bluuebunny/crossref_metadata_2025 huggingface dataset:
TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration
Authors: Wils Hans , Kleinberger Gernot , Janssens Jonathan , Pereson Sandra , Joris Geert , Cuijt Ivy , Smits Veerle , Ceuterick-de Groote Chantal , Van Broeckhoven Christine , Kumar-Singh Samir
Published: February 2010

Neuronal cytoplasmic and intranuclear aggregates of RNA-binding protein TDP-43 are a hallmark feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). ALS and FTLD show a considerable clinical and pathological overlap and occur as both familial and sporadic forms. Though missense mutations in TDP-43 cause rare forms of familial ALS, it is not yet known whether this is due to loss of TDP-43 function or gain of aberrant function. Moreover, the role of wild-type (WT) TDP-43, associated with the majority of familial and sporadic ALS/FTLD patients, is also currently unknown. Generating homozygous and hemizygous WT human TDP-43 transgenic mouse lines, we show here a dose-dependent degeneration of cortical and spinal motor neurons and development of spastic quadriplegia reminiscent of ALS. A dose-dependent degeneration of nonmotor cortical and subcortical neurons characteristic of FTLD was also observed. Neurons in the affected spinal cord and brain regions showed accumulation of TDP-43 nuclear and cytoplasmic aggregates that were both ubiquitinated and phosphorylated as observed in ALS/FTLD patients. Moreover, the characteristic ≈25-kDa C-terminal fragments (CTFs) were also recovered from nuclear fractions and correlated with disease development and progression in WT TDP-43 mice. These findings suggest that ≈25-kDa TDP-43 CTFs are noxious to neurons by a gain of aberrant nuclear function.
FragBag, an accurate representation of protein structure, retrieves structural neighbors from the entire PDB quickly and accurately
Authors: Budowski-Tal Inbal , Nov Yuval , Kolodny Rachel
Published: February 2010

Fast identification of protein structures that are similar to a specified query structure in the entire Protein Data Bank (PDB) is fundamental in structure and function prediction. We present FragBag: An ultrafast and accurate method for comparing protein structures. We describe a protein structure by the collection of its overlapping short contiguous backbone segments, and discretize this set using a library of fragments. Then, we succinctly represent the protein as a “bags-of-fragments”—a vector that counts the number of occurrences of each fragment—and measure the similarity between two structures by the similarity between their vectors. Our representation has two additional benefits: (i) it can be used to construct an inverted index, for implementing a fast structural search engine of the entire PDB, and (ii) one can specify a structure as a collection of substructures, without combining them into a single structure; this is valuable for structure prediction, when there are reliable predictions only of parts of the protein. We use receiver operating characteristic curve analysis to quantify the success of FragBag in identifying neighbor candidate sets in a dataset of over 2,900 structures. The gold standard is the set of neighbors found by six state of the art structural aligners. Our best FragBag library finds more accurate candidate sets than the three other filter methods: The SGM, PRIDE, and a method by Zotenko et al. More interestingly, FragBag performs on a par with the computationally expensive, yet highly trusted structural aligners STRUCTAL and CE.
COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis
Authors: Qin Jun , Chen Xinpu , Xie Xin , Tsai Ming-Jer , Tsai Sophia Y.
Published: February 2010

Tumor growth depends on nutrients and oxygen supplied by the vasculature through angiogenesis. Here, we show that the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), a member of the nuclear receptor family, is a major angiogenesis regulator within the tumor microenvironment. Conditional ablation of COUP-TFII in adults severely compromised neoangiogenesis and suppressed tumor growth in xenograft mouse models. In addition, tumor growth and tumor metastasis were also impaired in a spontaneous mammary-gland tumor model in the absence of COUP-TFII. We showed that COUP-TFII directly regulates the transcription of Angiopoietin-1 in pericytes to enhance neoangiogenesis. Importantly, provision of Angiopoietin-1 partially restores the angiogenic defects exhibited by the COUP-TFII–deficient mice, which supports the notion that COUP-TFII controls Angiopoietin-1/Tie2 signaling to regulate tumor angiogenesis. Because COUP-TFII has little impact on normal adult physiological function, our results raise an interesting possibility that inhibition of COUP-TFII may offer a therapeutic approach for anticancer intervention.
Capillarity-based switchable adhesion
Authors: Vogel Michael J. , Steen Paul H.
Published: February 2010

Drawing inspiration from the adhesion abilities of a leaf beetle found in nature, we have engineered a switchable adhesion device. The device combines two concepts: The surface tension force from a large number of small liquid bridges can be significant (capillarity-based adhesion) and these contacts can be quickly made or broken with electronic control (switchable). The device grabs or releases a substrate in a fraction of a second via a low-voltage pulse that drives electroosmotic flow. Energy consumption is minimal because both the grabbed and released states are stable equilibria that persist with no energy added to the system. Notably, the device maintains the integrity of an array of hundreds to thousands of distinct interfaces during active reconfiguration from droplets to bridges and back, despite the natural tendency of the liquid toward coalescence. We demonstrate the scaling of adhesion strength with the inverse of liquid contact size. This suggests that strengths approaching those of permanent bonding adhesives are possible as feature size is scaled down. In addition, controllability is fast and efficient because the attachment time and required voltage also scale down favorably. The device features compact size, no solid moving parts, and is made of common materials.
PML/RARα fusion protein transactivates the tissue factor promoter through a GAGC-containing element without direct DNA association
Authors: Yan Jinsong , Wang Kankan , Dong Leiming , Liu Hongchen , Chen Weiqin , Xi Wenda , Ding Qiulan , Kieffer Nelly , Caen Jacques P. , Chen Saijuan , Chen Zhu , Xi Xiaodong
Published: February 2010

A severe coagulopathy is a life-threatening complication of acute promyelocytic leukemia (APL) and is ascribable mainly to the excessive levels of tissue factor (TF) in APL cells regulated in response to the promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein. The underlying molecular mechanisms for this regulation remain ill-defined. With U937-PR9 cell lines stably expressing luciferase reporter gene under the control of different mutants of the TF promoter, both luciferase and ChIP data allowed the localization of the
PML/RARα
-responsive sequence in a previously undefined region of the TF promoter at position −230 to −242 devoid of known mammalian transcription factor binding sites. Within this sequence a GAGC motif (−235 to −238) was shown to be crucial because deletion or mutation of these nucleotides impaired both PML/RARα interaction and promoter transactivation. However, EMSA results showed that PML/RARα did not bind to DNA probes encompassing the −230 to −242 sequences, precluding a direct DNA association. Mutational experiments further suggest that the activator protein 1 (AP-1) sites of the TF promoter are dispensable for PML/RARα regulation. This study shows that PML/RARα transactivates the TF promoter through an indirect interaction with an element composed of a GAGC motif and the flanking nucleotides, independent of AP-1 binding.
Indole-3-Carbinol Triggers Aryl Hydrocarbon Receptor-dependent Estrogen Receptor (ER)α Protein Degradation in Breast Cancer Cells Disrupting an ERα-GATA3 Transcriptional Cross-Regulatory Loop
Authors: Marconett Crystal N. , Sundar Shyam N. , Poindexter Kevin M. , Stueve Theresa R. , Bjeldanes Leonard F. , Firestone Gary L.
Published: February 2010

Estrogen receptor (ER)α is a critical target of therapeutic strategies to control the proliferation of hormone-dependent breast cancers. Preferred clinical options have significant adverse side effects that can lead to treatment resistance due to the persistence of active estrogen receptors. We have established the cellular mechanism by which indole-3-carbinol (I3C), a promising anticancer phytochemical from Brassica vegetables, ablates ERα expression, and we have uncovered a critical role for the GATA3 transcription factor in this indole-regulated cascade. I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ERα protein. I3C inhibits endogenous binding of ERα with the 3′-enhancer region of GATA3 and disrupts endogenous GATA3 interactions with the ERα promoter, leading to a loss of GATA3 and ERα expression. Ectopic expression of GATA3 has no effect on I3C-induced ERα protein degradation but does prevent I3C inhibition of ERα promoter activity, demonstrating the importance of GATA3 in this I3C-triggered cascade. Our preclinical results implicate I3C as a novel anticancer agent in human cancers that coexpress ERα, GATA3, and AhR, a combination found in a large percentage of breast cancers but not in other critical ERα target tissues essential to patient health.
Evasion of Endoplasmic Reticulum Surveillance Makes Wsc1p an Obligate Substrate of Golgi Quality Control
Authors: Wang Songyu , Ng Davis T.W.
Published: February 2010

In the endoplasmic reticulum (ER), most newly synthesized proteins are retained by quality control mechanisms until folded. Misfolded molecules are sorted to ER-associated degradation (ERAD) pathways for disposal. Reports of mutant proteins degraded in the vacuole/lysosome suggested an independent Golgi-based mechanism also at work. Although little is understood of the post-ER pathway, the growing number of variants using it suggests a major role in quality control. Why seemingly redundant mechanisms in sequential compartments are needed is unclear. To understand their physiological relationship, the identification of endogenous pathway-specific substrates is a prerequisite. With ERAD substrates already well characterized, the discovery of Wsc1p as an obligate substrate of Golgi quality control enabled detailed cross-pathway analyses for the first time. By analyzing a panel of engineered substrates, the data show that the surveillance mode is determined by each polypeptide's intrinsic design. Although most secretory pathway proteins can display ERAD determinants when misfolded, the lack thereof shields Wsc1p from inspection by ER surveillance. Additionally, a powerful ER export signal mediates transport whether the luminal domain is folded or not. By evading ERAD through these passive and active mechanisms, Wsc1p is fully dependent on the post-ER system for its quality control.
PICH and Cotargeted Plk1 Coordinately Maintain Prometaphase Chromosome Arm Architecture
Authors: Kurasawa Yasuhiro , Yu-Lee Li-yuan
Published: February 2010

To maintain genomic stability, chromosome architecture needs to be tightly regulated as chromosomes undergo condensation during prophase and separation during anaphase, but the mechanisms remain poorly understood. Here, we show that the Plk1-binding protein PICH and Plk1 kinase coordinately maintain chromosome architecture during prometaphase. PICH knockdown results in a loss of Plk1 from the chromosome arm and an increase in highly disorganized “wavy” chromosomes that exhibit an “open” or “X-shaped” configuration, consistent with a loss of chromosome arm cohesion. Such chromosome disorganization occurs with essentially no change in the localization of condensin or cohesin on chromosomes. Interestingly, the chromosome disorganization could be prevented by treatment with a topoisomerase II inhibitor ICRF-193, suggesting that the PICH–Plk1 complex normally maintains chromosome architecture in a manner that involves topoisomerase II activity. PICH knockdown does not affect initial chromosome compaction at prophase but causes anaphase DNA bridge formation and failed abscission. Our studies suggest that the PICH–Plk1 complex plays a critical role in maintaining prometaphase chromosome architecture.
Visualizing SNP statistics in the context of linkage disequilibrium using LD-Plus
Authors: Bush William S. , Dudek Scott M. , Ritchie Marylyn D.
Published: February 2010

Summary: Often in human genetic analysis, multiple tables of single nucleotide polymorphism (SNP) statistics are shown alongside a Haploview style correlation plot. Readers are then asked to make inferences that incorporate knowledge across these multiple sets of results. To better facilitate a collective understanding of all available data, we developed a Ruby-based web application, LD-Plus, to generate figures that simultaneously display physical location of SNPs, binary SNP attributes (such as coding/non-coding or presence on genotyping platforms), common haplotypes and their frequencies and continuously scaled values (such as Fst, minor allele frequency, genotyping efficiency or P-values), all in the context of the D′ and r2 linkage disequilibrium structures. Combining these results into one comprehensive figure reduces dereferencing between figures and tables, and can provide unique insights into genetic features that are not clearly seen when results are partitioned across multiple figures and tables.

Availability: LD-Plus is freely available for non-commercial research institutions. For full details see http://chgr.mc.vanderbilt.edu/ritchielab/ldplus.

Contact:  ritchie@chgr.mc.vanderbilt.edu
Six Rossmannoid folds, including the Class I aminoacyl-tRNA synthetases, share a partial core with the anti-codon-binding domain of a Class II aminoacyl-tRNA synthetase
Authors: Cammer Stephen , Carter Charles W.
Published: February 2010

Motivation: Similarities in core residue packing provide evidence for divergence or convergence not reported using other methods.

Results: We apply a new method for rapid structure comparison based on Simplicial Neighborhood Analysis of Protein Packing (SNAPP) to the diverse structural classification of proteins (SCOP) α/β-class of protein folds. The procedure identifies inter-residue packing motifs shared by protein pairs from different folds. A threshold of 0.67 Å RMSD for all atoms of corresponding residues ensures inclusion of only highly significant similarities comparable with those observed for identical catalytic residues in homologues. Many tertiary packing motifs are shared among the three classical Rossmannoid folds, as well as thousands of other motifs that occur in at least two distinct folds. Merging of neighboring packing motifs facilitated recognition of larger, recurrent substructures or cores. The anti-codon-binding domain of an archeal aminoacyl-tRNA synthetase (aaRS) was discovered to possess a packed core in which eight identical amino acid residues are within 0.55 Å RMSD of the comparable structure in the FixJ receiver, a member of the Rossmannoid family that also includes the CheY signaling protein and flavodoxin-like proteins. Further investigation identified close variants of this core in five other Rossmannoid folds, including a functionally relevant core in Class Ia aminoacyl-tRNA synthetases. Although it is possible that the two essentially identical cores in the ProRS anti-codon-binding domain and the FixJ receiver converged to the same structure, the consensus core obtained from the structural and sequence alignments suggests that all the implicated protein folds descended from a simpler ancestral protein in which this core provided nucleotide binding and proto-allosteric functions.

Availability: Programs are available at http://staff.vbi.vt.edu/cammer/snapp/download/

Implementation: Programs were written in Perl and c and run under Linux.

Contact:  cammer@vbi.vt.edu
SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors
Authors: Goya Rodrigo , Sun Mark G.F. , Morin Ryan D. , Leung Gillian , Ha Gavin , Wiegand Kimberley C. , Senz Janine , Crisan Anamaria , Marra Marco A. , Hirst Martin , Huntsman David , Murphy Kevin P. , Aparicio Sam , Shah Sohrab P.
Published: February 2010

Motivation: Next-generation sequencing (NGS) has enabled whole genome and transcriptome single nucleotide variant (SNV) discovery in cancer. NGS produces millions of short sequence reads that, once aligned to a reference genome sequence, can be interpreted for the presence of SNVs. Although tools exist for SNV discovery from NGS data, none are specifically suited to work with data from tumors, where altered ploidy and tumor cellularity impact the statistical expectations of SNV discovery.

Results: We developed three implementations of a probabilistic Binomial mixture model, called SNVMix, designed to infer SNVs from NGS data from tumors to address this problem. The first models allelic counts as observations and infers SNVs and model parameters using an expectation maximization (EM) algorithm and is therefore capable of adjusting to deviation of allelic frequencies inherent in genomically unstable tumor genomes. The second models nucleotide and mapping qualities of the reads by probabilistically weighting the contribution of a read/nucleotide to the inference of a SNV based on the confidence we have in the base call and the read alignment. The third combines filtering out low-quality data in addition to probabilistic weighting of the qualities. We quantitatively evaluated these approaches on 16 ovarian cancer RNASeq datasets with matched genotyping arrays and a human breast cancer genome sequenced to >40× (haploid) coverage with ground truth data and show systematically that the SNVMix models outperform competing approaches.

Availability: Software and data are available at http://compbio.bccrc.ca

Contact:  sshah@bccrc.ca

Supplemantary information:  Supplementary data are available at Bioinformatics online.
Identifying biologically relevant differences between metagenomic communities
Authors: Parks Donovan H. , Beiko Robert G.
Published: February 2010

Motivation: Metagenomics is the study of genetic material recovered directly from environmental samples. Taxonomic and functional differences between metagenomic samples can highlight the influence of ecological factors on patterns of microbial life in a wide range of habitats. Statistical hypothesis tests can help us distinguish ecological influences from sampling artifacts, but knowledge of only the P-value from a statistical hypothesis test is insufficient to make inferences about biological relevance. Current reporting practices for pairwise comparative metagenomics are inadequate, and better tools are needed for comparative metagenomic analysis.

Results: We have developed a new software package, STAMP, for comparative metagenomics that supports best practices in analysis and reporting. Examination of a pair of iron mine metagenomes demonstrates that deeper biological insights can be gained using statistical techniques available in our software. An analysis of the functional potential of ‘Candidatus Accumulibacter phosphatis’ in two enhanced biological phosphorus removal metagenomes identified several subsystems that differ between the A.phosphatis stains in these related communities, including phosphate metabolism, secretion and metal transport.

Availability: Python source code and binaries are freely available from our website at http://kiwi.cs.dal.ca/Software/STAMP

Contact:  beiko@cs.dal.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
The presence of an avian co-forager reduces vigilance in a cooperative mammal
Authors: Sharpe Lynda L. , Joustra Abigail S. , Cherry Michael I.
Published: February 2010

Many animals must trade-off anti-predator vigilance with other behaviours. Some species facilitate predator detection by joining mixed-species foraging parties and ‘eavesdropping’ on the predator warnings given by other taxa. Such use of heterospecific warnings presumably reduces the likelihood of predation, but it is unclear whether it also provides wider benefits, by allowing individuals to reduce their own vigilance. We examine whether the presence of an avian co-forager, the fork-tailed drongo (
Dicrurus adsimilis
), affects rates of vigilance (including sentinel behaviour) in wild dwarf mongooses (
Helogale parvula
). We simulate the presence of drongos—using playbacks of their non-alarm vocalizations—to show that dwarf mongooses significantly reduce their rate of vigilance when foraging with this species. This is, to our knowledge, the first study to demonstrate experimentally that a mammal reduces vigilance in the presence of an avian co-forager.
Fluctuating feather asymmetry in relation to corticosterone levels is sex-dependent in Eurasian treecreeper (Certhia familiaris) nestlings
Authors: Helle Samuli , Suorsa Petri , Huhta Esa , Hakkarainen Harri
Published: February 2010

Fluctuating asymmetry (FA) has been widely used as a stress-related phenotypic marker of developmental instability. However, previous studies relating FA to various stressful conditions have produced inconsistent results and we still lack quantitative individual-level evidence that high FA is related to stress in wild vertebrate species. We studied how baseline plasma levels of corticosterone predicted FA of wing and tail feathers in free-living Eurasian treecreeper (Certhia familiaris) nestlings. We found a sex-specific association between corticosterone levels and FA: high corticosterone levels were related to an increased FA in male but not in female nestlings. These results suggest that in treecreepers, FA may correlate with individual stress hormone levels, male developmental trajectory being potentially more sensitive to stress than that of the female.
The impact of clonal mixing on the evolution of social behaviour in aphids
Authors: Bryden John , Jansen Vincent A. A.
Published: February 2010

Reports of substantial clonal mixing measured in social aphid colonies seem, on the face of it, to rule out population structure as an explanation of this enigmatic insect's social behaviour. To clarify how selection operates in aphids, and to disentangle direct and indirect fitness components, we present a model of the life cycle of a typical colony-dwelling aphid. The model incorporates ecological factors and includes a trade-off between investing in social behaviour and investing in reproduction. Our focus on inclusive fitness contrasts with previous approaches that optimize colony output. Through deriving a variant of Hamilton's rule, we show that a simple relationship can be established between the patch-carrying capacity and immigration rates into patches. Our results indicate that the levels of clonal mixing reported are not inconsistent with social behaviour. We discuss our model in terms of the evolutionary origins of social behaviour in aphids.
Evolutionary bi-stability in pathogen transmission mode
Authors: van den Bosch F. , Fraaije B. A. , van den Berg F. , Shaw M. W.
Published: February 2010

Many pathogens transmit to new hosts by both infection (horizontal transmission) and transfer to the infected host's offspring (vertical transmission). These two transmission modes require specific adaptations of the pathogen that can be mutually exclusive, resulting in a trade-off between horizontal and vertical transmission. We show that in mathematical models such trade-offs can lead to the simultaneous existence of two evolutionary stable states (evolutionary bi-stability) of allocation of resources to the two modes of transmission. We also show that jumping between evolutionary stable states can be induced by gradual environmental changes. Using quantitative PCR-based estimates of abundance in seed and vegetative parts, we show that the pathogen of wheat,Phaeosphaeria nodorum, has jumped between two distinct states of transmission mode twice in the past 160 years, which, based on published evidence, we interpret as adaptation to environmental change. The finding of evolutionary bi-stability has implications for human, animal and other plant diseases. An ill-judged change in a disease control programme could cause the pathogen to evolve a new, and possibly more damaging, combination of transmission modes. Similarly, environmental changes can shift the balance between transmission modes, with adverse effects on human, animal and plant health.
Many hexapod groups originated earlier and withstood extinction events better than previously realized: inferences from supertrees
Authors: Davis Robert B. , Baldauf Sandra L. , Mayhew Peter J.
Published: February 2010

Comprising over half of all described species, the hexapods are central to understanding the evolution of global biodiversity. Direct fossil evidence suggests that new hexapod orders continued to originate from the Jurassic onwards, and diversity is presently higher than ever. Previous studies also suggest that several shifts in net diversification rate have occurred at higher taxonomic levels. However, their inferred timing is phylogeny dependent. We re-examine these issues using the supertree approach to provide, to our knowledge, the first composite estimates of hexapod order-level phylogeny. The Purvis matrix representation with parsimony method provides the most optimal supertree, but alternative methods are considered. Inferring ghost ranges shows richness of terminal lineages in the order-level phylogeny to peak just before the end-Permian extinction, rather than the present day, indicating that at least 11 more lineages survived this extinction than implied by fossils alone. The major upshift in diversification is associated with the origin of wings/wing folding and for the first time, to our knowledge, significant downshifts are shown associated with the origin of species-poor taxa (e.g. Neuropterida, Zoraptera). Polyneopteran phylogeny, especially the position of Zoraptera, remains important resolve because this influences findings regarding shifts in diversification. Our study shows how combining fossil with phylogenetic information can improve macroevolutionary inferences.
Behavioural display systems across nine
Anolis
lizard species: sexual dimorphisms in structure and function
Authors: Johnson Michele A. , Wade Juli
Published: February 2010

Relationships between structure and function are a primary focus in biology, yet they are most often considered within individual species. Sexually dimorphic communication behaviours and the morphology of associated structures can vary widely, even among closely related species, and these traits provide an ideal opportunity to investigate the evolution of structure–function patterns. Using nine
Anolis
lizard species, we addressed a series of questions regarding sex differences in and the evolution of relationships between extension of the throat fan (dewlap) and morphology of the muscles and cartilage controlling it. The main results indicated that within species, males displayed the dewlap more often than females and consistently exhibited larger associated structures. These data are consistent with work in other vertebrates in which corresponding sex differences in reproductive morphology and behaviour have been documented. Across species, however, we found no evidence that the rate of dewlap extension evolved in association with dewlap morphology. Thus, we provide an example of traits that, when considered in a phylogenetic framework, exhibited limited associations between behaviour and morphology, perhaps as the result of constraints imposed by the ecological contexts in which different species occur.
The twilight zone: ambient light levels trigger activity in primitive ants
Authors: Narendra Ajay , Reid Samuel F. , Hemmi Jan M.
Published: February 2010

Many animals become active during twilight, a narrow time window where the properties of the visual environment are dramatically different from both day and night. Despite the fact that many animals including mammals, reptiles, birds and insects become active in this specific temporal niche, we do not know what cues trigger this activity. To identify the onset of specific temporal niches, animals could anticipate the timing of regular events or directly measure environmental variables. We show that the Australian bull ant,Myrmecia pyriformis, starts foraging only during evening twilight throughout the year. The onset occurs neither at a specific temperature nor at a specific time relative to sunset, but at a specific ambient light intensity. Foraging onset occurs later when light intensities at sunset are brighter than normal or earlier when light intensities at sunset are darker than normal. By modifying ambient light intensity experimentally, we provide clear evidence that ants indeed measure light levels and do not rely on an internal rhythm to begin foraging. We suggest that the reason for restricting the foraging onset to twilight and measuring light intensity to trigger activity is to optimize the trade-off between predation risk and ease of navigation.
Spawning salmon and the phenology of emergence in stream insects
Authors: Moore Jonathan W. , Schindler Daniel E.
Published: February 2010

Phenological dynamics are controlled by environmental factors, disturbance regimes and species interactions that alter growth or mortality risk. Ecosystem engineers can be a key source of disturbance, yet their effects on the phenologies of co-occurring organisms are virtually unexplored. We investigated how the abundance of a dominant ecosystem engineer, spawning sockeye salmon (
Oncorhynchus nerka
), alters the emergence phenology of stream insects. In streams with high densities of salmon, peak insect emergence occurred in early July, immediately prior to salmon spawning. By contrast, peak insect emergence in streams with low densities of salmon was weeks later and more protracted. The emergence of specific taxa was also significantly related to salmon density. A common rearing experiment revealed that differences in emergence timing are maintained in the absence of spawning salmon. We hypothesize that these patterns are probably driven by predictable and severe disturbance from nest-digging salmon driving local adaptation and being a trait filter of insect emergence. Thus, salmon regulate the timing and duration of aquatic insect emergence, a cross-ecosystem flux from streams to riparian systems.
The dynein–tubulin motor powers active oscillations and amplification in the hearing organ of the mosquito
Authors: Warren Ben , Lukashkin Andrei N. , Russell Ian J.
Published: February 2010

The design principles and specific proteins of the dynein–tubulin motor, which powers the flagella and cilia of eukaryotes, have been conserved throughout the evolution of life from algae to humans. Cilia and flagella can support both motile and sensory functions independently, or sometimes in parallel to each other. In this paper we show that this dual sensory–motile role of eukaryotic cilia is preserved in the most sensitive of all invertebrate hearing organs, the Johnston's organ of the mosquito. The Johnston's organ displays spontaneous oscillations, which have been identified as being a characteristic of amplification in the ears of mosquitoes andDrosophila. In the auditory organs ofDrosophilaand vertebrates, the molecular basis of amplification has been attributed to the gating and adaptation of the mechanoelectrical transducer channels themselves. On the basis of their temperature-dependence and sensitivity to colchicine, we attribute the molecular basis of spontaneous oscillations by the Johnston's organ of the mosquitoCulex quinquefasciatus, to the dynein–tubulin motor of the ciliated sensillae. If, as has been claimed for insect and vertebrate hearing organs, spontaneous oscillations epitomize amplification, then in the mosquito ear, this process is independent of mechanotransduction.
Abscisic Acid-Induced Resistance against the Brown Spot Pathogen Cochliobolus miyabeanus in Rice Involves MAP Kinase-Mediated Repression of Ethylene Signaling
Authors: De Vleesschauwer David , Yang Yinong , Vera Cruz Casiana , Höfte Monica
Published: February 2010

The plant hormone abscisic acid (ABA) is involved in an array of plant processes, including the regulation of gene expression during adaptive responses to various environmental cues. Apart from its well-established role in abiotic stress adaptation, emerging evidence indicates that ABA is also prominently involved in the regulation and integration of pathogen defense responses. Here, we demonstrate that exogenously administered ABA enhances basal resistance of rice (Oryza sativa) against the brown spot-causing ascomycete Cochliobolus miyabeanus. Microscopic analysis of early infection events in control and ABA-treated plants revealed that this ABA-inducible resistance (ABA-IR) is based on restriction of fungal progression in the mesophyll. We also show that ABA-IR does not rely on boosted expression of salicylic acid-, jasmonic acid -, or callose-dependent resistance mechanisms but, instead, requires a functional Gα-protein. In addition, several lines of evidence are presented suggesting that ABA steers its positive effect on brown spot resistance through antagonistic cross talk with the ethylene (ET) response pathway. Exogenous ethephon application enhances susceptibility, whereas genetic disruption of ET signaling renders plants less vulnerable to C. miyabeanus attack, thereby inducing a level of resistance similar to that observed on ABA-treated wild-type plants. Moreover, ABA treatment alleviates C. miyabeanus-induced activation of the ET reporter gene EBP89, while derepression of pathogen-triggered EBP89 transcription via RNA interference-mediated knockdown of OsMPK5, an ABA-primed mitogen-activated protein kinase gene, compromises ABA-IR. Collectively, these data favor a model whereby exogenous ABA enhances resistance against C. miyabeanus at least in part by suppressing pathogen-induced ET action in an OsMPK5-dependent manner.
A Novel MYBS3-Dependent Pathway Confers Cold Tolerance in Rice
Authors: Su Chin-Fen , Wang Yi-Chieh , Hsieh Tsai-Hung , Lu Chung-An , Tseng Tung-Hai , Yu Su-May
Published: February 2010

Rice (Oryza sativa) seedlings are particularly sensitive to chilling in early spring in temperate and subtropical zones and in high-elevation areas. Improvement of chilling tolerance in rice may significantly increase rice production. MYBS3 is a single DNA-binding repeat MYB transcription factor previously shown to mediate sugar signaling in rice. In this study, we observed that MYBS3 also plays a critical role in cold adaptation in rice. Gain- and loss-of-function analyses indicated that MYBS3 was sufficient and necessary for enhancing cold tolerance in rice. Transgenic rice constitutively overexpressing MYBS3 tolerated 4°C for at least 1 week and exhibited no yield penalty in normal field conditions. Transcription profiling of transgenic rice overexpressing or underexpressing MYBS3 led to the identification of many genes in the MYBS3-mediated cold signaling pathway. Several genes activated by MYBS3 as well as inducible by cold have previously been implicated in various abiotic stress responses and/or tolerance in rice and other plant species. Surprisingly, MYBS3 repressed the well-known DREB1/CBF-dependent cold signaling pathway in rice, and the repression appears to act at the transcriptional level. DREB1 responded quickly and transiently while MYBS3 responded slowly to cold stress, which suggests that distinct pathways act sequentially and complementarily for adapting short- and long-term cold stress in rice. Our studies thus reveal a hitherto undiscovered novel pathway that controls cold adaptation in rice.
Contextual risk, maternal parenting and adolescent externalizing behaviour problems: the role of emotion regulation
Authors: Walton A. , Flouri E.
Published: February 2010

Background  The objective of this study was to test if emotion regulation mediates the association between mothers' parenting and adolescents' externalizing behaviour problems (conduct problems and hyperactivity). The parenting dimensions were warmth, psychological control and behavioural control (measured with knowledge, monitoring and discipline). Adjustment was made for contextual risk (measured with the number of proximal adverse life events experienced), gender, age and English as an additional language.

Method  Data were from a UK community sample of adolescents aged 11–18 from a comprehensive school in a disadvantaged area.

Results  At the multivariate level, none of the parenting variables predicted hyperactivity, which was associated only with difficulties in emotion regulation, contextual risk and English as a first language. The parenting variables predicting conduct problems at the multivariate level were warmth and knowledge. Knowledge did not predict emotion regulation. However, warmth predicted emotion regulation, which was negatively associated with conduct problems. Contextual risk was a significant predictor of both difficulties in emotion regulation and externalizing behaviour problems. Its effect on conduct problems was independent of parenting and was not via its association with difficulties in emotion regulation.

Conclusions  The findings add to the evidence for the importance of maternal warmth and contextual risk for both regulated emotion and regulated behaviour. The small maternal control effects on both emotion regulation and externalizing behaviour could suggest the importance of paternal control for adolescent outcomes.
Testicular dysgenesis syndrome comprises some but not all cases of hypospadias and impaired spermatogenesis
Authors: Jørgensen N. , Meyts E. Rajpert‐De , Main K. M. , Skakkebæk N. E.
Published: February 2010

In 2001, when the testicular dysgenesis syndrome (TDS) concept was proposed, it suggested that impaired development of foetal testes could lead to increased risks of cryptorchidism, hypospadias, decreased spermatogenesis or testis cancer. The TDS concept links the pathogenesis of the four disorders together, but does not imply that all affected men develop all four symptoms. The least affected men may merely have a slightly reduced spermatogenic capacity, and only the most severely affected may present all symptoms. A majority of cases of testicular germ cell cancers (TGCC) and cryptorchidism are most likely caused by TDS. However, the frequency of the syndrome in the general population and to what extent poor semen quality and hypospadias are actually biologically related through a foetal mechanism remain unresolved. Hypospadias and impaired spermatogenesis can be classified as TDS if combined with cryptorchidism or TGCC. By contrast, recent studies demonstrated that among men with isolated hypospadias, only a fraction of cases are linked to TDS. There is no doubt that TDS contributes to impaired semen quality. This is most obvious for cases with visible dysgenetic features in testis histology, but in the majority of men with impaired semen quality as the only symptom, an association with TDS is less clear. Such cases have a very heterogeneous aetiology and may be caused by a host of other – often post‐natal‐factors. In conclusion, the TDS as a holistic concept has inspired new research activities and led to a better understanding of the early origin of male reproductive problems, but it clearly encompasses only a fraction of cases of hypospadias and impaired spermatogenesis.
Atomic force microscopy: probing the spatial organization, interactions and elasticity of microbial cell envelopes at molecular resolution
Authors: Scheuring Simon , Dufrêne Yves F.
Published: February 2010

Although much is known about the structure and biosynthesis of microbial cell envelope constituents, the three‐dimensional organization, assembly and interactions of the individual components remain poorly understood. How do cell walls remodel during cell growth or incubation with drugs? What is the supramolecular architecture of proteins in bacterial surface layers, in outer membranes and in intracytoplasmic membranes? What is the spatial arrangement of cell surface receptors, clustered or homogeneous? What are the adhesive and mechanical properties of cell surface proteins and how are they related to function? Traditionally, these questions have been difficult – or impossible – to address owing to the lack of high‐resolution single‐cell and single‐molecule probing techniques. With its ability to observe and force probe the cell envelope down to the molecular level under physiological conditions, atomic force microscopy (AFM) has recently offered new opportunities in molecular microbiology. While high‐resolution AFM imaging is a powerful tool for visualizing the architecture of cells and membranes in buffer solution, force spectroscopy offers a means to analyse the localization, interactions and elasticity of their individual constituents. These nanoscale experiments complement microscopy, genetics and biochemical methods traditionally used to analyse the microbial envelope.
Staphylococcus aureus enterotoxin B augments granulocyte migration and survival via airway epithelial cell activation
Authors: Huvenne W. , Callebaut I. , Reekmans K. , Hens G. , Bobic S. , Jorissen M. , Bullens D. M. A. , Ceuppens J. L. , Bachert C. , Hellings P. W.
Published: February 2010

To cite this article: Huvenne W, Callebaut I, Reekmans K, Hens G, Bobic S, Jorissen M, Bullens DMA, Ceuppens JL, Bachert C, Hellings PW. Staphylococcus aureus enterotoxin B augments granulocyte migration and survival via airway epithelial cell activation. Allergy 2010; 65: 1013–1020.

Background:  Staphylococcus aureus enterotoxin B (SEB) has recently been postulated to be involved in the pathology of granulocyte‐dominated disease. Studying the immunologic interaction between SEB and airway epithelial cells in immortalized cell lines or long‐term epithelial cell cultures has obvious disadvantages.

Methods:  We used a novel technique of freshly isolated and purified human nasal epithelial cells (HNEC) from healthy, nonallergic individuals, which were incubated for 24 h without/with SEB at different concentrations. Chemokine production was evaluated in the supernatant using Cytometric Bead Array. The chemotactic activity of the supernatant was studied in vitro using a Boyden chamber. Survival was evaluated with flow cytometry, using propidium iodide to identify dead cells.

Results:  Staphylococcus aureus enterotoxin B showed a dose‐dependent induction of interferon‐inducible protein‐10, monokine induced by interferon‐γ, regulated upon activation normal T cell expressed and secreted, monocyte chemoattractant protein 1 (MCP‐1) and granulocyte colony stimulating factor production by epithelial cells in vitro. The supernatant of epithelial cells had chemotactic activity for granulocytes in vitro, which was enhanced in the supernatant of SEB‐stimulated epithelial cells. Reduced number of propidium iodide positive granulocytes was found in the conditions where supernatant of SEB‐stimulated epithelial cells was applied.

Conclusion:  Staphylococcus aureus enterotoxin B exerts a direct pro‐inflammatory effect on HNEC, with induction of chemokine and growth factor release, resulting in the migration and prolonged survival of granulocytes in vitro.
Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema
Authors: Jungersted J. M. , Scheer H. , Mempel M. , Baurecht H. , Cifuentes L. , Høgh J. K. , Hellgren L. I. , Jemec G. B. E. , Agner T. , Weidinger S.
Published: February 2010

To cite this article: Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK, Hellgren LI, Jemec GBE, Agner T, Weidinger S. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. Allergy 2010; 65: 911–918.

Background:  Prior to the discovery of filaggrin (FLG) mutations, evidence for an impaired skin barrier in atopic dermatitis (AD) has been documented, and changes in ceramide profile, altered skin pH and increased trans‐epidermal water loss (TEWL) in patients with AD have been reported. Until now, no studies have analysed stratum corneum (SC) lipids combined with skin barrier parameters in subjects of known FLG genotype.

Methods:  A cohort of 49 German individuals genotyped for the most common FLG mutations (R501X, 2282del4) had SC samples taken for lipid analysis by high‐performance thin layer chromatography. In addition, TEWL, erythema, skin hydration and pH were measured. In 27 of the 49 individuals, a 24‐h irritation patch test with sodium lauryl sulphate was performed. For the analysis, both the AD group and the control group were stratified by FLG mutation status (FLGmut/FLGwt).

Results:  In the FLGmut AD group, significantly lower levels of ceramide 4 and significantly higher levels of ceramide 7 were observed when compared to both healthy control groups. However, ceramide 7 levels also significantly differed between FLGwt AD and FLGwt controls, as did ceramide 1 levels. No significant differences were observed for ceramide 2, 3, 5 and 6. FLGmut individuals had significantly higher skin pH values than individuals not carrying FLG mutations. Patients with AD with FLG mutations had significantly higher erythema compared to patients with AD without FLG mutations.

Conclusion:  Our results confirm previous observations of altered ceramide levels in AD, which however appear to show no clear relationship with FLG mutations.
Novel and recurrent p14ARF mutations in Italian familial melanoma
Authors: Binni F , Antigoni I , De Simone P , Majore S , Silipo V , Crisi A , Amantea A , Pacchiarini D , Castori M , De Bernardo C , Catricalà C , Grammatico P
Published: February 2010

Binni F, Antigoni I, De Simone P, Majore S, Silipo V, Crisi A, Amantea A, Pacchiarini D, Castori M, De Bernardo C, Catricalà C, Grammatico P. Novel and recurrent p14ARF mutations in Italian familial melanoma.

CDKN2A and CDK4 are the only known high‐penetrant genes conferring proneness to cutaneous melanoma. The CDKN2A locus consists of four exons and encodes several alternate transcripts, two of which are p16INK4a and p14ARF, and originate from different open reading frames. Exon 1α is specific for p16INK4a, while exon 1β characterizes p14ARF. Most CDKN2A mutations are located in exons 1α and 2, while exon 1β variations have been identified in rare melanoma‐prone pedigrees. In a previous study, we investigated 155 Italian melanoma cases, including 94 familial melanomas (FAMs) and 61 sporadic multiple primary melanomas (MPMs), for p16INK4a/CDK4 germline alterations and identified 15 p16INK4a and 1 CDK4 point mutations. In the present work, we extended our search to p14ARF mutations and CDKN2A deletions in the remaining samples. We identified the recurrent g.193+1G> A mutation in two FAM cases, while an additional pedigree displayed the previously undescribed variant g.161G> A. Multiplex ligation‐dependent probe amplification (MLPA) screening for copy variations resulted negative in all cases. In Italy, the overall frequency of p14ARF mutations is 3.2% in FAM and 0% in sporadic MPM. Re‐evaluation of our patients' cohort emphasizes that the chance of identifying CDKN2A/CDK4 mutations in FAM is mainly influenced by the number of affected family members and the presence of one or more MPM cases. Accordingly, mutation rate rises to 61% in selected cases. Further studies are expected in order to investigate CDKN2A rarer mutations, including atypical deletions and inherited epimutations.