bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of complex pathways from observational data
Authors: Baurley James W. , Conti David V. , Gauderman W. James , Thomas Duncan C.
Published: June 2010

Unraveling complex interactions has been a challenge in epidemiologic research. We introduce a pathway modeling framework that discovers plausible pathways from observational data, and allows estimation of both the net effect of the pathway and the types of interactions occurring among genetic or environmental risk factors. Each discovered pathway structure links combinations of observed variables through intermediate latent nodes to a final node, the outcome. Biologic knowledge can be readily applied in this framework as a prior on pathway structure to give preference to more biologically plausible models, thereby providing more precise estimation of Bayes factors for pathways of greatest interest by Markov Chain Monte Carlo (MCMC) methods.

Data were simulated for binary inputs of which only a subset was involved in different pathway topologies. Our algorithm was then used to recover the pathway from the simulated data. The posterior distributions of inputs, pairwise and higher‐order interactions, and topologies were obtained by MCMC methods. The evidence in favor of a particular pathway or interaction was summarized using Bayes factors. Our method can correctly identify the risk factors and interactions involved in the simulated pathway. We apply our framework to an asthma case–control data set with polymorphisms in 12 genes. Copyright © 2010 John Wiley & Sons, Ltd.
The ‘distressed’ personality, coping and cardiovascular risk
Authors: Martin Luci A. , Doster Joseph A. , Critelli Joseph W. , Purdum Michael , Powers Catherine , Lambert Paul L. , Miranda Vanessa
Published: June 2010

Type D (or ‘distressed’) personality has shown success in predicting hard medical outcomes (e.g. morbidity and mortality) in cardiac patients. Little is known about the relationship between Type D individuals prior to disease, or the role that coping may play in individuals with the distressed personality. The present study examined the relationships among Type D Personality, coping strategies, and heart rate variability (HRV) in a non‐medical sample of young adults. Social supportive coping was found to moderate the relationship between Type D personality and HRV. Additionally, as compared to non‐Type Ds, Type D individuals more often relied on avoidant forms of coping, and they less often relied on positive/problem focused strategies or social support to cope. Implications for primary prevention and future research were discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Continuous multiparametric monitoring of cell metabolism in response to transient overexpression of the sirtuin deacetylase SIRT3
Authors: Dransfeld Christian-Lars , Alborzinia Hamed , Wölfl Stefan , Mahlknecht Ulrich
Published: June 2010

The analysis and visualisation of research data in an environment which is most similar to living conditions belong to the most challenging claims of present scientific research endeavours. To date, the effect of protein function on cell metabolism is most commonly assessed from a series of end point analyses, which finally allows an approximate estimation on how a specific effect takes its course. In the study presented herein, we demonstrate how the combination of transient transfection and a biosensor chip system gives the opportunity to analyse the effect of a specific protein on cell metabolism in living cells through real-time monitoring of metabolically relevant parameters, such as oxygen consumption, acidification rate and cell adhesion. In addition, this method allows online monitoring of the time course of metabolic changes due to changes in expression levels of metabolic regulative proteins from the time of transfection to maximum overexpression. The methodology presented herein was assessed for the transient overexpression of the sirtuin deacetylase SIRT3, a mitochondrial key element in the regulation of energy metabolism, metabolic disease, cancer and ageing.
Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain
Authors: Schröder Wolfgang , De Vry Jean , Tzschentke Thomas M. , Jahnel Ulrich , Christoph Thomas
Published: June 2010

The novel analgesic tapentadol combines μ‐opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule and shows potent analgesia in various rodent models of pain. We analyzed the contribution of opioid and monoaminergic mechanisms to the activity of tapentadol in rat models of nociceptive and neuropathic pain. Antinociceptive efficacy was inferred from tail withdrawal latencies of experimentally naive rats using a tail flick test. Antihypersensitive efficacy was inferred from ipsilateral paw withdrawal thresholds toward an electronic von Frey filament in a spinal nerve ligation model of mononeuropathic pain. Dose–response curves of tapentadol (intravenous) were determined in combination with vehicle or a fixed dose (intraperitoneal) of the μ‐opioid receptor antagonist naloxone (1 mg/kg), the α2‐adrenoceptor antagonist yohimbine (2.15 mg/kg), or the serotonin 5‐HT2Areceptor antagonist ritanserin (0.316 mg/kg). Tapentadol showed clear antinociceptive and antihypersensitive effects (>90% efficacy) with median effective dose (ED50) values of 3.3 and 1.9 mg/kg, respectively. While the antinociceptive ED50value of tapentadol was shifted to the right 6.4‐fold by naloxone (21.2 mg/kg) and only 1.7‐fold by yohimbine (5.6 mg/kg), the antihypersensitive ED50value was shifted to the right 4.7‐fold by yohimbine (8.9 mg/kg) and only 2.7‐fold by naloxone (5.2 mg/kg). Ritanserin did not affect antinociceptive or antihypersensitive ED50values of tapentadol. Activation of both μ‐opioid receptors and α2‐adrenoceptors contribute to the analgesic effects of tapentadol. The relative contribution is, however, dependent on the particular pain indication, as μ‐opioid receptor agonism predominantly mediates tapentadol's antinociceptive effects, whereas noradrenaline reuptake inhibition predominantly mediates its antihypersensitive effects.
Evolution of MHC class I genes in two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis)
Authors: Wang Dengqiang , Zhong Lei , Wei Qiwei , Gan Xiaoni , He Shunping
Published: June 2010

Here we present the first isolation of major histocompatibility complex (MHC) class I genes from two ancient fish, paddlefish (Polyodon spathula) and Chinese sturgeon (Acipenser sinensis). Seventeen sequences obtained showed high polymorphism and positive natural selection with d
N/d
S
> 1. Evolutionary relationships revealed that sequences from paddlefish and Chinese sturgeon distinguished from other vertebrate class I and had an intermingling of alleles, which indicates that Acipenseriformes have a common ancestral gene of class I and a trans‐species polymorphism across Acipenseriformes. We also found clear evidence of recombination among class I genes of paddlefish and Chinese sturgeon.
Assaying and investigating Alternative Lengthening of Telomeres activity in human cells and cancers
Authors: Henson Jeremy D. , Reddel Roger R.
Published: June 2010

Alternative Lengthening of Telomeres (ALT) activity can be deduced from the presence of telomere length maintenance in the absence of telomerase activity. More convenient assays for ALT utilize phenotypic markers of ALT activity, but only a few of these assays are potentially definitive. Here we assess each of the current ALT assays and their implications for understanding the ALT mechanism. We also review the clinical situations where availability of an ALT activity assay would be advantageous. The prevalence of ALT ranges from 25% to 60% in sarcomas and 5% to 15% in carcinomas. Patients with many of these types of ALT[+] tumors have a poor prognosis.
PPARγ in adipocyte differentiation and metabolism – Novel insights from genome‐wide studies
Authors: Siersbæk Rasmus , Nielsen Ronni , Mandrup Susanne
Published: June 2010

Adipocyte differentiation is controlled by a tightly regulated transcriptional cascade in which PPARγ and members of the C/EBP family are key players. Here we review the roles of PPARγ and C/EBPs in adipocyte differentiation with emphasis on the recently published genome‐wide binding profiles for PPARγ and C/EBPα. Interestingly, these analyses show that PPARγ and C/EBPα binding sites are associated with most genes that are induced during adipogenesis suggesting direct activation of many more adipocyte genes than previously anticipated. Furthermore, an extensive overlap between the C/EBPα and PPARγ cistromes indicate a hitherto unrecognized direct crosstalk between these transcription factors. As more genome‐wide data emerge in the future, this crosstalk will likely be found to include several other adipogenic transcription factors.
Metformin compared with glyburide for the management of gestational diabetes
Authors: Silva Jean Carl , Pacheco Carina , Bizato Juliana , de Souza Bárbara Vicente , Ribeiro Thaís Engel , Bertini Anna Maria
Published: June 2010

Objective

To assess blood glucose control and neonatal outcomes when women with gestational diabetes mellitus (GDM) were treated with metformin or glyburide.

Methods

When an appropriate diet was insufficient to control their blood glucose levels, women with GDM were randomized to a glyburide or a metformin treatment group. If the maximum dose was reached, the assessed drug was replaced by insulin. The primary outcome measures analyzed were maternal glucose levels during pregnancy, birth weight, and neonatal glucose levels.

Results

The only significant difference in outcome between the 2 treatment drugs was that maternal weight gain during pregnancy was less in the metformin (n = 40) than in the glyburide group (n = 32) (10.3 kg vs 7.6 kg; P = 0.02). No differences were found in treatment failure, mean level of fasting or postprandial plasma glucose, rate of participants with glycated hemoglobin, birth weight, rate of large‐for‐gestational‐age newborns, or newborns with hypoglycemia.

Conclusion

The treatment of GDM with metformin or glyburide was found to be equivalent for both women and newborns.
Cytogenomics of cancers: From chromosome to sequence
Authors: Bernheim Alain
Published: June 2010

The role of acquired chromosomal rearrangements in oncogenesis (cytogenomics) and tumor progression is now well established. These alterations are multiple and diverse and the products of these rearranged genes play an essential role in the transformation and growth of cancer cells. The validity of this assumption is demonstrated by the development of specific inhibitors or antibodies that eliminate tumoral cells by targeting some of these changes. Imatinib, an inhibitor of the tyrosine kinase ABL, the prototype of these targeting drugs, is yielding complete remissions in most CML patients. Knowledge of chromosomal abnormalities is becoming an essential contribution to the diagnosis and prognosis of cancers but also for monitoring minimal residual disease or relapse. The concept of the “cytogenetic uniqueness” of each cancer has resulted in personalized treatment. This investigation will expound upon, besides the recurrent genomic alterations, the numerous products of perverted Darwinian selection at the cellular level.
New Zealand's strategic interests in Antarctica
Authors: Brady Anne-Marie
Published: June 2010

New Zealand has important strategic interests in Antarctica that are as much about geography and the country's geostrategic needs, as they are about history and the politics of maintaining rights gained in an earlier era. This paper outlines the reasons behind New Zealand's involvement in and commitment to Antarctica; profiles the various bodies involved in maintaining and negotiating New Zealand's Antarctic presence and voice on Antarctic affairs; and discusses New Zealand's core interests in the Antarctic continent that help to shape its Antarctic policy.
Away from ethnocentrism and anthropocentrism: Towards a scientific understanding of “what makes us human”
Authors: Boesch Christophe
Published: June 2010

The quest to understand “what makes us human” has been heading towards an impasse, when comparative psychology compares primarily individuals that are not representative of their species. Captives experience such divergent socioecological niches that they cannot stand for their wild counterparts. Only after removing ethnocentrism and anthropocentrism will we be able to progress in our understanding of “what makes us human.”
Wired but not WEIRD: The promise of the Internet in reaching more diverse samples
Authors: Gosling Samuel D. , Sandy Carson J. , John Oliver P. , Potter Jeff
Published: June 2010

Can the Internet reach beyond the U. S. college samples predominant in social science research? A sample of 564,502 participants completed a personality questionnaire online. We found that 19% were not from advanced economies; 20% were from non-Western societies; 35% of the Western-society sample were not from the United States; and 66% of the U. S. sample were not in the 18–22 (college) age group.
REGIONAL VERSUS STANDARDIZED COINAGE IN EARLY MODERN JAPAN: THE TOKUGAWA KAN'EI TSŪHŌ 寛永通宝
Authors: Yasukuni Ryoichi , Sekimori Gaynor
Published: June 2010

In the currency system of early modern Japan, concurrent with gold coins and silver ingots issued under monopoly by the Tokugawa shogunal government from the beginning of its rule, in 1636 a new standard for copper coins was introduced with the Kan'ei tsūhō 寛永通宝, and subsequently a three-currency system spread throughout the country. Prior to that, no central Japanese authority had issued its own copper currency since the ancient imperial court discontinued minting coins bearing its own era-names in the tenth century. In the late sixteenth and early seventeenth century, imitation Chinese Song copper coins minted domestically, known as kyōsen 京銭, played an indispensable role in interregional payments, while separate regional coinages circulated in many of the feudal domains. Imitation Song coins from Japan were also in such strong demand in Southeast Asia that merchants Japanese as well as foreign made large profits by exporting them. The decision to mint the Kan'ei tsūhō arose in part from a strategy to unify the currency domestically, and also to prevent further production and export of the kyōsen at a time when the Tokugawa government was seeking to limit and control foreign trade. This study explores the context in which the Kan'ei tsūhō was introduced, drawing on both documentary and archaeological evidence, to establish a more comprehensive picture of the new coinage than has previously been available. It will be demonstrated that currency unification within the Japanese archipelago represented a breakaway from the East Asian currency sphere, which was dominated by purer silver ingots and Song coins, both originals and later imitations. As a result of the diffusion of the Kan'ei tsūhō, coins circulating domestically tended to become increasingly homogenized nationwide, though in fact a greater degree of regionality and stratification remained than has previously been thought.
Power transmission and particle acceleration along the Io flux tube
Authors: Hess S. L. G. , Delamere P. , Dols V. , Bonfond B. , Swift D.
Published: June 2010

Io's motion relative to the Jovian magnetic field generates a power of about 1012 W, which is thought to propagate as an Alfvén wave along the magnetic field line. This power is transmitted to the electrons, which will then precipitate and generate the observed auroral phenomena from UV to radio wavelengths. A more detailed look at this hypothesis shows some difficulties: Can the Alfvén waves escape the torus or are they trapped inside? Where and how are the particles accelerated? In which direction? Is there enough power transmitted to the particles to explain the strong brightness of the auroral emissions in UV, IR, visible, and radio? In other words, can we make a global, consistent model of the Io‐Jupiter interaction that matches all the observations? To answer these questions, we review the models and studies that have been proposed so far. We show that the Alfvén waves need to be filamented by a turbulent cascade process and accelerate the electrons at high latitude in order to explain the observations and to form a consistent scheme of the Io‐Jupiter interaction.
Functional implications of sterol transport by the oxysterol-binding protein gene family
Authors: Ngo Mike H. , Colbourne Terry R. , Ridgway Neale D.
Published: June 2010

Cholesterol and its numerous oxygenated derivatives (oxysterols) profoundly affect the biophysical properties of membranes, and positively and negatively regulate sterol homoeostasis through interaction with effector proteins. As the bulk of cellular sterols are segregated from the sensory machinery that controls homoeostatic responses, an important regulatory step involves sterol transport or signalling between membrane compartments. Evidence for rapid, energy-independent transport between organelles has implicated transport proteins, such as the eukaryotic family of OSBP (oxysterol-binding protein)/ORPs (OSBP-related proteins). Since the founding member of this family was identified more than 25 years ago, accumulated evidence has implicated OSBP/ORPs in sterol signalling and/or sterol transport functions. However, recent evidence of sterol transfer activity by OSBP/ORPs suggests that other seemingly disparate functions could be the result of alterations in membrane sterol distribution or ancillary to this primary activity.
The Language Phenotype of Children and Adolescents With Noonan Syndrome
Authors: Pierpont Elizabeth I. , Ellis Weismer Susan , Roberts Amy E. , Tworog-Dube Erica , Pierpont Mary Ella , Mendelsohn Nancy J. , Seidenberg Mark S.
Published: June 2010

Purpose

This study presents an analysis of language skills in individuals with Noonan syndrome (NS), an autosomal dominant genetic disorder. We investigated whether the language impairments affecting some individuals arise from deficits specifically within the linguistic system or whether they are associated with cognitive, perceptual, and motor factors. Comparisons of language abilities among the different NS genotypes were also conducted.

Method

Sixty-six children and adolescents with NS were evaluated using standardized speech, language, and literacy assessments. Additional cognitive, perceptual, and motor tasks were administered to examine the relation of these factors to language development. Genotype was noted for those who underwent genetic testing.

Results

Language impairments were more frequent in NS than in the general population and were associated with higher risk for reading and spelling difficulties. Language was significantly correlated with nonverbal cognition, hearing ability, articulation, motor dexterity, and phonological memory. Genotype analyses suggest that the higher performance of
SOS1-
positive than
PTPN11-
positive individuals on language tasks was largely mediated by differences in cognitive ability.

Conclusions

Our results indicate that variation in language skill in NS is closely related to cognitive, perceptual, and motor factors. It does not appear that specific aspects of language are selectively affected in this syndrome.
Differentiating the Effects of Phonotactic Probability and Neighborhood Density on Vocabulary Comprehension and Production: A Comparison of Preschool Children With Versus Without Phonological Delays
Authors: Storkel Holly L. , Maekawa Junko , Hoover Jill R.
Published: June 2010

Purpose

To differentiate the effect of phonotactic probability from that of neighborhood density on a vocabulary probe administered to preschool children with or without phonological delays.

Method

Twenty preschool children with functional phonological delays and 34 preschool children with typical language development completed a 121-item vocabulary probe in both an expressive and receptive response format. Words on the vocabulary probe orthogonally varied on phonotactic probability and neighborhood density but were matched on age of acquisition, word frequency, word length, semantic set size, concreteness, familiarity, and imagability.

Results

Results show a Phonotactic Probability × Neighborhood Density interaction with variation across groups. Specifically, the optimal conditions for typically developing children were rare phonotactic probability with sparse neighborhoods and common phonotactic probability with dense neighborhoods. In contrast, only rare phonotactic probability with sparse neighborhoods was optimal for children with phonological delays.

Conclusions

Rare sound sequences and sparse neighborhoods may facilitate triggering of word learning for typically developing children and children with phonological delays. In contrast, common sound sequences and dense neighborhoods may facilitate configuration and engagement for typically developing children but not for children with phonological delays because of their weaker phonological and/or lexical representations.
The Fock space method of vibrational analysis
Authors: Jung Christof , Taylor Howard S.
Published: June 2010

A reformulation of a semiclassical theory that presently seems uniquely capable of interpreting generic complex multiresonant vibrational spectra is presented. Once given the spectroscopic Hamiltonian which reveals the set of possible resonant couplings and its eigenstates, the new and old formulations both yield without any further computation level by level dynamical assignments for the spectra. Computing a simple trajectory in phase space reveals the motions that when quantized yield the assigned levels. The reformulation introduces two new projected representations of the wave functions. The first is in action space and the second in angle space. The projected representations often allow the reduced angle space, where nodal searches are made, to be of lower dimension than formally occurred. In addition the action representation is a similarly lower dimension lattice representation whose discreteness and regularity allow higher reduced dimensions to be studied. The lattice representation is used to produce a significantly more complete and detailed assignment of the thiophosgene spectrum than previously published.
Auxin regulates distal stem cell differentiation in
Arabidopsis
roots
Authors: Ding Zhaojun , Friml Jiří
Published: June 2010

The stem cell niche in the root meristem is critical for the development of the plant root system. The plant hormone auxin acts as a versatile trigger in many developmental processes, including the regulation of root growth, but its role in the control of the stem cell activity remains largely unclear. Here we show that local auxin levels, determined by biosynthesis and intercellular transport, mediate maintenance or differentiation of distal stem cells in the
Arabidopsis thaliana
roots. Genetic analysis shows that auxin acts upstream of the major regulators of the stem cell activity, the homeodomain transcription factor WOX5, and the AP-2 transcription factor PLETHORA. Auxin signaling for differentiation of distal stem cells requires the transcriptional repressor IAA17/AXR3 as well as the ARF10 and ARF16 auxin response factors. ARF10 and ARF16 activities repress the
WOX5
transcription and restrict it to the quiescent center, where WOX5, in turn, is needed for the activity of PLETHORA. Our investigations reveal that long-distance auxin signals act upstream of the short-range network of transcriptional factors to mediate the differentiation of distal stem cells in roots.
Downsizing human, bacterial, and viral proteins to short water-stable alpha helices that maintain biological potency
Authors: Harrison Rosemary S. , Shepherd Nicholas E. , Hoang Huy N. , Ruiz-Gómez Gloria , Hill Timothy A. , Driver Russell W. , Desai Vishal S. , Young Paul R. , Abbenante Giovanni , Fairlie David P.
Published: June 2010

Recombinant proteins are important therapeutics due to potent, highly specific, and nontoxic actions in vivo. However, they are expensive medicines to manufacture, chemically unstable, and difficult to administer with low patient uptake and compliance. Small molecule drugs are cheaper and more bioavailable, but less target-specific in vivo and often have associated side effects. Here we combine some advantages of proteins and small molecules by taking short amino acid sequences that confer potency and selectivity to proteins, and fixing them as small constrained molecules that are chemically and structurally stable and easy to make. Proteins often use short α-helices of just 1–4 helical turns (4–15 amino acids) to interact with biological targets, but peptides this short usually have negligible α-helicity in water. Here we show that short peptides, corresponding to helical epitopes from viral, bacterial, or human proteins, can be strategically fixed in highly α-helical structures in water. These helix-constrained compounds have similar biological potencies as proteins that bear the same helical sequences. Examples are (
i
) a picomolar inhibitor of Respiratory Syncytial Virus F protein mediated fusion with host cells, (
ii
) a nanomolar inhibitor of RNA binding to the transporter protein HIV-Rev, (
iii
) a submicromolar inhibitor of
Streptococcus pneumoniae
growth induced by quorum sensing pheromone Competence Stimulating Peptide, and (
iv
) a picomolar agonist of the GPCR pain receptor opioid receptor like receptor ORL-1. This approach can be generally applicable to downsizing helical regions of proteins with broad applications to biology and medicine.
mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1
Authors: Kantidakis Theodoros , Ramsbottom Ben A. , Birch Joanna L. , Dowding Sarah N. , White Robert J.
Published: June 2010

Synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is regulated by the mTOR pathway in mammalian cells. The mTOR kinase localizes to tRNA and 5S rRNA genes, providing an opportunity for direct control. Its presence at these sites can be explained by interaction with TFIIIC, a DNA-binding factor that recognizes the promoters of these genes. TFIIIC contains a TOR signaling motif that facilitates its association with mTOR. Maf1, a repressor that binds and inhibits pol III, is phosphorylated in a mTOR-dependent manner both in vitro and in vivo at serine 75, a site that contributes to its function as a transcriptional inhibitor. Proximity ligation assays confirm the interaction of mTOR with Maf1 and TFIIIC in nuclei. In contrast to Maf1 regulation in yeast, no evidence is found for nuclear export of Maf1 in response to mTOR signaling in HeLa cells. We conclude that mTOR associates with TFIIIC, is recruited to pol III–transcribed genes, and relieves their repression by Maf1.
Identification of
BERP
(brain-expressed RING finger protein) as a p53 target gene that modulates seizure susceptibility through interacting with GABA
A
receptors
Authors: Cheung Carol C. , Yang Caimei , Berger Thorsten , Zaugg Kathrin , Reilly Patrick , Elia Andrew J. , Wakeham Andrew , You-Ten Annick , Chang Ning , Li Lijun , Wan Qi , Mak Tak Wah
Published: June 2010

p53 is a central player in responses to cellular stresses and a major tumor suppressor. The identification of unique molecules within the p53 signaling network can reveal functions of this important transcription factor. Here, we show that brain-expressed RING finger protein (
BERP
) is a gene whose expression is up-regulated in a p53-dependent manner in human cells and in mice. We generated BERP-deficient mice by gene targeting and demonstrated that they exhibit increased resistance to pentylenetetrazol-induced seizures. Electrophysiological and biochemical studies of cultured cortical neurons of BERP-deficient mice showed a decrease in the amplitude of GABA
A
receptor (GABA
A
R)-mediated miniature inhibitory postsynaptic currents as well as reduced surface protein expression of GABA
A
Rs containing the γ2-subunit. However, BERP deficiency did not decrease GABA
A
Rγ2 mRNA levels, raising the possibility that BERP may act at a posttranscriptional level to regulate the intracellular trafficking of GABA
A
Rs. Our results indicate that
BERP
is a unique p53-regulated gene and suggest a role for p53 within the central nervous system.
Two-photon single-cell optogenetic control of neuronal activity by sculpted light
Authors: Andrasfalvy Bertalan K. , Zemelman Boris V. , Tang Jianyong , Vaziri Alipasha
Published: June 2010

Recent advances in optogenetic techniques have generated new tools for controlling neuronal activity, with a wide range of neuroscience applications. The most commonly used approach has been the optical activation of the light-gated ion channel channelrhodopsin-2 (ChR2). However, targeted single-cell-level optogenetic activation with temporal precessions comparable to the spike timing remained challenging. Here we report fast (≤1 ms), selective, and targeted control of neuronal activity with single-cell resolution in hippocampal slices. Using temporally focused laser pulses (TEFO) for which the axial beam profile can be controlled independently of its lateral distribution, large numbers of channels on individual neurons can be excited simultaneously, leading to strong (up to 15 mV) and fast (≤1 ms) depolarizations. Furthermore, we demonstrated selective activation of cellular compartments, such as dendrites and large presynaptic terminals, at depths up to 150 μm. The demonstrated spatiotemporal resolution and the selectivity provided by TEFO allow manipulation of neuronal activity, with a large number of applications in studies of neuronal microcircuit function in vitro and in vivo.
On the merits of heating and current drive for tearing mode stabilization
Authors: D. De Lazzari and E. Westerhof
Published: June 2010

Please see the pdf for the erratum content.
Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery
Authors: Korcsmáros Tamás , Farkas Illés J. , Szalay Máté S. , Rovó Petra , Fazekas Dávid , Spiró Zoltán , Böde Csaba , Lenti Katalin , Vellai Tibor , Csermely Péter
Published: June 2010

Motivation: Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult.

Results: We present SignaLink, a database containing eight major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster and humans. Based on 170 review and ∼800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the eight pathways can cross-talk. We quantified the possible tissue- and cancer-specific activity of cross-talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery.

Conclusions: We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease, and underscore its importance in network-based drug target selection.

Availability:  http://SignaLink.org

Contact:  csermely@eok.sote.hu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Bioenergy research: a new paradigm in multidisciplinary research
Authors: Kalluri Udaya C. , Keller Martin
Published: June 2010

The field of biology is becoming increasingly interdisciplinary and cross-cutting. This changing research atmosphere is creating the way for a new kind of enquiry that while building upon the traditional research establishment is providing a new multidisciplinary framework to more effectively address scientific grand challenges. Using the US Department of Energy sponsored BioEnergy Science Center as an example, we highlight how impactful breakthroughs in biofuel science can be achieved within a large cross-disciplinary team environment. Such transformational insights are key to furthering our understanding and in generating models, theories and processes that can be used to overcome recalcitrance of biomass for sustainable biofuel production. Multidisciplinary approaches have an increasingly greater role to play in meeting rising demands for food, fibre, energy, clean environment and good health. Discoveries achieved by diverse minds and cross-applications of tools and analytical approaches have tremendous potential to fill existing knowledge gaps, clear roadblocks and facilitate translation of basic sciences discoveries as solutions towards addressing some of the most pressing global issues.
Vagococcus acidifermentans sp. nov., isolated from an acidogenic fermentation bioreactor
Authors: Wang Liang , Cui Ying-Shun , Kwon Chang Seob , Lee Sung-Taik , Lee Jung-Sook , Im Wan-Taek
Published: June 2010

A Gram-staining-positive, coccus-shaped, non-spore-forming, facultatively anaerobic bacterium, designated AC-1T, was isolated from an acidogenic fermentation bioreactor treating food wastewater. On the basis of 16S rRNA gene sequence analysis, strain AC-1T was shown to belong to the genus Vagococcus. The closest phylogenetic relatives were Vagococcus elongatus PPC9T (97.4 % 16S rRNA gene sequence similarity), Vagococcus penaei CD276T (96.7 %) and Vagococcus carniphilus ATCC BAA-640T (96.6 %). The major fatty acids were C18 : 1ω9c (24.8 %) and C16 : 0 (19.5 %) and the G+C content of genomic DNA was 44.2 mol%, which supported the affiliation of strain AC-1T to the genus Vagococcus. Strain AC-1T and V. elongatus DSM 21480T exhibited 11 % DNA–DNA relatedness. Physiological and biochemical tests differentiated strain AC-1T from the type strains of recognized species of the genus Vagococcus. Therefore, strain AC-1T is considered to represent a novel species, for which the name Vagococcus acidifermentans sp. nov. is proposed. The type strain is AC-1T ( = KCTC 13418T  = LMG 24798T).
Brachybacterium squillarum sp. nov., isolated from salt-fermented seafood
Authors: Park Seong-Kyu , Kim Min-Soo , Jung Mi-Ja , Nam Young-Do , Park Eun-Jin , Roh Seong Woon , Bae Jin-Woo
Published: June 2010

A Gram-positive bacterium, strain M-6-3T, was isolated from salt-fermented seafood in Korea. The organism grew in 0–10 % (w/v) NaCl and at 25–37 °C, with optimal growth occurring in 5 % NaCl and at 28–30 °C. The peptidoglycan type was variation A4γ with meso-diaminopimelic acid as the diagnostic cell-wall diamino acid. The polar lipid profile of strain M-6-3T consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unknown glycolipid. Strain M-6-3T contained MK-7 as the major component of the quinone system and anteiso-C15 : 0 (62.1 %) as the predominant fatty acid. Based on 16S rRNA gene sequence similarity studies, strain M-6-3T was most closely related to Brachybacterium rhamnosum LMG 19848T (98.5 %). The G+C content of the genomic DNA was 71.5 mol% and the mean DNA–DNA hybridization value with reference strains was 14.32±2.0 %. Based on phenotypic, genotypic and phylogenetic analyses, it is proposed that strain M-6-3T represents a novel species for which the name Brachybacterium squillarum sp. nov. is proposed; the type strain is M-6-3T ( = KACC 14221T  = JCM 16464T).
Halostagnicola alkaliphila sp. nov., an alkaliphilic haloarchaeon from commercial rock salt
Authors: Nagaoka Shuhei , Minegishi Hiroaki , Echigo Akinobu , Shimane Yasuhiro , Kamekura Masahiro , Usami Ron
Published: June 2010

A Gram-negative, pleomorphic, aerobic, haloalkaliphilic archaeon, strain 167-74T, was isolated from commercial rock salt imported into Japan from China. Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that strain 167-74T is closely related to Halostagnicola larsenii XH-48T (98.3 %) and Halostagnicola kamekurae 194-10T (97.2 %). The major polar lipids of the isolate were C20C20 and C20C25 derivatives of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. A glycolipid was not detected, in contrast to the two existing, neutrophilic species of the genus Halostagnicola. The DNA G+C content of strain 167-74T was 60.7 mol%. and it gave DNA–DNA reassociation values of 19.5 and 18.8 %, respectively, with Hst. larsenii JCM 13463T and Hst. kamekurae 194-10T. Therefore, strain 167-74T represents a novel species, for which the name Halostagnicola alkaliphila sp. nov. is proposed, with the type strain 167-74T ( = JCM 16592T  = CECT 7631T).
Paenibacillus tianmuensis sp. nov., isolated from soil
Authors: Wu Xuechang , Fang Haihuan , Qian Chaodong , Wen Yanping , Shen Xiaobo , Li Ou , Gao Haichun
Published: June 2010

Two closely related, Gram-stain-negative, rod-shaped, spore-forming strains, B27T and F6-B70, were isolated from soil samples of Tianmu Mountain National Natural Reserve in Zhejiang, China. Phylogenetic analysis based on 16S rRNA gene and rpoB sequences indicated that the isolates were members of the genus Paenibacillus. Both isolates were closely related to Paenibacillus ehimensis IFO 15659T, Paenibacillus elgii SD17T and Paenibacillus koreensis YC300T (≥95.2 % 16S rRNA gene sequence similarity). DNA–DNA relatedness between strain B27T and P. ehimensis DSM 11029T, P. elgii NBRC 100335T and P. koreensis KCTC 2393T was 21.2, 28.6 and 16.8 %, respectively. The major cellular fatty acids of strains B27T and F6-B70 were anteiso-C15 : 0 and iso-C15 : 0. The cell wall contained meso-diaminopimelic acid. The two isolates differed from their closest neighbours in terms of phenotypic characteristics and cellular fatty acid profiles (such as variable for oxidase, negative for methyl red test, unable to produce acid from d-fructose and glycogen and relatively higher amounts of iso-C15 : 0 and lower amounts of C16 : 0 and iso-C16 : 0). Strains B27T and F6-B70 represent a novel species of the genus Paenibacillus, for which the name Paenibacillus tianmuensis sp. nov. is proposed. The type strain is B27T ( = DSM 22342T  = CGMCC 1.8946T).
Halorubrum aquaticum sp. nov., an archaeon isolated from hypersaline lakes
Authors: Gutiérrez M. C. , Castillo A. M. , Corral P. , Kamekura M. , Ventosa A.
Published: June 2010

Two halophilic archaea, strains EN-2T and SH-4, were isolated from the saline lakes Erliannor and Shangmatala, respectively, in Inner Mongolia, China. Cells were strictly aerobic, motile rods. Colonies were red. Strains EN-2T and SH-4 were able to grow at 25–50 °C (optimum 35–40 °C), with 2.5–5.0 M NaCl (optimum 3.4 M NaCl) and at pH 6.0–9.0 (optimum pH 7.5). MgCl2 was not required for growth. Cells lysed in distilled water and the lowest NaCl concentration that prevented cell lysis was 12 % (w/v). On the basis of 16S rRNA gene sequence analysis, strains EN-2T and SH-4 were closely related to Halorubrum cibi B31T (97.9 and 98.0 % similarity, respectively), Hrr. tibetense 8W8T (97.3 and 97.7 %), Hrr. alkaliphilum DZ-1T (96.8 and 97.1 %), Hrr. luteum CGSA15T (96.8 and 97.0 %) and Hrr. lipolyticum 9-3T (96.8 and 97.0 %). DNA–DNA hybridization showed that strains EN-2T and SH-4 did not belong to the same species as any of these strains (≤45 % DNA–DNA relatedness) but that they are members of the same species (>70 % DNA–DNA relatedness). Polar lipid analysis revealed that strains EN-2T and SH-4 contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, sulfated diglycosyl diethers and several unidentified glycolipids. The DNA G+C content of both isolates was 62.1 mol%. It was concluded that strains EN-2T and SH-4 represent a novel species of the genus Halorubrum, for which the name Halorubrum aquaticum sp. nov. is proposed. The type strain is EN-2T ( = CECT 7174T  = CGMCC 1.6377T  = JCM 14031T).
Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor
Authors: Yang Haihua , An Yang , Wang Linqi , Zhang Shuli , Zhang Yue , Tian Yuqing , Liu Gang , Tan Huarong
Published: June 2010

HpdR, an IclR-family regulator in Streptomyces coelicolor, is a substrate-dependent repressor for the tyrosine catabolic gene hppD. In this study, S1 nuclease protection assays revealed that hpdR is subject to a negative autoregulation. Purified HpdR showed specific DNA-binding activity for the promoter region of hpdR, indicating that the autoregulation of hpdR is performed directly. The disruption of hpdR led to reduced production of CDA by S. coelicolor J1501, suggesting a positive effect of hpdR on CDA biosynthesis. Electrophoretic mobility shift assays showed that HpdR specifically bound to the promoter region of hmaS (SCO3229 in the CDA gene cluster), encoding 4-hydroxymandelic acid synthase. Disruption of hmaS in J1501 abolished CDA production. It is possible that hpdR regulates CDA biosynthesis by controlling the transcription of hmaS.
Differential PilA pilus assembly by a hospital-acquired and a community-derived Enterococcus faecium isolate
Authors: Hendrickx Antoni P. A. , Schapendonk Claudia M. E. , van Luit-Asbroek Miranda , Bonten Marc J. M. , van Schaik Willem , Willems Rob J. L.
Published: June 2010

Pili are hair-like structures protruding from the cell envelope of bacterial cells. Here, we describe the conditional and differential display of PilA-type pili, and PilE and PilF proteins, encoded from pilin gene cluster 1 at the surface of a hospital-acquiredEnterococcus faeciumbloodstream isolate (E1165) and a community-derived stool isolate (E1039), at two different temperatures. Both strains have virtually identicalpilAgene clusters, as determined by sequencing. Western blotting and transmission immunoelectron microscopy revealed that PilA and PilF assembled into high-molecular-mass pilus-like structures at 37 °C in the E1165 strain, whereas PilE was not produced at either of the temperatures used; at 21 °C, PilA and PilF were cell-wall-anchored proteins. In contrast, in strain E1039, PilA, PilE and PilF pilin proteins were found to be displayed as cell-wall-anchored proteins at 37 °C only, and they were not associated with pilus-like structures. The discrepancy in pilus assembly between E1039 and E1165 cannot be explained by differences in expression of the genes encoding the predicted sortases in thepilAgene cluster, as these had similar expression levels in both strains at 21 and 37 °C. Double-labelling electron microscopy revealed that PilA formed the pilus backbone in E1165, and PilF the minor subunit which was distributed along the PilA pilus shaft and positioned at the tip; however, it was deposited as a cell-wall-anchored protein in apilAisogenic mutant. The differential deposition of surface proteins from pilin gene cluster 1 and differences in pilus assembly in the two strains suggest a complex post-transcriptional regulatory mechanism of pilus biogenesis inE. faecium.
Peroxisomal Hydrogen Peroxide Is Coupled to Biotic Defense Responses by ISOCHORISMATE SYNTHASE1 in a Daylength-Related Manner
Authors: Chaouch Sejir , Queval Guillaume , Vanderauwera Sandy , Mhamdi Amna , Vandorpe Michaël , Langlois-Meurinne Mathilde , Van Breusegem Frank , Saindrenan Patrick , Noctor Graham
Published: June 2010

While it is well established that reactive oxygen species can induce cell death, intracellularly generated oxidative stress does not induce lesions in the Arabidopsis (Arabidopsis thaliana) photorespiratory mutant cat2 when plants are grown in short days (SD). One interpretation of this observation is that a function necessary to couple peroxisomal hydrogen peroxide (H2O2)-triggered oxidative stress to cell death is only operative in long days (LD). Like lesion formation, pathogenesis-related genes and camalexin were only induced in cat2 in LD, despite less severe intracellular redox perturbation compared with SD. Lesion formation triggered by peroxisomal H2O2 was modified by introducing secondary mutations into the cat2 background and was completely absent in cat2 sid2 double mutants, in which ISOCHORISMATE SYNTHASE1 (ICS1) activity is defective. In addition to H2O2-induced salicylic acid (SA) accumulation, the sid2 mutation in ICS1 abolished a range of LD-dependent pathogen responses in cat2, while supplementation of cat2 with SA in SD activated these responses. Nontargeted transcript and metabolite profiling identified clusters of genes and small molecules associated with the daylength-dependent ICS1-mediated relay of H2O2 signaling. The effect of oxidative stress in cat2 on resistance to biotic challenge was dependent on both growth daylength and ICS1. We conclude that (1) lesions induced by intracellular oxidative stress originating in the peroxisomes can be genetically reverted; (2) the isochorismate pathway of SA synthesis couples intracellular oxidative stress to cell death and associated disease resistance responses; and (3) camalexin accumulation was strictly dependent on the simultaneous presence of both H2O2 and SA signals.
Biochemical and Immunocytological Characterizations of Arabidopsis Pollen Tube Cell Wall
Authors: Dardelle Flavien , Lehner Arnaud , Ramdani Yasmina , Bardor Muriel , Lerouge Patrice , Driouich Azeddine , Mollet Jean-Claude
Published: June 2010

During plant sexual reproduction, pollen germination and tube growth require development under tight spatial and temporal control for the proper delivery of the sperm cells to the ovules. Pollen tubes are fast growing tip-polarized cells able to perceive multiple guiding signals emitted by the female organ. Adhesion of pollen tubes via cell wall molecules may be part of the battery of signals. In order to study these processes, we investigated the cell wall characteristics of in vitro-grown Arabidopsis (Arabidopsis thaliana) pollen tubes using a combination of immunocytochemical and biochemical techniques. Results showed a well-defined localization of cell wall epitopes. Low esterified homogalacturonan epitopes were found mostly in the pollen tube wall back from the tip. Xyloglucan and arabinan from rhamnogalacturonan I epitopes were detected along the entire tube within the two wall layers and the outer wall layer, respectively. In contrast, highly esterified homogalacturonan and arabinogalactan protein epitopes were found associated predominantly with the tip region. Chemical analysis of the pollen tube cell wall revealed an important content of arabinosyl residues (43%) originating mostly from (1→5)-α-l-arabinan, the side chains of rhamnogalacturonan I. Finally, matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of endo-glucanase-sensitive xyloglucan showed mass spectra with two dominant oligosaccharides (XLXG/XXLG and XXFG), both being mono O-acetylated, and accounting for over 68% of the total ion signals. These findings demonstrate that the Arabidopsis pollen tube wall has its own characteristics compared with other cell types in the Arabidopsis sporophyte. These structural features are discussed in terms of pollen tube cell wall biosynthesis and growth dynamics.