Cytogenetics of collared lemmings (Dicrostonyx groenlandicus). II. Meiotic behavior of B chromosomes suggests a Y-chromosome origin of supernumerary chromosomes

The patterns of synapsis and chiasma formation of the B chromosomes of male collared lemmings (Dicrostonyx groenlandicus) were analyzed by light and electron microscopy and compared to expectations for various hypotheses for the intragenomic origin of supernumerary chromosomes. Pachytene analysis revealed a variety of synaptic configurations including B-chromosome univalents, bivalents and trivalents. In approximately one-half of the pachytene nuclei examined, B chromosomes were in synaptic associations with the normally unpaired portion of the Y chromosome. The B-chromosome configurations at pachynema, including those involving the Y chromosome, were maintained into diakinesis and metaphase I. The meiotic behavior of the B chromosomes was inconsistent with their derivation from centric-fusion products, isochromosome formation, small-autosome polysomy, or the X chromosome. However, the frequent synapsis and apparent recombination between B chromosomes and the Y chromosome implicate this sex chromosome as a possible source of the B chromosomes in collared lemmings.     

Relationship between airway microvascular leakage, edema, and baseline airway functions

Matheson, Melissa, Ann-Christine Rynell, Melissa McClean,and Norbert Berend. Relationship between airway microvascular leakage, edema, and baseline airway functions. J. Appl. Physiol. 84(1): 77-81, 1998.This study wasdesigned to examine the relationship among microvascular leakage,edema, and baseline airway function. Microvascular leakage was inducedin the airways of anesthetized, tracheostomized New Zealand Whiterabbits (n = 22) by using nebulized N-formyl-methionyl-leucyl-phenylalanine(10 mg) and was measured in the trachea by using the Evans blue dyetechnique. Airway wall thickness was assessed morphometrically in theright main bronchus after Formalin fixation at a pressure of 25 cmH₂O. Areas calculated includedthe mucosal wall area, the adventitial wall area, the total wall area,and the percentage of total wall area consisting of blood vessels. Aneutrophil count was also performed by analyzing numbers of cells inboth the mucosal wall area and the adventitial wall area. Airwayfunction was assessed before and 30 min after challenge withN-formyl-methionyl-leucyl-phenylalanineby determining airway resistance, functional residual capacity,specific airway resistance, and flow-volume and pressure-volume curves(after paralysis of the animals with suxamethonium). The concentration of Evans blue dye in tracheal tissue ranged from 31.3 to 131.2 µg.There was a significant correlation between this concentration and boththe adventitial wall area (P < 0.01)and mucosal neutrophil numbers (P < 0.005). There was no correlation between Evans blue concentration andeither blood vessel area or changes in respiratory physiologyparameters before and after challenge. There was no significantdifference between any respiratory physiology measurements before andafter challenge. We conclude that an increase in microvascular leakagecorrelates with airway edema in the adventitia; however, these airwaychanges have no significant effect on airway elastic or resistiveproperties.

     

Identification of homologs in insignificant blast hits by exploiting extrinsic gene properties

Background  

Homology is a key concept in both evolutionary biology and genomics. Detection of homology is crucial in fields like the functional annotation of protein sequences and the identification of taxon specific genes. Basic homology searches are still frequently performed by pairwise search methods such as BLAST. Vast improvements have been made in the identification of homologous proteins by using more advanced methods that use sequence profiles. However additional improvement could be made by exploiting sources of genomic information other than the primary sequence or tertiary structure.     

Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet homeostasis

The Wnt pathway, which controls crucial steps of the development and differentiation programs, has been proposed to influence lipid storage and homeostasis. In this paper, using an unbiased strategy based on high-content genome-wide RNAi screens that monitored lipid distribution and amounts, we find that Wnt3a regulates cellular cholesterol. We show that Wnt3a stimulates the production of lipid droplets and that this stimulation strictly depends on endocytosed, LDL-derived cholesterol and on functional early and late endosomes. We also show that Wnt signaling itself controls cholesterol endocytosis and flux along the endosomal pathway, which in turn modulates cellular lipid homeostasis. These results underscore the importance of endosome functions for LD formation and reveal a previously unknown regulatory mechanism of the cellular programs controlling lipid storage and endosome transport under the control of Wnt signaling.     

RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G‐nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome‐scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE‐mediated entry. Follow‐up assays assigned these ‘hits’ to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella‐containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI‐facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs.     

Simulating the effect of alcohol on the structure of a membrane

Adsorption of alcohol molecules or other small amphiphilic molecules in the cell membrane can induce significant changes in the structure of the membrane. To understand the molecular mechanisms underlying these structural changes, we developed a mesoscopic membrane model. Molecular simulations on this model nicely reproduce the experimental phase diagrams. We find that alcohol can induce an interdigitated structure in which the normal bilayer structure changes into a monolayer in which the alcohol molecules screen the hydrophobic tails from the water phase. We compute the effect of the chain length of the alcohol on the phase behaviour of the membrane. At low concentrations of alcohol, the membrane has domains of the interdigitated phase that are in coexistence with the normal membrane phase. We use our model to clarify some of the experimental questions related to the structure of the interdigitated phase and put forward a simple model that explains the alcohol chain length dependence of the stability of this interdigitated phase.     

Evolution and function of the mitotic checkpoint

The mitotic checkpoint evolved to prevent cell division when chromosomes have not established connections with the chromosome segregation machinery. Many of the fundamental molecular principles that underlie the checkpoint, its spatiotemporal activation, and its timely inactivation have been uncovered. Most of these are conserved in eukaryotes, but important differences between species exist. Here we review current concepts of mitotic checkpoint activation and silencing. Guided by studies in model organisms and our phylogenomics analysis of checkpoint constituents and their functional domains and motifs, we highlight ancient and taxa-specific aspects of the core checkpoint modules in the context of mitotic checkpoint function.