Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium

Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel.     

An A alpha Ser-434 to N-glycosylated Asn substitution in a dysfibrinogen, fibrinogen Caracas II, characterized by impaired fibrin gel formation.

We have identified a unique N-glycosylated Asn substitution for a Ser at position 434 of the A alpha chain of an abnormal fibrinogen designated fibrinogen Caracas II. This dysfibrinogen was characterized by impaired fibrin monomer aggregation. Since there were 4 Thr residues immediately following the mutation, a new Asn-X-Thr/Ser-type consensus sequence, Asn-Thr-Thr arose for N-glycosylation of the Asn. The extra oligosaccharide was found to consist mainly of a disialylated biantennary structure comprising 81.9%, while a neutral and a monosialylated biantennary oligosaccharide represented only 3.6% and 14.5%, respectively. The mutation resides in the carboxyl-terminal region of the A alpha chain, which could fold back to form an extra small globular region located near the central region of the molecule (Erickson, H.P., and Fowler, W.E. (1983) Ann. N. Y. Acad. Sci. 408, 146-163; Weisel, H.P., Stauffacher, C.V., Bullitt, E., and Cohen, C. (1985) Science 230, 3124-3133). Therefore, the participation of this region, referred to as an additional central domain or an alpha domain, in fibrin gel formation is strongly implicated.     

Extreme differences in rates of molecular evolution of foraminifera revealed by comparison of ribosomal DNA sequences and the fossil record

Foraminifera have one of the best known fossil records among the unicellular eukaryotes. However, the origin and phylogenetic relationships of the extant foraminiferal lineages are poorly understood. To test the current paleontological hypotheses on evolution of foraminifera, we sequenced about 1,000 base pairs from the 3' end of the small subunit rRNA gene (SSU rDNA) in 22 species representing all major taxonomic groups. Phylogenies were derived using neighbor- joining, maximum-parsimony, and maximum-likelihood methods. All analyses confirm the monophyletic origin of foraminifera. Evolutionary relationships within foraminifera inferred from rDNA sequences, however, depend on the method of tree building and on the choice of analyzed sites. In particular, the position of planktonic foraminifera shows important variations. We have shown that these changes result from the extremely high rate of rDNA evolution in this group. By comparing the number of substitutions with the divergence times inferred from the fossil record, we have estimated that the rate of rDNA evolution in planktonic foraminifera is 50 to 100 times faster than in some benthic foraminifera. The use of the maximum-likelihood method and limitation of analyzed sites to the most conserved parts of the SSU rRNA molecule render molecular and paleontological data generally congruent.      

Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.     

Body proportions,microhabitat selection,and adaptive radiation of Liolaemus lizards in central Chile

Summary A biometric analysis of body proportions with presumably functional meaning for microhabitat selection was made on 12 species of Liolaemus lizards in central Chile. Characters studied were forelimb length, hindlimb length, tail length (all standardized by the corresponding snout-vent length), and the ratio forelimb/hindlimb length. It is shown that irrespective of terrestrial, saxicolous, or arboreal habits, Liolaemus species are remarkably similar in body proportions. The only exceptions are: L. lemniscatus, an open ground-dweller which exhibits significantly shorter limbs; and L. chiliensis and L. schroederi, both shrub-climbers which exhibit significantly longer tail. It is concluded that the adaptive radiation of Liolaemus lizards in central Chile has been accomplished mainly by diversification of activity time, food size, and microhabitat type. Morphological divergence in body proportions seems to have played an unimportant role.     

OBSERVATTVNS ON THE UNDERWATER LIGHT FIELD OF TWO HWERTROPHIC,SOUTH AFRICAN IMPOUNDMENTS

SUMMARY

The spectral composition of the underwater light field was examined in two hypertrophic South African Impoundments (Hartbeespoort and Roodeplaat Dams) under a range of inorganic turbidities and chlorophyll α concentrations. The data indicated that inorganic turbidity and gilvin were dominant to chlorophyll in regulating underwater light attenuation during the present study. Under all conditions the wavelengths between 405 and 510 nm were attenuated more rapidly than near UV and the wavelengths above 510 nm and the 623 nm component penetrated deepest. Under low turbidities the 546 nm wavelength was the next most penetrating component, but its attenuation increased with increasing turbidity. This characteristic of the underwater light field may be important to the cyanobacteria which dominate in these hypertrophic lakes.     

A comparative assessment of plant flammability through a functional approach: The case of woody species from Argentine Chaco region

Recent changes to fire regimes in many regions of the world have led to renewed interest in plant flammability experiments to understand and predict the consequences of such changes. These experiments require the development of practical and standardised flammability testing protocols. The research aims were (i) to compare plant flammability assessments carried out using two different approaches, namely functional trait analysis and testing with a shoot‐level device; and (ii) to evaluate the effect of disturbances and seasonal variability on flammability. The study area was located in the Western Chaco region, Argentina, and 11 species were selected based on their representativeness in forests. We studied six functional traits related to flammability, growth habit and foliar persistence, in forests without disturbances over the three last decades as well as in disturbed forests. The seasonal variation of these functional traits was evaluated over two consecutive years. Functional trait flammability index (FI) and shoot‐level measurements followed standard protocols. Sixty per cent of the species measured presented a high to very high FI. The results of both assessment methods were significantly correlated. Both methods identified the same species as having medium flammability, but differed in regards to the most flammable species. Senegalia gilliesii was identified as the most flammable species when using functional trait analysis, whereas shoot‐level assessments found Larrea divaricata and Schinus johnstonii to be the most flammable. There were no disturbance effects on the FI but there was seasonal variation. Our results validate the use of functional traits as a predictive method of flammability testing and represent the first global effort comparing flammability obtained through functional trait analysis with empirical measurements. The significant correlation between both methods allows the selection of the one that is more appropriate for the size of the area to be evaluated and for the availability of technical resources. Abstract in Spanish is available with online material.     

Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families

BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17% of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.