Characterization of kinetochores in multicentric chromosomes

Long-term cultures of certain rat and mouse cell lines carry several dicentric and some multicentric chromosomes. Using antikinetochore antibodies obtainable from serum of scleroderma (var. CREST) patients we studied the number of kinetochores formed along the length of these chromosomes. The rat cells displayed as many kinetochores as there were centromeres. However, mouse cells showed the synthesis of only one kinetochore in dicentric and multicentric chromosomes which had been in the culture for a period of 1 year or more. When translocations were induced by bleomycin in mouse L cells, the newly formed dicentric chromosomes showed the formation of two kinetochores. It is not known when the accessory centromeres lose their capacity to assemble kinetochore proteins. Possibly, in the rat the latent kinetochores lack a specific component which renders them ineffective for microtubule binding. The reason for the formation of only one kinetochore in mouse multicentric chromosomes is not clear. It may be due to the accumulation of mutations, modification of the kinetochore protein so that it lacks the antibody binding component, or a more effective regulatory gene than in the rat.     

Changes in relationships of nulliparous and parous females of Japanese monkeys at arashiyama with some aspects of troop organization

Social interactions of the adult females (nulliparous, primiparous, multiparous young, and multiparous old) of the Arashiyama-B troop of Japanese monkeys were studied. Using focal-animal and instantaneous sampling techniques, specifically identified social interactions involving allogrooming, social play, and agonism, nonspecific body-contact with and proximity to other animals were recorded from 1975 to 1978. By identifying the animals who had the above mentioned social interactions with the focal females, an attempt has been made to analyze the changes in relationships between the females of different classes and their closest kins, distant kins, and non-kins. Multiparous young females spend more time in social interactions involving allogrooming, nonspecific body-contact, and proximity than do females of the other classes and most of their social interactions are centered around their own offspring. Social interactions of the nulliparous females are fewer than those of the young mothers. But, the social interactions of the nulliparous females with their kins are much more frequent than those of the other females, i.e., once a female bears offspring, she concentrates her efforts in raising it and her social life becomes closed than before. Social interactions of the old mothers decrease and their social life is also centered more around their own young offspring. However, the social interactions of the females with non-kins, the interactions which strengthen troop integration, are independent of the class of the females. This report constitutes one part of the thesis submitted by the author to the Faculty of Science of Kyoto University in 1979 for the award of degree of Doctor of Science.     

Sequence of centromere separation: Analysis of mitotic chromosomes in man

Summary Mitotic chromosomes from human peripheral lymphocytes studied at the junction of metaphase and anaphase show that the centromeres of various chromosomes separate in a nonrandom, apparently genetically controlled sequence. It does not depend upon the position of the centromere in the chromosome, the length of the chromosome or total amount of detectable C-chromatin. In man, several chromosomes e.g. 18, 17, 2, separate very early. Such early cells do not include nos. 1, 13, 14, 15, and Y and very rarely nos. 21 and 22. The last separating chromosomes are those from group D, G, no. 1, 16, and Y. The possible implication of these findings in evolution, non-disjunction and the control of centromere separation sequences is discussed.This study was supported by a grant from National Institure of Health (GM 24591)     

Induced sex reversal in Tilapia nilotica (Cichlidae) with methyl testosterone

Gonadally undifferentiated Tilapia nilotica fry were fed with methyl testosterone at the dosage of 50 mg/kg of dry diet. The fry used in the investigation belonged to two age groups with a mean total length of 10 mm and 13.5 mm. Treatment lasted for a minimum of four weeks and a maximum of six weeks. 100% males were obtained in all the various groups under androgen treatment.     

Recombination between chloroplast genomes of Trachystoma ballii and Brassica juncea following protoplast fusion

We document here the presence of a recombinant plastome in a cytoplasmic male sterile (CMS) line of Brassica juncea developed from the somatic hybrid Trachystoma ballii?+?B. juncea. Restriction endonuclease digestion of the chloroplast (cp) DNA has revealed that the recombinant plastome gives rise to novel fragments in addition to the parent-specific fragments. Analysis of the 16S rRNA region by Southern hybridization shows no variation between B. juncea, T. ballii and the CMS line. The rbcL gene region of the recombinant plastome is identical to that in T. ballii. Analysis with probes for psbA and psbD using single and double DNA digests indicates that the hybridization patterns of the recombinant plastome are identical to those of the parents in digests obtained with some restriction enzymes, while novel bands hybridize to probes in other digests. In the psbA region, a B. juncea-specific PstI site and a T. ballii-specific EcoRI site are found in the recombinant plastome. The psbD region of the recombinant plastome contains a B. juncea-specific HindIII site and T. ballii-specific BamHI and HpaII sites. These results indicate the occurrence of intergenomic recombination between the chloroplasts of T. ballii and B. juncea in the somatic hybrid from which the CMS line was developed. The recombined plastome appears to be a mosaic of fragments specific to both parents and the recombination event has occurred in the single-copy regions. These recombinational events have not caused any imbalance in the recombinant plastome in terms of chloroplast-related functions, which have remained stable over generations.     

Broadening the genetic base of European maize heterotic pools with US Cornbelt germplasm using field and molecular marker data

Maize (Zea mays L.) breeders are concerned about the narrowing of the genetic base of elite germplasm. To reverse this trend, elite germplasm from other geographic regions can be introgressed, but due to lack of adaptation it is difficult to assess their breeding potential in the targeted environment. The objectives of this study were to (1) investigate the relationship between European and US maize germplasm, (2) examine the suitability of different mega-environments and measures of performance to assess the breeding potential of exotics, and (3) study the relationship of genetic distance with mid-parent heterosis (MPH). Eight European inbreds from the Dent and Flint heterotic groups, 11 US inbreds belonging to Stiff Stalk (SS), non-Stiff Stalk (NSS), and CIMMYT Pool 41, and their 88 factorial crosses in F₁ and F₂ generations were evaluated for grain yield and dry matter concentration. The experiments were conducted in three mega-environments: Central Europe (target mega-environment), US Cornbelt (mega-environment where donor lines were developed), and Southeast Europe (an intermediate mega-environment). The inbreds were also fingerprinted with 266 SSR markers. Suitable criteria to identify promising exotic germplasm were F₁ hybrid performance in the targeted mega-environment and F₁ and parental performance in the intermediate mega-environment. Marker-based genetic distances reflected relatedness among the inbreds, but showed no association with MPH. Based on genetic distance, MPH, and F₁ performance, we suggest to introgress SS germplasm into European Dents and NSS into European Flints, in order to exploit the specific adaptation of European flint germplasm and the excellent combining ability of US germplasm in European maize breeding programs.     

Dendritic cells induce MUC1 expression and polarization on human T cells by an IL-7-dependent mechanism

The MUC1 transmembrane mucin is expressed on the surface of activated human T cells; however, the physiologic signals responsible for the regulation of MUC1 in T cells are not known. The present studies demonstrate that IL-7, but not IL-2 or IL-4, markedly induces MUC1 expression on CD3+ T cells. MUC1 was also up-regulated by IL-15, but to a lesser extent than that found with IL-7. The results show that IL-7 up-regulates MUC1 on CD4+, CD8+, CD25+, CD69+, naive CD45RA+, and memory CD45RO+ T cells. In concert with induction of MUC1 expression by IL-7, activated dendritic cells (DC) that produce IL-7 up-regulate MUC1 on allogeneic CD3+ T cells. DC also induce MUC1 expression on autologous CD3+ T cells in the presence of recall Ag. Moreover, DC-induced MUC1 expression on T cells is blocked by a neutralizing anti-IL-7 Ab. The results also demonstrate that DC induce polarization of MUC1 on T cells at sites opposing the DC-T cell synapse. These findings indicate that DC-mediated activation of Ag-specific T cells is associated with induction and polarization of MUC1 expression by an IL-7-dependent mechanism.     

A review on coumarins as acetylcholinesterase inhibitors for Alzheimer's disease

Acetylcholinesterase (AChE) enzyme inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the main stay drugs for its management. Coumarins are the phytochemicals with wide range of biological activities including AChE inhibition. The scientists have attempted to explore the coumarin template for synthesizing novel AChE inhibitors with additional pharmacological activities including decrease in beta-amyloid (Aβ) deposition and beta-secretase inhibition that are also important for AD management. Most of the designed schemes have involved incorporation of a catalytic site interacting moiety at 3- and 4-positions of the coumarin ring. The present review describes these differently synthesized coumarin derivatives as AChE inhibitors for management of AD.     

Synthesis and evaluation of novel 4-[(3H,3aH,6aH)-3-phenyl)-4,6-dioxo-2-phenyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents

The present study was designed to synthesize and evaluate pyrrolo-isoxazole benzoic acid derivatives as potential acetylcholinesterase (AChE) inhibitors for the management of Alzheimer's disease. The synthesis of pyrrolo-isoxazole benzoic acid derivatives involved ring opening cyclization of p-aminobenzoic acid with maleic anhydride to yield maleanilic acid, which in turn afforded N-arylmaleimide via ring closed cyclization. Azomethine-N-oxides were obtained by condensation of N-arylhydroxylamine with differently substituted benzaldehydes followed by refluxing of N-arylmaleimide with differently substituted azomethine-N-oxides to pyrrolo-isoxazole benzoic acid derivatives as cis- and trans-stereoisomers. The synthesized compounds were evaluated in vitro for AChE inhibitory activity in rat brain homogenate with donepezil as standard AChE inhibitor. Thereafter, the most potent test compound was evaluated for in vitro butyrylcholinesterase inhibitory activity and in vivo memory evaluation in scopolamine (0.4mg/kg)-induced amnesia in mice by employing Morris water maze test. All pyrrolo-isoxazole benzoic acid derivatives demonstrated potent AChE inhibitory activity. Most of compounds exhibited similar activity to donepezil and four of them (7h, 7i, 8i, and 8h, IC(50)=19.1±1.9-17.5±1.5nM) displayed higher inhibitory activity as compared to donepezil (21.5±3.2nM) with compound 8ia (IC(50)=17.5±1.5nM) being the most active one. The test compound 8ia also ameliorated scopolamine-induced amnesia in mice in terms of restoration of time spent in target quadrant (TSTQ) and escape latency time (ELT). It may be concluded that pyrrolo-isoxazole benzoic acid derivatives may be employed as potential AChE inhibitors.