Repair Sequences Research Articles

A membrane scaffold for repairing DNA

DNA Repair Many cellular processes inadvertently cause DNA damage, so cell survival critically depends on high-fidelity DNA repair. In Escherichia coli , the protein RecA plays a central role in repairing damaged DNA. RecA forms filaments on the ends of broken DNA, which allow the DNA repair machinery to search the genome for homologous sequences for accurate repair of the DNA break. Rajendram et al. now show that RecA interacts with specific lipids in the inner plasma membrane of E. coli. This membrane scaffolding acts to store RecA in the absence of DNA breaks. It also helps to nucleate and stabilize RecA filament bundles when breaks form, promoting DNA repair. Mol. Cell. 10.1016/j.molcel.2015.09.009 (2015).

Universal Principles in the Repair of Communication Problems.

There would be little adaptive value in a complex communication system like human language if there were no ways to detect and correct problems. A systematic comparison of conversation in a broad sample of the world’s languages reveals a universal system for the real-time resolution of frequent breakdowns in communication. In a sample of 12 languages of 8 language families of varied typological profiles we find a system of ‘other-initiated repair’, where the recipient of an unclear message can signal trouble and the sender can repair the original message. We find that this system is frequently used (on average about once per 1.4 minutes in any language), and that it has detailed common properties, contrary to assumptions of radical cultural variation. Unrelated languages share the same three functionally distinct types of repair initiator for signalling problems and use them in the same kinds of contexts. People prefer to choose the type that is the most specific possible, a principle that minimizes cost both for the sender being asked to fix the problem and for the dyad as a social unit. Disruption to the conversation is kept to a minimum, with the two-utterance repair sequence being on average no longer that the single utterance which is being fixed. The findings, controlled for historical relationships, situation types and other dependencies, reveal the fundamentally cooperative nature of human communication and offer support for the pragmatic universals hypothesis: while languages may vary in the organization of grammar and meaning, key systems of language use may be largely similar across cultural groups. They also provide a fresh perspective on controversies about the core properties of language, by revealing a common infrastructure for social interaction which may be the universal bedrock upon which linguistic diversity rests.

Emergent vocabulary in second language socialization among learners

In general, second language (L2) learners have limited vocabulary knowledge. In addition, they often have difficulty identifying, recognizing, or recalling the vocabulary necessary for a certain situation. This limitation and those three factors result in problematic talk where repair, improvement, and practice are merited. The purpose of the present study, following a conversation analytic (CA) perspective, explores how vocabulary-related communication problems are resolved when a low proficient learner (LPL) and a high proficient learner (HPL) communicate during their pair-work activities. In particular, this research studies the sequence of turns and repair in the talk. The study revealed that (1) the repair is mostly initiated by the LPL, (2) the HPL can be a crucial language source in the classroom, and (3) problems are caused by insufficient vocabulary knowledge and not comprehending a correctly-pronounced word. This study reveals the importance of students’ pair-work (especially pair-work activities when the students have disparate English proficiency) in the language classroom and suggests communication strategies.

Segmental repair and interactional intelligibility: The relationship between consonant deletion, consonant insertion, and pronunciation intelligibility in English as a Lingua Franca in Japan

This is a qualitative study of the relationship between consonant deletion, consonant insertion, and the pragmatic strategies that maintain mutual intelligibility in English as a Lingua Franca (hereafter, ELF) interactions among university and exchange students at a Japanese university (Jenkins, 2000; Matsumoto, 2011; O’Neal, 2015). Some ELF research claims that consonant deletion attenuates mutual intelligibility in ELF interactions, especially if the consonant deletion occurs in word-initial and word-medial consonant clusters or in consonant clusters in syllable onsets and codas (Jenkins, 2000, 2007; Deterding, 2013). This study assesses the effect of consonant deletion and consonant insertion on the mutual intelligibility of pronunciation in ELF interactions in Japan. Using conversation analytic methodology to examine a corpus of miscommunications among ELF speakers at a Japanese university, within which miscommunications are defined as repair sequences, this study claims that consonant deletion can attenuate mutual intelligibility, and that the insertion of a deleted consonant into a word can help restore mutual intelligibility. Furthermore, this is true regardless of deviance from or approximation to a native speaker pronunciation standard. This study concludes that segmental repair is an effective strategy with which English speakers can maintain mutual intelligibility.

Multiple repair sequences in everyday conversations involving people with Parkinson's disease.

Features of dysarthria associated with Parkinson's disease (PD), such as low volume, variable rate of speech and increased pauses, impact speaker intelligibility. Those affected report restricted interactional participation, although this area is under explored. To examine naturally occurring instances of problems with intelligibility that resulted in multiple attempts at repair in order to consider repair initiation strategies that might restrict or enhance participation. Thirteen people with PD (PwPD) video-recorded over 10 h of informal conversation data in their home setting involving familiar conversation partners (CPs). Using a conversation analytic (CA) approach, and drawing on an existing typology of repair initiators (RIs) for everyday talk-in-interaction and their relative power to locate a turn's repairable element, the design and ordering of RIs used by CPs was addressed, alongside their local consequences. CPs tended to increase the specificity of their RIs in line with the existing typology, progressing from open class forms (e.g. 'mm?') to more specific forms (e.g. questions/partial repeats). Repeated open class repair initiators (OCRIs) were used where PD speakers' self-repair attempts provided limited information. Sometimes, however, specificity was increased too soon, before enough syntactic knowledge was gleaned, which resulted in an extended repair sequence. Where one OCRI followed another, the second always took a different form: lexically or in terms of prosodic/non-verbal features. RI forms not described in the existing typology were also identified, such as 'prompts to modify speech' (e.g. 'Speak louder') and repeating/rephrasing the original first pair part (e.g. question), and their effectiveness examined. First steps are presented towards the design of a communication intervention promoting the efficient resolution of repair to moderate social withdrawal and increase participation for this client group. Future research will need to explore the feasibility and acceptability of such a resource.

Interactional intelligibility: the relationship between consonant modification and pronunciation intelligibility in English as a Lingua Franca in Japan

This is a qualitative study of the relationship between consonant modification and pronunciation intelligibility in English as a Lingua Franca interactions in Japan. Some research has claimed that the full articulation of many consonants is critical to the maintenance of mutual intelligibility in English as a Lingua Franca interactions. Utilizing conversation analytic methodology to examine a corpus of segmental repair sequences among English speakers using English as a Lingua Franca at a Japanese university, this study claims that English speakers identify which words are unintelligible, and then modify the distinctive features of problematic consonants into more intelligible variants in order to successfully achieve mutual understanding. This study concludes that intelligible pronunciation is an interactional phenomenon that is dependent more on adjusting pronunciation during interaction and less on approximating the phonological standards of any one variety of English.

Teaching facial fracture repair: A novel method of surgical skills training using three-dimensional biomodels

Background The facial fracture biomodel is a three-dimensional physical prototype of an actual facial fracture. The biomodel can be used as a novel teaching tool to facilitate technical skills training in fracture reduction and fixation, but more importantly, can help develop diagnostic and management competence. Objective To introduce the ‘facial fracture biomodel’ as a teaching aid, and to provide preliminary evidence of its effectiveness in teaching residents the principles of panfacial fracture repair. Method Computer three-dimensional image processing and rapid prototyping were used to generate an accurate physical model of a panfacial fracture, mounted in a silicon ‘soft tissue’ base. Senior plastic surgery residents in their third, fourth and fifth years of training across Canada were invited to participate in a workshop using this biomodel to simulate panfacial fracture repair. A short didactic presentation outlining the ‘patient's’ clinical and radiological findings, and key principles of fracture repair, was given by a consultant plastic surgeon before the exercise. The residents completed a pre- and postbiomodel questionnaire soliciting information regarding background, diagnosis and management, and feedback. Result A total of 29 residents completed both pre- and postbiomodel questionnaires. Statistically significant results were found in the following areas: diagnosis of all fracture patterns (P=8.2×10−7 [t test]), choice of incisions for adequate exposure (P=0.04 [t test]) and identifying sequence of repair (P=0.019 [x2 test]). Subjective evaluation of workshop effectiveness revealed a statistically significant increase in ‘comfort level’ only among third year trainees. Overall, positive feedback was reported among all participants. Conclusions Biomodelling is a promising ancillary teaching aid that can assist in teaching residents technical skills, as well as how to assess and plan surgical repair.

Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution.

We developed a method for genome-wide mapping of DNA excision repair named XR-seq (excision repair sequencing). Human nucleotide excision repair generates two incisions surrounding the site of damage, creating an ∼30-mer. In XR-seq, this fragment is isolated and subjected to high-throughput sequencing. We used XR-seq to produce stranded, nucleotide-resolution maps of repair of two UV-induced DNA damages in human cells: cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts [(6-4)PPs]. In wild-type cells, CPD repair was highly associated with transcription, specifically with the template strand. Experiments in cells defective in either transcription-coupled excision repair or general excision repair isolated the contribution of each pathway to the overall repair pattern and showed that transcription-coupled repair of both photoproducts occurs exclusively on the template strand. XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers. XR-seq data also uncovered the repair characteristics and novel sequence preferences of CPDs and (6-4)PPs. XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells.

Timing of Visual Bodily Behavior in Repair Sequences: Evidence From Three Languages

This article expands the study of other-initiated repair in conversation—when one party signals a problem with producing or perceiving another's turn at talk—into the domain of visual bodily behavior. It presents one primary cross-linguistic finding about the timing of visual bodily behavior in repair sequences: if the party who initiates repair accompanies their turn with a “hold”—when relatively dynamic movements are temporarily and meaningfully held static—this position will not be disengaged until the problem is resolved and the sequence closed. We base this finding on qualitative and quantitative analysis of corpora of conversational interaction from three unrelated languages representing two different modalities: Northern Italian, the Cha'palaa language of Ecuador, and Argentine Sign Language. The cross-linguistic similarities uncovered by this comparison suggest that visual bodily practices have been semiotized for similar interactive functions across different languages and modalities due to common pressures in face-to-face interaction.

Problematic topic transitions in dysarthric conversation

Purpose: This study examined the nature of topic transition problems associated with acquired progressive dysarthric speech in the everyday conversation of people with motor neurone disease.Method: Using conversation analytic methods, a video collection of five naturally occurring problematic topic transitions was identified, transcribed and analysed. These were extracted from a main collection of over 200 other-initiated repair sequences and a sub-set of 15 problematic topic transition sequences. The sequences were analysed with reference to how the participants both identified and resolved the problems.Result: Analysis revealed that topic transition by people with dysarthria can prove problematic. Conversation partners may find transitions problematic not only because of speech intelligibility but also because of a sequential disjuncture between the dysarthric speech turn and whatever topic has come prior. In addition the treatment of problematic topic transition as a complaint reveals the potential vulnerability of people with dysarthria to judgements of competence.Conclusion: These findings have implications for how dysarthria is conceptualized and how specific actions in conversation, such as topic transition, might be suitable targets for clinical intervention.

Teaching facial fracture repair: A novel method of surgical skills training using three-dimensional biomodels.

The facial fracture biomodel is a three-dimensional physical prototype of an actual facial fracture. The biomodel can be used as a novel teaching tool to facilitate technical skills training in fracture reduction and fixation, but more importantly, can help develop diagnostic and management competence. To introduce the 'facial fracture biomodel' as a teaching aid, and to provide preliminary evidence of its effectiveness in teaching residents the principles of panfacial fracture repair. Computer three-dimensional image processing and rapid prototyping were used to generate an accurate physical model of a panfacial fracture, mounted in a silicon 'soft tissue' base. Senior plastic surgery residents in their third, fourth and fifth years of training across Canada were invited to participate in a workshop using this biomodel to simulate panfacial fracture repair. A short didactic presentation outlining the 'patient's' clinical and radiological findings, and key principles of fracture repair, was given by a consultant plastic surgeon before the exercise. The residents completed a pre- and postbiomodel questionnaire soliciting information regarding background, diagnosis and management, and feedback. A total of 29 residents completed both pre- and postbiomodel questionnaires. Statistically significant results were found in the following areas: diagnosis of all fracture patterns (P=8.2×10(-7) [t test]), choice of incisions for adequate exposure (P=0.04 [t test]) and identifying sequence of repair (P=0.019 [χ(2) test]). Subjective evaluation of workshop effectiveness revealed a statistically significant increase in 'comfort level' only among third year trainees. Overall, positive feedback was reported among all participants. Biomodelling is a promising ancillary teaching aid that can assist in teaching residents technical skills, as well as how to assess and plan surgical repair.

Use of Mesenchymal Stem Cells to Grow Cartilage and Bone

Regardless of the fact that bones have a tremendous capacity to be repaired, there are various clinical situations where allographs seek to enhance the regeneration of bones through promotion of osteogenesis [1]. Precarious botches linked to the present grafting treatments include osteonecrosis along with restricted combination between the grafted and host tissues. It is considered that the fundamental issue with the present approaches to bone grafting is the fact that they lead to bone regeneration by means of direct osteogenesis. Therefore, it may be hypothesized that the use of cartilage in the promotion of endochondral regeneration of bones may leverage normal development and repair sequences resulting in a properly vascularized regenerate capable of integrating with the host tissues. Various tests have demonstrated that cartilage grafts are able to support the regeneration of vascularized and integrated bone tissues in vivo, while lineage tracing experiments have revealed graft derived regenerates.

Moments of Meeting: A Self Psychological Approach

In their attempt to understand what promotes growth in the clinical setting, the Boston Change Process Study Group retrospectively examined the microprocess of analytic hours and determined that moments of meeting (the events that rearrange the intersubjective experience for the dyad) are a powerful agent of therapeutic change. In this article, following a thorough definition of moments of meeting, I look at what clinicians can do prospectively in order to facilitate moments of meeting. In contrast to the Boston Change Process Study Group’s delineation of specific phases that comprise a moment of meeting and their belief that moments of meeting exist outside of standard technique, I suggest that when the therapist is empathically immersed in the patient’s subjective world, moments of meeting are an organic outgrowth of the process and within the bounds of conventional technique. Clinical examples illustrate how a self psychological approach including understanding selfobject longings, active engagement in the rupture repair sequence, as well as imagining one’s way into the patient’s inner experience lead to the unfolding of moments of meeting. I then contrast the moments of meeting that emerge from empathic immersion with the relational shifts that derive from other listening modes.

The impact of cleft lip and palate repair on maxillofacial growth.

Surgical correction is central to current team-approached cleft treatment. Cleft surgeons are always concerned about the impact of their surgical maneuver on the growth of the maxilla. Hypoplastic maxilla, concaved mid-face and deformed dental arch have constantly been reported after cleft treatments. It is very hard to completely circumvent these postoperative complications by current surgical protocols. In this paper, we discussed the factors that inhibit the maxillofacial growth on cleft patients. These factors included pre-surgical intervention, the timing of cleft palate and alveolae repair, surgical design and treatment protocol. Also, we made a review about the influence on the maxillary growth in un-operated cleft patients. On the basis of previous researches, we can conclude that most of scholars express identity of views in these aspects: early palatoplasty lead to maxilla growth inhibition in all dimensions; secondary alveolar bone graft had no influence on maxilla sagittal growth; cleft lip repair inhibited maxilla sagittal length in patients with cleft lip and palate; Veau's pushback palatoplasty and Langenbeck's palatoplasty with relaxing incisions were most detrimental to growth; Furlow palatoplasty showed little detrimental effect on maxilla growth; timing of hard palate closure, instead of the sequence of hard or soft palate repair, determined the postoperative growth. Still, scholars hold controversial viewpoints in some issues, for example, un-operated clefts have normal growth potential or not, pre-surgical intervention and pharyngoplasty inhibited maxillofacial growth or not.

Parameters sensitivity and optimization for composite scarf repair

Scarf repair is the preferred method to restore the load-carrying capacity of the damaged structure of fiber-reinforced composite material when stiffness, strength, and flushness are needed. However, shear stress concentration occurs along the scarf bond line coinciding with the location of 0° plies. Previous studies did not consider the sensitivity of parameters systematically and involve the interaction effect. In this paper, sensitivities of scarf angle, adhesive thickness, and stacking sequence are evaluated synthetically through main effect and interaction effect by using the method of design of experiment. The general strategy of decreasing scarf angle needs to remove more materials from parent laminate. Thus, a new strategy of changing the stacking sequence of repair is performed to reduce the adhesive stress concentration by means of the optimization based on genetic algorithm. In spite of this, optimization results may not have good reliability especially when manufacture, load, and other fluctuations happen. Robustness analysis based on Monte Carlo simulation is used to estimate the reliability of optimization results.

Partial repetitions as other-initiations of repair in second language talk: Re-establishing understanding and doing learning

This conversation analytical paper examines other-initiated repair sequences in everyday interactions between first and second language speakers of Finnish. More specifically, it focuses on sequences that are initiated by a second language speaker by repeating a part of the trouble source turn and shows that the repetitions are recurrently treated as actions indicating specific language-related problems of understanding. The analysis suggests that the linguistic asymmetry in second language interactions is a resource that is drawn upon in situations in which other resources for action formation and recognition are not sufficient. In addition, the analysis illustrates why and how certain linguistic elements become objects of language learning in everyday interaction and informs our understanding of everyday encounters as language learning environments. It has implications for the discussion on the identities of second language users and learners and highlights the importance of keeping these concepts analytically separate.

Emerging models for DNA repair: Dictyostelium discoideum as a model for nonhomologous end-joining

DNA double strand breaks (DSBs) are a particularly cytotoxic variety of DNA lesion that can be repaired by homologous recombination (HR) or nonhomologous end-joining (NHEJ). HR utilises sequences homologous to the damage DNA template to facilitate repair. In contrast, NHEJ does not require homologous sequences for repair but instead functions by directly re-joining DNA ends. These pathways are critical to resolve DSBs generated intentionally during processes such as meiotic and site-specific recombination. However, they are also utilised to resolve potentially pathological DSBs generated by mutagens and errors during DNA replication. The importance of DSB repair is underscored by the findings that defects in these pathways results in chromosome instability that contributes to a variety of disease states including malignancy. The general principles of NHEJ are conserved in eukaryotes. As such, relatively simple model organisms have been instrumental in identifying components of these pathways and providing a mechanistic understanding of repair that has subsequently been applied to vertebrates. However, certain components of the NHEJ pathway are absent or show limited conservation in the most commonly used invertebrate models exploited to study DNA repair. Recently, however, it has become apparent that vertebrate DNA repair pathway components, including those involved in NHEJ, are unusually conserved in the amoeba Dictyostelium discoideum. Traditionally, this genetically tractable organism has been exploited to study the molecular basis of cell type specification, cell motility and chemotaxis. Here we discuss the use of this organism as an additional model to study DNA repair, with specific reference to NHEJ.

Preference structure in L2 Arabic requests

Preference structure is a fundamental organizational principle of talk, and research has shown that preferred actions tend to be done immediately and without mitigation whereas dispreference is indicated by delays, elaboration, hesitation, and mitigation. However, little research exists on how second language learners do preference and dispreference. In this study, we investigate how 67 learners of Arabic at four proficiency levels managed preference structure in requests and how their management of preference changed over a five-month period. We found a strong increase in the use of preliminary moves with proficiency level, and also greater occurrence of preliminary moves over the five-month period among lower-level learners. Absence of clear dispreference marking with lower-proficiency learners led to repair sequences, and only high-proficiency learners used multiple preliminary moves. Offers by the interlocutor were rare and limited to interactions with high-proficiency learners. We conclude that interactions involving second language learners can be affected by the learners' developing L2 proficiency, which limits their ability to carry out social actions in a conventional way in the target language.

Stem cell-derived endochondral cartilage stimulates bone healing by tissue transformation.

Although bone has great capacity for repair, there are a number of clinical situations (fracture non-unions, spinal fusions, revision arthroplasty, segmental defects) in which auto- or allografts attempt to augment bone regeneration by promoting osteogenesis. Critical failures associated with current grafting therapies include osteonecrosis and limited integration between graft and host tissue. We speculated that the underlying problem with current bone grafting techniques is that they promote bone regeneration through direct osteogenesis. Here we hypothesized that using cartilage to promote endochondral bone regeneration would leverage normal developmental and repair sequences to produce a well-vascularized regenerate that integrates with the host tissue. In this study, we use a translational murine model of a segmental tibia defect to test the clinical utility of bone regeneration from a cartilage graft. We further test the mechanism by which cartilage promotes bone regeneration using in vivo lineage tracing and in vitro culture experiments. Our data show that cartilage grafts support regeneration of a vascularized and integrated bone tissue in vivo, and subsequently propose a translational tissue engineering platform using chondrogenesis of mesenchymal stem cells (MSCs). Interestingly, lineage tracing experiments show the regenerate was graft derived, suggesting transformation of the chondrocytes into bone. In vitro culture data show that cartilage explants mineralize with the addition of bone morphogenetic protein (BMP) or by exposure to human vascular endothelial cell (HUVEC)-conditioned medium, indicating that endothelial cells directly promote ossification. This study provides preclinical data for endochondral bone repair that has potential to significantly improve patient outcomes in a variety of musculoskeletal diseases and injuries. Further, in contrast to the dogmatic view that hypertrophic chondrocytes undergo apoptosis before bone formation, our data suggest cartilage can transform into bone by activating the pluripotent transcription factor Oct4A. Together these data represent a paradigm shift describing the mechanism of endochondral bone repair and open the door for novel regenerative strategies based on improved biology.

Inclined to better understanding—The coordination of talk and ‘leaning forward’ in doing repair

This paper advocates an approach to CA studies of talk and body movements that focuses on the employment of various resources observable as methods for interaction that are sequentially consequential. It aims to demonstrate such an approach by analysing the combination of talk and the body movement ‘leaning forward’ in specific interactional environments. These environments are characterized by extended repair sequences, i.e. by troubles in understanding an action and by troubles in achieving a common understanding through repair. The paper shows how a combination of talk and the body movement ‘leaning forward’ is used as means to construct a repair in this local context. The components are ordered in specific ways. The use and the ordering of them are sequentially consequential and oriented to by the co-participant, who may construct his subsequent action by employing similar components and ordering them in similar ways. The paper also aims at discussing if and how a CA analysis can ascertain that a speaker is for instance relying upon both body movement and talk in a prior turn and not simply upon the talk in it if he restricts himself to deploying the component talk in the construction of his subsequent turn.