Epigenetically-Inherited Centromere and Neocentromere DNA Replicates Earliest in S-Phase

Eukaryotic centromeres are maintained at specific chromosomal sites over many generations. In the budding yeast Saccharomyces cerevisiae, centromeres are genetic elements defined by a DNA sequence that is both necessary and sufficient for function; whereas, in most other eukaryotes, centromeres are maintained by poorly characterized epigenetic mechanisms in which DNA has a less definitive role. Here we use the pathogenic yeast Candida albicans as a model organism to study the DNA replication properties of centromeric DNA. By determining the genome-wide replication timing program of the C. albicans genome, we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. Importantly, epigenetic formation of new ectopic centromeres (neocentromeres) was accompanied by shifts in replication timing, such that a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. Furthermore, changing the level of the centromere-specific histone H3 isoform led to a concomitant change in levels of ORC association with centromere regions, further supporting the idea that centromere proteins determine origin activity. Finally, analysis of centromere-associated DNA revealed a replication-dependent sequence pattern characteristic of constitutively active replication origins. This strand-biased pattern is conserved, together with centromere position, among related strains and species, in a manner independent of primary DNA sequence. Thus, inheritance of centromere position is correlated with a constitutively active origin of replication that fires at a distinct early time. We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position.     

Odontode morphology and skin surface features of Andean astroblepid catfishes (Siluriformes,Astroblepidae)

Two types of odontodes, or dermal teeth, occur in the neotropical Andean astroblepid catfishes. Both odontode types conform in structure to dermal teeth of gnathostomes in having dentine surrounding a central pulp cavity covered by a superficial layer of enameloid, but differ from one another in terms of attachment and association with other epidermis features. Type I odontodes in astroblepids, also found in all representatives of the superfamily Loricarioidea, are larger (40-50 microm base diameter), generally conical and sharply pointed, occur on the fin rays, and are associated with dermal bone. Type I odontodes attach to an elevated pediment of dermal bone of the fin lepidotrich, and to dermal bone generally in loricarioids, via a ring of connective tissue. Type II odontodes of astroblepids are smaller (15-20 microm base diameter) and blunt, occur in the skin of the head, maxillary barbels, nasal flap, and lip margins, and are not associated with dermal bone. Observations based on histology and scanning electron microscopy indicate that Type II odontodes are associated with other epithelial structures to form a putative mechanosensory organ. The odontode base lies deep in the dermis. The shaft is surrounded by a dense patch of microvillous epithelium and projects from within a pit formed by an elevated ring of laminar epithelial cells bearing several columnar, knob-like putative mechanosensory structures. Type II odontode organs have thus far been observed in only three astroblepid species, Astroblepus longifilis, A. chotae, A. rosei, where they occur in especially dense arrays on the maxillary barbels, surrounded by discrete patches of microvilli and separate mechanoreceptors. Type II odontode organs are less dense elsewhere on the body, but also occur in the skin of the snout, head, and lips. Typical taste buds are absent from the barbels of these species, but present in other astroblepids. The presence of Type II odontodes and their association with specialized epithelial pit organs are unique to astroblepids among siluriforms and may be potentially important adaptations to life in torrential mountain streams.     

The effects of cold-pretreatment,auxins and carbon source on anther culture of rice

The effects of a cold pretreatment, the concentration of different auxins (2,4-D, NAA and IAA) and the type of carbon source (maltose and sucrose) on the induction of callus from anthers of three parental lines and four rice F₁ hybrids (Japonica × Indica, Indica × Japonica) were studied. The results indicated that a cold pretreatment was essential for the induction of callus from anthers of the parental lines and the F₁ hybrids. These effects were genotype dependent. Auxins were essential for the induction of callus, and the type and concentration of auxins also influenced this process, as well as the type of carbon source. The greatest induction of callus was by the hybrid Morelos A92 × Koshihikari after a cold pretreatment of 8 days using 10.74 M –napthaleneacetic acid and 30 g l^–1 maltose.     

Altered distribution of the debrisoquine oxidative phenotypes in children with type 1 diabetes mellitus

OBJECTIVE: The recently observed increase in the incidence of type 1 diabetes mellitus (Type 1 DM) suggests a major role of environmental factors in the etiopathogenesis of the disease. The individual variation in cytochrome P(450)IID6 may influence the individual susceptibility to environmentally linked diseases. We aimed to evaluate the prevalence of cytochrome P(450)IID6 phenotypes in Hungarian children with Type 1 DM (n = 69) compared to healthy controls (n = 100). METHODS: Debrisoquine was administered orally and debrisoquine hydroxylation phenotype was determined as a metabolic ratio of urinary recovered debrisoquine and 4-hydroxydebrisoquine. RESULTS: Eight of the 100 healthy subjects (8%) and 15 of the 69 diabetic children (22%) (p < 0.05) had cytochrome P(450)IID6 poor metabolizer phenotype (metabolic ratio > or =12.6). CONCLUSION: Cytochrome P(450)IID6's activity may play a role in the development of Type 1 DM.     

Synthesis of 2,3:4,6-di-O-isopropylidene-D-allopyranose from D-glucose

2,3:4,6-Di-O-isopropylidene-d-allopyranose can be conveniently prepared from d-glucose via a synthetic sequence, which includes Mitsunobu inversion at O-3, di-O-isopropylidenation of phenyl-1-thio-d-alloside and anomeric deprotection on treatment with NBS/CaCO3.     

Dynamics of learning-induced cellular modifications in the cortex

This aim of this review is to describe the dynamics of learning-induced cellular modifications in the rat piriform (olfactory) cortex after olfactory discrimination learning and to describe their functional significance to long-term memory consolidation. The first change to occur is in the intrinsic properties of the neurons. One day after learning, pyramidal neurons show enhanced neuronal excitability. This enhancement results from reduction in calcium-dependent conductance that mediates the post burst after-hyperpolarization. Such enhanced excitability lasts for 3 days and is followed by a series of synaptic modifications. Several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons in the piriform cortex accompany olfactory learning. Enhanced synaptic release is indicated by reduced paired-pulse facilitation. Post-synaptic enhancement of synaptic transmission is indicated by reduced rise time of post-synaptic potentials and formation of new synaptic connections is indicated by increased spine density along dendrites of these neurons. Such modifications last for up to 5 days. Thus, olfactory discrimination rule learning is accompanied by a series of cellular modifications which occur and then disappear at different times. These modifications overlap partially, allowing the maintenance of the cortical system in a ‘learning mode’ in which memories for specific odors can be acquired rapidly and efficiently.     

Interpreting clone-mediated perturbations of morphogen profiles

Generating clones of mutated cells within a wild-type tissue is a powerful experimental paradigm for elucidating gene function. Recently, this approach was employed for identifying genes that shape morphogen profiles in the Drosophila wing-imaginal disc. Interpreting such experiments poses a theoretical challenge. We present a general framework that links specific features of the morphogen profile in the clone vicinity to three basic morphogen properties: diffusion, degradation, and binding to immobile elements. Our results provide rigorous criteria to examine existing data and can facilitate the design and interpretation of future clone experiments.