Functional communication between IP3R and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE

Stromal interaction molecules, STIM1 and STIM2, sense decreases in the endoplasmic reticulum (ER) [Ca2+] ([Ca2+]ER) and cluster in ER–plasma membrane (ER–PM) junctions where they recruit and activate Orai1. While STIM1 responds when [Ca2+]ER is relatively low, STIM2 displays constitutive clustering in the junctions and is suggested to regulate basal Ca2+ entry. The cellular cues that determine STIM2 clustering under basal conditions is not known. By using gene editing to fluorescently tag endogenous STIM2, we report that endogenous STIM2 is constitutively localized in mobile and immobile clusters. The latter associate with ER–PM junctions and recruit Orai1 under basal conditions. Agonist stimulation increases immobile STIM2 clusters, which coordinate recruitment of Orai1 and STIM1 to the junctions. Extended synaptotagmin (E-Syt)2/3 are required for forming the ER–PM junctions, but are not sufficient for STIM2 clustering. Importantly, inositol 1,4,5-triphosphate receptor (IP3R) function and local [Ca2+]ER are the main drivers of immobile STIM2 clusters. Enhancing, or decreasing, IP3R function at ambient [IP3] causes corresponding increase, or attenuation, of immobile STIM2 clusters. We show that immobile STIM2 clusters denote decreases in local [Ca2+]ER mediated by IP3R that is sensed by the STIM2 N terminus. Finally, under basal conditions, ambient PIP2-PLC activity of the cell determines IP3R function, immobilization of STIM2, and basal Ca2+ entry while agonist stimulation augments these processes. Together, our findings reveal that immobilization of STIM2 clusters within ER–PM junctions, a first response to ER-Ca2+ store depletion, is facilitated by the juxtaposition of IP3R and marks a checkpoint for initiation of Ca2+ entry.

DUbbing Language-therapy CINEma-based in Aphasia post-Stroke (DULCINEA): study protocol for a randomized crossover pilot trial

Background Communication is one of the most important predictors of social reintegration after stroke. Approximately 15–42% of stroke survivors experience post-stroke aphasia. Helping people recover from aphasia is one of the research priorities after a stroke. Our aim is to develop and validate a new therapy integrating dubbing techniques to improve functional communication. Methods The research project is structured as three work packages (WP). WP1: development of the dubbed language cinema-based therapy: Two research assistants (a speech therapist and a dubbing actor) will select the clips, mute specific words/sentences in progressive speech difficulty, and guide patients to dub them across sessions. Words to be dubbed will be those considered to be functionally meaningful by a representative sample of aphasic patients and relatives through an online survey. WP2: a randomized, crossover, interventional pilot study with the inclusion of 54 patients with post-stroke non-fluent aphasia. Patients will be treated individually in 40-min sessions twice per week for 8 weeks. Primary outcomes will be significant pre/post differences in scores in the Communicative Activity Log (CAL) questionnaire and Boston Diagnostic Aphasia Examination (BDAE) administered by a psychologist blinded to the patients’ clinical characteristics. Secondary outcomes: General Health Questionnaire (GHQ)-12, Stroke Aphasia Quality of Life Scale (SAQOL-39), Western Aphasia Battery Revised (WAB-R), and the Stroke Aphasic Depression Questionnaire (SADQ10). WP3: educational activities and dissemination of results. WP3 includes educational activities to improve public knowledge of aphasia and dissemination of the results, with the participation of the Spanish patients’ association Afasia Activa. Discussion This pilot clinical trial will explore the efficacy of a new therapeutic tool based on dubbing techniques and computer technology to improve functional communication of patients suffering from post-stroke aphasia with the use of standardized test assessment. Trial registration ClinicalTrials.govNCT04289493. Registered on 28 February 2020.

Technology-Aided Interventions to Reduce Challenging Behaviors for Individuals With Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) display a variety of challenging behaviors, such as tantrums, aggression, stereotypy, and disruption. Challenging behaviors can have a serious negative impact on the development of social relations, in the learning process, and education. To this aim, there is a need for appropriate interventions in order to improve the quality of life of individuals with ASD. This chapter aims to provide data with regard to different types of interventions and technological tools used for the reduction of challenging behaviors of students with ASD. Functional communication training with the use of speech-generating devices, video self-modeling, self-monitoring with the use of technological devices, and social stories presented in electronic form reflect types of interventions used for challenging behavior reduction. Research data indicate that technology-aided interventions are generally effective in reducing challenging behaviors of students with ASD.

A functional communication training for developing verbal behavior and treatment of challenging behavior in individuals with autism spectrum disorders

Communication problems are one of the symptoms of autism spectrum disorders. Challenging behaviors may be a form of communication with the environment, and when other forms of communication are not available, they may be the only way to meet their needs. The purpose of this article is to demonstrate the potential use of functional communication training in reducing problem behaviors of individuals with ASD, as well as developing acceptable ways of communication. In a research process based on behavior analysis, the method of single-subject experiment with multiple-baseline design was used. The results of the study show that the research participants developed communication skills on the basic level, and the frequency of their challenging behaviors has significantly decreased.

Contingency-based delay to reinforcement following functional communication training for autistic individuals: A multilevel meta-analysis

Functional communication training, an intervention for challenging behavior rooted in principles of applied behavior analysis, has copious empirical support dating back to the mid-1980s for autistic individuals. Recently, there has been a concerted effort to thin reinforcement delivery during functional communication training using contingency-based delays that, in turn, are designed to enhance practicality and feasibility while not compromising on efficacy. In this synthesis, we meta-analyzed the literature using log response ratio effect sizes to investigate (a) combined and across type effectiveness of contingency-based delays and (b) moderating variables that might impact intervention outcomes. Findings showed that contingency-based delays were effective for autistic individuals (log response ratio = −2.17; 95% CI = (−2.76, −1.58)) and most effective when the contingency incorporated positive reinforcement (log response ratio = −2.30; 95% CI = (−2.83, −1.78)). In addition, delay procedures that included differential reinforcement of alternative behavior were overall more effective (log response ratio = −2.13; 95% CI = (−2.72, −1.55)) than those that involved differential reinforcement of other behavior (log response ratio = −1.24; 95% CI = (−3.84, 1.37)). Noteworthy moderating variables found to impact contingency-based delay efficacy included the intervention dosage and the topography of behavior. We discuss these findings and highlight directions where additional empirical research is warranted to improve our understanding about contingency-based delays for autistic individuals. Lay abstract Functional communication training, an intervention for challenging behavior rooted in principles of applied behavior analysis, has copious empirical support dating back to the mid-1980s for autistic individuals. Recently, there has been a concerted effort to thin reinforcement delivery during functional communication training using contingency-based delays that, in turn, are designed to enhance practicality and feasibility while not compromising efficacy. In this synthesis, we meta-analyzed the literature base with the goal of investigating both combined and across type effectiveness of contingency-based delays. We also aimed to investigate moderating variables that might impact intervention outcomes. Findings showed that contingency-based delays were effective for individuals with an autism spectrum disorder diagnosis and most effective when the delay incorporated some form of positive reinforcement. In addition, differential reinforcement of alternative-based delays was overall more effective when compared to differential reinforcement of other behavior-based delays. Noteworthy moderating variables found to impact contingency-based delay efficacy included the intervention dosage and the topography of behavior. We discuss these findings and highlight directions where additional empirical research is warranted to improve our understanding about contingency-based delays for individuals diagnosed with autism spectrum disorder.

Internet of Things Based Intelligent Techniques in Workable Computing: An Overview

With the constant developments in Internet communication and the rise of the Internet of Things (IoT), technologies incorporating intelligent manufacturing have given birth to the growing industry and production lines. The network of IoT is generally interconnected with different devices through the Internet. The interactions of the IoT devices form smooth and functional communication require the connectivity of billions of objects. The devices of IoT can preserve, capture, share, and analyze data with nodes connected to the world. Various issues of the IoT such as monitoring the data, stealing the data, privacy of the data, tracking of the data, and many other aspects of the data are becoming challenges for the modern-day industry. The role of computational intelligence in proper analysis, managing, and many different perspectives of the IoT is prominent. Such computational intelligence can solve real-time problems with low cost and time. The IoT has provided solutions for poor scalability, system integration, and difficulties in coordinated operation across the emerging systems. The influence of the proposed study is to offer a wide-ranging overview of the current literature related to the Internet of Things based on intelligent techniques in workable computing. The study has considered the search process in the most popular libraries and presented an analysis of the research work done so far. The analysis and results of the study support the progress in the field, which will help researchers come up with new solutions.

A Systematically Conducted Scoping Review of the Evidence and Fidelity of Treatments for Verb and Sentence Deficits in Aphasia: Sentence Treatments

Purpose: This review article synthesizes and evaluates the evidence for sentence production treatments in aphasia, systematically charting impairment-based and functional communication outcomes. It reports (a) the level of evidence and fidelity of sentence treatments; (b) the impact of treatment on production of trained and untrained verbs and sentences, functional communication, and discourse; and (c) the potential active ingredients of treatment. Method: The search included studies from January 1980 to June 2019. The level of evidence of each study was documented, as was fidelity in terms of treatment delivery, enactment, and receipt. Studies were also categorized according to treatment methods used. Results: Thirty-three studies were accepted into the review and predominantly constituted Level 4 evidence (e.g., case control studies and case series). Thirty studies (90%) described treatment in sufficient detail to allow replication, but dosage was poorly reported, and fidelity of treatment was rarely assessed. The most commonly reported treatment techniques were mapping (10 studies: 30%), predicate argument structure treatment (six studies: 18%), and verb network strengthening treatment (five studies: 15%). Production of trained sentences improved for 83% of participants, and improvements generalized to untrained sentences for 59% of participants. Functional communication was rarely assessed, but discourse production improved for 70% of participants. Conclusions: The evidence for sentence treatments is predominantly generated from Level 4 studies. Treatments were effective for the majority of participants regarding trained sentence and discourse production. However, there is inconsistent use of statistical analysis to verify improvements, and diverse outcome measures are used, which makes interpretation of the evidence difficult. The quality of sentence treatment research would be improved by agreeing a core set of outcome measures and extended by ascertaining the views of participants on sentence treatments.

Discussion of Validation Issues in Signed and Spoken Assessments for Adult L2 Learners

The use of argument-based validity as a framework for discussion of validity issues in spoken and signed second language (L2) assessment reveals many areas of commonality. Common areas include the role of systematic test development practices in the validity argument, the complexity of rating issues, the need to define and assess a construct of functional communication of meaning, and the centrality of test use in the validity argument. Examining these areas of commonality in this chapter reveals the fundamental similarities in the basic validity issues faced in spoken and signed language assessment. This chapter is a joint discussion of key items related to validation issues related to signed and spoken language assessment that were discussed in Chapters 8.1 and 8.2.

Mast Cell Tryptase Potentiates Neutrophil Extracellular Trap Formation

Previous research has indicated an intimate functional communication between mast cells (MCs) and neutrophils during inflammatory conditions, but the nature of such communication is not fully understood. Activated neutrophils are known to release DNA-containing extracellular traps (neutrophil extracellular traps [NETs]) and, based on the known ability of tryptase to interact with negatively charged polymers, we here hypothesized that tryptase might interact with NET-contained DNA and thereby regulate NET formation. In support of this, we showed that tryptase markedly enhances NET formation in phorbol myristate acetate-activated human neutrophils. Moreover, tryptase was found to bind vividly to the NETs, to cause proteolysis of core histones and to cause a reduction in the levels of citrullinated histone-3. Secretome analysis revealed that tryptase caused increased release of numerous neutrophil granule compounds, including gelatinase, lactoferrin, and myeloperoxidase. We also show that DNA can induce the tetrameric, active organization of tryptase, suggesting that NET-contained DNA can maintain tryptase activity in the extracellular milieu. In line with such a scenario, DNA-stabilized tryptase was shown to efficiently degrade numerous pro-inflammatory compounds. Finally, we showed that tryptase is associated with NET formation in vivo in a melanoma setting and that NET formation in vivo is attenuated in mice lacking tryptase expression. Altogether, these findings reveal that NET formation can be regulated by MC tryptase, thus introducing a novel mechanism of communication between MCs and neutrophils.