Sequence S1 Research Articles

Glutamate Binding and Conformational Flexibility of Ligand-binding Domains Are Critical Early Determinants of Efficient Kainate Receptor Biogenesis

Intracellular glutamate binding within the endoplasmic reticulum (ER) is thought to be necessary for plasma membrane expression of ionotropic glutamate receptors. Here we determined the importance of glutamate binding to folding and assembly of soluble ligand-binding domains (LBDs), as well as full-length receptors, by comparing the secretion of a soluble GluR6-S1S2 protein versus the plasma membrane localization of GluR6 kainate receptors following mutagenesis of the LBD. The mutations were designed to either eliminate glutamate binding, thereby trapping the bilobate LBD in an "open" conformation, or "lock" the LBD in a closed conformation with an engineered interdomain disulfide bridge. Analysis of plasma membrane localization, medium secretion of soluble LBD proteins, and measures of folding efficiency suggested that loss of glutamate binding affinity significantly impacted subunit protein folding and assembly. In contrast, receptors with conformationally restricted LBDs also exhibited decreased PM expression and altered oligomeric receptor assembly but did not exhibit any deficits in subunit folding. Secretion of the closed LBD protein was enhanced compared with wild-type GluR6-S1S2. Our results suggest that glutamate acts as a chaperone molecule for appropriate folding of nascent receptors and that relaxation of LBDs from fully closed states during oligomerization represents a critical transition that necessarily engages other determinants within receptor dimers. Glutamate receptor LBDs therefore must access multiple conformations for efficient biogenesis.

Discriminative learning in sequential pattern recognition

In this article, we studied the objective functions of MMI, MCE, and MPE/MWE for discriminative learning in sequential pattern recognition. We presented an approach that unifies the objective functions of MMI, MCE, and MPE/MWE in a common rational-function form of (25). The exact structure of the rational-function form for each discriminative criterion was derived and studied. While the rational-function form of MMI has been known in the past, we provided the theoretical proof that the similar rational-function form exists for the objective functions of MCE and MPE/MWE. Moreover, we showed that the rational function forms for objective functions of MMI, MCE, and MPE/MWE differ in the constant weighting factors CDT (s1 . . . sR) and these weighting factors depend only on the labeled sequence s1 . . . sR, and are independent of the parameter set - to be optimized. The derived rational-function form for MMI, MCE, and MPE/MWE allows the GT/EBW-based parameter optimization framework to be applied directly in discriminative learning. In the past, lack of the appropriate rational-function form was a difficulty for MCE and MPE/MWE, because without this form, the GT/EBW-based parameter optimization framework cannot be directly applied. Based on the unified rational-function form, in a tutorial style, we derived the GT/EBW-based parameter optimization formulas for both discrete HMMs and CDHMMs in discriminative learning using MMI, MCE, and MPE/MWE criteria. The unifying review provided in this article has been based upon a large number of earlier contributions that have been cited and discussed throughout the article. Here we provide a brief summary of such background work. Extension to large-scale speech recognition tasks was accomplished in the work of [59] and [60]. The dissertation of [47] further improved the MMI criterion to that of MPE/MWE. In a parallel vein, the work of [20] provided an alternative approach to that of [41], with an attempt to more rigorously provide a CDHMM model re-estimation formula that gives positive growth of the MMI objective function. A crucial error of this attempt was corrected in [2] for establishing an existence proof of such positive growth. The main goal of this article is to provide an underlying foundation for MMI, MCE, and MPE/MWE at the objective function level to facilitate the development of new parameter optimization techniques and to incorporate other pattern recognition concepts, e.g., discriminative margins [66], into the current discriminative learning paradigm.

<i>vacA</i> Genotypes of <i>Helicobacter pylori</i> in Relation to <i>cagA</i> Status and Clinical Outcomes in Iranian Populations

Mosaicism in vacA alleles with two distinct families of vacA signal sequences (s1 and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. Research suggests that the vacA s1 genotype is closely associated with duodenal ulcer disease and with high cytotoxin production. The aims of this study were to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, and clinical presentation in Iranian populations. Genomic DNA of biopsy specimens from patients with gastritis, peptic ulcer disease (PUD), or gastric cancer (GC) were characterized based on ureC (glmM), cagA, and vacA genotyping by using polymerase chain reaction. Of 167 patients including 33 with PUDs, 129 with non-ulcer dyspepsia (NUD), and 5 with GC, 96 (57.5%) cases were infected by Helicobacter pylori. Among these patients, H. pylori were isolated from 19 (57.7%) PUD patients, 74 (68.7%) NUD patients, and 3 (60%) GC patients. The cagA was detected in 76% of H. pylori-positive cases. The vacA s1-m2 genotype was the most prevalent in 7/19 PUD (37%) and 30/74 NUD (40.5%) patients with H. pylori infection. The prevalence of vacA s2-m1 (8%) was high in Iranian isolates. A significant association was not found between H. pylori genotypes and clinical outcomes. The vacA genotypes and cagA status were not useful markers for gastroduodenal diseases in Tehran, Iran.

Role of sea-level forced sedimentary processes on the distribution of organic carbon-rich marine sediments: A review of the Late Quaternary sapropels in the Mediterranean Sea

The 124 ka to present sapropel S5–S1 series in the eastern Mediterranean Sea, correspond to the last Glacial–Interglacial period, and permit detailed investigation of 5th order sedimentary frequencies. The Sapropel layers are clustered in high-frequency Milankovian cycle that occur within sequence stratigraphic 4th order cycles of late Pleistocene-Holocene sea-level oscillations. The sea-level changes had an amplitude exceeding 120 m and have been correlated to the glacial-interglacial cycles modulated by the 100 ka eccentricity. Using published data we examined occurrences of the complete S5–S1 series in the Mediterranean Sea and then we focussed on two stratigraphic sequences in the central Adriatic shelf and Middle Adriatic Depression where sapropels S5 and S1 were deposited during periods of sea-level rise recorded by the Transgressive Systems Tract (Marine Isotopic Stage 5 and 1, respectively). Sapropels S4 and S3 were deposited during the Highstand Systems Tract, that developed throughout MIS 5 of the late Pleistocene sequence. Sapropel S2 should have been deposited during the warm MIS 3.3 and followed the MIS 4 sea-level drop when sediment supply was enhanced during the late highstand and falling stage of sea-level of the late Pleistocene sequence. The pronounced MIS 2 cold stage led to a lowstand and to the regional erosional surface (Sequence Boundary). We also compared the Adriatic sapropel S5–S2 sequence (4th order) to the Mid-Pliocene cluster “O” sequence (3rd order). In both cases, sapropels are well formed before the increase of sediment supply due to progradation of the shelf wedge, that occurs in the late high stand and initial falling stage in sea-level. Finally, we considered the influence of sea-level lowering which could cause a weakening of North Adriatic Deep Water formation, therefore influencing the Mediterranean deep water circulation. This condition would favour oxygen depletion, but it does not correspond to a well developed sapropel (as in the case of S2). Based on the assumption that productivity increases related to insolation play a dominant role in their sedimentation, sapropel S2 is the result of low amplitude insolation maxima, that were unable to generate a productivity increase leading to the burial of conspicuous amount of organic matter. Therefore, in the Adriatic Sea the absence of the S2 sapropel is correlated to the high sedimentation rate diluting the signal, whereas in the eastern Mediterranean basin this sapropel is virtually absent because of a weak orbital forcing combined with oxidation that erased its record.

Space Efficient Computation of Rare Maximal Exact Matches between Multiple Sequences

In this article, we propose a new method for computing rare maximal exact matches between multiple sequences. A rare match between k sequences S(1), ... , S(k) is a string that occurs at most t(i)-times in the sequence S(i), where the t(i) > 0 are user-defined thresholds. First, the suffix tree of one of the sequences (the reference sequence) is built, and then the other sequences are matched separately against this suffix tree. Second, the resulting pairwise exact matches are combined to multiple exact matches. A clever implementation of this method yields a very fast and space efficient program. This program can be applied in several comparative genomics tasks, such as the identification of synteny blocks between whole genomes.

Seismic stratigraphy, tectonics and depositional history in the Halk el Menzel region, NE Tunisia

In the Halk el Menzel area, the proximal- to pelagic platform transition and related tectonic events during the Upper Cretaceous–Lower Miocene have not been taken into adequate consideration. The integrated interpretation of outcrop and subsurface data help define a seismic stratigraphic model and clarify the geodynamic evolution of the Halk el Menzel block. The sedimentary column comprises marls and limestones of the Campanian to Upper Eocene, overlain by Oligocene to Lower Miocene aged siliciclastics and carbonates. Well to well correlations show sedimentary sequences vary considerably in lithofacies and thicknesses over short distances with remarkable gaps. The comparison of sedimentary sequences cut by borehole and seismic stratigraphic modelling as well help define ten third order depositional sequences (S1–S10). Sequences S1 through S6 (Campanian–Paleocene) are mainly characterized by oblique to sigmoid configurations with prograding sedimentary structures, whereas, sequences S7–S10 (Ypresian to Middle Miocene) are organized in shallow water deposits with marked clinoform ramp geometry. Sedimentary discontinuities developed at sequence boundaries are thought to indicate widespread fall in relative sea level. Angular unconformities record a transpressive tectonic regime that operated from the Campanian to Upper Eocene. The geometry of sequences with reduced thicknesses, differential dipping of internal seismic reflections and associated normal faulting located westerly in the area, draw attention to a depositional sedimentary system developed on a gentle slope evolving from a tectonically driven steepening towards the Northwest. The seismic profiles help delimit normal faulting control environments of deposition. In contrast, reef build-ups in the Eastern parts occupy paleohighs NE–SW in strike with bordering Upper Maastrichtian-Ypresian seismic facies onlapping Upper Cretaceous counterparts. During the Middle–Upper Eocene, transpressive stress caused reactivation of faults from normal to reverse play. This has culminated in propagation folds located to the west; whereas, the eastern part of the block has suffered progressive subsidence. Transgressive carbonate depositional sequences have predominated during the Middle Miocene and have sealed pre-existing tectonic structures.

A Faster and More Space-Efficient Algorithm for Inferring Arc-Annotations of RNA Sequences through Alignment

The nested arc-annotation of a sequence is an important model used to represent structural information for RNA and protein sequences. Given two sequences S1 and S2 and a nested arc-annotation P1 for S1, this paper considers the problem of inferring the nested arc-annotation P2 for S2 such that (S1, P1) and (S2, P2) have the largest common substructure. The problem has a direct application in predicting the secondary structure of an RNA sequence given a closely related sequence with known secondary structure. The currently most efficient algorithm for this problem requires O(nm3) time and O(nm2) space where n is the length of the sequence with known arc-annotation and m is the length of the sequence whose arc-annotation is to be inferred. By using sparsification on a new recursive dynamic programming algorithm and applying a Hirschberg-like traceback technique with compression, we obtain an improved algorithm that runs in min{O(nm2 + n2m),O(nm2 log n), O(nm3)} time and min{O(m2 + mn), O(m2 log n + n)} space.

Sequence elements critical for efficient RNA editing of a tobacco chloroplast transcript in vivo and in vitro.

In tobacco chloroplast transcripts 34 nt are efficiently edited to U. No common consensus region is present around all editing sites; however, sites can be grouped in clusters that share short common sequences. Transgene transcripts carrying either the wild-type −31/+22 or −31/+60 sequence near NTrpoB C473, an editing site within tobacco rpoB transcripts, or three different mutated sequences, were all highly edited in vivo. Endogenous transcripts of rpoB, psbL and rps14, all of which contain common sequences S1, S2 and S3 5′ to NTrpoB C473, NTpsbL C2 and NTrps14 C80, were less edited in transgenic plants that over-express transcripts from NTrpoB C473 transgenes. Extent of reduction of endogenous editing differed between transgenic lines expressing mutated −31/+22 regions, depending on the abundance of the transgene transcripts. The −20/−5 sequence contains critical 5′ sequence elements. Synthetic RNA templates with alterations within this 5′ region were less efficiently edited in vitro than wild-type templates, by either tobacco or maize chloroplast extracts. The tobacco chloroplast extract supports both RNA editing and processing of 3′ transcript termini. We conclude that within the −20/−5 region, sequences common to editing sites in the transcripts of rpoB, psbL and rps14 are critical for efficient NTrpoB C473 editing.

Helicobacter pylori vacAs1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution

To establish the most common vacA alleles in Helicobacter pylori (H pylori) strains isolated from Chilean patients and its relationship with gastritis and gastroduodenal ulcers. Two hundred and forty five H pylori clinical isolates were obtained from 79 biopsies from Chilean infected patients suffering from gastrointestinal diseases. An average of 2-3 strains per patient was isolated and the vacA genotype was analyzed by PCR and 3% agarose electrophoresis. Some genotypes were checked by DNA sequencing. The most prevalent vacA genotype in Chilean patients was s1b m1 (76%), followed by s1a m1 (21%). In contrast, the s2 m2 genotype was scarcely represented (3%). The s1b m1 genotype was found most frequently linked to gastropathies (P<0.05) rather than ulcers. Ulcers were found more commonly in male and older patients. Curiously, patients living in cities located North and far South of Santiago, the capital and largest Chilean city, carried almost exclusively strains with the s1b m1 genotype. In contrast, patients from Santiago and cities located South of Santiago carried strains with either one or both s1a m1 and s1b m1 genotypes. Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that Chilean s2 sequence was identical to those of Australian, American, and Colombian strains but quite different from those of Alaska and India. Differences in geographic distribution of the s and m vacA alleles in Chile and a relationship of s1b m1 genotype with gastritis were found. Sequence data in part support a hispanic origin for the vacA genotype. Asymmetric distribution of genotypes s1b m1 and s2 m2 recedes H Pylori strain distribution in Spain and Portugal.

Hard problems in similarity searching

The Closest Substring Problem is one of the most important problems in the field of computational biology. It is stated as follows: given a set of t sequences s1,s2,...,st over an alphabet @S, a...

Immunological, structural, and preliminary X-ray diffraction characterizations of the fusion core of the SARS-coronavirus spike protein

The SARS-CoV spike protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two peptides denoted HR-N(SN50) and HR-C(SC40), corresponding to the Leu/Ile/Val-rich heptad-repeat regions from the N-terminal and C-terminal segments of the SARS-CoV spike S2 sequence, respectively, were synthesized and predicted to form trimeric assembly of hairpin-like structures. The polyclonal antibodies produced by recombinant S2 protein were tested for antigenicity of the two heptad repeats. We report here the first crystallographic study of the SARS spike HR-N/HR-C complex. The crystal belongs to the triclinic space group P1 and the data-set collected to 2.98Å resolution showed noncrystallographic pseudo-222 and 3-fold symmetries. Based on these data, comparative modeling of the SARS-CoV fusion core was performed. The immunological and structural information presented herein may provide a more detailed understanding of the viral fusion mechanism as well as the development of effective therapy against SARS-CoV infection.

Tectonic control on the evolution of the fluvial systems of the Vinchina Formation (Miocene), northwestern Argentina

The Miocene Vinchina Formation accumulated in a large foreland basin is related to the uplift of the Andes Mountains. This 5100m thick unit was mostly deposited in fluvial environments, but short episodes of eolian and lacustrine sedimentation also occurred. Low-angle intraformational unconformities and dramatic facies changes define three depositional sequences. Sequence S1 is composed of sandstones and mudstones deposited in anastomosing river systems during a period of tectonic quiescence. Sequence S2, formed by conglomerates and sandstones with scarce intercalations of mudstones, rests on a low-angle erosional surface and represents deposition in fluvial braided systems. S2 probably resulted from progradation of clastic wedges after an episode of uplift of the fold-thrust belt. Sequence S3, dominated by sandstones, mudstones, and sparse intraformational conglomerates, was deposited in ephemeral braided and meandering rivers governed by a complex balance between subsidence and supply. Fluvial styles in the Vinchina Formation allowed the recognition of three major stages in the foreland basin evolution. During the underfilled stage (S1), high subsidence rates favored the development of axial anastomosing rivers with well-preserved floodplain sediments. Early post-tectonic sedimentation marks initial overfilled conditions (S2), characterized by high sediment supply and progradation of clastic wedges as braided rivers deposits. Finally, more advanced overfilled conditions (S3) were reached when sediment supply matched subsidence, giving birth to ephemeral braided and meandering systems.

Helicobacter pylori: análisis de cagA y genotipificación de vacA en Chile. Detección de una cepa s2/m1

The genes cagA and vacA encode H pylori virulence factors. To genotype these genes in H pylori strains isolated from patients with upper gastrointestinal symptoms. We studied 50 patients who underwent an upper gastrointestinal endoscopy, with positive culture for H pylori. Detection of cagA and vacA genotyping was done using polymerase chain reactions. The gene cagA was detected in 19 samples (38%). Signal sequences s1 and s2 of vacA gene were detected in 16 samples each (32%). There was simultaneous amplification of s1 and s2 in 6 samples and they were not detected in 9 samples. The middle region of vacA was m1 in 9 samples, m2 in 29 samples and there was simultaneous amplification of m1 and m2 in 12 samples. In 16 samples (32%), more than one type of signal sequence or medial region was detected. Of those patients in whom vacA was the only genotype detected, 15 were s2/m2, 7 were s1/m1, 4 were s1/m2 and 1 was s2/m1. In these patients, the infection with cagA- H pylori strains, predominates, the prevalence of infection with s1 or s2 strains is similar and the predominant medial region is m2.

Screening of drug resistance-related genes from human ovarian cancer cell line OC3/ADR by DD-PCR

Objective: To screen novel genes related to adriamycin (Adr) resistance from human ovarian cancer resistance cell line OC3/Adr. Methods: Multidrug resistant ovarian cancer cell line OC3/Adr was induced by intermittent treatment of the human parent cell line OC3 with high concentration Adr. The difference of gene expression was screened by using different display analysis to the acquired Adr-resistance subline OC3/Adr and its parent cell line OC3. Results: OC3/Adr cell line was obtained which was more resistance to Adr than the parent cell line OC3 with the resistance index (RI) of 15.4. The OC3/Adr cell line also showed cross-resistance to other anti-cancer drugs (VP16, CDDP,5FU). It grew slowly and exhibited changes of cell cycle. A number of differentially expressed ESTs (Expressed Sequence Tags, ESTs) were identified at mRNA level between the OC3/Adr and OC3. Four of 18 different ESTs were sequenced. The 431/432 base pair S1 was homologous to human sperm zona pellucida binding protein, while the other two ESTs, S3 and S4, were new gene segments, which were registered to GenBank with the number of AF 117656 and AF 126507 respectively. Particularly, the expression of S2 sequence increased in all the drug-resistance cell lines and S3 sequence overexpressed in human ovarian cancer tissues as compared with benign ovarian tumors. Conclusion: Drug resistance induced by Adr in ovarian cancer OC3/Adr is involved with changes of multiple gene expressions.

On Score Sequences ofk-Hypertournaments

Given two nonnegative integers n and k withn≥k> 1, a k -hypertournament on n vertices is a pair (V, A), where V is a set of vertices with | V | =n and A is a set of k -tuples of vertices, called arcs, such that for any k -subset S ofV , A contains exactly one of the k!k -tuples whose entries belong to S. We show that a nondecreasing sequence (r1, r2,⋯ , rn) of nonnegative integers is a losing score sequence of a k -hypertournament if and only if for each j(1 ≤j≤n),with equality holding whenj=n. We also show that a nondecreasing sequence (s1,s2 ,⋯ , sn) of nonnegative integers is a score sequence of somek -hypertournament if and only if for each j(1 ≤j≤n),with equality holding whenj=n. Furthermore, we obtain a necessary and sufficient condition for a score sequence of a strong k -hypertournament. The above results generalize the corresponding theorems on tournaments.

One-step polymerase chain reaction-based typing of Helicobacter pylori vacA gene: association with gastric histopathology.

Heterogeneity of the Helicobacter pylori vacA gene may be associated with bacterial virulence and presentation. In this study, the possible correlation between vacA genotypes and gastric histopathology was investigated. Using a modified one-step polymerase chain reaction (PCR)-based method, 122 of 131 H. pylori isolates obtained from 63 of 67 patients from Germany were classified into distinct vacA genotypes according to their signal sequence (s1 or s2) and their midregion alleles (m1 or m2). A possible subtype of ml, now alluded to as m3, was identified in one-third of the isolates. Signal sequence s1 was significantly associated with higher H. pylori density but not with gastric inflammation parameters as compared with s2. Compared with m2, ml initially appeared to correlate with higher mononuclear cell scores in corpus, although not with H. pylori density. Upon differentiation between ml and m3, however, only the latter was associated with the high cell scores. Moreover, m3 also correlated with a higher antral H. pylori density. Positive cagA status correlated significantly with vacA signal sequence s1, and higher gastric mononuclear cell scores and corpus neutrophil score. H. pylori density was always associated with enhanced gastric neutrophil and corpus mononuclear cell scores. These data indicate a significant association of specific vacA genotypes with enhanced bacterial density and gastric inflammation. PCR-based identification of the respective alleles can now easily be performed in the diagnostic laboratory using a one-step PCR assay.

Evidence that a single EF-Ts suffices for the recycling of multiple and divergent EF-Tu species in Streptomyces coelicolor A3(2) and Streptomyces ramocissimus.

The tsf genes from Streptomyces coelicolor A3(2) and Streptomyces ramocissimus, encoding the guanine-nucleotide exchange factor EF-Ts, were cloned and sequenced. Streptomycetes have multiple and highly divergent EF-Tu species, with EF-Tu1 and EF-Tu3 showing only about 65% amino acid sequence identity, and yet these can apparently interact with a single EF-Ts species. tsf lies in an operon with rpsB, which encodes ribosomal protein S2. The amino acid sequence of S2 from S. coelicolor differs from most other bacterial S2 homologues in having a C-terminal extension of 70 aa residues with a highly repetitive organization, the function of which is unknown. Transcription analysis of the rpsB-tsf operon of S. coelicolor by promoter probing, nuclease S1 mapping and Northern blotting revealed that the genes give rise to a bicistronic transcript from a single promoter upstream of rpsB. An attenuator was identified in the rpsB-tsf intergenic region; it results in an approximately 2:1 ratio of rpsB vs tsf transcripts. Although tuf1, encoding the major EF-Tu, is located in the rpsL ribosomal protein operon, an additional promoter in the fus-tuf1 intergenic region leads to a significant excess of EF-Tu over ribosomes. Most amino acid residues known from the Escherichia coli crystal structure of the EF-Tu-EF-Ts complex to be directly involved in interaction between the two elongation factors are conserved between E. coli and Streptomyces. However, whenever interaction residues in the EF-Tu moiety show divergence among Streptomyces EF-Tu1, EF-Tu2 and EF-Tu3, the single Streptomyces EF-Ts exhibits compensatory substitutions of the corresponding residues. These apparently enable productive interaction to occur with all three EF-Tus.

Capping and dynamic relation between domains 1 and 2 of gelsolin.

Gelsolin is a protein that severs and caps actin filaments. The two activities are located in the N-terminal half of the gelsolin molecules. Severing and subsequent capping requires the binding of domains 2 and 3 (S2-3) to the side of the filaments to position the N-terminal domain 1 (S1) at the barbed end of actin (actin subdomains 1 and 3). The results provide a structural basis for the gelsolin capping mechanism. The effects of a synthetic peptide derived from the sequence of a binding site located in gelsolin S2 on actin properties have been studied. CD and IR spectra indicate that this peptide presented a secondary structure in solution which would be similar to that expected for the native full length gelsolin molecule. The binding of the synthetic peptide induces conformational changes in actin subdomain 1 and actin oligomerization. An increase in the polymerization rate was observed, which could be attributed to a nucleation kinetics effect. The combined effects of two gelsolin fragments, the synthetic peptide derived from an S2 sequence and the purified segment 1 (S1), were also investigated as a molecule model. The two fragments induced nucleation enhancement and inhibited actin depolymerization, two characteristic properties of capping. In conclusion, for the first time it is reported that the binding of a small synthetic fragment is sufficient to promote efficient capping by S1 at the barbed end of actin filaments.

Capping and dynamic relation between domains 1 and 2 of gelsolin

Gelsolin is a protein that severs and caps actin filaments. The two activities are located in the N-terminal half of the gelsolin molecules. Severing and subsequent capping requires the binding of domains 2 and 3 (S2–3) to the side of the filaments to position the N-terminal domain 1 (S1) at the barbed end of actin (actin subdomains 1 and 3). The results provide a structural basis for the gelsolin capping mechanism. The effects of a synthetic peptide derived from the sequence of a binding site located in gelsolin S2 on actin properties have been studied. CD and IR spectra indicate that this peptide presented a secondary structure in solution which would be similar to that expected for the native full length gelsolin molecule. The binding of the synthetic peptide induces conformational changes in actin subdomain 1 and actin oligomerization. An increase in the polymerization rate was observed, which could be attributed to a nucleation kinetics effect. The combined effects of two gelsolin fragments, the synthetic peptide derived from an S2 sequence and the purified segment 1 (S1), were also investigated as a molecule model. The two fragments induced nucleation enhancement and inhibited actin depolymerization, two characteristic properties of capping. In conclusion, for the first time it is reported that the binding of a small synthetic fragment is sufficient to promote efficient capping by S1 at the barbed end of actin filaments. ©1998 European Peptide Society and John Wiley & Sons, Ltd.

Ramp facies and sequence stratigraphic models in an epeiric sea: the Upper Ordovician mixed carbonate-siliciclastic Glenwood and Platteville Formations, Wisconsin, USA

Abstract Variability in lithofacies and depositional environments of the Upper Ordovician mixed carbonate-siliciclastic Glenwood and Platteville Formations in Wisconsin are studied and analysed within a sequence framework. Two depositional sequences are identified in these strata. Sequence boundaries correspond to identified and interpreted exposure surfaces with or without angular discordance. These surfaces mark an abrupt upward increase in shale, and correspond to widespread discontinuity surfaces interpreted to represent time-stratigraphic breaks. Sequences show a base with either sandstones or shales grading upward into carbonate lithologies devoid of terrigenous clastic deposits. Cycles are the smallest stratigraphic packages of regional significance (tens to hundreds of kilometres) and correspond to interpreted upward-shallowing successions. Cycle attributes change from sequence to sequence. Depositional environments are interpreted similarly to many ancient carbonate ramps. Sequence S1 contains diverse facies indicating deposition in wide palaeowater depth ranges from tidal-flat to deep subtidal outer ramp environments. Rapid lateral facies change with irregular spatial distribution observed in sequence S1 is interpreted to be related to the high ramp gradient and irregular antecedent topography during deposition of sequence S1. Facies succession in sequence S2 shows upward changes from storm-dominated mid-ramp to low-energy inner ramp environments without intervening high-energy shallow-water shoal belts. This differs from most storm-dominated carbonate ramp facies models in the geological record, in which storm bed rich mid-ramp deposits show transition to inner ramp successions that contain shoreface barrier sediments such as ooid-skeletal grainstone and boundstone. This model is interpreted as a consequence of infrequency of significant wave activity, in which incoming oceanic waves lost their energy very gradually over a wide area. Without inherited topography, the broad epeiric sea modified circulation and the overall result is a decrease in energy landward. A low wave-energy, microtidal, storm-dominated ramp model is postulated for such successions.