Drosophila 3′ UTRs are more complex than protein-coding sequences

The 3′ UTRs of eukaryotic genes participate in a variety of post-transcriptional (and some transcriptional) regulatory interactions. Some of these interactions are well characterised, but an undetermined number remain to be discovered. While some regulatory sequences in 3′ UTRs may be conserved over long evolutionary time scales, others may have only ephemeral functional significance as regulatory profiles respond to changing selective pressures. Here we propose a sensitive segmentation methodology for investigating patterns of composition and conservation in 3′ UTRs based on comparison of closely related species. We describe encodings of pairwise and three-way alignments integrating information about conservation, GC content and transition/transversion ratios and apply the method to three closely related Drosophila species: D. melanogaster, D. simulans and D. yakuba. Incorporating multiple data types greatly increased the number of segment classes identified compared to similar methods based on conservation or GC content alone. We propose that the number of segments and number of types of segment identified by the method can be used as proxies for functional complexity. Our main finding is that the number of segments and segment classes identified in 3′ UTRs is greater than in the same length of protein-coding sequence, suggesting greater functional complexity in 3′ UTRs. There is thus a need for sustained and extensive efforts by bioinformaticians to delineate functional elements in this important genomic fraction. C code, data and results are available upon request.

Visualization of long-duration acoustic recordings of the environment

Acoustic recordings of the environment are an important aid to ecologists monitoring biodiversity and environmental health. However, rapid advances in recording technology, storage and computing make it possible to accumulate thousands of hours of recordings, of which, ecologists can only listen to a small fraction. The big-data challenge addressed in this paper is to visualize the content of long-duration audio recordings on multiple scales, from hours, days, months to years. The visualization should facilitate navigation and yield ecologically meaningful information. Our approach is to extract (at one minute resolution) acoustic indices which reflect content of ecological interest. An acoustic index is a statistic that summarizes some aspect of the distribution of acoustic energy in a recording. We combine indices to produce false-color images that reveal acoustic content and facilitate navigation through recordings that are months or even years in duration.

Long-term exploration and tours for energy constrained robots with online proprioceptive traversability estimation

This paper is concerned with how a localised and energy-constrained robot can maximise its time in the field by taking paths and tours that minimise its energy expenditure. A significant component of a robot's energy is expended on mobility and is a function of terrain traversability. We estimate traversability online from data sensed by the robot as it moves, and use this to generate maps, explore and ultimately converge on minimum energy tours of the environment. We provide results of detailed simulations and parameter studies that show the efficacy of this approach for a robot moving over terrain with unknown traversability as well as a number of a priori unknown hard obstacles.

Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: Potential markers for aggressive phenotypes

BACKGROUND AND OBJECTIVES Polymorphisms of the VEGF gene are known to affect the biological behaviour of cancers but have seldom been studied in thyroid cancer. The aim of the current study is to evaluate the prevalence and relevance of VEGF-A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC). MATERIALS AND METHODS Genomic DNA and total RNA were isolated from paraffin-embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and 78 control thyroid tissues. Three DNA polymorphisms (+936C > T, +405C > G and -141A > C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues was studied by real-time PCR. RESULTS Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (p = 0.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (p = 0.009). Within the group of patients with conventional PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA expression than other patients (p = 0.0003). CONCLUSION These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.

Effect of broadcast baiting on abundance patterns of red imported fire ants (Hymenoptera: Formicidae) and key local ant genera at long-term monitoring sites in Brisbane, Australia

In 2001, the red imported fire ant (Solenopsis invicta Buren) was identified in Brisbane, Australia. An eradication program involving broadcast bait treatment with two insect growth regulators and a metabolic inhibitor began in September of that year and is currently ongoing. To gauge the impacts of these treatments on local ant populations, we examined long-term monitoring data and quantified abundance patterns of S. invicta and common local ant genera using a linear mixed-effects model. For S. invicta, presence in pitfalls reduced over time to zero on every site. Significantly higher numbers of S. invicta workers were collected on high-density polygyne sites, which took longer to disinfest compared with monogyne and low-density polygyne sites. For local ants, nine genus groups of the 10 most common genera analyzed either increased in abundance or showed no significant trend. Five of these genus groups were significantly less abundant at the start of monitoring on high-density polygyne sites compared with monogyne and low-density polygyne sites. The genus Pheidole significantly reduced in abundance over time, suggesting that it was affected by treatment efforts. These results demonstrate that the treatment regime used at the time successfully removed S. invicta from these sites in Brisbane, and that most local ant genera were not seriously impacted by the treatment. These results have important implications for current and future prophylactic treatment efforts, and suggest that native ants remain in treated areas to provide some biological resistance to S. invicta.

The Saccharomyces cerevisiae RNA-binding protein Rbp29 functions in cytoplasmic mRNA metabolism

Here we report that the Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encodes a 29-kDa cytoplasmic protein that binds to mRNA in vivo. Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosageand RNA-dependent manner. In addition, recombinant Rbp29p binds preferentially to poly(A) with nanomolar binding affinity in vitro. Although RBP29 is not essential for cell viability, its deletion exacerbates the slow growth phenotype of yeast strains harboring mutations in the eIF4G genes TIF4631 and TIF4632. Furthermore, overexpression of RBP29 suppresses the temperaturesensitive growth phenotype of specific tif4631, tif4632, and pab1 alleles. These data suggest that Rbp29p is an mRNA-binding protein that plays a role in modulating the expression of cytoplasmic mRNA.

Yhh1p/Cft1p directly links poly(A) site recognition and RNA polymerase II transcription termination

RNA polymerase II (pol II) transcription termination requires co‐transcriptional recognition of a functional polyadenylation signal, but the molecular mechanisms that transduce this signal to pol II remain unclear. We show that Yhh1p/Cft1p, the yeast homologue of the mammalian AAUAAA interacting protein CPSF 160, is an RNA‐binding protein and provide evidence that it participates in poly(A) site recognition. Interestingly, RNA binding is mediated by a central domain composed of predicted β‐propeller‐forming repeats, which occurs in proteins of diverse cellular functions. We also found that Yhh1p/Cft1p bound specifically to the phosphorylated C‐terminal domain (CTD) of pol II in vitro and in a two‐hybrid test in vivo. Furthermore, transcriptional run‐on analysis demonstrated that yhh1 mutants were defective in transcription termination, suggesting that Yhh1p/Cft1p functions in the coupling of transcription and 3′‐end formation. We propose that direct interactions of Yhh1p/Cft1p with both the RNA transcript and the CTD are required to communicate poly(A) site recognition to elongating pol II to initiate transcription termination.

An adaptive appearance-based map for long-term topological localization of mobile robots

"This work considers a mobile service robot which uses an appearance-based representation of its workplace as a map, where the current view and the map are used to estimate the current position in the environment. Due to the nature of real-world environments such as houses and offices, where the appearance keeps changing, the internal representation may become out of date after some time. To solve this problem the robot needs to be able to adapt its internal representation continually to the changes in the environment. This paper presents a method for creating an adaptive map for long-term appearance-based localization of a mobile robot using long-term and short-term memory concepts, with omni-directional vision as the external sensor."--publisher website

Long-term experiments with an adaptive spherical view representation for navigation in changing environments

Real-world environments such as houses and offices change over time, meaning that a mobile robot’s map will become out of date. In this work, we introduce a method to update the reference views in a hybrid metrictopological map so that a mobile robot can continue to localize itself in a changing environment. The updating mechanism, based on the multi-store model of human memory, incorporates a spherical metric representation of the observed visual features for each node in the map, which enables the robot to estimate its heading and navigate using multi-view geometry, as well as representing the local 3D geometry of the environment. A series of experiments demonstrate the persistence performance of the proposed system in real changing environments, including analysis of the long-term stability.

Toward an object-based semantic memory for long-term operation of mobile service robots

Throughout a lifetime of operation, a mobile service robot needs to acquire, store and update its knowledge of a working environment. This includes the ability to identify and track objects in different places, as well as using this information for interaction with humans. This paper introduces a long-term updating mechanism, inspired by the modal model of human memory, to enable a mobile robot to maintain its knowledge of a changing environment. The memory model is integrated with a hybrid map that represents the global topology and local geometry of the environment, as well as the respective 3D location of objects. We aim to enable the robot to use this knowledge to help humans by suggesting the most likely locations of specific objects in its map. An experiment using omni-directional vision demonstrates the ability to track the movements of several objects in a dynamic environment over an extended period of time.

miRPlant : an integrated tool for identification of plant miRNA from RNA sequencing data

Background Small RNA sequencing is commonly used to identify novel miRNAs and to determine their expression levels in plants. There are several miRNA identification tools for animals such as miRDeep, miRDeep2 and miRDeep*. miRDeep-P was developed to identify plant miRNA using miRDeep’s probabilistic model of miRNA biogenesis, but it depends on several third party tools and lacks a user-friendly interface. The objective of our miRPlant program is to predict novel plant miRNA, while providing a user-friendly interface with improved accuracy of prediction. Result We have developed a user-friendly plant miRNA prediction tool called miRPlant. We show using 16 plant miRNA datasets from four different plant species that miRPlant has at least a 10% improvement in accuracy compared to miRDeep-P, which is the most popular plant miRNA prediction tool. Furthermore, miRPlant uses a Graphical User Interface for data input and output, and identified miRNA are shown with all RNAseq reads in a hairpin diagram. Conclusions We have developed miRPlant which extends miRDeep* to various plant species by adopting suitable strategies to identify hairpin excision regions and hairpin structure filtering for plants. miRPlant does not require any third party tools such as mapping or RNA secondary structure prediction tools. miRPlant is also the first plant miRNA prediction tool that dynamically plots miRNA hairpin structure with small reads for identified novel miRNAs. This feature will enable biologists to visualize novel pre-miRNA structure and the location of small RNA reads relative to the hairpin. Moreover, miRPlant can be easily used by biologists with limited bioinformatics skills.

Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models

Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, we established stable populations of BPH-1, PNT1B and RWPE-1 immortalized human PrEC lines that constitutively express flag-tagged ERG3 (fERG). All fERG-expressing populations exhibited characteristics of in vitro and in vivo transformation. Microarray analysis revealed >2000 commonly dysregulated genes in the fERG-PrEC lines. Functional analysis revealed evidence that fERG cells underwent EMT and acquired invasive characteristics. The fERG-induced EMT transcript signature was exemplified by suppressed expression of E-cadherin and keratins 5, 8, 14 and 18; elevated expression of N-cadherin, N-cadherin 2 and vimentin, and of the EMT transcriptional regulators Snail, Zeb1 and Zeb2, and lymphoid enhancer-binding factor-1 (LEF-1). In BPH-1 and RWPE-1-fERG cells, fERG expression is correlated with increased expression of integrin-linked kinase (ILK) and its downstream effectors Snail and LEF-1. Interfering RNA suppression of ERG decreased expression of ILK, Snail and LEF-1, whereas small interfering RNA suppression of ILK did not alter fERG expression. Interfering RNA suppression of ERG or ILK impaired fERG-PrEC Matrigel invasion. Treating fERG-BPH-1 cells with the small molecule ILK inhibitor, QLT-0267, resulted in dose-dependent suppression of Snail and LEF-1 expression, Matrigel invasion and reversion of anchorage-independent growth. These results suggest that ILK is a therapeutically targetable mediator of ERG-induced EMT and transformation in PCa.

In for the long haul : family business succession at HaulageCo

This is a case about family business succession. Because many successions fail, the 'problem of succession' is a key issue in the family business field (see Aronoff 1998; Bird eta/. 2002; Dyer & Sanchez 1998; Sharma 2004; Zalu·a & Sharma 2004). Indeed, from the non-family business literature, we know one third of relay successions - like this case where there is an identified successor - will fail, with the prospective CEO leaving before succeeding the incumbent CEO (Cmmella & Shen 2001). Research on next generation family business members is limited. Successor ath·ibutes (Chrisman, Chua & Sharma 1998; Sharma & Rao 2000), as well as various characteristics such as socialisation (Garcia-Aivmez, L6pez-Sintas & Gonzalvo 2002) a11d gender (Haberman & Danes 2007; Vera & Dean 2005) have all been considered to play a role. So too have successor intentions (Stavrou & Swiercz 1998), motivation (Le Breton-Miller, Miller & Steier 2004), commitment (Sharma & Irving 2005) and transformation from follower to leadership (Cater & Justis 2009). In this case, by outlining the socialisation of the successors, explanations of their motivations for joining a11d their current employment we can begin to see some of the underlying mechanisms at work motivating the next generation to join and stay in the family business.

Biceps femoris long-head architecture: A reliability and retrospective injury study

Purpose: To determine i) the reliability of two-dimensional ultrasonography for the assessment of biceps femoris long head (BFlh) architectural characteristics; ii) if limbs with a history of strain injury in the BFlh display different architecture and eccentric strength compared to uninjured limbs. Methods: This case-control study (control [n=20], injured group [n=16], males) assessed the BFlh architecture at rest and during graded isometric contractions using two-dimensional ultrasonography. The control group were assessed three times (>24hrs apart) to determine reliability. Previously injured individuals were evaluated once. Results The assessment of BFlh architecture was highly reliable (intraclass correlations >0.90). Fascicle length (p<0.001; d range: 0.67 to 1.34) and fascicle length relative to muscle thickness (p<0.001; d range: 0.58 to 0.85) of the previously injured BFlh were significantly less than the contralateral uninjured BFlh at all intensities. Pennation angle of the previously injured BFlh was significantly greater (p<0.001; d range: 0.62 to 0.88) than the contralateral uninjured BFlh at all intensities. Eccentric strength in the previously injured limb was significantly lower than the contralateral limb (-15.4%; -52.5N; 95% CI=-28.45 to -76.23; p<0.001, d=0.56). Conclusion These data indicate that two-dimensional ultrasonography is reliable for assessing BFlh architecture at rest and during graded isometric contractions. Fascicle length, fascicle length relative to muscle thickness and pennation angle are significantly different in previously injured BFlh compared to an uninjured contralateral BFlh. Eccentric strength of the previously injured limb is also significantly lower than the uninjured contralateral limb. These findings have implications for rehabilitation and injury prevention practices which should consider altered architectural characteristics.

Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing

Increasing evidence suggests that chromatin modifications have important roles in modulating constitutive or alternative splicing. Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically recognize tri-methylated H3K36 and that, like this histone modification, the Psip1 short (p52) isoform is enriched at active genes. We show that the p52, but not the long (p75), isoform of Psip1 co-localizes and interacts with Srsf1 and other proteins involved in mRNA processing. The level of H3K36me3 associated Srsf1 is reduced in Psip1 mutant cells and alternative splicing of specific genes is affected. Moreover, we show altered Srsf1 distribution around the alternatively spliced exons of these genes in Psip1 null cells. We propose that Psip1/p52, through its binding to both chromatin and splicing factors, might act to modulate splicing.