Of coiled bodies,gems, and salmon

Coiled bodies (CBs) are nuclear organelles whose morphology and composition have been conserved from plants to animals. They are highly enriched in components of three different RNA processing pathways. Small nuclear RNAs (snRNAs) involved in pre-mRNA splicing, rRNA processing, and histone mRNA 3′ end maturation all take up residence in CBs. However, CB function(s) remain obscure. This review will focus on recent developments in several aspects of CB structure and function, including exciting new results on their twin organelles, called gems. In particular, the reader will be introduced to a novel hypothesis called the “salmon theory of snRNP biogenesis.” Questions arising from and experiments necessary to test this hypothesis will be discussed. J. Cell. Biochem. 70:181–192, 1998. © 1998 Wiley-Liss, Inc.     

Kinetic gait analysis in English Bulldogs

Background

Canine breed conformation may interfere with locomotion and may predispose to orthopedic disease. Bulldogs have a high incidence of orthopedic diseases such as hip dysplasia. Kinetic gait analysis provides an objective way to assess and analyze locomotion. The aim of this study was to study the vertical forces of English Bulldogs during walk using a pressure sensitive walkway. We hypothesize that Bulldogs affected by orthopedic diseases have decreased weight bearing and asymmetric locomotion in the limbs despite having mild to no sings during clinical examination. Thirty English Bulldogs were tested. Peak vertical force, vertical impulse, rate of loading, stance phase duration, symmetry index, goniometry and incidence of orthopedic diseases were recorded.

Results

Although none of the dogs showed signs of pain or discomfort upon manipulation of the hip joints, all dogs had radiographic evidences of hip dysplasia and lack of significant peak vertical force, vertical impulse and stance time differences. The dogs had a mean hind limb symmetry index of 19.8 ± 19.5% and rates of loading ranged from 1.0 to 3.1.

Conclusions

Despite the lack of evident decrease in weight bearing, subclinical lameness can be inferred. The examined dogs had a mean hind limb symmetry index of 19.8 ± 19.5%. Symmetry indices reported in dogs free from orthopedic diseases range from 0.3 to 9.6%. Given non-lame dogs are expected to have a symmetry index close to 0%, data from this study suggests that Bulldogs have gait dysfunctions, which translates into hind limb asymmetries and rate of loading was consistent with severe hip dysplasia despite no visible signs of gait dysfunction. Future studies comparing lame and non-lame Bulldogs are warranted.

     

Design, synthesis, and biological evaluation of pirenzepine analogs bearing a 1,2-cyclohexanediamine and perhydroquinoxaline units in exchange for the piperazine ring as antimuscarinics

Pirenzepine (2) is one of the most selective muscarinic M(1) versus M(2) receptor antagonists known. A series of 2 analogs, in which the piperazyl moiety was replaced by a cis- and trans-cyclohexane-1,2-diamine (3-6) or a trans- and cis-perhydroquinoxaline rings (7 and 8) were prepared, with the aim to investigate the role of the piperazine ring of 2 in the interaction with the muscarinic receptors. The structural change leading to compounds 3-6 abolished in binding assays the muscarinic M(1)/M(2) selectivity of 2, due to an increased M(2) affinity. Rather, compounds 3-6 displayed a reversed selectivity showing more affinity at the muscarinic M(2) receptor than at all the other subtypes tested.     

Human genes encoding U3 snRNA associate with coiled bodies in interphase cells and are clustered on chromosome 17p11.2 in a complex inverted repeat structure.

Coiled bodies (CBs) are nuclear organelles whose morphological structure and molecular composition have been conserved from plants to animals. Furthermore, CBs are often found to co-localize with specific DNA loci in both mammalian somatic nuclei and amphibian oocytes. Much as rDNA sequences are called nucleolus organizers, we term these coiled body-associated sequences 'coiled body organizers' (CBORs). The only sequences that have been shown to be CBORs in human cells are the U1, U2 and histone gene loci. We wanted to determine whether other snRNA genes might also act as CBORs. In this paper we show that human U3 genes (the RNU3 locus) preferentially associate with CBs in interphase cells. In addition, we have analyzed the genomic organization of the RNU3 locus by constructing a BAC and P1 clone contig. We found that, unlike the RNU1 and RNU2 loci, U3 genes are not tandemly repeated. Rather, U3 genes are clustered on human chromosome 17p11.2, with evidence for large inverted duplications within the cluster. Thus all of the CBORs identified to date are composed of either tandemly repeated or tightly clustered genes. The evolutionary and cell biological consequences of this type of organization are discussed.     

Structure and evolution of the U2 small nuclear RNA multigene family in primates: gene amplification under natural selection?

The organization of U2 genes was compared in apes, Old World monkeys, and the prosimian galago. In humans and all apes (gibbon, orangutan, gorilla, and chimpanzee), the U2 genes were organized as a tandem repeat of a 6-kb element; however, the restriction maps of the 6-kb elements in these divergent species differed slightly, demonstrating that mechanisms must exist for maintaining sequence homogeneity within this tandem array. In Old World monkeys, the U2 genes were organized as a tandem repeat of an 11-kb element; the restriction maps of the 11-kb elements in baboon and two closely related macaques, bonnet and rhesus monkeys, also differed slightly, confirming that efficient sequence homogenization is an intrinsic property of the U2 tandem array. Interestingly, the 11-kb monkey repeat unit differed from the 6-kb hominid repeat unit by a 5-kb block of monkey-specific sequence. Finally, we found that the U2 genes of the prosimian galago were dispersed rather than tandemly repeated, suggesting that the hominid and Old World monkey U2 tandem arrays resulted from independent amplifications of a common ancestral U2 gene. Alternatively, the 5-kb monkey-specific sequence could have been inserted into the 6-kb array or deleted from the 11-kb array soon after divergence of the hominid and Old World monkey lineages.