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Sitticus inexpectus (Araneae, Salticidae) new to Italy (1998)

Torbjörn Kronestedt

In spring 1997, while "surfing" on the Internet, I came across the zoological database of "Archivio faunistico delta Laguna di Venezia". Among the species listed was Sitticus rupicola (C. L. KOCH), a species newly studied in connection with the description of the allied species Sitticus inexpectus LOGUNOV & KRONESTEDT (1997). The information in the database caught my interest because it referred to a record from an area close to the sea. While S. rupicola is confined to higher altitudes, S. inexpectus [previously confused with S. rupicola and S. caricis (WESTRING)] has been found in lowland localities, part of them close to the sea.

New records of spiders from pond littorals in the Czech Republic (1998)

Vlastimil Ruzicka Michael Holec

Tmeticus affinis (BLACKWALL, 1855), Tetragnatha shoshone LEVI, 1981, Clubiona juvenis SIMON, 1878, Marpissa Canestrinii NINNI, 1868, and Theridiosoma gemmosum (L. KOCH, 1877) are new records for the Czech Republic. New data about Enoplognatha caricis (FICKERT, 1876), Theridion hemerobium SIMON, 1914, Rugathodes instabilis (O. P. CAMBRIDGE, 1871), Tetragnatha striata L. KOCH, 1862, and Dolomedes plantarius (CLERCK, 1757) are given. The validity of the name Enoplognatha caricis (FICKERT, 1876) is supported.

Remarkable harvestmen from the Czech Republic (1998)

Leos Klimes Antonin Rousar

The fauna of harvestmen of the Czech Republic is relatively well-known (SILHAVY 1956, MARTENS 1978). Still, species new for the country have recently been found both in natural (KLlMES & BEZDECKA 1995) and synanthropic habitats (KLlMES 1995). Our knowledge of the distribution of most species is, however, far from complete. For several species, including ones found relatively frequently, only a few localities have been reported from the Czech Republic up to now. In this paper we present some interesting findings of harvestmen in Bohemia (western Czech Republic) and Moravia (eastern part) which may stimulate further faunistic research in the territory (fig. 1).

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders (2012)

Claire S. Leblond Jutta Heinrich Richard Delorme Christian Proepper Catalina Betancur Guillaume Huguet Marina Konyukh Pauline Chaste Elodie Ey Maria Rastam Henrik Anckarsäter Gudrun Nygren I. Carina Gillberg Jonas Melke Roberto Toro Beatrice Regnault Fabien Fauchereau Oriane Mercati Nathalie Lemière David Skuse Martin Poot Richard Holt Anthony P. Monaco Irma Järvelä Katri Kantojärvi Raija Vanhala Sarah Curran David A. Collier Patrick Bolton Andreas Chiocchetti Sabine M. Klauck Fritz Poustka Christine M. Freitag Regina Waltes Marnie Kopp Eftichia Duketis Elena Bacchelli Fiorella Minopoli Liliana Ruta Agatino Battaglia Luigi Mazzone Elena Maestrini Ana F. Sequeira Barbara Oliveira Astrid Vicente Guiomar Oliveira Dalila Pinto Stephen W. Scherer Diana Zelenika Marc Delepine Mark Lathrop Dominique Bonneau Vincent Guinchat Françoise Devillard Brigitte Assouline Marie-Christine Mouren Marion Leboyer Christopher Gillberg Tobias M. Boeckers Thomas Bourgeron

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Atomic-Level Structure Characterization of an Ultrafast Folding Mini-Protein Denatured State (2012)

Per Rogne Przemysław Ozdowy Christian Richter Krishna Saxena Harald Schwalbe Lars T. Kuhn

Atomic-level analyses of non-native protein ensembles constitute an important aspect of protein folding studies to reach a more complete understanding of how proteins attain their native form exhibiting biological activity. Previously, formation of hydrophobic clusters in the 6 M urea-denatured state of an ultrafast folding mini-protein known as TC5b from both photo-CIDNP NOE transfer studies and FCS measurements was observed. Here, we elucidate the structural properties of this mini-protein denatured in 6 M urea performing 15N NMR relaxation studies together with a thorough NOE analysis. Even though our results demonstrate that no elements of secondary structure persist in the denatured state, the heterogeneous distribution of R2 rate constants together with observing pronounced heteronuclear NOEs along the peptide backbone reveals specific regions of urea-denatured TC5b exhibiting a high degree of structural rigidity more frequently observed for native proteins. The data are complemented with studies on two TC5b point mutants to verify the importance of hydrophobic interactions for fast folding. Our results corroborate earlier findings of a hydrophobic cluster present in urea-denatured TC5b comprising both native and non-native contacts underscoring their importance for ultra rapid folding. The data assist in finding ways of interpreting the effects of pre-existing native and/or non-native interactions on the ultrafast folding of proteins; a fact, which might have to be considered when defining the starting conditions for molecular dynamics simulation studies of protein folding.

Hypoxia-induced alternative splicing in endothelial cells (2012)

Julia E. Weigand Jes-Niels Boeckel Pascal Gellert Stefanie Dimmeler

BACKGROUND: Adaptation to low oxygen by changing gene expression is vitally important for cell survival and tissue development. The sprouting of new blood vessels, initiated from endothelial cells, restores the oxygen supply of ischemic tissues. In contrast to the transcriptional response induced by hypoxia, which is mainly mediated by members of the HIF family, there are only few studies investigating alternative splicing events. Therefore, we performed an exon array for the genome-wide analysis of hypoxia-related changes of alternative splicing in endothelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Human umbilical vein endothelial cells (HUVECs) were incubated under hypoxic conditions (1% O(2)) for 48 h. Genome-wide transcript and exon expression levels were assessed using the Affymetrix GeneChip Human Exon 1.0 ST Array. We found altered expression of 294 genes after hypoxia treatment. Upregulated genes are highly enriched in glucose metabolism and angiogenesis related processes, whereas downregulated genes are mainly connected to cell cycle and DNA repair. Thus, gene expression patterns recapitulate known adaptations to low oxygen supply. Alternative splicing events, until now not related to hypoxia, are shown for nine genes: six which are implicated in angiogenesis-mediated cytoskeleton remodeling (cask, itsn1, larp6, sptan1, tpm1 and robo1); one, which is involved in the synthesis of membrane-anchors (pign) and two universal regulators of gene expression (cugbp1 and max). CONCLUSIONS/SIGNIFICANCE: For the first time, this study investigates changes in splicing in the physiological response to hypoxia on a genome-wide scale. Nine alternative splicing events, until now not related to hypoxia, are reported, considerably expanding the information on splicing changes due to low oxygen supply. Therefore, this study provides further knowledge on hypoxia induced gene expression changes and presents new starting points to study the hypoxia adaptation of endothelial cells.

Dealing with Varying Detection Probability, Unequal Sample Sizes and Clumped Distributions in Count Data (2012)

D. Johan Kotze Robert B. O'Hara Susanna Lehvävirta

Temporal variation in the detectability of a species can bias estimates of relative abundance if not handled correctly. For example, when effort varies in space and/or time it becomes necessary to take variation in detectability into account when data are analyzed. We demonstrate the importance of incorporating seasonality into the analysis of data with unequal sample sizes due to lost traps at a particular density of a species. A case study of count data was simulated using a spring-active carabid beetle. Traps were ‘lost’ randomly during high beetle activity in high abundance sites and during low beetle activity in low abundance sites. Five different models were fitted to datasets with different levels of loss. If sample sizes were unequal and a seasonality variable was not included in models that assumed the number of individuals was log-normally distributed, the models severely under- or overestimated the true effect size. Results did not improve when seasonality and number of trapping days were included in these models as offset terms, but only performed well when the response variable was specified as following a negative binomial distribution. Finally, if seasonal variation of a species is unknown, which is often the case, seasonality can be added as a free factor, resulting in well-performing negative binomial models. Based on these results we recommend (a) add sampling effort (number of trapping days in our example) to the models as an offset term, (b) if precise information is available on seasonal variation in detectability of a study object, add seasonality to the models as an offset term; (c) if information on seasonal variation in detectability is inadequate, add seasonality as a free factor; and (d) specify the response variable of count data as following a negative binomial or over-dispersed Poisson distribution.

No influence of dabigatran anticoagulation on hemorrhagic transformation in an experimental model of ischemic stroke (2012)

Ferdinand Bohmann Ana Mirceska Josef Martin Pfeilschifter Edelgard Lindhoff-Last Helmuth Steinmetz Christian Foerch Waltraud Pfeilschifter

Background: Dabigatran etexilate (DE) is a new oral direct thrombin inhibitor. Clinical trials point towards a favourable risk-to-benefit profile of DE compared to warfarin. In this study, we evaluated whether hemorrhagic transformation (HT) occurs after experimental stroke under DE treatment as we have shown for warfarin. Methods: 44 male C57BL/6 mice were pretreated orally with 37.5 mg/kg DE, 75 mg/kg DE or saline and diluted thrombin time (dTT) and DE plasma concentrations were monitored. Ischemic stroke was induced by transient middle cerebral artery occlusion (tMCAO) for 1 h or 3 h. We assessed functional outcome and HT blood volume 24 h and 72 h after tMCAO. Results: After 1 h tMCAO, HT blood volume did not differ significantly between mice pretreated with DE 37.5 mg/kg and controls (1.5±0.5 µl vs. 1.8±0.5 µl, p>0.05). After 3 h tMCAO, DE-anticoagulated mice did also not show an increase in HT, neither at the dose of 37.5 mg/kg equivalent to anticoagulant treatment in the therapeutic range (1.3±0.9 µl vs. control 2.3±0.5 µl, p>0.05) nor at 75 mg/kg, clearly representing supratherapeutic anticoagulation (1.8±0.8 µl, p>0.05). Furthermore, no significant increase in HT under continued anticoagulation with DE 75 mg/kg could be found at 72 h after tMCAO for 1 h (1.7±0.9 µl vs. control 1.6±0.4 µl, p>0.05). Conclusion: Our experimental data suggest that DE does not significantly increase hemorrhagic transformation after transient focal cerebral ischemia in mice. From a translational viewpoint, this indicates that a continuation of DE anticoagulation in case of an ischemic stroke might be safe, but clearly, clinical data on this question are warranted.

Diversity and Distribution Patterns in High Southern Latitude Sponges (2012)

Rachel V. Downey Huw J. Griffiths Katrin Linse Dorte Janussen

Sponges play a key role in Antarctic marine benthic community structure and dynamics and are often a dominant component of many Southern Ocean benthic communities. Understanding the drivers of sponge distribution in Antarctica enables us to understand many of general benthic biodiversity patterns in the region. The sponges of the Antarctic and neighbouring oceanographic regions were assessed for species richness and biogeographic patterns using over 8,800 distribution records. Species-rich regions include the Antarctic Peninsula, South Shetland Islands, South Georgia, Eastern Weddell Sea, Kerguelen Plateau, Falkland Islands and north New Zealand. Sampling intensity varied greatly within the study area, with sampling hotspots found at the Antarctic Peninsula, South Georgia, north New Zealand and Tierra del Fuego, with limited sampling in the Bellingshausen and Amundsen seas in the Southern Ocean. In contrast to previous studies we found that eurybathy and circumpolar distributions are important but not dominant characteristics in Antarctic sponges. Overall Antarctic sponge species endemism is ~43%, with a higher level for the class Hexactinellida (68%). Endemism levels are lower than previous estimates, but still indicate the importance of the Polar Front in isolating the Southern Ocean fauna. Nineteen distinct sponge distribution patterns were found, ranging from regional endemics to cosmopolitan species. A single, distinct Antarctic demosponge fauna is found to encompass all areas within the Polar Front, and the sub-Antarctic regions of the Kerguelen Plateau and Macquarie Island. Biogeographical analyses indicate stronger faunal links between Antarctica and South America, with little evidence of links between Antarctica and South Africa, Southern Australia or New Zealand. We conclude that the biogeographic and species distribution patterns observed are largely driven by the Antarctic Circumpolar Current and the timing of past continent connectivity.

Conformational dynamics of the tetracycline-binding aptamer (2011)

Ute Förster Julia E. Weigand Peter Trojanowski Beatrix Süß Josef Wachtveitl

The conformational dynamics induced by ligand binding to the tetracycline-binding aptamer is monitored via stopped-flow fluorescence spectroscopy and time-correlated single photon counting experiments. The fluorescence of the ligand is sensitive to changes within the tertiary structure of the aptamer during and after the binding process. In addition to the wild-type aptamer, the mutants A9G, A13U and A50U are examined, where bases important for regulation are changed to inhibit the aptamer’s function. Our results suggest a very fast two-step-mechanism for the binding of the ligand to the aptamer that can be interpreted as a binding step followed by a reorganization of the aptamer to accommodate the ligand. Binding to the two direct contact points A13 and A50 was found to occur in the first binding step. The exchange of the structurally important base A9 for guanine induces an enormous deceleration of the overall binding process, which is mainly rooted in an enhancement of the back reaction of the first binding step by several orders of magnitude. This indicates a significant loss of tertiary structure of the aptamer in the absence of the base A9, and underlines the importance of pre-organization on the overall binding process of the tetracycline-binding aptamer. Previous SectionNext Section

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