lysozyme from eggs of 85 species of birds showed a strongpositive relationship between brightness of male plumage andegg lysozyme, even when controlling for potentially confoundingvariables. These findings suggest that maternal immune factorsmay play a role in the evolution of secondary sexual characters.     

Differentiation of the avian secondary palate

The avian secondary palate exhibits the unique feature of a midline cleft. Cryostat sections indicated that although extensive contact between homologous shelves was present, chick palatal medial edge epithelium (MEE) failed to fuse. The failure of fusion and subsequent clefting of the avian palate were correlated with continued proliferation of the avian MEE, a failure of selective MEE cell death, and an absence of elevated levels of intracellular cAMP. Moreover, immunohistochemical staining for cAMP and microspectrophotometric quantitation of staining intensity indicated that staining of chick MEE was significantly (p less than .01) less than murine MEE at comparable gestational ages. These data indicate that differentiation of the avian secondary palate is fundamentally different than reported for the mammalian palate in that many developmental events known to be associated with normal mammalian palate formation (cessation of MEE proliferation, MEE cell death, elevated levels of MEE cAMP) fail to occur in the chick. The developing avian secondary palate, with its midline cleft, thus provides an interesting and useful model system with which to compare mammalian palate formation where the palate is normally fused in the midline.     

Computer-assisted analysis of hyaluronate distribution during morphogenesis of the mouse secondary palate

Hyaluronate mediated extracellular matrix swelling has been hypothesized to play a major role in reorientation of the secondary palatal shelves. A computer-assisted method utilizing image registration and subtraction was used to visualize the distribution of hyaluronate (HA) during morphogenesis of the secondary palate. Patterns of HA distribution in anterior, posterior and presumptive soft palate were examined in the secondary palatal shelves of CD-1 mouse fetuses that were 30, 24 and 18 h prior to, and at the time of, shelf reorientation. Adjacent serial sections were taken from each shelf region of three to six specimens from a minimum of three litters for each gestational age. One section was incubated in buffer as a control, the other digested with Streptomyces hyaluronidase to specifically remove HA. Both sections were stained with Alcian blue to visualize the extracellular matrix and counterstained with nuclear fast red to visualize cells. Two different videoimages were then digitized for each tissue section, one using wavelengths of light that were at or near the maximum absorbance of the matrix stain, the other using wavelengths that were at the maximum absorbance of the cellular stain. Thus, a matrix image and a cell image of both control and digested sections were produced. Next, the cell image was subtracted from its respective matrix image, resulting in a control matrix-only image and a digested (HA-removed) matrix-only image. These images were mathematically warped to one another, if necessary, and registered with one another. The digested image was then subtracted from the control image. The resultant difference picture displayed the pattern and relative intensities of HA distribution across the tissue section. Prior to and during shelf reorientation, unique region-specific patterns of HA distribution and relative intensity were identified which became homogeneous after reorientation. Presumptive soft palate shows the most extensive and intense patterns of HA distribution, followed by the posterior region. The anterior region has the most sparse pattern of the three regions examined. The results are consistent with the hypothesized role of HA in shelf reorientation.     

A theoretical analysis of secondary structural characteristics of anticancer peptides

Here, cluster analysis showed that a database of 158 anticancer peptides formed 21 clusters based on net positive charge, hydrophobicity and amphiphilicity. In general, these clusters showed similar median toxicities (P = 0.176) against eukaryotic cell lines and no single combination of these properties was found optimal for efficacy. The database contained 14 peptides, which showed selectivity for tumour cell lines only (ACP_CT), 123 peptides with general toxicity to eukaryotic cells (ACP_GT) and 21 inactive peptides (ACP_I). Hydrophobic arc size analysis showed that there was no significant difference across the datasets although peptides with wide hydrophobic arcs (>270°) appeared to be associated with decreased toxicity. Extended hydrophobic moment plot analysis predicted that over 50% of ACP_CT and ACP_GT peptides would be surface active, which led to the suggestion that amphiphilicity is a key driver of the membrane interactions for these peptides but probably plays a role in their efficacy rather than their selectivity. This analysis also predicted that only 14% of ACP_CT peptides compared to 45% of ACP_GT peptides were candidates for tilted peptide formation, which led to the suggestion that the absence of this structure may support cancer cell selectivity. However, these analyses predicted that ACP_I peptides, which possess no anticancer activity, would also form surface active and tilted α-helices, clearly showing that other factors are involved in determining the efficacy and selectivity of ACPs.     

Saltatory search: a theoretical analysis

Many animal search in a saltatory fashion: they move forward,pause briefly, and move forward again. Although many optimal-foragingmodels have been developed, most do not address how an animalsearches for food. We view search strategies as "time-distance"functions to allow not only for the possibility of oscillationsin body speed, as implied by saltatory search, but other movementpatterns as well, including cruise search. The key feature ofour models is distinguishing between the body position and thescan position (where the forager is looking). We see the varyingmovement of saltatory search as a consequence of the curvaturein the functions that relate body speed to benefits (Jensen'sinequality)     

Function and molecular evolution of mammalian Sox15, a singleton in the SoxG group of transcription factors

In mammals, the group G of the Sry-related high-mobility-group (HMG) box genes (Sox) contains only one member, Sox15. Comparative genomic analysis of the Sox genes in the B1 and G groups indicates that an ancestral gene may have originated as an intron-containing gene belonging to group B1 and evolved into zebrafish Sox19a/b, Xenopus SoxD, and mammalian Sox15. Although these genes have different names, they are orthologous. The zebrafish and Xenopus orthologues are highly expressed in the central nervous system, whereas mouse Sox15 only shows strong expression in the placenta, an organ characteristic of all mammals except monotremes. Interestingly, Sox15 appears to be a pseudogene in the marsupial opossum. Sox15-deficient mice exhibit delayed skeletal muscle regeneration, indicating that Sox15 plays a crucial role in this process. On the other hand, Xenopus SoxD induces anterior neural development. Thus, there appears to be little functional overlap between Sox15 and its orthologues, Sox19a/b and SoxD. In this review, I discuss the roles of Sox15, its functional redundancy with SoxB1 group members, and its molecular evolution.     

An analysis of the dynamics of mammalian mitochondrial DNA sequence evolution

The dynamics of the substitution process for mammalian mitochondrial DNAhave been modeled. The temporal behavior of several quantities has beenstudied and the model's predictions have been compared with estimatesobtained from recent mtDNA sequence data for an increasingly divergentseries of primates, the mouse and the cow (Anderson et al. 1981, 1982; Bibbet al. 1981; Brown et al. 1982). The results are consistent with thehypothesis that the decrease in the proportion of transitions observed asdivergence increases is a consequence of the highly biased substitutionprocess. In addition, the results support the hypothesis that, although aportion of the mtDNA molecule evolves at an extremely rapid rate, asignificant portion of the molecule is under strong selective constraints.     

Parallel evolution in mammalian and avian brains: comparative cytoarchitectonic and cytochemical analysis

Summary Comparative morphology, which is based on the selection theory of evolution, analyses the impact of function upon structure and, therefore, emphasizes the adaptive events and biological advantage during the evolution of organs. A comparison based on analogies is described here as an adequate method. The hypothesis is proposed that the evolution of the brain follows the same trends in birds as in mammals. This hypothesis is proved by (1) allometric studies of brain weight and brain structure volume in relation to body weight in mammals and birds; (2) architectonic studies using image analysis on cell and fibre stains as well as on histochemical preparations and receptor autoradiography; and (3) hodological studies with injections of [³H]leucin, HRP and WGA-HRP. The results reveal a vast amount of structural and functional similarities in avian and mammalian brain organization, especially an expansion of structures that permit multimodal integration capacity in the telencephalon. Thus, a parallel evolution occurred in these two groups of vertebrates. It is argued that this may be a general phenomenon in evolution. A cladistic approach, which is based on the concept of homologies (plesio-, apomorphies), pushes aside the existence of analogies. For this reason, cladism does not seem to be a method to answer questions of evolutionary morphology adequately.     

On the evolution of polygyny: a theoretical examination of the polygyny threshold model

The polygyny threshold model states that if costs incurred areless than the benefits gained from mating polygynously in termsof breeding-situation quality, then polygyny is favored andcould evolve. We constructed mathematical models and computersimulations to evaluate this hypothesis. In the basic model,there is a single locus with two alleles, which regulates whetherthe female is receptive to polygyny. There are two breedingsituations of differing quality on which males randomly assort.Females then select a mate based on the associated breedingsituation and whether the male already has mates. This basicmodel is extended mathematically to include a cost for the initialfemale of a male with multiple mates and again to include geneexpression in males. The computer simulations extend the basicmodel to multiple loci and alleles and to multiple breedingsituations. The results presented here suggest that the polygynythreshold model is valid in a population genetic context: ifthe fitness of females that actually mate polygynously is greaterthan the fitness of monogamous females on poorer breeding situations,polygyny evolves. However, this approach reveals interestingdynamics not apparent from the verbal model. If the trait isexpressed in males and females, then polygyny can evolve evenif females mating polygynously have a lower fitness than femalesmating monogamously. In the multiple breeding-situations model,the polygyny allele increases to some equilibrium value abovewhich it experiences no selection. Surprisingly, as the costof polygyny increases, the equilibrium frequency of the polygynyallele also increases. The difference between this evolutionarymodel and the ideal free distribution is discussed.     

Molecular control of secondary palate development

Compared with the embryonic development of other organs, development of the secondary palate is seemingly simple. However, each step of palatogenesis, from initiation until completion, is subject to a tight molecular control that is governed by epithelial-mesenchymal interactions. The importance of a rigorous molecular regulation of palatogenesis is reflected when loss of function of a single protein generates cleft palate, a frequent malformation with a complex etiology. Genetic studies in humans and targeted mutations in mice have identified numerous factors that play key roles during palatogenesis. This review highlights the current understanding of the molecular and cellular mechanisms involved in normal and abnormal palate development with special respect to recent advances derived from studies of mouse models.     

The quest for adaptive evolution: a theoretical challenge in a maze of data

Advances in sequencing technology have brought opportunities to refine our searches for adaptive evolution and to address and identify new questions regarding how adaptive evolution has shaped genomic diversity. Recent theoretical developments incorporate demographic and complex selective histories into tests of non-neutral evolution, thereby significantly improving our power to detect selection. These analyses combined with large data sets promise to identify targets of selection for which there was no a priori expectation. Moreover, they contribute to elucidate the role selection has played in shaping diversity in transposable elements, conserved noncoding DNA, gene family size, and other multicopy features of genomes.     

An essay on the evolution of cognition: Constructing a theoretical conceptual framework

In this essay we provide an interdisciplinary approach to the problem of the evolution of human cognition and suggest the theoretical framework of genetic system theory (GST) for organizing the relevant content of several disciplines. This bio-social-cultural theory is based on the assumption that organisms are dynamic systems which interact with one another and their environment and are themselves composed of dynamic internal relations at several levels. Special emphasis will be placed upon these internal cellular and molecular mechanisms underlying the physiological mechanisms of learning and memory. The human individual organism is emphasized because in its experiential activity over time it is the site of integration for social, and cultural stimuli and because of its unique properties among living things. The primary disciplines for our discussion are drawn from the biological, social, and humanistic sciences and several concrete examples are given from each science.     

Identification of adenylate cyclase-coupled beta-adrenergic receptors in the developing mammalian palate

A direct radioligand binding technique utilizing a beta-adrenergic antagonist [3H]Dihydroalprenolol [( 3H]DHA) was employed in the identification and characterization of fetal palatal beta-adrenergic receptors. [3H]DHA binding was saturable (Bmax 16 fmol/mg protein) with high affinity and an apparent equilibrium dissociation constant (KD) of 1.5 nM. Binding of [3H]DHA was displaced by the competitive beta-adrenergic antagonist propranolol in a concentration-dependent manner. Dissociation kinetic studies demonstrated almost complete reversibility of radioligand binding within 60 min. The functionality of these beta-adrenergic receptors was demonstrated by showing that fetal palatal mesenchymal cells responded to catecholamine agonists with dose-dependent accumulations of intracellular cAMP. This effect could be entirely blocked by the beta-antagonist, propranolol. The relative potency order of catecholamines in eliciting an elevation of cellular cAMP was characteristic of a beta 2-adrenergic receptor-mediated response: (-) isoproterenol greater than (-) epinephrine greater than (-) norepinephrine. In addition, this response was found to be stereospecific with (-) isoproterenol being significantly more potent than (+) isoproterenol. Both the [3H]DHA binding characteristics and the catecholamine sensitivity of fetal palatal tissue support the presence of adenylate cyclase-coupled beta-adrenergic receptors in the developing mammalian secondary palate.