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Structure and function of eukaryotic DNA methyltransferases.

DNA methylation is a common epigenetic modification found in eukaryotic organisms ranging from fungi to mammals. Over the past 15 years, a number of eukaryotic DNA methyltransferases have been identified from various model organisms. These enzymes exhibit distinct biochemical properties and biological functions, partly due to their structural differences. The highly variable N-terminal extensions of these enzymes harbor various evolutionarily conserved domains and motifs, some of which have been shown to be involved in functional specializations. DNA methylation has divergent functions in different organisms, consistent with the notion that it is a dynamically evolving mechanism that can be adapted to fulfill various functions. Genetic studies using model organisms have provided evidence suggesting the progressive integration of DNA methylation into eukaryotic developmental programs during evolution.

Animals↗

T-box genes in development: from hydra to humans.

The T-box gene family was uncovered less than a decade ago but has been recognized as important in controlling many and varied aspects of development in metazoans from hydra to humans. Extensive screening and database searching has revealed several subfamilies of genes with orthologs in species as diverse as Caenorhabditis elegans and humans. The defining feature of the family is a conserved sequence coding for a DNA-binding motif known as the T-box, named after the first-discovered T-box gene, T or Brachyury. Although several T-box proteins have been shown to function as transcriptional regulators, to date only a handful of downstream target genes have been discovered. Similarly, little is known about regulation of the T-box genes themselves. Although not limited to the embryo, expression of T-box genes is characteristically seen in dynamic and highly specific patterns in many tissues and organs during embryogenesis and organogenesis. The essential role of several T-box genes has been demonstrated by the developmental phenotypes of mutant animals.

Amino Acid Sequence↗

Developmental language learning impairments.

Developmental language learning impairments (LLI) are one of the most prevalent of all developmental disabilities, can occur in children for a wide variety of reasons, and have been shown to co-occur frequently with other developmental social, emotional and behavioral disorders, as well as with academic achievement problems. Research pertaining to developmental LLI of unknown origin, with an emphasis on the continuum between oral and written language impairment, is the focus of this review. Given the complexity of language learning, research has focused on multiple levels of analysis, including linguistic, neuropsychological, genetic, neurobiological, and remediation studies. To date, the vast majority of data on LLI derive from studies focused on a single level of analysis. Although attempts have been made to integrate data across studies and multiple levels of analysis, this has proven to be problematic, given the heterogeneity of the subject populations used to study LLI, as well as the differences in ages, degree of impairment, and types of impairment included in each study. Given that LLI is a complex developmental disability, it is suggested that future research would benefit from taking a multiple levels of analysis approach with the same individuals, incorporating mathematical models designed to analyze dynamically changing complex systems, and studying individual differences in language learning, prospectively and longitudinally, throughout the most dynamic stages of the process.

Brain↗

Developmental selection within the angiosperm style: using gamete DNA to visualize interspecific pollen competition.

Among flowering plants, females often have little control over the genetic relatedness of pollen deposited on stigmas. Thus, postpollination processes are of primary importance for mate discrimination. The ability to screen and select among male gametes during pollen tube growth within the female tissues of the stigma, style, and ovary is critical to the process of mate choice and reproductive isolation. However, direct evidence of the mechanistic/developmental processes associated with mate choice in flowering plants is sparse. We studied the contribution of postpollination, prefertilization processes to reproductive isolation in two wind-pollinated species of birch (Betula) that commonly hybridize in nature. We exploited the 3-fold difference in ploidy level between these two species to determine the paternity of individual pollen tubes growing within female reproductive tissues. We then tracked their developmental fate in conspecific, heterospecific, and mixed-species crosses. This design allowed a direct comparison of developmental processes responsible for reproductive isolation in both single-species and mixed-species pollinations. Our results have important implications for the population genetic outcome of hybridization dynamics in natural populations. Paternity analysis of progeny from mixed-species pollinations revealed that conspecific pollen tubes sired more than 98% of seedlings. Biased siring success was not the result of differential embryo abortion. We detected strong, early postpollination barriers such as pollen tube incompatibility, slower pollen tube growth, and delayed generative cell mitosis. Conspecific fertilization precedence was mediated by favorable or unfavorable male-female interactions, but there was no evidence for antagonistic male-male interactions.

Crosses, Genetic↗

Suicide among African Americans: reflections and a call to action.

Suicide among African Americans is increasing at an alarming rate, and it deserves attention from numerous sectors in the society. This paper discusses some of the historical issues related to mental health care and African Americans. It suggests that sociocultural contexts are significant developmental shapers in the lives of African Americans. Several theoretical perspectives on suicide are presented, and Durkheim's concept of fatalism is useful in helping to unravel the dynamics of suicide. Issues related to the mental health system as currently experienced by African Americans conclude the discussion, along with a brief list of helpful resources.

Adolescent↗

The role of the extracellular matrix in skeletal development.

The extracellular matrix of cartilage and bone is composed mostly of collagen with lesser amounts of other constituents such as proteoglycans. The focus of this brief review will be on the dynamic expression of collagens and proteoglycans in the cartilage and bone extracellular matrices. Recent research has shown the presence of different collagen types and proteoglycans that are differentially expressed in cartilage, in the transition from cartilage to bone, and in the bone extracellular matrices. These findings suggest the complexity of the skeletal extracellular matrix as well as its dynamic expression. Although the composition of both the cartilage and bone extracellular matrices are largely known, the function of each of the macromolecules composing these matrices and their developmental regulation is not well understood. Defects that modify the extracellular matrix, like the chicken chondrodysplasia, nanomelia, and tibial dyschondroplasia, have profound affects on skeletal structure. The poultry industry is currently confronting a high percentage of skeletal deformities due to selection for increased growth rate and needs to consider the effect of extracellular matrix modifications and how to maintain extracellular matrix integrity.

Animals↗

Seasonal and spatial variations in leaf nitrogen content and resorption in a Quercus serrata canopy.

To elucidate the relationships between spatiotemporal changes in leaf nitrogen (N) content and canopy dynamics, changes in leaf N and distribution in the canopy of a 26-year-old deciduous oak (Quercus serrata Thunb. ex. Murray) stand were monitored throughout the developmental sequence from leaf expansion to senescence, by estimating the leaf mass and N concentrations of all the canopy layers. Seasonal changes were observed in leaf N concentration per unit leaf dry mass (N (m)), which peaked after bud burst, declined for two weeks shortly thereafter, and then remained constant for the rest of the growing season for each canopy layer. Leaf N concentration per unit leaf area (N (a)) was higher in the upper layer than in the lower layer throughout the growing season, and was closely correlated with relative irradiance (RI) in the summer when the air temperature was moderately high. The N concentrations of all leaf layers started to decrease in November, and reached their lowest values in late November, whereas LMA scarcely changed throughout the season. The lowest N concentrations did not differ significantly among the canopy layers. Seasonal changes in the relationship between N (a) and RI were detected, indicating that N (a) is optimized temporally as well as spatially. Nitrogen resorption efficiency was highest in the upper canopy layers where larger amounts of N were invested. Based on the estimates of leaf mass and leaf N concentrations of the canopy layers, total leaf N concentration of the whole canopy was estimated to be 84.1 kg ha(-1) in the summer, and 37.3 kg ha(-1) in late November. Therefore, 46.8 kg ha(-1) of leaf N in the canopy (about 56% of the total N) was resorbed just before leaf abscission.

Nitrogen↗

Genome reorganisation and expansion shape 3D genome architecture and define a distinct regulatory landscape in coleoid cephalopods.

How genomic changes translate into organismal novelties is often confounded by the multi-layered nature of genome architecture and the long evolutionary timescales over which molecular changes accumulate. Coleoid cephalopods (squid, cuttlefish, and octopus) provide a unique system to study these processes due to a large-scale chromosomal rearrangement in the coleoid ancestor that resulted in highly modified karyotypes, followed by lineage-specific fusions, translocations, and repeat expansions. How these events have shaped gene regulatory patterns underlying the evolution of coleoid innovations, including their large and elaborately structured nervous systems, novel organs, and complex behaviours, remains poorly understood. To address this, we integrate Micro-C, RNA-seq, and ATAC-seq across multiple coleoid species, developmental stages, and tissues. We find that while topological compartments are broadly conserved, hundreds of chromatin loops are species- and context-specific, with distinct regulation signatures and dynamic expression profiles. CRISPR-Cas9 knockout of a putative regulatory sequence within a conserved region demonstrates the role of loops in neural development and the prevalence of long-range, inter-compartmental interactions. We propose that differential evolutionary constraints across the coleoid 3D genome allow macroevolutionary processes to shape genome topology in distinct ways, facilitating the emergence of novel regulatory entanglements and ultimately contributing to the evolution and maintenance of complex traits in coleoids.

Journal Article↗

Psychological needs and the facilitation of integrative processes.

The assumption that there are innate integrative or actualizing tendencies underlying personality and social development is reexamined. Rather than viewing such processes as either nonexistent or as automatic, I argue that they are dynamic and dependent upon social-contextual supports pertaining to basic human psychological needs. To develop this viewpoint, I conceptually link the notion of integrative tendencies to specific developmental processes, namely intrinsic motivation; internalization; and emotional integration. These processes are then shown to be facilitated by conditions that fulfill psychological needs for autonomy, competence, and relatedness, and forestalled within contexts that frustrate these needs. Interactions between psychological needs and contextual supports account, in part, for the domain and situational specificity of motivation, experience, and relative integration. The meaning of psychological needs (vs. wants) is directly considered, as are the relations between concepts of integration and autonomy and those of independence, individualism, efficacy, and cognitive models of "multiple selves."

Emotions↗

Mouse submandibular gland morphogenesis: a paradigm for embryonic signal processing.

Signal processing is the sine qua non of embryogenesis. At its core, any single signal transduction pathway may be understood as classic Information Theory, adapted as an open system such that, because of networking, the "receiver" is presented with more information than was initially signaled by the "source". Over 40 years ago, Waddington presented his "Epigenetic Landscape" as a metaphor for the hierarchical nature of embryogenesis. Mathematically, Waddington's landscape may be modeled as a neural net. The "black box" of the neural net is an interacting network of signal transduction pathways (using hormones, growth factors, cytokines, neurotransmitters, and others) which inform the Boolean logic gates. An emerging theme in developmental biology is that defined sets of epigenetic circuits are used in multiple places, at multiple times, for similar and sometimes different purposes during organogenesis. As we show here, submandibular gland embryonic and fetal development is a splendid paradigm of these epigenetic circuits and their phenotypic outcomes, such as branching and lumen formation.

Animals↗

Prevalence of dementia and impact on intellectual disability services.

In a statewide survey, dementia was found in 3% of adults age 40+; 6%, age 60+; and 12%, age 80+. Among adults with Down syndrome, the rates were 22% for adults age 40+ and 56% for adults age 60+. Observed onset occurred in the mid-60s (early 50s for those with Down syndrome). Alzheimer-type dementia was the most frequent diagnosis. With the occurrence of dementia expected to rise proportionately with the increase of longevity among adults with intellectual disabilities, care systems will have to raise the "index of suspicion" among staff and families, become "dementia capable," and improve their diagnostic and technical resources, as well as their care management supports designed to prolong the "aging in place" of adults affected by dementia.

Adult↗

Adolescent individuation and alcohol use.

OBJECTIVE: This study evaluates a developmental psychosocial model of adolescent drinking. Specifically, the role of two aspects of adolescent individuation-separation and intergenerational individuation-is examined within the context of family dynamics, stress and peer associations. These measures parallel an ongoing debate regarding the nature of individuation. The separation measure captures aspects of individuation related to detachment or rebelliousness. Intergenerational individuation measures increasing self-reliance and control with maintenance of supportive family bonds. METHOD: A structural equation model describing adolescent alcohol use as a function of two measures of individuation, family conflict, communication with mother, stress and peer use of alcohol was tested in two independent samples. The first included 6th- through 12th-grade adolescents and the second was composed of 6th- through 8th-grade students. RESULTS: In both studies, significant direct and indirect paths were found from individuation measures and family, peer use and stress constructs to adolescent alcohol use. Separation had a stronger relationship to alcohol use than did intergenerational individuation and was associated with higher levels of stress and alcohol use by peers. CONCLUSIONS: The findings support the role of individuation as a contributing factor in adolescent alcohol use. They indicate the importance of family and parent-adolescent relationships in adolescent alcohol use and suggest directions for both family-based and school-based preventive interventions.

Adolescent↗

Functional role of a specific ganglioside in neuronal migration and neurite outgrowth.

Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3) localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

Animals↗

Bilateral facial nerve palsy in the course of neuroborreliosis in children-dynamics, laboratory tests and treatment.

PURPOSE: Presentation of four patients with bilateral peripheral facial nerve palsy as a clinical manifestation of neuroborreliosis in children--diagnostic, treatment and prognosis. MATERIAL AND METHODS: In 2002-2004 in The Chair and Department of Developmental Neurology, 24 children from the Wielkopolska region were admitted with diagnosis of borreliosis. Among all the children with borreliosis, confirmed by serologic examination, 4 (16.7%) demonstrated bilateral peripheral facial palsy (PFP). We investigated the presence of IgM class and IgG class specific antibodies in the sera and cerebrospinal fluid (CSF) of 4 patients with bilateral PFP. (Detected by immunoenzymatic methods--ELISA.) RESULTS: Before the occurrence of PFP all the children manifested unspecified systemic symptoms such as headaches, muscle and articulation pains, weakness and in two cases a mood depression. At first all patients demonstrated elevated IgM antibodies and proper levels of IgG antibodies. Control tests administered within 2-14 months later reduction of antibodies was indicated. Two patients demonstrated significant pleocytosis in CSF test, (without the meningeal symptoms). All children were treated with physiotherapeutic procedures and were administered antibiotic intravenously. CONCLUSIONS: PFP is one of the most frequent neurological symptoms of borreliosis in children. In case of acute PFP and especially the bilateral form of PFP, neuroborreliosis is the most probable diagnosis. All children reported PFP at one side first and after several weeks the paresis of the facial nerve on the opposite side usually appeared. The clinical state of children started to improve after the introduction of physiotherapy and this process usually lasted several months.

Adolescent↗

A Drosophila homologue of the Schizosaccharomyces pombe act2 gene.

Diverse proteins that are 35% to 55% identical to actins have been discovered recently in yeasts, nematodes, and vertebrates. In order to study these proteins systematically and relate their functions to those of conventional actins, we are isolating the corresponding genes from the genetically tractable eukaryote, Drosophila melanogaster. Here we report the isolation and partial characterization of a Drosophila homologue of the Schizosaccharomyces pombe act2 gene. Degenerate oligonucleotide primers specifying peptides that are highly conserved within the actin protein superfamily were used in conjunction with polymerase chain reaction (PCR) to amplify a portion of the Drosophila gene that we have named actr66B. The corresponding full-length cDNA sequence encodes a protein of 418 residues that is 65% identical to the product of the S. pombe act2 gene, 80% identical to the bovine act2 homologue, but only 48% identical to the principal Drosophila cytoplasmic actin encoded by the Act5C actin gene. Alignment of the yeast, bovine, and Drosophila actin-related proteins shows that they have four peptide insertions, relative to conventional actins, three of which are well placed to modify actin polymerization and one that is likely to perturb the binding of myosin. Locations of two of the five actr66B introns are conserved between Drosophila and yeast genes, further attesting that they evolved from a common ancestor and are likely to encode proteins having similar functions. We demonstrate that the Drosophila gene is located on the left arm of chromosome 3, within subdivision 66B. Finally, we show by RNA blot-hybridization that the gene is expressed at low levels, relative to conventional nonmuscle actin, in all developmental stages. From these and other observations we infer that the actr66B protein is a minor component of all cells, perhaps serving to modify the polymerization, structure, and dynamic behavior of actin filaments.

Actins↗

The evolution of environmental and genetic sex determination in fluctuating environments.

Twenty years ago, Bulmer and Bull suggested that disruptive selection, produced by environmental fluctuations, can result in an evolutionary transition from environmental sex determination (ESD) to genetic sex determination (GSD). We investigated the feasibility of such a process, using mutation-limited adaptive dynamics and individual-based computer simulations. Our model describes the evolution of a reaction norm for sex determination in a metapopulation setting with partial migration and variation in an environmental variable both within and between local patches. The reaction norm represents the probability of becoming a female as a function of environmental state and was modeled as a sigmoid function with two parameters, one giving the location (i.e., the value of the environmental variable for which an individual has equal chance of becoming either sex) and the other giving the slope of the reaction norm for that environment. The slope can be interpreted as being set by the level of developmental noise in morph determination, with less noise giving a steeper slope and a more switchlike reaction norm. We found convergence stable reaction norms with intermediate to large amounts of developmental noise for conditions characterized by low migration rates, small differential competitive advantages between the sexes over environments, and little variation between individual environments within patches compared to variation between patches. We also considered reaction norms with the slope parameter constrained to a high value, corresponding to little developmental noise. For these we found evolutionary branching in the location parameter and a transition from ESD toward GSD, analogous to the original analysis by Bulmer and Bull. Further evolutionary change, including dominance evolution, produced a polymorphism acting as a GSD system with heterogamety. Our results point to the role of developmental noise in the evolution of sex determination.

Adaptation, Biological↗

Dynamics of sleep-wake cyclicity in developing rats.

Adult mammals cycle between periods of sleep and wakefulness. Recent assessments of these cycles in humans and other mammals indicate that sleep bout durations exhibit an exponential distribution, whereas wake bout durations exhibit a power-law distribution. Moreover, it was found that wake bout distributions, but not sleep bout distributions, exhibit scale invariance across mammals of different body sizes. Here we test the generalizability of these findings by examining the distributions of sleep and wake bout durations in infant rats between 2 and 21 days of age. In agreement with Lo et al., we find that sleep bout durations exhibit exponential distributions at all ages examined. In contrast, however, wake bout durations also exhibit exponential distributions at the younger ages, with a clear power-law distribution only emerging at the older ages. Further analyses failed to find substantial evidence either of short- or long-term correlations in the data, thus suggesting that the durations of current sleep and wake bouts evolve through time without memory of the durations of preceding bouts. These findings further support the notion that bouts of sleep and wakefulness are regulated independently. Moreover, in light of recent evidence that developmental changes in sleep and wake bouts can be attributed in part to increasing forebrain influences, these findings suggest the possibility of identifying specific neural circuits that modulate the changing complexity of sleep and wake dynamics during development.

Age Factors↗

The NASA Biosatellite Program.

The United States Biosatellite Program includes critical and sophisticated experiments to study the effects of weightlessness and decreased gravity at the cellular, tissue, organ, and organism levels during orbital periods of 3 to 30 days. The experiments involve a wide variety of plants and animals from single-celled organisms to primates. The effects of weightlessness combined with a known source of radiation will be studied to determine if there are any antagonistic or synergistic genetic or somatic effects on various organisms. Experiments are included to study the effect of removal from the Earth's rotation in relation to biological rhythms of organisms. The experimental test organisms have been exposed to the simulated dynamic forces of launch and flight profiles.

Adaptation, Physiological↗