Novel OTOF mutations in Brazilian patients with auditory neuropathy

The OTOF gene encoding otoferlin is associated with auditory neuropathy (AN), a type of non-syndromic deafness. We investigated the contribution of OTOF mutations to AN and to non-syndromic recessive deafness in Brazil. A test for the Q829X mutation was carried out on a sample of 342 unrelated individuals with non-syndromic hearing loss, but none presented this mutation. We selected 48 cases suggestive of autosomal recessive inheritance, plus four familial and seven isolated cases of AN, for genotyping of five microsatellite markers linked to the OTOF gene. The haplotype analysis showed compatibility with linkage in 11 families (including the four families with AN). Samples of the 11 probands from these families and from seven isolated cases of AN were selected for an exon-by-exon screening for mutations in the OTOF gene. Ten different pathogenic variants were detected, among which six are novel. Among the 52 pedigrees with autosomal recessive inheritance (including four familial cases of AN), mutations were identified in 4 (7.7%). Among the 11 probands with AN, seven had at least one pathogenic mutation in the OTOF gene. Mutations in the OTOF gene are frequent causes of AN in Brazil and our results confirm that they are spread worldwide. Journal of Human Genetics (2009) 54, 382-385; doi: 10.1038/jhg.2009.45; published online 22 May 2009

Semantic oscillations : encoding context and structure in complex valued holographic vectors

In computational linguistics, information retrieval and applied cognition, words and concepts are often represented as vectors in high dimensional spaces computed from a corpus of text. These high dimensional spaces are often referred to as Semantic Spaces. We describe a novel and efficient approach to computing these semantic spaces via the use of complex valued vector representations. We report on the practical implementation of the proposed method and some associated experiments. We also briefly discuss how the proposed system relates to previous theoretical work in Information Retrieval and Quantum Mechanics and how the notions of probability, logic and geometry are integrated within a single Hilbert space representation. In this sense the proposed system has more general application and gives rise to a variety of opportunities for future research.

Identification of a cryptic Prokaryotic promoter within the cDNA encoding the 5′ End of Dengue Virus RNA Genome

Infectious cDNA clones of RNA viruses are important research tools, but flavivirus cDNA clones have proven difficult to assemble and propagate in bacteria. This has been attributed to genetic instability and/or host cell toxicity, however the mechanism leading to these difficulties has not been fully elucidated. Here we identify and characterize an efficient cryptic bacterial promoter in the cDNA encoding the dengue virus (DENV) 5′ UTR. Following cryptic transcription in E. coli, protein expression initiated at a conserved in-frame AUG that is downstream from the authentic DENV initiation codon, yielding a DENV polyprotein fragment that was truncated at the N-terminus. A more complete understanding of constitutive viral protein expression in E. coli might help explain the cloning and propagation difficulties generally observed with flavivirus cDNA.

A tensor encoding model for semantic processing

This paper develops and evaluates an enhanced corpus based approach for semantic processing. Corpus based models that build representations of words directly from text do not require pre-existing linguistic knowledge, and have demonstrated psychologically relevant performance on a number of cognitive tasks. However, they have been criticised in the past for not incorporating sufficient structural information. Using ideas underpinning recent attempts to overcome this weakness, we develop an enhanced tensor encoding model to build representations of word meaning for semantic processing. Our enhanced model demonstrates superior performance when compared to a robust baseline model on a number of semantic processing tasks.

Semantic judgement of medical concepts : combining syntagmatic and paradigmatic information with the tensor encoding model

This paper outlines a novel approach for modelling semantic relationships within medical documents. Medical terminologies contain a rich source of semantic information critical to a number of techniques in medical informatics, including medical information retrieval. Recent research suggests that corpus-driven approaches are effective at automatically capturing semantic similarities between medical concepts, thus making them an attractive option for accessing semantic information. Most previous corpus-driven methods only considered syntagmatic associations. In this paper, we adapt a recent approach that explicitly models both syntagmatic and paradigmatic associations. We show that the implicit similarity between certain medical concepts can only be modelled using paradigmatic associations. In addition, the inclusion of both types of associations overcomes the sensitivity to the training corpus experienced by previous approaches, making our method both more effective and more robust. This finding may have implications for researchers in the area of medical information retrieval.

On robust face recognition via sparse encoding : the good, the bad, and the ugly

In the field of face recognition, Sparse Representation (SR) has received considerable attention during the past few years. Most of the relevant literature focuses on holistic descriptors in closed-set identification applications. The underlying assumption in SR-based methods is that each class in the gallery has sufficient samples and the query lies on the subspace spanned by the gallery of the same class. Unfortunately, such assumption is easily violated in the more challenging face verification scenario, where an algorithm is required to determine if two faces (where one or both have not been seen before) belong to the same person. In this paper, we first discuss why previous attempts with SR might not be applicable to verification problems. We then propose an alternative approach to face verification via SR. Specifically, we propose to use explicit SR encoding on local image patches rather than the entire face. The obtained sparse signals are pooled via averaging to form multiple region descriptors, which are then concatenated to form an overall face descriptor. Due to the deliberate loss spatial relations within each region (caused by averaging), the resulting descriptor is robust to misalignment & various image deformations. Within the proposed framework, we evaluate several SR encoding techniques: l1-minimisation, Sparse Autoencoder Neural Network (SANN), and an implicit probabilistic technique based on Gaussian Mixture Models. Thorough experiments on AR, FERET, exYaleB, BANCA and ChokePoint datasets show that the proposed local SR approach obtains considerably better and more robust performance than several previous state-of-the-art holistic SR methods, in both verification and closed-set identification problems. The experiments also show that l1-minimisation based encoding has a considerably higher computational than the other techniques, but leads to higher recognition rates.

A tensor encoding model of word meaning : theory and application to information retrieval

This project was a step forward in developing and evaluating a novel, mathematical model that can deduce the meaning of words based on their use in language. This model can be applied to a wide range of natural language applications, including the information seeking process most of us undertake on a daily basis.

Some extensions to representation and encoding of structure in models of distributional semantics

This thesis makes several contributions towards improved methods for encoding structure in computational models of word meaning. New methods are proposed and evaluated which address the requirement of being able to easily encode linguistic structural features within a computational representation while retaining the ability to scale to large volumes of textual data. Various methods are implemented and evaluated on a range of evaluation tasks to demonstrate the effectiveness of the proposed methods.

“Freer than we Feel” : Applying the Critical Dimension of Consciousness to Children’s Multimodal Encoding

Reports of children and teachers taking transformative social action in schools are becoming rare. This session illustrates how teachers, while feeling the weight of accountability testing in schools, are active agents who can re-imagine literacy pedagogy to change elements of their community. It reports the critical dimensions of a movie-making unit with Year 5 students within a school reform project. The students filmed interviews with people in the local shops to gather lay-knowledge and experiences of the community. The short documentaries challenged stereotypes about what it is like to live in Logan, and critically identified potential improvements to public spaces in the local community. A student panel presented these multimodal texts at a national conference of social activists and community leaders. The report does not valorize or privilege local or lay knowledge over dominant knowledge, but argues that prescribed curriculum should not hinder the capacity for critical consciousness.

Small RNA sequencing of potato leafroll virus-infected plants reveals an additional subgenomic RNA encoding a sequence-specific RNA-binding protein

Potato leafroll virus (PLRV) is a positive-strand RNA virus that generates subgenomic RNAs (sgRNA) for expression of 3' proximal genes. Small RNA (sRNA) sequencing and mapping of the PLRV-derived sRNAs revealed coverage of the entire viral genome with the exception of four distinctive gaps. Remarkably, these gaps mapped to areas of PLRV genome with extensive secondary structures, such as the internal ribosome entry site and 5' transcriptional start site of sgRNA1 and sgRNA2. The last gap mapped to ~500. nt from the 3' terminus of PLRV genome and suggested the possible presence of an additional sgRNA for PLRV. Quantitative real-time PCR and northern blot analysis confirmed the expression of sgRNA3 and subsequent analyses placed its 5' transcriptional start site at position 5347 of PLRV genome. A regulatory role is proposed for the PLRV sgRNA3 as it encodes for an RNA-binding protein with specificity to the 5' of PLRV genomic RNA. © 2013.

A single copy of a virus-derived transgene encoding hairpin RNA gives immunity to barley yellow dwarf virus

Barley yellow dwarf virus-PAV (BYDV-PAV) is the most serious and widespread virus of cereals worldwide. Natural resistance genes against this luteovirus give inadequate control, and previous attempts to introduce synthetic resistance into cereals have produced variable results. In an attempt to generate barley with protection against BYDV-PAV, plants were transformed with a transgene designed to produce hairpin (hp)RNA containing BYDV-PAV sequences. From 25 independent barley lines transformed with the BYDV-PAV hpRNA construct, nine lines showed extreme resistance to the virus and the majority of these contained a single transgene. In the progeny of two independent transgenic lines, inheritance of a single transgene consistently correlated with protection against BYDV-PAV. This protection was rated as immunity because the virus could not be detected in the challenged plants by ELISA nor recovered by aphid feeding experiments. In the field, BYDV-PAV is sometimes associated with the related luteovirus Cereal yellow dwarf virus-RPV (CYDV-RPV). When the transgenic plants were challenged with BYDV-PAV and CYDV-RPV together, the plants were susceptible to CYDV-RPV but immune to BYDV-PAV. This shows that the immunity is virus-specific and not broken down by the presence of CYDV. It suggests that CYDV-RPV does not encode a silencing-suppressor gene or that its product does not protect BYDV-PAV against the plant's RNAi-like defence mechanism. Either way, our results indicate that the BYDV-PAV immunity will be robust in the field and is potentially useful in minimizing losses in cereal production worldwide.

A gene encoding a new cold-active lipase from an Antarctic isolate of Penicillium expansum

Cold-active lipases are of significant interest as biocatalysts in industrial processes. We have identified a lipase that displayed activity towards long carbon-chain-p-nitrophenyl substrates (C12–C18) at 25 °C from the culture supernatant of an Antarctic Penicillium expansum strain assigned P. expansum SM3. Zymography revealed a protein band of around 30 kDa with activity towards olive oil. DNA fragments of a lipase gene designated as lipPE were isolated from the genomic DNA of P. expansum SM3 by genomic walking PCR. Subsequently, the complete genomic lipPE gene was amplified using gene-specific primers designed from the 5′- and 3′-regions. Reverse transcription PCR was used to amplify the lipPE cDNA. The deduced amino acid sequence consisted of 285 residues that included a predicted signal peptide. Three peptides identified by LC/MS/MS analysis of the proteins in the culture supernatant of P. expansum were also present in the deduced amino acid sequence of the lipPE gene suggesting that this gene encoded the lipase identified by initial zymogram activity analysis. Full analysis of the nucleotide and the deduced amino acid sequences indicated that the lipPE gene encodes a novel P. expansum lipase. The lipPE gene was expressed in E. coli for further characterization of the enzyme with a view of assessing its suitability for industrial applications.

The organisation and expression of the genes encoding the mitochondrial glycine decarboxylase complex and serine hydroxymethyltransferase in pea (Pisum sativum)

Restriction fragment length polymorphisms have been used to determine the chromosomal location of the genes encoding the glycine decarboxylase complex (GDC) and serine hydroxymethyltransferase (SHMT) of pea leaf mitochondria. The genes encoding the H subunit of GDC and the genes encoding SHMT both show linkage to the classical group I marker i. In addition, the genes for the P protein of GDC show linkage to the classic group I marker a. The genes for the L and T proteins of GDC are linked to one another and are probably situated on the satellite of chromosome 7. The mRNAs encoding the five polypeptides that make up GDC and SHMT are strongly induced when dark-grown etiolated pea seedlings are placed in the light. Similarly, when mature plants are placed in the dark for 48 h, the levels of both GDC protein and SHMT mRNAs decline dramatically and then are induced strongly when these plants are returned to the light. During both treatments a similar pattern of mRNA induction is observed, with the mRNA encoding the P protein of GDC being the most rapidly induced and the mRNA for the H protein the slowest. Whereas during the greening of etiolated seedlings the polypeptides of GDC and SHMT show patterns of accumulation similar to those of the corresponding mRNAs, very little change in the level of the polypeptides is seen when mature plants are placed in the dark and then re-exposed to the light.

Suppression of mRNAs encoding tegument tetraspanins from schistosoma mansoni results in impaired tegument turnover

Schistosomes express a family of integral membrane proteins, called tetraspanins (TSPs), in the outer surface membranes of the tegument. Two of these tetraspanins, Sm-TSP-1 and Sm-TSP-2, confer protection as vaccines in mice, and individuals who are naturally resistant to S. mansoni infection mount a strong IgG response to Sm-TSP-2. To determine their functions in the tegument of S. mansoni we used RNA interference to silence expression of Sm-tsp-1 and Sm-tsp-2 mRNAs. Soaking of parasites in Sm-tsp dsRNAs resulted in 61% (p = 0.009) and 74% (p = 0.009) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in adult worms, and 67%–75% (p = 0.011) and 69%–89% (p = 0.004) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in schistosomula compared to worms treated with irrelevant control (luciferase) dsRNA. Ultrastructural morphology of adult worms treated in vitro with Sm-tsp-2 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Schistosomula exposed in vitro to Sm-tsp-2 dsRNA had a significantly thinner and more vacuolated tegument, and morphology consistent with a failure of tegumentary invaginations to close. Injection of mice with schistosomula that had been electroporated with Sm-tsp-1 and Sm-tsp-2 dsRNAs resulted in 61% (p = 0.005) and 83% (p = 0.002) reductions in the numbers of parasites recovered from the mesenteries four weeks later when compared to dsRNA-treated controls. These results imply that tetraspanins play important structural roles impacting tegument development, maturation or stability.