bluuebunny/crossref_metadata_2025 huggingface dataset:
Scale invariance in the dynamics of spontaneous behavior
Authors: Proekt Alex , Banavar Jayanth R. , Maritan Amos , Pfaff Donald W.
Published: June 2012

Typically one expects that the intervals between consecutive occurrences of a particular behavior will have a characteristic time scale around which most observations are centered. Surprisingly, the timing of many diverse behaviors from human communication to animal foraging form complex self-similar temporal patterns reproduced on multiple time scales. We present a general framework for understanding how such scale invariance may arise in nonequilibrium systems, including those that regulate mammalian behaviors. We then demonstrate that the predictions of this framework are in agreement with detailed analysis of spontaneous mouse behavior observed in a simple unchanging environment. Neural systems operate on a broad range of time scales, from milliseconds to hours. We analytically show that such a separation between time scales could lead to scale-invariant dynamics without any fine tuning of parameters or other model-specific constraints. Our analyses reveal that the specifics of the distribution of resources or competition among several tasks are not essential for the expression of scale-free dynamics. Rather, we show that scale invariance observed in the dynamics of behavior can arise from the dynamics intrinsic to the brain.
What to Do About Adolescent Psychopathy? Commentary on Dawson et al.
Authors: Vincent GinaM.
Published: June 2012

Dawson et al. tackle the controversial issue of assessing psychopathic personality disorder in children and adolescents. They use two case studies assessed with the CAPP and the PCL:YV to suggest that 1) symptoms of psychopathy look different in youth than in adults, and 2) the CAPP may be a better assessment tool for youth than the PCL:YV. They also suggest youth psychopathy researchers conduct studies using the CAPP and PCL:YV together to examine more distinctive features of psychopathy in youth. I agree with the authors’ conclusions in part. The CAPP is a very promising tool for the assessment of psychopathic personality. I would add several caveats, however, including the limited evidence for the CAPP's construct validity (currently) and unanswered questions about its developmental appropriateness. The potential advantages to research with the CAPP may include 1) aiding our understanding of developmental changes in symptoms, and 2) further exploration of the variants of psychopathy. However, until the CAPP establishes construct validity and developmental applicability, I suggest any future studies include the PCL:YV/PCL-R, known psychopathy correlates, and compare youth to adult samples.
Schelling, Jung and the Imaginatio Vera
Authors: Nicolaus Georg
Published: June 2012

While Jung hardly mentions Schelling in his writings, Schelling's philosophy anticipates many elements of his psychology. In Schelling'sPhilosophical Investigations into the Essence of Human Freedomphilosophy reaches a crisis point, which prepares the way for Schelling's positive philosophy as well as existentialism and the later ascendancy of depth psychology as Jung conceived it. A closer examination of the nature of this crisis as it finds expression in Schelling'sInvestigations,which takes clues from Berdyaev's and Kierkegaard's existential philosophy, provides a revealing perspective on the present post-modern condition of our culture. This essay is an attempt to examine Schelling's text with regard to the role the imagination plays in it in order to gain deeper insight into the cultural relevance of Jung's psychology.
GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes
Authors: Orlandi Cesare , Posokhova Ekaterina , Masuho Ikuo , Ray Thomas A. , Hasan Nazarul , Gregg Ronald G. , Martemyanov Kirill A.
Published: June 2012

The extent and temporal characteristics of G protein–coupled receptor (GPCR) signaling are shaped by the regulator of G protein signaling (RGS) proteins, which promote G protein deactivation. With hundreds of GPCRs and dozens of RGS proteins, compartmentalization plays a key role in establishing signaling specificity. However, the molecular details and mechanisms of this process are poorly understood. In this paper, we report that the R7 group of RGS regulators is controlled by interaction with two previously uncharacterized orphan GPCRs: GPR158 and GPR179. We show that GPR158/179 recruited RGS complexes to the plasma membrane and augmented their ability to regulate GPCR signaling. The loss of GPR179 in a mouse model of night blindness prevented targeting of RGS to the postsynaptic compartment of bipolar neurons in the retina, illuminating the role of GPR179 in night vision. We propose that the interaction of RGS proteins with orphan GPCRs promotes signaling selectivity in G protein pathways.
Analysis on some infinite modules, inner projection, and applications
Authors: Han Kangjin , Kwak Sijong
Published: June 2012

A projective scheme

X
X

is called ‘quadratic’ if

X
X

is scheme-theoretically cut out by homogeneous equations of degree

2
2

. Furthermore, we say that

X
X

satisfies ‘property

N

2
,
p

\textbf {N}_{2,p}

’ if it is quadratic and the quadratic ideal has only linear syzygies up to the first

p
p

-th steps. In the present paper, we compare the linear syzygies of the inner projections with those of

X
X

and obtain a theorem on ‘embedded linear syzygies’ as one of our main results. This is the natural projection-analogue of ‘restricting linear syzygies’ in the linear section case. As an immediate corollary, we show that the inner projections of

X
X

satisfy property

N

2
,
p
−
1

\textbf {N}_{2,p-1}

for any reduced scheme

X
X

with property

N

2
,
p

\textbf {N}_{2,p}

.

Moreover, we also obtain the neccessary lower bound

(
codim
⁡
X
)
⋅
p
−

p
(
p
−
1
)

2

(\operatorname {codim} X)\cdot p -\frac {p(p-1)}{2}

, which is sharp, on the number of quadrics vanishing on

X
X

in order to satisfy

N

2
,
p

\textbf {N}_{2,p}

and show that the arithmetic depths of inner projections are equal to that of the quadratic scheme

X
X

. These results admit an interesting ‘syzygetic’ rigidity theorem on property

N

2
,
p

\textbf {N}_{2,p}

which leads the classifications of extremal and next-to-extremal cases.

For these results we develop the elimination mapping cone theorem for infinitely generated graded modules and improve the partial elimination ideal theory initiated by M. Green. This new method allows us to treat a wider class of projective schemes which cannot be covered by the Koszul cohomology techniques because these are not projectively normal in general.
Extending ontologies by finding siblings using set expansion techniques
Authors: Fabian Götz , Wächter Thomas , Schroeder Michael
Published: June 2012

Motivation: Ontologies are an everyday tool in biomedicine to capture and represent knowledge. However, many ontologies lack a high degree of coverage in their domain and need to improve their overall quality and maturity. Automatically extending sets of existing terms will enable ontology engineers to systematically improve text-based ontologies level by level.

Results: We developed an approach to extend ontologies by discovering new terms which are in a sibling relationship to existing terms of an ontology. For this purpose, we combined two approaches which retrieve new terms from the web. The first approach extracts siblings by exploiting the structure of HTML documents, whereas the second approach uses text mining techniques to extract siblings from unstructured text. Our evaluation against MeSH (Medical Subject Headings) shows that our method for sibling discovery is able to suggest first-class ontology terms and can be used as an initial step towards assessing the completeness of ontologies. The evaluation yields a recall of 80% at a precision of 61% where the two independent approaches are complementing each other. For MeSH in particular, we show that it can be considered complete in its medical focus area. We integrated the work into DOG4DAG, an ontology generation plugin for the editors OBO-Edit and Protégé, making it the first plugin that supports sibling discovery on-the-fly.

Availability: Sibling discovery for ontology is available as part of DOG4DAG (www.biotec.tu-dresden.de/research/schroeder/dog4dag) for both Protégé 4.1 and OBO-Edit 2.1.

Contact:  ms@biotec.tu-dresden.de; goetz.fabian@biotec.tu-dresden.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Novel domain combinations in proteins encoded by chimeric transcripts
Authors: Frenkel-Morgenstern Milana , Valencia Alfonso
Published: June 2012

Motivation: Chimeric RNA transcripts are generated by different mechanisms including pre-mRNA trans-splicing, chromosomal translocations and/or gene fusions. It was shown recently that at least some of chimeric transcripts can be translated into functional chimeric proteins.

Results: To gain a better understanding of the design principles underlying chimeric proteins, we have analyzed 7,424 chimeric RNAs from humans. We focused on the specific domains present in these proteins, comparing their permutations with those of known human proteins. Our method uses genomic alignments of the chimeras, identification of the gene–gene junction sites and prediction of the protein domains. We found that chimeras contain complete protein domains significantly more often than in random data sets. Specifically, we show that eight different types of domains are over-represented among all chimeras as well as in those chimeras confirmed by RNA-seq experiments. Moreover, we discovered that some chimeras potentially encode proteins with novel and unique domain combinations. Given the observed prevalence of entire protein domains in chimeras, we predict that certain putative chimeras that lack activation domains may actively compete with their parental proteins, thereby exerting dominant negative effects. More generally, the production of chimeric transcripts enables a combinatorial increase in the number of protein products available, which may disturb the function of parental genes and influence their protein–protein interaction network.

Availability: our scripts are available upon request.

Contact:  avalencia@cnio.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Improved synapse detection for mGRASP-assisted brain connectivity mapping
Authors: Feng Linqing , Zhao Ting , Kim Jinhyun
Published: June 2012

Motivation: A new technique, mammalian green fluorescence protein (GFP) reconstitution across synaptic partners (mGRASP), enables mapping mammalian synaptic connectivity with light microscopy. To characterize the locations and distribution of synapses in complex neuronal networks visualized by mGRASP, it is essential to detect mGRASP fluorescence signals with high accuracy.

Results: We developed a fully automatic method for detecting mGRASP-labeled synapse puncta. By modeling each punctum as a Gaussian distribution, our method enables accurate detection even when puncta of varying size and shape partially overlap. The method consists of three stages: blob detection by global thresholding; blob separation by watershed; and punctum modeling by a variational Bayesian Gaussian mixture models. Extensive testing shows that the three-stage method improved detection accuracy markedly, and especially reduces under-segmentation. The method provides a goodness-of-fit score for each detected punctum, allowing efficient error detection. We applied this advantage to also develop an efficient interactive method for correcting errors.

Availability: The software is available on http://jinny.kist.re.kr

Contact:  tingzhao@gmail.com; kimj@kist.re.kr
Towards 3D structure prediction of large RNA molecules: an integer programming framework to insert local 3D motifs in RNA secondary structure
Authors: Reinharz Vladimir , Major François , Waldispühl Jérôme
Published: June 2012

Motivation: The prediction of RNA 3D structures from its sequence only is a milestone to RNA function analysis and prediction. In recent years, many methods addressed this challenge, ranging from cycle decomposition and fragment assembly to molecular dynamics simulations. However, their predictions remain fragile and limited to small RNAs. To expand the range and accuracy of these techniques, we need to develop algorithms that will enable to use all the structural information available. In particular, the energetic contribution of secondary structure interactions is now well documented, but the quantification of non-canonical interactions—those shaping the tertiary structure—is poorly understood. Nonetheless, even if a complete RNA tertiary structure energy model is currently unavailable, we now have catalogues of local 3D structural motifs including non-canonical base pairings. A practical objective is thus to develop techniques enabling us to use this knowledge for robust RNA tertiary structure predictors.

Results: In this work, we introduce RNA-MoIP, a program that benefits from the progresses made over the last 30 years in the field of RNA secondary structure prediction and expands these methods to incorporate the novel local motif information available in databases. Using an integer programming framework, our method refines predicted secondary structures (i.e. removes incorrect canonical base pairs) to accommodate the insertion of RNA 3D motifs (i.e. hairpins, internal loops and k-way junctions). Then, we use predictions as templates to generate complete 3D structures with the MC-Sym program. We benchmarked RNA-MoIP on a set of 9 RNAs with sizes varying from 53 to 128 nucleotides. We show that our approach (i) improves the accuracy of canonical base pair predictions; (ii) identifies the best secondary structures in a pool of suboptimal structures; and (iii) predicts accurate 3D structures of large RNA molecules.

Availability:  RNA-MoIP is publicly available at: http://csb.cs.mcgill.ca/RNAMoIP.

Contact:  jeromew@cs.mcgill.ca
Detection of allele-specific methylation through a generalized heterogeneous epigenome model
Authors: Peng Qian , Ecker Joseph R.
Published: June 2012

Motivations: High-throughput sequencing has made it possible to sequence DNA methylation of a whole genome at the single-base resolution. A sample, however, may contain a number of distinct methylation patterns. For instance, cells of different types and in different developmental stages may have different methylation patterns. Alleles may be differentially methylated, which may partially explain that the large portions of epigenomes from single cell types are partially methylated, and may have major effects on transcriptional output. Approaches relying on DNA sequence polymorphism to identify individual patterns from a mixture of heterogeneous epigenomes are insufficient as methylcytosines occur at a much higher density than SNPs.

Results: We have developed a mixture model-based approach for resolving distinct epigenomes from a heterogeneous sample. In particular, the model is applied to the detection of allele-specific methylation (ASM). The methods are tested on a synthetic methylome and applied to an Arabidopsis single root cell methylome.

Contact:  qpeng@cs.ucsd.edu
Integration of environmental and fishery management in Europe
Authors: Jennings Simon , Le Quesne Will J. F.
Published: June 2012

Jennings, S., and Le Quesne, W. J. F. 2012. Integration of environmental and fishery management in Europe. – ICES Journal of Marine Science, 69: . Policy drivers for integrating environmental and fishery management in Europe have never been so strong. Scientists calling for better integration now have the opportunity to help deliver it. The main challenge is providing relevant evidence on short time-scales using existing knowledge. Policies, scientists, and society largely agree that management targets should be linked to achieving sustainability, but research often fails to show when fishing impacts ‘matter’ in relation to sustainability criteria. If targets for ecosystem functions or processes are to complement more tractable targets for species and habitats, scientists will need to show why impacts ‘matter’ and when they become unsustainable. For now, and to meet ambitious and pressing policy timetables, priority should be given to developing credible targets for impacts with a high risk of compromising sustainability, rather than dissipating research and advisory effort to achieve broader coverage of state, function, and process. Impacts on sensitive species and habitats often compromise sustainability; thus, setting targets for them is a priority. Meeting these targets will often require management measures that are expected to diminish risks of other unsustainable impacts. Fast and significant progress towards integration could be achieved by incorporating measures to meet environmental targets for sensitive species and habitats into fishery management plans.
Pattern perception and computational complexity: introduction to the special issue
Authors: Fitch W. Tecumseh , Friederici Angela D. , Hagoort Peter
Published: June 2012

Research on pattern perception and rule learning, grounded in formal language theory (FLT) and using artificial grammar learning paradigms, has exploded in the last decade. This approach marries empirical research conducted by neuroscientists, psychologists and ethologists with the theory of computation and FLT, developed by mathematicians, linguists and computer scientists over the last century. Of particular current interest are comparative extensions of this work to non-human animals, and neuroscientific investigations using brain imaging techniques. We provide a short introduction to the history of these fields, and to some of the dominant hypotheses, to help contextualize these ongoing research programmes, and finally briefly introduce the papers in the current issue.
Early and late steps in telomere overhang processing in normal human cells: the position of the final RNA primer drives telomere shortening
Authors: Chow Tracy T. , Zhao Yong , Mak Sabrina S. , Shay Jerry W. , Wright Woodring E.
Published: June 2012

Telomere overhangs are essential for telomere end protection and telomerase extension, but how telomere overhangs are generated is unknown. Leading daughter strands synthesized by conventional semiconservation DNA replication are initially blunt, while lagging daughter strands are shorter by at least the size of the final RNA primer, which is thought to be located at extreme chromosome ends. We developed a variety of new approaches to define the steps in the processing of these overhangs. We show that the final lagging RNA primer is not terminal but is randomly positioned ∼70–100 nucleotides from the ends and is not removed for more than an hour. This identifies an important intrinsic step in replicative aging. Telomeric termini are processed in two distinct phases. During the early phase, which occupies 1–2 h following replication of the duplex telomeric DNA, several steps occur on both leading and lagging daughters. Leading telomere processing remains incomplete until late S/G2, when the C-terminal nucleotide is specified—referred to as the late phase. These observations suggest the presence of previously unsuspected complexes and signaling events required for the replication of the ends of human chromosomes.
Shh maintains dermal papilla identity and hair morphogenesis via a Noggin–Shh regulatory loop
Authors: Woo Wei-Meng , Zhen Hanson H. , Oro Anthony E.
Published: June 2012

During hair follicle morphogenesis, dermal papillae (DPs) function as mesenchymal signaling centers that cross-talk with overlying epithelium to regulate morphogenesis. While the DP regulates hair follicle formation, relatively little is known about the molecular basis of DP formation. The morphogen Sonic hedgehog (Shh) is known for regulating hair follicle epithelial growth, with excessive signaling resulting in basal cell carcinomas. Here, we investigate how dermal-specific Shh signaling contributes to DP formation and hair growth. Using a Cre-lox genetic model and RNAi in hair follicle reconstitution assays, we demonstrate that dermal Smoothened (Smo) loss of function results in the loss of the DP precursor, the dermal condensate, and a stage 2 hair follicle arrest phenotype reminiscent of Shh−/− skin. Surprisingly, dermal Smo does not regulate cell survival or epithelial proliferation. Rather, molecular screening and immunostaining studies reveal that dermal Shh signaling controls the expression of a subset of DP-specific signature genes. Using a hairpin/cDNA lentiviral system, we show that overexpression of the Shh-dependent gene Noggin, but not Sox2 or Sox18, can partially rescue the dermal Smo knockdown hair follicle phenotype by increasing the expression of epithelial Shh. Our findings suggest that dermal Shh signaling regulates specific DP signatures to maintain DP maturation while maintaining a reciprocal Shh–Noggin signaling loop to drive hair follicle morphogenesis.
Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention
Authors: Yap Karen , Lim Zhao Qin , Khandelia Piyush , Friedman Brad , Makeyev Eugene V.
Published: June 2012

Differentiated cells acquire unique structural and functional traits through coordinated expression of lineage-specific genes. An extensive battery of genes encoding components of the synaptic transmission machinery and specialized cytoskeletal proteins is activated during neurogenesis, but the underlying regulation is not well understood. Here we show that genes encoding critical presynaptic proteins are transcribed at a detectable level in both neurons and nonneuronal cells. However, in nonneuronal cells, the splicing of 3′-terminal introns within these genes is repressed by the polypyrimidine tract-binding protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the cytoplasm and triggers their nuclear degradation. Clearance of these intron-containing transcripts occurs independently of the nonsense-mediated decay (NMD) pathway but requires components of the nuclear RNA surveillance machinery, including the nuclear pore-associated protein Tpr and the exosome complex. When Ptbp1 expression decreases during neuronal differentiation, the regulated introns are spliced out, thus allowing the accumulation of translation-competent mRNAs in the cytoplasm. We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context.
RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair
Authors: Galanty Yaron , Belotserkovskaya Rimma , Coates Julia , Jackson Stephen P.
Published: June 2012

Protein ubiquitylation and sumoylation play key roles in regulating cellular responses to DNA double-strand breaks (DSBs). Here, we show that human RNF4, a small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, is recruited to DSBs in a manner requiring its SUMO interaction motifs, the SUMO E3 ligases PIAS1 and PIAS4, and various DSB-responsive proteins. Furthermore, we reveal that RNF4 depletion impairs ubiquitin adduct formation at DSB sites and causes persistent histone H2AX phosphorylation (γH2AX) associated with defective DSB repair, hypersensitivity toward DSB-inducing agents, and delayed recovery from radiation-induced cell cycle arrest. We establish that RNF4 regulates turnover of the DSB-responsive factors MDC1 and replication protein A (RPA) at DNA damage sites and that RNF4-depleted cells fail to effectively replace RPA by the homologous recombination factors BRCA2 and RAD51 on resected DNA. Consistent with previous data showing that RNF4 targets proteins to the proteasome, we show that the proteasome component PSMD4 is recruited to DNA damage sites in a manner requiring its ubiquitin-interacting domains, RNF4 and RNF8. Finally, we establish that PSMD4 binds MDC1 and RPA1 in a DNA damage-induced, RNF4-dependent manner and that PSMD4 depletion cause MDC1 and γH2AX persistence in irradiated cells. RNF4 thus operates as a DSB response factor at the crossroads between the SUMO and ubiquitin systems.
Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity
Authors: Kim Youngmi , Kim Eunhee , Wu Qiulian , Guryanova Olga , Hitomi Masahiro , Lathia Justin D. , Serwanski David , Sloan Andrew E. , Weil Robert J. , Lee Jeongwu , Nishiyama Akiko , Bao Shideng , Hjelmeland Anita B. , Rich Jeremy N.
Published: June 2012

Growth factor-mediated proliferation and self-renewal maintain tissue-specific stem cells and are frequently dysregulated in cancers. Platelet-derived growth factor (PDGF) ligands and receptors (PDGFRs) are commonly overexpressed in gliomas and initiate tumors, as proven in genetically engineered models. While PDGFRα alterations inform intertumoral heterogeneity toward a proneural glioblastoma (GBM) subtype, we interrogated the role of PDGFRs in intratumoral GBM heterogeneity. We found that PDGFRα is expressed only in a subset of GBMs, while PDGFRβ is more commonly expressed in tumors but is preferentially expressed by self-renewing tumorigenic GBM stem cells (GSCs). Genetic or pharmacological targeting of PDGFRβ (but not PDGFRα) attenuated GSC self-renewal, survival, tumor growth, and invasion. PDGFRβ inhibition decreased activation of the cancer stem cell signaling node STAT3, while constitutively active STAT3 rescued the loss of GSC self-renewal caused by PDGFRβ targeting. In silico survival analysis demonstrated that PDGFRB informed poor prognosis, while PDGFRA was a positive prognostic factor. Our results may explain mixed clinical responses of anti-PDGFR-based approaches and suggest the need for integration of models of cancer as an organ system into development of cancer therapies.
Telomere end processing: unexpected complexity at the end game: Figure 1.
Authors: Lundblad Victoria
Published: June 2012

Most human cells lack telomerase, the enzyme that elongates telomeres. The resulting telomere erosion eventually limits cell proliferation and tissue renewal, thereby impacting age-dependent pathologies. In this issue of Genes & Development, a technical tour-de-force by Chow and colleagues (pp. 1167–1178) reveals a highly choreographed sequence of events that processes newly replicated chromosome ends into mature telomeres. This sheds new light on an underappreciated contribution to telomere dynamics that may be as important as telomerase in dictating the correlation between life span and telomere length.
Phosphorylation puts the pRb tumor suppressor into shape: Figure 1.
Authors: Heilmann Andreas M.F. , Dyson Nicholas J.
Published: June 2012

In this issue of Genes & Development, Burke and colleagues (pp. 1156–1166) describe how the structure of retinoblastoma protein (pRb) is altered by phosphorylation at T373 or S608. These modifications cause specific conformational changes and alter pRb's interaction with E2F via two distinct mechanisms. The structures suggest that the panel of phosphorylation sites represents a versatile set of tools that are used to sculpt pRb in precise, but very different, ways.
A Medicago truncatula Tobacco Retrotransposon Insertion Mutant Collection with Defects in Nodule Development and Symbiotic Nitrogen Fixation
Authors: Pislariu Catalina I. , D. Murray Jeremy , Wen JiangQi , Cosson Viviane , Muni RajaSekhara Reddy Duvvuru , Wang Mingyi , A. Benedito Vagner , Andriankaja Andry , Cheng Xiaofei , Jerez Ivone Torres , Mondy Samuel , Zhang Shulan , Taylor Mark E. , Tadege Million , Ratet Pascal , Mysore Kirankumar S. , Chen Rujin , Udvardi Michael K.
Published: June 2012

A Tnt1-insertion mutant population of Medicago truncatula ecotype R108 was screened for defects in nodulation and symbiotic nitrogen fixation. Primary screening of 9,300 mutant lines yielded 317 lines with putative defects in nodule development and/or nitrogen fixation. Of these, 230 lines were rescreened, and 156 lines were confirmed with defective symbiotic nitrogen fixation. Mutants were sorted into six distinct phenotypic categories: 72 nonnodulating mutants (Nod−), 51 mutants with totally ineffective nodules (Nod+ Fix−), 17 mutants with partially ineffective nodules (Nod+ Fix+/−), 27 mutants defective in nodule emergence, elongation, and nitrogen fixation (Nod+/− Fix−), one mutant with delayed and reduced nodulation but effective in nitrogen fixation (dNod+/− Fix+), and 11 supernodulating mutants (Nod++Fix+/−). A total of 2,801 flanking sequence tags were generated from the 156 symbiotic mutant lines. Analysis of flanking sequence tags revealed 14 insertion alleles of the following known symbiotic genes: NODULE INCEPTION (NIN), DOESN’T MAKE INFECTIONS3 (DMI3/CCaMK), ERF REQUIRED FOR NODULATION, and SUPERNUMERARY NODULES (SUNN). In parallel, a polymerase chain reaction-based strategy was used to identify Tnt1 insertions in known symbiotic genes, which revealed 25 additional insertion alleles in the following genes: DMI1, DMI2, DMI3, NIN, NODULATION SIGNALING PATHWAY1 (NSP1), NSP2, SUNN, and SICKLE. Thirty-nine Nod− lines were also screened for arbuscular mycorrhizal symbiosis phenotypes, and 30 mutants exhibited defects in arbuscular mycorrhizal symbiosis. Morphological and developmental features of several new symbiotic mutants are reported. The collection of mutants described here is a source of novel alleles of known symbiotic genes and a resource for cloning novel symbiotic genes via Tnt1 tagging.
Ova fecundity in Scottish Atlantic salmon Salmo salar: predictions, selective forces and causal mechanisms
Authors: Bacon P. J. , MacLean J. C. , Malcolm I. A. , Gurney W. S. C.
Published: June 2012

Ova fecundities of Scottish Atlantic salmon Salmo salar, predicted from log10 regression of ova numbers and female fork length (LF), differed widely between upland and lowland stocks within the same river, whereas sea‐age, river and year factors had insignificant effects on fecundity once LF was accounted for. For upland fish, the relationship between log10 LF and log10 ova mass (MO) was stable between two datasets collected 40 years apart. Although upland and lowland females both produced comparable log10MO(log10LF)−1, lowland females partitioned this into 45% more, but smaller ova, whereas upland females produced fewer, but larger, eggs. The possible causes and implications of this are discussed for evolutionary perspectives (lifetime production), population structure (local tributary v. large catchments; environmental effects), population dynamics and stability (density‐dependent control mechanisms) and fisheries management (stock–recruitment; short and long‐term stock sustainability).
The effect of temperature on embryonic and yolk‐sac larval development in the burbot Lota lota
Authors: Lahnsteiner F. , Kletzl M. , Weismann T.
Published: June 2012

The present study investigated the effect of various temperature regimes on embryonic and yolk‐sac larval development of the burbot Lota lota. At constant temperature regimes a high percentage of ready‐to‐hatch embryos, hatched larvae and normally shaped larvae was observed at the lowest temperature (2° C), which significantly decreased with increasing temperatures (4 and 6° C). No larvae hatched at 9° C. The stream temperature regime had no effect on the percentage of ready‐to‐hatch embryos, but significantly decreased the percentage of hatched larvae and of normally shaped larvae. The lake temperature regime did not affect the viability variables. Also an abrupt temperature increase from 2 to 4° C after 8 days and from 2 to 9° C after 48 days had no effect on the evaluated viability variables. For yolk‐sac larvae no temperature related mortalities or abnormalities were observed between 2 and 9° C.
The chemical cues of male sea liceLepeophtheirus salmonisencourage others to move between host Atlantic salmonSalmo salar
Authors: Stephenson J. F.
Published: June 2012

Adult male sea liceLepeophtheirus salmoniswere more likely to leave host fish Atlantic salmonSalmo salarif they detected the chemical cues of other adult male lice than if they detect cues of female lice. The detection of both male and female chemical cues yielded an intermediate response. These results suggest that males use chemical cues to balance competition for resources and mate acquisition, and they highlight the need for further studies of the chemical ecology of this important parasite.
The Post‐SOX Evolution of the Client Portfolio of the Second Tier: A Focus on Restatement and Internal Control Risk
Authors: Dey R. Mithu , Robin Ashok
Published: June 2012

The Post‐SOX era coincides with the rise of the Second Tier auditing firms. Our study tests risk characteristics of new (and departing) clients versus continuing clients of the Second Tier to judge overall risks faced by this auditing tier. We add to the prior literature by focusing on prevalence and severity of restatement and internal control weaknesses (ICW). We show that the new clients of the Second Tier indeed have higher prevalence and severity of restatements and ICW. Departing clients also show a high risk profile compared to continuing clients, but the difference is perhaps not as strong as that indicated in the new versus continuing comparison. We confirm the widely held belief that the Second Tier is gaining market share, but this gain appears to be achieved in a somewhat controlled manner.
Sea‐level and ocean‐current control on carbonate‐platform growth, Maldives, Indian Ocean
Authors: Betzler Christian , Fürstenau Jörn , Lüdmann Thomas , Hübscher Christian , Lindhorst Sebastian , Paul Andreas , Reijmer John J. G. , Droxler André W.
Published: June 2012

Multichannel high‐resolution seismic and multibeam data were acquired from the Maldives‐isolated carbonate platform in the Indian Ocean for a detailed characterization of the Neogene bank architecture of this edifice. The goal of the research is to decipher the controlling factors of platform evolution, with a special emphasis on sea‐level changes and changes of the oceanic currents. The stacking pattern of Lower to Middle Miocene depositional sequences, with an evolution of a ramp geometry to a flat‐topped platform, reflects variations of accommodation, which here are proposed to be primarily governed by fluctuations of relative sea level. Easterly currents during this stage of bank growth controlled an asymmetric east‐directed progradation of the bank edge. During the late middle Miocene, this system was replaced by a twofold configuration of bank development. Bank growth continued synchronously with partial bank demise and associated sediment‐drift deposition. This turnover is attributed to the onset and/or intensification of the Indian monsoon and related upwelling and occurrence of currents, locally changing environmental conditions and impinging upon the carbonate system. Mega spill over lobes, shaped by reversing currents, formed as large‐scale prograding complexes, which have previously been interpreted as deposits formed during a forced regression. On a regional scale, a complex carbonate‐platform growth can occur, with a coexistence of bank‐margin progradation and aggradation, as well as partial drowning. It is further shown that a downward shift of clinoforms and offlapping geometries in carbonate platforms are not necessarily indicative for a sea‐level driven forced regression. Findings are expected to be applicable to other examples of Cenozoic platforms in the Indo‐Pacific region.
Assessment of environmental factors in disabled children 2–12 years: development and reliability of the Craig Hospital Inventory of Environmental Factors (CHIEF) for Children–Parent Version
Authors: McCauley D. , Gorter J. W. , Russell D. J. , Rosenbaum P. , Law M. , Kertoy M.
Published: June 2012

Background  Children with disabilities and their families experience environmental barriers in the school and community environments. There is a need to understand and appropriately measure environmental factors that influence activity and participation for disabled children. The purpose of this paper is to describe the adaptation process of the Craig Hospital Inventory of Environmental Factors (CHIEF) to make it suitable as a parent proxy measure for disabled children aged 2–12 years.

Methods  The adaptation process consisted of four steps using data from previous research conducted at CanChild: (i) analysis of item–total correlations from all items on the CHIEF; (ii) frequency of endorsement; (iii) determination of the representativeness of the questions; and (iv) correlations on selected items. Once the items were selected, a test–retest reliability study was conducted.

Results  The internal consistencies (α) for the time 1 and time 2 administrations were 0.76 and 0.78, respectively. Test–retest reliability of the questionnaire was ICC = 0.73 for the total product score.

Conclusion  The 10‐item CHIEF for Children–Parent Version is an acceptable, easy‐to‐complete and reliable measure of perceived environmental barriers for disabled children 2–12 years of age.
Spanish version of the Sleep Self‐Report (SSR): factorial structure and psychometric properties
Authors: Orgilés M. , Owens J. , Espada J. P. , Piqueras J. A. , Carballo J. L.
Published: June 2012

Background  The Sleep Self‐Report (SSR) is a questionnaire initially created for use with a sample from the USA to assess sleep patterns and problems in school‐aged children. The objective of this study was to validate the SSR among a Spanish sample.

Methods  Participants were 1228 Spanish children from 8 to 12 years of age who completed the questionnaires at school anonymously.

Results  Internal consistency was good (ω= 0.85). Convergent validity with anxiety (r= 0.54) and perceived welfare (r=−0.53) measures, and divergent validity with a measure of academic performance and positive influence of peers (r=−0.22) were acceptable. Exploratory analysis suggested a factorial structure composed by four subscales: sleep quality, sleep anxiety, bedtime refusal and sleep routines. Confirmatory analysis indicated a good fit for the model (RMSEA = 0.04; GFI = 0.95; AGFI = 0.93; χ2/gl = 2.48).

Conclusions  The SSR has demonstrated to have good psychometric properties in the Spanish‐speaking sample of children. The factorial structure supported by exploratory and confirmatory analysis examines the most relevant areas of sleep in children. The satisfactory psychometric properties support the use of the Spanish version of the SSR by researchers and clinicians.
A four‐part ecological model of community‐focused therapeutic recreation and life skills services for children and youth with disabilities
Authors: King G. , Curran C. J. , McPherson A.
Published: June 2012

Aim This article presents a four‐part model of community‐focused therapeutic recreation and life skills services for children's rehabilitation centres.

Method and Results The model is based on 15 years of clinical and management practice in a Canadian context combined with evidence from the literature on community‐focused service delivery. The model incorporates an ecological approach and principles from models of therapeutic recreation, community capacity building, and health promotion, as well as client/family‐centred care. The four pillars of the model reflect a set of integrated services and principles designed to support the participation of children and youth with disabilities in community activities. The pillars involve providing community outreach services, providing community development services, sharing physical and educational resources with community partners, and promoting the organization as a community facility that provides adapted physical space and specialized instruction. The lessons learned in implementing the model are discussed, including the importance of ensuring the sustainability of community recreation programmes.

Conclusions The model will be of use to managers and service organizations seeking to develop an integrated programme of community‐focused therapeutic recreation and life skills services based on a collaborative capacity‐building approach.
Do Chinese parents with HIV tell their children the truth? A qualitative preliminary study of parental HIV disclosure in China
Authors: Zhou Y. , Zhang L. , Li X. , Kaljee L.
Published: June 2012

Background  With the extended lifespan of people living with human immunodeficiency virus (HIV) due to the advent of antiretroviral therapy, the disclosure of HIV serostatus to their uninfected children is becoming more critical. However, limited data are available regarding parental HIV disclosure to children in China. We explore patterns of parental HIV disclosure and the reasons for disclosure or non‐disclosure to children.

Methods  A preliminary study was conducted using open‐ended questions in Guangxi, China in 2011 with 39 parents living with HIV.

Results  A majority of participants (77%) had not disclosed their HIV serostatus to their children. Participants who voluntarily disclosed tended to be older and were more likely to disclose to their adult children. Among parents who disclosed, reasons included a need for emotional and financial support, as well as feelings of obligation to their children. Among non‐disclosing parents, primary reasons included concerns that children were too young to understand, fear of being stigmatized, and fear of increased psychological burden to children.

Conclusions  Few parents with HIV disclosed their HIV status to their children. These data indicate the need for future research to explore disclosure issues in relation to children's age and the implementation of developmentally appropriate interventions and support systems for parents and children affected by HIV in China.
Predictors of psychological adjustment, experienced parenting burden and chronic sorrow symptoms in parents of children with cerebral palsy
Authors: Whittingham K. , Wee D. , Sanders M. R. , Boyd R.
Published: June 2012

Aim  To investigate the role of child behaviour, parental coping and experiential avoidance in predicting the psychological outcomes of: (i) psychological symptoms; (ii) chronic sorrow symptoms; and (iii) experienced parenting burden in parents of children with cerebral palsy (CP).

Method  This study is a cross‐sectional, correlational study. Ninety‐four parents of children (aged 2–12 years) with CP (various levels of motor functioning GMFCS I–V) participated.

Results  Together, the three predictors of child behaviour, parental coping and experiential avoidance explained 36.8% of the variance in psychological symptoms with child behavioural problems and experiential avoidance as significant unique predictors. In addition, 15.8% of the variance in chronic sorrow symptoms was explained by the three predictors with experiential avoidance alone as a significant unique predictor. Lastly, the predictors together explained 24.3% of the variance in experienced parenting burden with child behavioural problems and experiential avoidance as significant unique predictors.

Conclusions  This study demonstrates a relationship between child behavioural problems and parental psychological symptoms and experienced parenting burden as well as a relationship between experiential avoidance and parental psychological symptoms, experienced parenting burden and chronic sorrow symptoms.
The role of endothelial cell adhesion molecules P‐selectin, E‐selectin and intercellular adhesion molecule‐1 in leucocyte recruitment induced by exogenous methylglyoxal
Authors: Su Yang , Lei Xi , Wu Lingyun , Liu Lixin
Published: June 2012

Methylglyoxal (MG) is a reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. In hyperglycaemic conditions, increased MG level has been linked to the development of diabetes and its vascular complications at the macrovascular and microvascular levels where inflammation plays a role. To study the mechanism of MG‐induced inflammation in vivo, we applied MG locally to healthy mice and used intravital microscopy to investigate the role of endothelial cell adhesion molecules in MG‐induced leucocyte recruitment in cremasteric microvasculature. Administration of MG (25 and 50 mg/kg) to the tissue dose‐dependently induced leucocyte recruitment at 4·0–5·5 hr, with 84–92% recruited cells being neutrophils. Such MG treatment up‐regulated the expression of endothelial cell adhesion molecules P‐selectin, E‐selectin, intercellular adhesion molecule‐1, but not vascular cell adhesion molecule‐1. Activation of the nuclear factor‐κB signalling pathway contributed to MG‐induced up‐regulation of these adhesion molecules and leucocyte recruitment. The role of the up‐regulated endothelial cell adhesion molecules in MG‐induced leucocyte recruitment was determined by applying specific functional blocking antibodies to MG‐treated animals and observing changes in leucocyte recruitment parameters. Our data demonstrate that the up‐regulation of P‐selectin, E‐selectin and intercellular adhesion molecule‐1 contributes to the increased leucocyte rolling flux, reduced leucocyte rolling velocity, and increased leucocyte adhesion, respectively. Our results reveal the role of endothelial cell adhesion molecules in MG‐induced leucocyte recruitment in microvasculature, an inflammatory condition related to diabetic vascular complications.
Phylogeography and molecular phylogeny of Macaronesian island Tarphius (Coleoptera: Zopheridae): why are there so few species in the Azores?
Authors: Amorim Isabel R. , Emerson Brent C. , Borges Paulo A. V. , Wayne Robert K.
Published: June 2012

Aim  We used a phylogenetic framework to examine island colonization and predictions pertaining to differentiation within Macaronesian Tarphius (Insecta, Coleoptera, Zopheridae), and explain the paucity of endemics in the Azores compared with other Macaronesian archipelagos. Specifically, we test whether low diversity in the Azores could be due to recent colonization (phylogenetic lineage youth), cryptic speciation (distinct phylogenetic entities within species) or the young geological age of the archipelago.

Location  Macaronesian archipelagos (Azores, Madeira and the Canary Islands), northern Portugal and Morocco.

Methods  Phylogenetic analyses of mitochondrial and nuclear genes of Tarphius beetles of the Azores, other Macaronesian islands and neighbouring continental areas were used to investigate the origin of island biodiversity and to compare patterns of colonization and differentiation. A comparative nucleotide substitution rate test was used to select the appropriate substitution rate to infer clade divergence times.

Results  Madeiran and Canarian Tarphius species were found to be more closely related to each other, while Azorean taxa grouped separately. Azorean taxa showed concordance between species and phylogenetic clades, except for species that occur on multiple islands, which segregated by island of origin. Divergence time estimates revealed that Azorean Tarphius are an old group and that the most recent intra‐island speciation event on Santa Maria, the oldest island, occurred between 3.7 and 6.1 Ma.

Main conclusions  Our phylogenetic approach provides new evidence to understand the impoverishment of Azorean endemics: (1) Tarphius have had a long evolutionary history within the Azores, which does not support the hypothesis of fewer radiation events due to recent colonization; (2) the current taxonomy of Azorean Tarphius does not reflect common ancestry and cryptic speciation is responsible for the underestimation of endemics; (3) intra‐island differentiation in the Azores was found only in the oldest island, supporting the idea that young geological age of the archipelago limits the number of endemics; and (4) the lack of evidence for recent intra‐island diversification in Santa Maria could also explain the paucity of Azorean endemics. Phylogenetic reconstructions of other species‐rich taxa that occur on multiple Macaronesian archipelagos will reveal whether our conclusions are taxon specific, or of a more general nature.