Genetic consequences of polygyny and social structure in an Indian fruit bat, Cynopterus sphinx. I. Inbreeding, outbreeding, and population subdivision

Population subdivision into behaviorally cohesive kin groups influences rates of inbreeding and genetic drift and has important implications for the evolution of social behavior. Here we report the results of a study designed to test the hypothesis that harem social structure promotes inbreeding and genetic subdivision in a population with overlapping generations. Genetic consequences of harem social structure were investigated in a natural population of a highly polygynous fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae), in western India. The partitioning of genetic variance within and among breeding groups was assessed using 10-locus microsatellite genotypes for 431 individually marked bats. Genetic analysis of the C. sphinx study population was integrated with field data on demography and social structure to determine the specific ways in which mating, dispersal, and new social group formation influenced population genetic structure. Microsatellite data revealed striking contrasts in genetic structure between consecutive offspring cohorts and between generations. Relative to the 1998 (dry-season) offspring cohort, the 1997 (wet-season) cohort was characterized by a more extensive degree of within-group heterozygote excess (F(IS) = -0.164 vs. -0.050), a greater degree of among-group subdivision (F(ST) = 0.123 vs. 0.008), and higher average within-group relatedness (r = 0.251 vs. 0.017). Differences in genetic structure between the two offspring cohorts were attributable to seasonal differences in the number and proportional representation of male parents. Relative to adult age-classes, offspring cohorts were characterized by more extensive departures from allelic and genotypic equilibria and a greater degree of genetic subdivision. Generational differences in F-statistics indicated that genetic structuring of offspring cohorts was randomized by natal dispersal prior to recruitment into the breeding population. Low relatedness among harem females (r = 0.002-0.005) was primarily attributable to high rates of natal dispersal and low rates of juvenile survivorship. Kin selection is therefore an unlikely explanation for the formation and maintenance of behaviorally cohesive breeding groups in this highly social mammal.     

Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.     

The posterior determinant gene nanos is required for the maintenance of the adult germline stem cells during Drosophila oogenesis

In a variety of tissues in eukaryotes, multipotential stem cells are responsible for maintaining a germinal population and generating a differentiated progeny. The Drosophila germline is one such tissue where a continuous supply of eggs or sperm relies on the normal functioning of stem cells. Recent studies have implicated a possible role for the posterior determinant gene nanos (nos) in stem cells. Here, I report that nanos is required in the Drosophila female germline as well as in the male germline. In the female, nos is required for the functioning of stem cells. In nos mutants, while the stem cells are specified, these cells divide only a few times at the most and then degenerate. The loss of germline stem cells in nos mutant mothers appears to be due to a progressive degeneration of the plasma membrane. Furthermore, following germ cell loss, the germaria in the nos mutant mothers appear to carry on massive mitochondrial biogenesis activity. Thus, the syncytia of such germaria are filled with mitochondria. In the male germline, the male fertility assay indicates that nos appears to be also required for the maintenance of stem cells. In these mutant males, spermatogenesis is progressively affected and these males eventually become sterile. These results indicate novel requirements for nos in the Drosophila germline.     

Enhancement of camptothecin-induced topoisomerase I cleavage complexes by the acetaldehyde adduct N2-ethyl-2'-deoxyguanosine

The activity of DNA topoisomerase I (Top1), an enzyme that regulates DNA topology, is impacted by DNA structure alterations and by the anticancer alkaloid camptothecin (CPT). Here, we evaluated the effect of the acetaldehyde-derived DNA adduct, N²-ethyl-2′-deoxyguanosine (N²-ethyl-dG), on human Top1 nicking and closing activities. Using purified recombinant Top1, we show that Top1 nicking-closing activity remains unaffected in N²-ethyl-dG adducted oligonucleotides. However, the N²-ethyl-dG adduct enhanced CPT-induced Top1–DNA cleavage complexes depending on the relative position of the N²-ethyl-dG adduct with respect to the Top1 cleavage site. The Top1-mediated DNA religation (closing) was selectively inhibited when the N²-ethyl-dG adduct was present immediately 3′ from the Top1 site (position +1). In addition, when the N²-ethyl-dG adduct was located at the −5 position, CPT enhanced cleavage at an alternate Top1 cleavage site immediately adjacent to the adduct, which was then at position +1 relative to this new alternate Top1 site. Modeling studies suggest that the ethyl group on the N²-ethyl-dG adduct located at the 5′ end of a Top1 site (position +1) sterically blocks the dissociation of CPT from the Top1–DNA complex, thereby inhibiting further the religation (closing) reaction.     

Immunolocalization and functional role of Sclerotium rolfsii lectin in development of fungus by interaction with its endogenous receptor

Many fungi are known to secrete lectins, but their functional roles are not clearly understood. Sclerotium rolfsii, a soilborne plant pathogenic fungus capable of forming fruiting bodies called sclerotial bodies, secrete a cell wall-associated Thomsen-Friedenreich antigen-specific lectin. To understand the functional role of this lectin, we examined its occurrence and expression during development of the fungus. Furthermore, putative endogenous receptors of the lectin were examined to substantiate the functional role of the lectin. Immunolocalization studies using FITC-labeled lectin antibodies revealed discrete distribution of lectin sites at the branching points of the developing mycelia and uniformly occurring lectin sites on the mature sclerotial bodies. During development of the fungus the lectin is expressed in small amounts on the vegetative mycelia and reaching very high levels in mature sclerotial bodies with a sudden spurt in secretion at the maturation stage. Capping of the lectin sites on the sclerotial bodies by lectin antibodies or haptens inhibit strongly the germination of these bodies, indicating functional significance of the lectin. At the maturation stage the lectin interacts with the cell wall-associated putative endogenous receptor leading to the aggregation of mycelium to form sclerotial bodies. The lectin-receptor complex probably acts as signaling molecule in the germination process of sclerotial bodies. Using biotinylated lectin, the receptors were identified by determining the specific lectin binding to lipid components, extracted from sclerotial bodies, and separated on thin-layer chromatograms. Preliminary characterization studies indicated that the receptors are glycosphingolipids and resemble inositolphosphoceramides. These findings together demonstrate the importance of lectin-receptor interactions to explain hitherto speculated functional role of the lectins and also the glycosphingolipids of fungi.     

Study of intestinal flow by combined videofluoroscopy, manometry, and multiple intraluminal impedance

Assessment of patterns of flow in the small bowel is difficult. Multiple intraluminal impedance has been recently used for study of flow dynamics in the esophagus. Our aims were 1) to validate multiple intraluminal impedance by correlating impedance events with intestinal flow as detected by fluoroscopy and 2) to determine intestinal flow patterns in the fasting and postprandial period and their correspondence with manometry. First, six healthy subjects underwent simultaneous video-fluoroscopic, manometric, and impedance recording from the duodenum. Videofluoroscopy was used to validate impedance patterns corresponding with barium flow in the fasting and postprandial periods. Next, 16 healthy subjects underwent prolonged simultaneous recording of impedance and manometry in both periods. Most flow events were short (10 cm or less), with antegrade flow being the most common. Correspondence between impedance and videofluoroscopy increased with increasing length of barium flow. Impedance corresponded better with flow, at any distance, than manometry. However, impedance and manometric events, when analyzed separately as index events, always corresponded with fluoroscopic flow. The fasting and postprandial periods showed comparable patterns of flow, with frequent, highly propulsive manometric and impedance sequences. Motility index was positively and significantly associated with length of impedance events. Phase 3 of the migrating motor complex could be easily recognized by impedance. Multiple intraluminal impedance can detect intestinal flow events and corresponds better with fluoroscopic flow than manometry.     

Simultaneous storage of medical images in the spatial and frequency domain: A comparative study

Background  

Digital watermarking is a technique of hiding specific identification data for copyright authentication. This technique is adapted here for interleaving patient information with medical images, to reduce storage and transmission overheads.     

Synthesis and antihyperglycemic activity profiles of novel thiazolidinedione derivatives

A number of thiazolidine-2,4-diones derivatives having carboxylic ester appendage at N-3 were synthesized and their antihyperglycemic activity was evaluated. Many of these derivatives as well as their corresponding carboxylic acid showed significant improvement on post-prandial hyperglycemia in normal rats, in contrast to their poor agonist activity at PPARgamma.