The role of structural symmetry in linearizing ocular reflexes

This work presents a simulation study using an anatomically relevant model of the vestibulo-ocular reflex (VOR). The aim is to explore the functional properties of a bilateral structure in the premotor circuits of the oculomotor system. The major conclusions using sinusoidal inputs are: A bilateral structure in a sensory-motor system improves its linear range beyond expected central limits, if provided with symmetric interconnections. Given a bilateral (push-pull) sensory arrangement, non-linear sensor characteristics are actually advantageous. The greatest improvement in linear range of the reflex (here VOR) relies on intact sensors on both sides. In the case of a single sensor (unilateral head velocity input), or unmatched bilateral sensors, this study predicts a decrease in the linear range and the appearance of a variable bias. These implications are compatible with available data and can be tested in a clinical invironment.     

Effects of fractionated x-irradiation on the Ly-6--Ril-1--Pol-5 region

Our laboratory has focused on defining, localizing, and understanding the mode of action of genes involved in fractionated x-irradiation (FXI) leukemia in susceptible and resistant mouse strains. We have described the genetic and molecular evidence suggesting the existence of multiple independent loci involved in FXI-induced leukemogenesis. These studies indicated that one of these, Ril-1, a locus on the distal portion of chromosome 15, is the major locus influencing susceptibility to the disease. Our data unequivocally place Ril-1 in the gene complex Ly-6--Ril-1--Sis--H-30--Pol-5. Ril-1 appears to be closest to Ly-6 and Sis. We report that in FXI-induced leukemias there are hypomethylation changes in the Ly-6 region as compared to normal thymocytes. In contrast, Sis was found to be hypermethylated and not expressed. In addition, we have noted DNA rearrangements in the Ly-6--Pol-5 region in the majority of tumors examined using the Ly-6 and spleen focus-forming virus (SFFLV) molecular probes. Increased expression of Ly-6 and other surface markers encoded in this region has been noted in FXI-induced thymomas. Address correspondence and offprint request to: N. M. B. Amari.     

Unexpected inactivation of acceptor consensus splice sequence by a −3 C to T transition in intron 2 of the CFTR gene

Human Genetics - Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Analysis of DNA from a pancreatic sufficient patient by means of...     

Protein phosphatases in higher plants: multiplicity of type 2A phosphatases in Arabidopsis thaliana

Two DNA fragments, AP-1 and AP-2, encoding amino acid sequences closely related to Ser/Thr protein phosphatases were amplified from Arabidopsis thaliana genomic DNA. Fragment AP-1 was used to screen. A. thaliana cDNA libraries and several positive clones were isolated. Clones EP8a and EP14a were sequenced and found to encode almost identical proteins (97% identity). Both proteins are 306 amino acids in length and are very similar (79–80% identity) to the mammalian isotypes of the catalytic subunit of protein phosphatase 2A. Therefore, they have been designated PP2A-1 and PP2A-2. A third cDNA clone, EP7, was isolated and sequenced. The polypeptide encoded (308 amino acids, lacking the initial Met codon) is 80% identical with human phosphatases 2A and was named PP2A-3. The PP2A-3 protein is extremely similar (95% identity) to the predicted protein from a cDNA clone previously found in Brassica napus. Southern blot analysis of genomic DNA using AP-1 and AP-2 probes, as well as probes derived from clones EP7, EP8a and EP14a strongly indicates that at least 6 genes closely related to type 2A phosphatases are present in the genome of A. thaliana. Northern blot analysis using the same set of probes demonstrates that, at the seedling stage, the mRNA levels for PP2A-1, PP2A-3 and the gene containing the AP-1 sequence are much higher than those of PP2A-2 and AP-2. These results demonstrate that a multiplicity of type 2A phosphatases might be differentially expressed in higher plants.     

Detection and minimization of H-phosphonate side reaction during phosphopeptide synthesis by a post-assembly global phosphorylation strategy

Summary In the course of solid-phase synthesis of phosphopeptides by a post-assembly global phosphorylation strategy, the corresponding H-phosphonate peptides form as byproducts. We describe model studies to investigate this side reaction as a function of reaction conditions, and use this information to develop conditions that minimize the problem, i.e., use of dibenzyl N,N-di-isopropyl phosphoramidite for phosphitylation, followed immediately by oxidation with anhydrous tert-butyl hydroperoxide in dry tetrahydrofuran under argon, and final acidolytic cleavage.This work was taken in part from the Ph.D. Theses of E.A. Ottinger (1994) and Q. Xu (1996), University of Minnesota, Minneapolis, MN, U.S.A. Preliminary presentations of portions of this work were made at the Twenty-Second European Peptide Symposium, Interlaken, Switzerland, September 13–19, 1992, see Ref. 1, at the 14th American Peptide Symposium, Columbus, OH, U.S.A., June 18–23, 1995, and at the Fourth International Symposium on Solid Phase Synthesis & Combinatorial Chemical Libraries, Edinburgh, Scotland, U.K., September 12–16, 1995, see Ref. 2. The title side reaction was first discussed for tyrosine (see Refs 1 and 3), but all of the mechanism studies discussed herein are for serine and threonine.Amino acid symbols denote the l-configuration, and abbreviations for amino acids and peptides follow rules of the IUPAC-IUB Commission of Biochemical Nomenclature [J. Biol. Chem., 247 (1972) 977].     

Speciation in monogonont rotifers

Monogonont rotifers are cyclical parthenogens livingin limnic habitats with considerable seasonalvariation and often with island-like features. Theoccurrence of bisexual reproduction in these organismsmakes it feasible to define fields for generecombination, i.e. biological species. In thispaper, we analyze the structure of the diversity inmonogonont rotifers using several data sets: taxonomicand intraspecific diversity as reported inidentification keys, morphological variation reportedin ecological studies, and allozyme and matingbehavior patterns. Our analysis suggests that siblingspecies may be frequent in rotifers. Monogonontrotifers seem to meet conditions for an activespeciation, which might be particularly promoted byseasonal specialization and timing of bisexualreproduction.     

In vivo and in vitro effects of boron on the plasma membrane proton pump of sunflower roots

The effect of boron excess and deficiency on H⁺ efflux from excised roots from sunflower ( Heliarahus annuus L. cv. Enano) seedlings and on plasma membrane H⁺-ATPase (EC 3.6.1.35) in isolated KI-washed microsomes has been investigated. When seedlings were grown in media with toxic levels of H₃BO₃ (5 m M ) or without added boron and exposed to light conditions, an inhibition of the capacity for external acidification by excised roots was observed as compared to roots from seedlings grown with optimal H₃BO₃ concentration (0.25 m M ). Toxic and deficient boron conditions also inhibited the vanadate-sensitive H⁺-ATPase of microsomes isolated from the roots. The mechanism of boron toxicity was investigated in vitro with microsorne vesicles. A strong effect of boron on the vanadate-sensitive, ATP-dependent H⁺ transport was found, but the vanadate-sensitive phospho-bydrolase activity was not affected. These results suggest that boron could exert an effect on the plasma membrane properties, directly or indirectly regulating, proton transport.     

Trisomy 11 q (q23.1 - qter) through maternal translocation t(11;22) (q23.1;q11.1). A new case]

A 4-year-old boy with partial trisomy 11q resulting from malsegregation of a maternal translocation, t(11;22)(q23.1;q11.1), exhibits the following malformations: severe mental deficiency; growth retardation and hypotonia; brachycephaly with flattened occiput and forehead; facial dysmorphia; pre-auricular fistula. These features are in good agreement with the syndrome recently described for partial trisomy 11q. The translocation appears to be identical in that in three other families already reported.     

Metabolic adaptations for isopod specialization in three species of Dysdera spiders from the Canary Islands

The spider genus Dysdera is considered to comprise specialist isopod feeders, although the degree of specialization varies between species, depending on morphological (shape of chelicerae), behavioural (attack tactics) and metabolic (food quality of prey) adaptations. Dysdera has radiated extensively in the Canary Islands (currently 47 endemic species are described) and codistributed species have different cheliceral shapes and body sizes indicating different feeding niches. In the present study, we investigate the existence of metabolic adaptations to feeding on isopods by three endemic species (Dysdera insulana Simon, Dysdera macra Simon and Dysdera verneaui Simon) from Tenerife. We hypothesize that there is enhanced extraction efficiency of fundamental macronutrients from isopods compared with control prey in species with special morphological and behavioural adaptations for this prey type. We measure quantitatively spider growth, dry mass consumption, lipid and nitrogen consumption, and calculate growth efficiency and efficiency of utilization of dry mass, lipid and nitrogen. The results show that all three species are able to utilize both prey types, indicating that none of them are strict isopod specialist. Dysdera insulana shows enhanced growth efficiency and D. macra shows enhanced nitrogen extraction efficiency compared with D. verneaui when feeding on Porcellio rather than on Musca. Both traits indicate likely adaptations for the utilization of isopods. Spider species, sex and prey type all affect lipid and nitrogen extraction efficiencies, indicating that spiders do not simply extract nutrients in the proportions available. The results support the hypothesis that adaptations for enhanced digestion of focal prey evolve in species that already have adaptations for enhanced capture success.     

Protein sieving characteristics of sub-20-nm pore size filters at varying ionic strength during nanofiltration of Coagulation Factor IX

Nanofiltration assures that protein therapeutics are free of adventitious agents such as viruses. Nanofilter pores must allow passage of protein drugs but be small enough to retain viruses. Five nanofilters have been evaluated to identify those that can be used interchangeably to yield a high purity Coagulation Factor IX product. When product preparations prior to nanofiltration were analyzed using electrophoresis, Western blot, liquid chromatography – tandem mass spectrometry and size exclusion HPLC, factor IX, inter – α – trypsin inhibitor and C4b binding protein (C4BP) were observed. C4BP was removed from product by all five nanofilters when nanofiltration was performed at physiological ionic strength. However, at high ionic strength, C4BP was removed by only two nanofilters. HPLC indicated that the Stokes radius of C4BP was larger at low ionic strength than at high ionic strength. The results suggest that C4BP exists in an open conformation at physiological ionic strength and is removed by nanofiltration whereas, at high ionic strength, the protein collapses to an extent that allows passage through some nanofilters. Manufacturers should be aware that protein contaminants in other nanofiltered protein drugs could behave similarly and conditions of nanofiltration must be evaluated to ensure consistent product purity.