Translocation (13q21q)

Summary A (13q21q) translocation was found in an infant with Down's syndrome. The 17-year-old mother and the grandmother carried the translocation 45,XX,t(13;21)(p12;q11). The great grandparents had normal karyotypes. Fluorescence marker studies suggested that the translocation originated in the great grandmother. The hypothesis was supported by satellite association studies which showed a significant excess of 13–21 and 13–15 associations in the great grandmother.     

A polarized epithelial cell mutant deficient in translocation of UDP-galactose into the Golgi complex

Two lectin-resistant mutants derived from a polarized epithelial cell line have been described (Meiss, H.K., Green, R.F., and Rodriguez-Boulan, E.J. (1982) Mol. Cell. Biol. 2, 1287-1294). One of these mutants, the Madin-Darby canine kidney strain II cell line resistant to Ricinus communis agglutinin (MDCKII-RCAr), has been further characterized, and the biochemical defect leading to its altered phenotype has been determined. MDCKII-RCAr cells are shown to be enriched in cell-surface glycoconjugates bearing terminal N-acetylglucosamine residues by in vitro exogalactosylation and by labeling with fluorescent lectins. Binding assays with a sialic acid-specific lectin reveal a 70-75% reduction in sialylation of cell-surface glycoconjugates. The defect is pleiotropic in nature, affecting glycoproteins as well as glycosphingolipids. Analysis of glycosphingolipids shows a strong reduction of galactose-containing glycosphingolipids. Almost 90% of the glycosphingolipids are identified as glucosyl-ceramide. The mutant is not deficient in galactosyl- and sialytransferase activities. However, Golgi vesicles isolated from MDCKII-RCAr cells translocate UDP-galactose at only 2% of the rate observed for vesicles from wild-type MDCKII cells. The deficiency is specific, because translocation rates of UDP-N-acetylglucosamine and CMP-sialic acid are comparable for vesicles isolated from MDCKII-RCAr cells and wild-type cells. Despite the inability to translocate UDP-galactose into the lumen of the Golgi apparatus, MDCKII-RCAr cells are able to form monolayers with normal apical and basolateral polarity as shown by plasma membrane domain-restricted exogalactosylation.     

Untreated asymptomatic bacteriuria in girls: I--Stability of urinary isolates.

OBJECTIVE--To assess the frequency of spontaneous changes of bacterial strains in patients with untreated asymptomatic bacteriuria. DESIGN--Retrospective analysis of samples from all patients with renal scarring and random sample of patients with normal kidneys. SETTING--Outpatient clinic for children with urinary tract infections. PATIENTS--54 Girls aged 3.3-15.5 years with untreated asymptomatic bacteriuria caused by Escherichia coli. INTERVENTION--None. END POINT--Change in bacterial strain. MEASUREMENTS AND RESULTS--Serotyping and electrophoretic analysis of sequential bacterial isolates, representing 151 patient years of untreated asymptomatic bacteriuria. A total of 24 changes of strain were identified. Eleven were related to medical interference such as treatment of other infections with antibiotics. CONCLUSIONS--Spontaneous changes of strain were uncommon, one change in 11.6 patient years, and thus are not a characteristic feature of the course of asymptomatic bacteriuria.     

Evolution of insect olfaction

Neuroethology utilizes a wide range of multidisciplinary approaches to decipher neural correlates of natural behaviors associated with an animal's ecological niche. By placing emphasis on comparative analyses of adaptive and evolutionary trends across species, a neuroethological perspective is uniquely suited to uncovering general organizational and biological principles that shape the function and anatomy of the nervous system. In this review, we focus on the application of neuroethological principles in the study of insect olfaction and discuss how ecological environment and other selective pressures influence the development of insect olfactory neurobiology, not only informing our understanding of olfactory evolution but also providing broader insights into sensory processing.     

Gall midge olfaction: Pheromone sensitive olfactory neurons in Contarinia nasturtii and Mayetiola destructor

This study describes the morphology and function of the antennal sensilla in two gall midge species, Contarinia nasturtii and Mayetiola destructor, where multi-component sex pheromones have been identified. Both species possess sensilla trichodea, s. coeloconica, s. chaetica and s. circumfila. Sensilla circumfila, which consist of several sensilla that bifurcate and fuse into one structure, are unique for the gall midges. In C. nasturtii s. circumfila are sexually dimorphic. In males, they form elongated loops suspended on cuticular spines, whereas in females they run like worm-like structures directly on the antennal surface. Single sensillum recordings demonstrated that olfactory sensory neurons housed in male s. circumfila in C. nasturtii responded to the female sex pheromone. In M. destructor, s. circumfila were attached to the antennal surface in both sexes, and displayed no response to sex pheromone components.A sexual dimorphism was also found in the number of s. trichodea per antennal segment in both C. nasturtii (male 1 vs. female 7) and M. destructor (male 13 vs. female 10). OSNs located in male M. destructor s. trichodea responded to the sex pheromone. This is the first gall midge single sensillum study, and the first demonstration of the functional significance of s. circumfila.     

Pen-2 is sequestered in the endoplasmic reticulum and subjected to ubiquitylation and proteasome-mediated degradation in the absence of presenilin

The gamma-secretase complex catalyzes intramembrane proteolysis of a number of transmembrane proteins, including amyloid precursor protein, Notch, ErbB4, and E-cadherin. gamma-Secretase is known to contain four major protein constituents: presenilin (PS), nicastrin, Aph-1, and Pen-2, all of which are integral membrane proteins. There is increasing evidence that the formation of the complex and the stability of the individual components are tightly controlled in the cell, assuring correct composition of functional complexes. In this report, we investigate the topology, localization, and mechanism for destabilization of Pen-2 in relation to PS function. We show that PS1 regulates the subcellular localization of Pen-2: in the absence of PS, Pen-2 is sequestered in the endoplasmic reticulum (ER) and not transported to post-ER compartments, where the mature gamma-secretase complexes reside. PS deficiency also leads to destabilization of Pen-2, which is alleviated by proteasome inhibitors. In keeping with this, we show that Pen-2, which adopts a hairpin structure with the N and C termini facing the luminal space, is ubiquitylated prior to degradation and presumably retrotranslocated from the ER to the cytoplasm. Collectively, our data suggest that failure to become incorporated into the gamma-secretase complex leads to degradation of Pen-2 through the ER-associated degradation-proteasome pathway.     

No Diagnostic Value of Plasma Clusterin in Alzheimer's Disease

There is an urgent need for biomarkers to enable early diagnosis of Alzheimer''s disease (AD). It has recently been shown that a variant within the clusterin gene is associated with increased risk of AD and plasma levels of clusterin have been found to be associated with the risk of AD. We, therefore, investigated the diagnostic value of clusterin by quantifying clusterin using an ELISA in plasma from 171 controls, 127 patients with AD, 82 patients with other dementias and 30 patients with depression. We observed similar plasma clusterin levels in controls, AD patients and patients with other dementias, suggesting that plasma clusterin levels have no diagnostic value for AD. There was a slight, but significant, increase in plasma clusterin in patients with depression compared to all other groups tested, which may warrant further investigation.     

Bacterial community diversity in paper mills processing recycled paper

Paper mills processing recycled paper suffer from biofouling causing problems both in the mill and final product. The total bacterial community composition and identification of specific taxa in the process water and biofilms at the stock preparation and paper machine areas in a mill with recycled paper pulp was described by using a DNA-based approach. Process water in a similar mill was also analyzed to investigate if general trends can be found between mills and over time. Bacterial community profiles, analyzed by terminal-restriction fragment length polymorphism (T-RFLP), in process water showed that the dominant peaks in the profiles were similar between the two mills, although the overall composition was unique for each mill. When comparing process water and biofilm at different locations within one of the mills, we observed a separation according to location and sample type, with the biofilm from the paper machine being most different. 16S rRNA gene clone libraries were generated and 404 clones were screened by RFLP analysis. Grouping of RFLP patterns confirmed that the biofilm from the paper machine was most different. A total of 99 clones representing all RFLP patterns were analyzed, resulting in sequences recovered from nine bacterial phyla, including two candidate phyla. Bacteroidetes represented 45% and Actinobacteria 23% of all the clones. Sequences with similarity to organisms implicated in biofouling, like Chryseobacterium spp. and Brevundimonas spp., were recovered from all samples even though the mill had no process problems during sampling, suggesting that they are part of the natural paper mill community. Moreover, many sequences showed little homology to as yet uncultivated bacteria implying that paper mills are interesting for isolation of new organisms, as well as for bioprospecting.     

Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis

Calpain is a ubiquitous protease with potential involvement in apoptosis. We report that in human melanoma cells, cisplatin-induced calpain activation occurs early in apoptosis. Calpain activation and subsequent apoptosis were inhibited by calpeptin and PD150606, two calpain inhibitors with different modes of action. Furthermore, cisplatin induced cleavage of the BH3-only protein Bid, yielding a 14-kDa fragment similar to proapoptotic, caspase-cleaved Bid. However, Bid cleavage was inhibited by inhibitors of calpain, but not by inhibitors of caspases or of cathepsin L. Recombinant Bid was cleaved in vitro by both recombinant calpain and by lysates of cisplatin-treated cells. Cleavage was calpeptin sensitive, and the cleavage site was mapped between Gly70 and Arg71. Calpain-cleaved Bid induced cytochrome c release from isolated mitochondria. While calpeptin did not affect cisplatin-induced modulation of Bak to its proapoptotic conformation, a dominant-negative mutant of MEKK1 (dnMEKK) inhibited Bak modulation. dnMEKK did not, however, block Bid cleavage. The combination of dnMEKK and calpeptin had an additive inhibitory effect on apoptosis. In summary, calpain-mediated Bid cleavage is important in drug-induced apoptosis, and cisplatin induces at least two separate apoptotic signaling pathways resulting in Bid cleavage and Bak modulation, respectively.