Kinetic and cross-linking studies indicate different receptors for endothelins and sarafotoxins in the ileum and cerebellum

AbstractKinetics of ligand/receptor interactions using ET-1, ET-3 and SRTX-b were studied and cross-linking experiments carried out in guinea pig ileum and rat cerebellar preparations. Dissociation studies indicate that the two regions are characterized by different receptor subtypes and different modes of ligand binding. Autoradiographic patterns obtained following cross-linking of ET-1 and ET-3 to the different issues support these conclusions

Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms

While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds

Does the Reading of Different Orthographies Produce Distinct Brain Activity Patterns? An ERP Study

Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics), and the other is the deep unpointed script (without diacritics). Event-related potentials (ERPs) were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only). At an early visual-perceptual stage of processing (∼165 ms after target onset), the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (∼340 ms after target onset) the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography

Adaptive Evolution of the Venom-Targeted vWF Protein in Opossums that Eat Pitvipers

The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae) and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role

A transcriptomic analysis of gene expression in the venom gland of the snake Bothrops alternatus (urutu)

<p>Abstract</p> <p>Background</p> <p>The genus <it>Bothrops </it>is widespread throughout Central and South America and is the principal cause of snakebite in these regions. Transcriptomic and proteomic studies have examined the venom composition of several species in this genus, but many others remain to be studied. In this work, we used a transcriptomic approach to examine the venom gland genes of <it>Bothrops alternatus</it>, a clinically important species found in southeastern and southern Brazil, Uruguay, northern Argentina and eastern Paraguay.</p> <p>Results</p> <p>A cDNA library of 5,350 expressed sequence tags (ESTs) was produced and assembled into 838 contigs and 4512 singletons. BLAST searches of relevant databases showed 30% hits and 70% no-hits, with toxin-related transcripts accounting for 23% and 78% of the total transcripts and hits, respectively. Gene ontology analysis identified non-toxin genes related to general metabolism, transcription and translation, processing and sorting, (polypeptide) degradation, structural functions and cell regulation. The major groups of toxin transcripts identified were metalloproteinases (81%), bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%), phospholipases A₂(5.6%), serine proteinases (1.9%) and C-type lectins (1.5%). Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. Phospholipases A₂were essentially acidic; no basic PLA₂were detected. Minor toxin transcripts were related to L-amino acid oxidase, cysteine-rich secretory proteins, dipeptidylpeptidase IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and double-specificity phosphatase Dusp6, showed high sequence identity to similar proteins from other snakes. In addition to the above features, single-nucleotide polymorphisms, microsatellites, transposable elements and inverted repeats that could contribute to toxin diversity were observed.</p> <p>Conclusions</p> <p><it>Bothrops alternatus </it>venom gland contains the major toxin classes described for other <it>Bothrops </it>venoms based on trancriptomic and proteomic studies. The predominance of type PIII metalloproteinases agrees with the well-known hemorrhagic activity of this venom, whereas the lower content of serine proteases and C-type lectins could contribute to less marked coagulopathy following envenoming by this species. The lack of basic PLA₂agrees with the lower myotoxicity of this venom compared to other <it>Bothrops </it>species with these toxins. Together, these results contribute to our understanding of the physiopathology of envenoming by this species.</p

Untersuchung des Aneignungsprozesses von visuellen Wortrepräsentationen bei Kindern mit Dyslexie

Skilled reading relies on the ability to access word representations, conceptualized as connections established between a word’s orthography, phonology and meaning in memory. This study set out to explore the process of acquisition of these representations. The central hypothesis was that dyslexic readers would present difficulties in forming and maintaining word representations in memory, presumably due to instability in processes of decoding. Their performance was compared to the performance of age-matched and reading-level-matched typical readers (n = 20 per group). The hypothesis was tested by repeatedly exposing the readers to the same target words embedded in word-lists and meaningful texts. The targets were words which the dyslexic participants had difficulty to read in a pre-test, while being part of their spoken vocabulary. The output of each encounter with a target word was analyzed. The results indicate reduced accuracy rates of dyslexic readers compared to typical readers, despite the repeated exposures to the same targets. In addition, dyslexic readers showed larger variability in types of output and higher rates of inconsistency in producing the same output across encounters with the same target. The results therefore uphold the hypothesis of a deficiency of dyslexic readers in forming and retaining word representations in reading, and point to instability in processes of decoding orthography to phonology. (DIPF/Orig.)Kompetentes Lesen stützt sich auf die Fähigkeit, auf Wortrepräsentationen, d. h. die im Gedächtnis hergestellten Verbindungen zwischen der Orthographie eines Wortes, seiner Phonologie und seiner Bedeutung, zugreifen zu können. Ziel der vorliegenden Studie ist es, den Aneignungsprozess dieser Repräsentationen zu untersuchen. Die zentrale Hypothese ist dabei, dass Kinder mit Dyslexie Probleme haben, diese Repräsentationen aufzubauen und im Gedächtnis zu speichern, wobei angenommen werden kann, dass dies auf Grund einer Instabilität während des Prozesses der Wortdekodierung erfolgt. Die Leseleistung von Kindern mit Dyslexie wurde dafür verglichen mit der Leistung von Leserinnen und Lesern gleichen Alters sowie mit Leserinnen und Lesern, die auf demselben Niveau lesen (n = 20 pro Gruppe). Getestet wurde die Hypothese, indem den Leserinnen und Leser mehrmals dieselben Zielwörter vorgelegt wurden, welche in Wortlisten und sinnvolle Texte eingebettet waren. Dabei handelte es sich um Worte, bei denen die Kinder mit Dyslexie in einem Pre-Test Leseschwierigkeiten hatten, die jedoch Teil ihres gesprochenen Vokabulars waren. Analysiert wurden die Ergebnisse der jeweiligen Konfrontationen mit einem Zielwort. Die Befunde zeigen für Kinder mit Dyslexie auch bei einer wiederholten Auseinandersetzung mit denselben Zielworten geringere Genauigkeitsraten im Vergleich zu typischen Leserinnen und Lesern. Darüber hinaus ergeben sich bei den Kindern mit Dyslexie stärkere Schwankungen in der Art der Ergebnisse und mehr Inkonsistenzen, wenn es darum geht, dasselbe Ergebnis bei mehreren Konfrontationen mit demselben Zielwort wiederzugeben. Insofern stützen die Ergebnisse die Hypothese eines Defizits beim Aufbau und der Speicherung von Wortrepräsentationen während des Lesens bei Leserinnen und Leser mit Dyslexie und weisen auf eine Instabilität im Prozess des Dekodierens von Orthographie zu Phonologie hin. (DIPF/Orig.

The training of morphological decomposition in word processing and its effects on literacy skills

This study set out to examine the effects of a morpheme-based training on reading and writing in 5th and 6th graders (N=47), who have poor literacy skills and speak German as a second language. A computerized training, consisting of a visual computerized lexical decision task (comprising 2880 inflections and derivations, presented in 12 sessions), was designed to encourage fast morphological analysis in word processing. The children were divided between two groups: the one underwent a morpheme-based training, in which word-stems of words were presented for a limited duration, while pre- and suffixes remained on screen until response. Another group received a control training consisting of the same task, except that the duration of presentation of a non-morphological unit was restricted. In a Word Disruption Task, participants read words under three conditions: morphological separation (with symbols separating between the words\u27 morphemes), non-morphological separation (with symbols separating between non-morphological units of words) and no-separation (with symbols presented at the beginning and end of each word). The group receiving the morpheme-based program improved more than the control group in terms of word reading fluency in the morphological condition. The former group also presented similar word reading fluency after training in the morphological condition and the in no-separation condition, thereby suggesting that the morpheme-based training contributed to the integration of morphological decomposition into the process of word recognition. At the same time, both groups similarly improved in other measures of word reading fluency. With regard to spelling, the morpheme-based training group showed a larger improvement than the control group in spelling of trained items, and a unique improvement in spelling of untrained items (untrained word-stems integrated into trained pre- and suffixes). The results further suggest some contribution of the morpheme-based training to performance in a standardized spelling task. The morpheme-based training did not, however, show any unique effect on comprehension. These results suggest that the morpheme-based training is effective in enhancing some basic literacy skill in the population examined, i.e. morphological analysis in word processing and the access to orthographic representations in spelling, with no specific effects on reading fluency and comprehension. (DIPF/Orig.