Modeling the distribution of crossovers and interference with mice DNA data

Chiasma and crossover are two related biological processes of great importance in the understanding genetic variation. The study of these processes is straightforward in organisms where all products of meiosis are recovered and can be observed. This is not the case in mammals. Our understanding of these processes depends on our ability to model them. In this study I describe the biological processes that underline chiasma and crossover as well as the two main inference problems associated with these processes: i) in mammals we only recover one of the four products of meiosis and, ii) in general, we do not observe where the crossovers actually happen, but we find an interval containing type-2 censored information. NPML estimate was proposed and used in this work and used to compare chromosome length and chromosome expansion through the crosses.

Toward an effective strategy in glioblastoma treatment. Part II: RNA interference as a promising way to sensitize glioblastomas to temozolomide.

International audience

Reverse flow and supersonic interference.

"AFOSR TN-58-625. ASTIA doc. no. AD 162 155."

The “handwriting brain”: a motor/linguistic network with specialized “writing-specific” areas?

International audience

Annotation Pro. Enhancing analyses of linguistic and paralinguistic features in speech

Annotation Pro - a description of techniques, methods implemented in the tool, as well as the list of all built in functionalities and features of the user interface, and usage tips.

Cross-linguistic influences in the phonetic and lexical component in English, Baque and Spanish: Contextual and individual factors in language acquisition and attrition.

350 p.

The acquisition of adjunct control: grammar and processing

This dissertation uses children’s acquisition of adjunct control as a case study to investigate grammatical and performance accounts of language acquisition. In previous research, children have consistently exhibited non-adultlike behavior for sentences with adjunct control. To explain children’s behavior, several different grammatical accounts have been proposed, but evidence for these accounts has been inconclusive. In this dissertation, I take two approaches to account for children’s errors. First, I spell out the predictions of previous grammatical accounts, and test these predictions after accounting for some methodological concerns that might have influenced children’s behavior in previous studies. While I reproduce the non-adultlike behavior observed in previous studies, the predictions of previous grammatical accounts are not borne out, suggesting that extragrammatical factors are needed to explain children’s behavior. Next, I consider the role of two different types of extragrammatical factors in predicting children’s non-adultlike behavior. With a new task designed to address the task demands in previous studies, children exhibit significantly higher accuracy than with previous tasks. This suggests that children’s behavior has been influenced by task- specific processing factors. In addition to the task, I also test the predictions of a similarity-based interference account, which links children’s errors to the same memory mechanisms involved in sentence processing difficulties observed in adults. These predictions are borne out, supporting a more continuous developmental trajectory as children’s processing mechanisms become more resistant to interference. Finally, I consider how children’s errors might influence their acquisition of adjunct control, given the distribution in the linguistic input. I discuss the results of a corpus analysis, including the possibility that adjunct control could be learned from the input. The kinds of information that could be useful to a learner become much more limited, however, after considering the processing limitations that would interfere with the representations available to the learner.

Shifting development in mid-childhood: the influence of between-task interference

Performance on the task-switching paradigm is greatly affected by the amount of conflict between tasks. Compared to adults, children appear to be particularly influenced by this conflict, suggesting that the ability to resolve interference between tasks improves with age. We used the task-switching paradigm to investigate how this ability develops in mid-childhood. Experiment 1 compared 5- to 8-year-olds’ and 9- to 11-year-olds’ ability to switch between decisions about the colour of an object and its shape. The 5- to 8-year-olds were slower to switch task and experienced more interference from the irrelevant task than the 9-to 11-year-olds, suggesting a developmental improvement in resolving conflict between tasks during mid-childhood. Experiment 2 explored this further, examining the influence of stimulus and response interference at different ages. This was done by separating the colour and shape dimensions of the stimulus and reducing overlap between responses. The results supported the development of conflict resolution in task-switching during mid-childhood. They also revealed that a complex interplay of factors, including the tasks used and previous experience with the task, affected children’s shifting performance.

EXPLICIT WRITTEN CORRECTIVE FEEDBACK AND LANGUAGE APTITUDE IN SLA: IMPLICATIONS FOR IMPROVEMENT OF LINGUISTIC ACCURACY

Most second language researchers agree that there is a role for corrective feedback in second language writing classes. However, many unanswered questions remain concerning which linguistic features to target and the type and amount of feedback to offer. This study examined two new pieces of writing by 151 learners of English as a Second Language (ESL), in order to investigate the effect of direct and metalinguistic written feedback on errors with the simple past tense, the present perfect tense, dropped pronouns, and pronominal duplication. This inquiry also considered the extent to which learner differences in language-analytic ability (LAA), as measured by the LLAMA F, mediated the effects of these two types of explicit written corrective feedback. Learners in the feedback groups were provided with corrective feedback on two essays, after which learners in all three groups completed two additional writing tasks to determine whether or not the provision of corrective feedback led to greater gains in accuracy compared to no feedback. Both treatment groups, direct and metalinguistic, performed better than the comparison group on new pieces of writing immediately following the treatment sessions, yet direct feedback was more durable than metalinguistic feedback for one structure, the simple past tense. Participants with greater LAA proved more likely to achieve gains in the direct feedback group than in the metalinguistic group, whereas learners with lower LAA benefited more from metalinguistic feedback. Overall, the findings of the present study confirm the results of prior studies that have found a positive role for written corrective feedback in instructed second language acquisition.

Investigation of the functional roles of host cell proteins involved in Coronavirus infection using highly specific and scalable RNA interference (RNAi) approach

Since its identification in the 1990s, the RNA interference (RNAi) pathway has proven extremely useful in elucidating the function of proteins in the context of cells and even whole organisms. In particular, this sequence-specific and powerful loss-of-function approach has greatly simplified the study of the role of host cell factors implicated in the life cycle of viruses. Here, we detail the RNAi method we have developed and used to specifically knock down the expression of ezrin, an actin binding protein that was identified by yeast two-hybrid screening to interact with the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) spike (S) protein. This method was used to study the role of ezrin, specifically during the entry stage of SARS-CoV infection.

Radio Frequency Superconducting Quantum Interference Device Meta-atoms and Metamaterials: Experiment, Theory, and Analysis

Metamamterials are 1D, 2D or 3D arrays of articial atoms. The articial atoms, called "meta-atoms", can be any component with tailorable electromagnetic properties, such as resonators, LC circuits, nano particles, and so on. By designing the properties of individual meta-atoms and the interaction created by putting them in a lattice, one can create a metamaterial with intriguing properties not found in nature. My Ph. D. work examines the meta-atoms based on radio frequency superconducting quantum interference devices (rf-SQUIDs); their tunability with dc magnetic field, rf magnetic field, and temperature are studied. The rf-SQUIDs are superconducting split ring resonators in which the usual capacitance is supplemented with a Josephson junction, which introduces strong nonlinearity in the rf properties. At relatively low rf magnetic field, a magnetic field tunability of the resonant frequency of up to 80 THz/Gauss by dc magnetic field is observed, and a total frequency tunability of 100% is achieved. The macroscopic quantum superconducting metamaterial also shows manipulative self-induced broadband transparency due to a qualitatively novel nonlinear mechanism that is different from conventional electromagnetically induced transparency (EIT) or its classical analogs. A near complete disappearance of resonant absorption under a range of applied rf flux is observed experimentally and explained theoretically. The transparency comes from the intrinsic bi-stability and can be tuned on/ off easily by altering rf and dc magnetic fields, temperature and history. Hysteretic in situ 100% tunability of transparency paves the way for auto-cloaking metamaterials, intensity dependent filters, and fast-tunable power limiters. An rf-SQUID metamaterial is shown to have qualitatively the same behavior as a single rf-SQUID with regards to dc flux, rf flux and temperature tuning. The two-tone response of self-resonant rf-SQUID meta-atoms and metamaterials is then studied here via intermodulation (IM) measurement over a broad range of tone frequencies and tone powers. A sharp onset followed by a surprising strongly suppressed IM region near the resonance is observed. This behavior can be understood employing methods in nonlinear dynamics; the sharp onset, and the gap of IM, are due to sudden state jumps during a beat of the two-tone sum input signal. The theory predicts that the IM can be manipulated with tone power, center frequency, frequency difference between the two tones, and temperature. This quantitative understanding potentially allows for the design of rf-SQUID metamaterials with either very low or very high IM response.

Linguistic expression of irony in social media

Dissertação de Mestrado, Ciências da Linguagem, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2014

Limits to tDCS effects in language:failures to modulate word production in healthy participants with frontal or temporal tDCS

Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation widely used to modulate cognitive functions. Recent studies, however, suggests that effects are unreliable, small and often non-significant at least when stimulation is applied in a single session to healthy individuals. We examined the effects of frontal and temporal lobe anodal tDCS on naming and reading tasks and considered possible interactions with linguistic activation and selection mechanisms as well possible interactions with item difficulty and participant individual variability. Across four separate experiments (N, Exp 1A = 18; 1B = 20; 1C = 18; 2 = 17), we failed to find any difference between real and sham stimulation. Moreover, we found no evidence of significant effects limited to particular conditions (i.e., those requiring suppression of semantic interference), to a subset of participants or to longer RTs. Our findings sound a cautionary note on using tDCS as a means to modulate cognitive performance. Consistent effects of tDCS may be difficult to demonstrate in healthy participants in reading and naming tasks, and be limited to cases of pathological neurophysiology and/or to the use of learning paradigms.

Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases

Arm/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of Escherichia coli, corresponding to the genotypes rsmF(+), ΔrsmF, rsmF(+) rmtC(+), and ΔrsmF rmtC(+). When analyzed for the antimicrobial resistance pattern, the ΔrsmF bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibility in E. coli. Competition experiments between the isogenic E. coli strains showed that, contrary to expectation, acquisition of rmtC does not entail a fitness cost for the bacterium. Finally, matrix-assisted laser desorption ionization (MALDI) mass spectrometry allowed us to determine that RmtC methylates the G1405 residue not only in presence but also in the absence of aminoglycoside antibiotics. Thus, the coupling between housekeeping and acquired methyltransferases subverts the methylation architecture of the 16S rRNA but elicits Arm/Rmt methyltransferases to be selected and retained, posing an important threat to the usefulness of aminoglycosides worldwide.

Convergent evolution of PICIs-mediated phage interference

Staphylococcal pathogenicity islands (SaPIs), the prototype members of the family of phage inducible chromosomal islands (PICIs), are extremely mobile phage satellites, which are transferred between bacterial hosts after their induction by a helper phage. The intimate relationship between SaPIs and their helper phages is one of the most studied examples of virus satellite interactions in prokaryotic cells. SaPIs encode and disseminate virulence and fitness factors, representing a driving force for bacterial adaptation and pathogenesis. Many SaPIs encode a conserved morphogenetic operon, including a core set of genes whose function allows them to parasitize and exploit the phage life cycle. One of the central mechanisms of this molecular piracy is the specific packaging of the SaPI genomes into reduced sized capsid structures derived from phage proteins. Pac phages were classically thought to be the only phages involved in the mobilisation of phage-mediated virulence genes, including the transfer of SaPIs within related and non-related bacteria. This study presents the involvement of S. aureus cos phages in the intra- and intergeneric transfer of cos SaPIs for the first time. A novel example of molecular parasitism is shown, by which this newly characterised group of cos SaPIs uses two distinct and complementary mechanisms to take over the helper phage packaging machinery for their own reproduction. SaPIbov5, the prototype of the cos SaPIs, does not encode the characteristic morphogenetic operon found in pac SaPIs. However, cos SaPIs features both pac and cos phage cleavage sequences in their genome, ensuring SaPI packaging in small- and full-sized phage particles, depending on the helper phage. Moreover, cos-site packaging in S. aureus was shown to require the activity of a phage HNH nuclease. The HNH protein functions together with the large terminase subunit, triggering cleavage and melting of the cos-site sequence. In addition, a novel piracy strategy, severely interfering with the helper phage reproduction, was identified in cos SaPIs and characterised. This mechanism of piracy depends on the cos SaPI-encoded ccm gene, which encodes a capsid protein involved in the formation of small phage particles, modifying the assembling process via a scaffolding mechanism. This strategy resembles the ones described for pac SaPIs and represents a remarkable example of convergent evolution. A further convergent mechanism of capsid size-reduction was identified and characterised for the Enterococcus faecalis EfCIV583 pathogenicity island, another member of the PICI family. In this case, the self-encoded CpmE conducts this molecular piracy through a putative scaffolding function. Similar to cos SaPIs, EfCIV583 carries the helper phage cleavage sequence in its genome enabling its mobilisation by the phage terminase complex. The results presented in this thesis show how two examples of non-related members of the PICI family follow the same evolutionary convergent strategy to interfere with their helper phage. These findings could indicate that the described strategies might be widespread among PICIs and implicate a significant impact of PICIs mediated-virulence gene transfer in bacterial evolution and the emergence of pathogenic bacteria.