CRISPR/Cas Derivatives as Novel Gene Modulating Tools:Possibilities and In Vivo Applications

The field of genome editing started with the discovery of meganucleases (e.g., the LAGLIDADG family of homing endonucleases) in yeast. After the discovery of transcription activator-like effector nucleases and zinc finger nucleases, the recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins (Cas) system has opened a new window of applications in the field of gene editing. Here, we review different Cas proteins and their corresponding features including advantages and disadvantages, and we provide an overview of the different endonuclease-deficient Cas protein (dCas) derivatives. These dCas derivatives consist of an endonuclease-deficient Cas9 which can be fused to different effector domains to perform distinct in vitro applications such as tracking, transcriptional activation and repression, as well as base editing. Finally, we review the in vivo applications of these dCas derivatives and discuss their potential to perform gene activation and repression in vivo, as well as their potential future use in human therapy

Koinonia

Spotlight on SpeakersHeeding the Call of the Ministry of the Towel, Siang-Yang Tan Being Honest About Why We Can\u27t All Just Get Along, William H. Willimon Perspectives on PracticesA Christian Philosophy of Student Development: The Ongoing Discussion and Debate, Carolyn Arthur A Life Worth Living, Damon Seacott The State of Our Seniors Address, Melanie Sunukjian ACSD MattersExecutive Committee Elections New Professionals Retreat ACSD 2002 at Lee University Regular FeaturesPresident\u27s Corner Editor\u27s Diskhttps://pillars.taylor.edu/acsd_koinonia/1019/thumbnail.jp

Reporting community involvement in autism research:Findings from the journal Autism

Participatory methods are having sweeping effects on research across the globe. To facilitate transparency around these methods, Autism introduced mandatory reporting of community involvement in January 2021. Here, we sought to determine the impact of this policy. To do so, we—a team of Autistic and non-autistic researchers—searched for articles published in Autism in 2019, two years before policy implementation, and in 2022, one year after. We read 283 eligible articles and double coded each article for general information and details of community involvement. We found a fivefold increase (10.3% pre-implementation vs. 54.5% post-implementation) in the reporting of community involvement. Most articles reported involving community members distally, in consulting roles, with researchers retaining full decision-making power. Furthermore, most community involvement was reported in more applied than basic research. A significant minority of papers (17%), however, could not be coded, owing to insufficient or vague information. While this increase in the reporting of community involvement is encouraging, more efforts need to be directed towards (i) improving the transparency in the reporting of community involvement and (ii) increasing the frequency with which community members, especially Autistic people, share decision-making power equally with researchers—or even assume control of the research process

BotPercent: Estimating Bot Populations in Twitter Communities

Twitter bot detection is vital in combating misinformation and safeguarding the integrity of social media discourse. While malicious bots are becoming more and more sophisticated and personalized, standard bot detection approaches are still agnostic to social environments (henceforth, communities) the bots operate at. In this work, we introduce community-specific bot detection, estimating the percentage of bots given the context of a community. Our method -- BotPercent -- is an amalgamation of Twitter bot detection datasets and feature-, text-, and graph-based models, adjusted to a particular community on Twitter. We introduce an approach that performs confidence calibration across bot detection models, which addresses generalization issues in existing community-agnostic models targeting individual bots and leads to more accurate community-level bot estimations. Experiments demonstrate that BotPercent achieves state-of-the-art performance in community-level Twitter bot detection across both balanced and imbalanced class distribution settings, %outperforming existing approaches and presenting a less biased estimator of Twitter bot populations within the communities we analyze. We then analyze bot rates in several Twitter groups, including users who engage with partisan news media, political communities in different countries, and more. Our results reveal that the presence of Twitter bots is not homogeneous, but exhibiting a spatial-temporal distribution with considerable heterogeneity that should be taken into account for content moderation and social media policy making. The implementation of BotPercent is available at https://github.com/TamSiuhin/BotPercent.Comment: Accepted to findings of EMNLP 202

The Impact of a 'Remotely-Delivered' Sports Nutrition Education Program on Dietary Intake and Nutrition Knowledge of Junior Elite Triathletes

Triathlon is a physically demanding sport, requiring athletes to make informed decisions regarding their daily food and fluid intake to align with daily training. With an increase in uptake for online learning, remotely delivered education programs offer an opportunity to improve nutritional knowledge and subsequent dietary intake in athletes. This single-arm observational study aimed to evaluate the effectiveness of a remotely delivered nutrition education program on sports nutrition knowledge and the dietary intake of junior elite triathletes (n = 21; female n = 9; male n = 12; 18.9 ± 1.6 y). A total of 18 participants completed dietary intake assessments (4-day food diary via Easy Diet DiaryTM) and 14 participants completed an 83-question sports nutrition knowledge assessment (Sports Nutrition Knowledge Questionnaire (SNKQ)) before and after the 8-week program. Sports nutrition knowledge scores improved by 15% (p < 0.001, ES = 0.9) following the program. Male participants reported higher energy intakes before (3348 kJ, 95% CI: 117–6579; p = 0.043) and after (3644 kJ, 95% CI: 451–6836; p = 0.028) the program compared to females. Carbohydrate intake at breakfast (p = 0.022), daily intakes of fruit (p = 0.033), dairy (p = 0.01) and calcium (p = 0.029) increased following nutrition education. Irrespective of gender, participants had higher intakes of energy (p < 0.001), carbohydrate (p = 0.001), protein (p = 0.007), and fat (p = 0.007) on heavy training days compared to lighter training days before and after the program with total nutrition knowledge scores negatively correlated with discretionary food intake (r = −0.695, p = 0.001). A remotely delivered nutrition education program by an accredited sports nutrition professional improved sports nutrition knowledge and subsequent dietary intake of junior elite triathletes, suggesting remote delivery of nutrition education may prove effective when social distancing requirements prevent face-to-face opportunities

Why unidimensional pain measurement prevails in the pediatric acute pain context and what multidimensional self-report methods can offer

Although pain is widely recognized to be a multidimensional experience and defined as such, unidimensional pain measurement focusing on pain intensity prevails in the pediatric acute pain context. Unidimensional assessments fail to provide a comprehensive picture of a child’s pain experience and commonly do little to shape clinical interventions. The current review paper overviews the theoretical and empirical literature supporting the multidimensional nature of pediatric acute pain. Literature reporting concordance data for children’s self-reported sensory, affective and evaluative pain scores in the acute pain context has been reviewed and supports the distinct nature of these dimensions. Multidimensional acute pain measurement holds particular promise for identifying predictive markers of chronicity and may provide the basis for tailoring clinical management. The current paper has described key reasons contributing to the widespread use of unidimensional, rather than multidimensional, acute pediatric pain assessment protocols. Implications for clinical practice, education and future research are considered

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent