While it has been argued that children with autism spectrum disorders are responsive to robot-like toys, very little research has examined the impact of robot-based intervention on gesture use. These children have delayed gestural development. We used a social robot in two phases to teach them to recognize and produce eight pantomime gestures that expressed feelings and needs. Compared to the children in the wait-list control group (N = 6), those in the intervention group (N = 7) were more likely to recognize gestures and to gesture accurately in trained and untrained scenarios. They also generalized the acquired recognition (but not production) skills to human-to-human interaction. The benefits and limitations of robot-based intervention for gestural learning were highlighted. Implications for Rehabilitation Compared to typically-developing children, children with autism spectrum disorders have delayed development of gesture comprehension and production. Robot-based intervention program was developed to teach children with autism spectrum disorders recognition (Phase I) and production (Phase II) of eight pantomime gestures that expressed feelings and needs. Children in the intervention group (but not in the wait-list control group) were able to recognize more gestures in both trained and untrained scenarios and generalize the acquired gestural recognition skills to human-to-human interaction. Similar findings were reported for gestural production except that there was no strong evidence showing children in the intervention group could produce gestures accurately in human-to-human interaction.

Multisubunit protein assemblies offer integrated functionalities for efficient cell signal transduction control. One example of such protein assemblies, the BRCA1-A macromolecular complex, couples ubiquitin recognition and metabolism and promotes cellular responses to DNA damage. Specifically, the BRCA1-A complex not only recognizes Lys 63 -linked ubiquitin (K63-Ub) adducts at the damaged chromatin but is endowed with K63-Ub deubiquitylase (DUB) activity. To explore how the BRCA1-A DUB activity contributes to its function at DNA double strand breaks (DSBs), we used RNAi and genome editing approaches to target BRCC36, the protein subunit that confers the BRCA1-A complex its DUB activity. Intriguingly, we found that the K63-Ub DUB activity, although dispensable for maintaining the integrity of the macromolecular protein assembly, is important in enforcing the accumulation of the BRCA1-A complex onto DSBs. Inactivating BRCC36 DUB attenuated BRCA1-A functions at DSBs and led to unrestrained DSB end resection and hyperactive DNA repair. Together, our findings uncover a pivotal role of BRCC36 DUB in limiting DSB processing and repair and illustrate how cells may physically couple ubiquitin recognition and metabolizing activities for fine tuning of DNA repair processes. Active hydrolysis of ubiquitin polymers by deubiquitylases (DUBs)2 has emerged as important biochemical processes that underlie diverse signal transduction pathways, including cell responses to DNA damage (1). To date, around 94 human DUBs have been identified and are classified into five families: ubiquitin C-terminal hydrolases, ubiquitin-specific proteases, ovarian tumor proteases, Josephins, and JAB1/MPN/MOV4 metalloproteases. Notably, the JAB1/MPN/MOV4 metalloprotease family members are zinc-dependent metalloproteases, and the other families are cysteine proteases (1).BRCC36, originally reported as the BRCA1/BRCA2-containing complex subunit 36 (2), is endowed with DUB activity for lysine 63-linked ubiquitin polymers (K63-Ub). BRCC36 DUB relies on its zinc-dependent JAB1/MPN/MOV4 metalloprotease domain (3) and its interaction with Abraxas/KIAA0157 (3-5). Although BRCC36 forms distinct nuclear and cytoplasmic complexes (5, 6) and plays pleiotropic roles during cell proliferation, the K63-Ub DUB is arguably best known for its strong links with the breast and ovarian susceptible gene product BRCA1 in DNA damage responses (DDRs). Indeed, BRCC36 resides within the BRCA1-A macromolecular protein complex, which comprises the ubiquitin-binding protein RAP80, BRCC45/BRE, Abraxas/CCDC98, Merit40/NBA1, and BRCA1. The BRCA1-A complex is targeted to chromatin domains surrounding DNA double strand breaks (DSBs) by the ubiquitin-binding protein RAP80, which preferentially binds to K63-Ub adducts generated by the ubiquitin-conjugating enzyme UBC13 (3, 7-12). Abraxas plays a major scaffolding role to support the integrity of the BRCA1-A assembly and directly anchors the tumor suppressor BRCA1 via a phosphorylation-dependent interaction (13-15). Indeed, BRCA1, via it...

Protein ubiquitination has emerged as a pivotal regulatory reaction that promotes cellular responses to DNA damage. With a goal to delineate the DNA damage signal transduction cascade, we systematically analyzed the human E2 ubiquitin- and ubiquitin-like-conjugating enzymes for their ability to mobilize the DNA damage marker 53BP1 onto ionizing radiation-induced DNA double strand breaks. An RNAi-based screen identified UBE2U as a candidate regulator of chromatin responses at double strand breaks. Further mining of the UBE2U interactome uncovered its cognate E3 RNF17 as a novel factor that, via the radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties (RIDDLE) syndrome protein RNF168, enforces DNA damage responses. Our screen allowed us to uncover new players in the mammalian DNA damage response and highlights the instrumental roles of ubiquitin machineries in promoting cell responses to genotoxic stress.

Background: Chinese medicine (CM) industry has developed rapidly in recent years, but the turnover rate among Chinese medicine practitioners (CMPs) in Hong Kong is relatively high. The research on this issue is insufficient, inevitably giving rise to hidden concerns regarding the development of the CM industry.  Purpose: explores the relationship between job satisfaction, work stress and organizational commitment among CMPs in Hong Kong and their turnover intention. Its results provide guidance regarding the CM industry's management and suggest future research directions.  Design: an online questionnaire was used to collect data on qualified CMPs in Hong Kong for investigation. After the pilot questionnaire, statistical analysis was used to correct the problem. The questionnaire was forwarded by the Chinese Medicine Association and Organization through instant messaging software and online social platforms. Descriptive analysis, reliability analysis, correlation analysis and regression analysis were used.  Findings: from August 1 to 16, 2019, 141 valid questionnaires were collected. The reliability analysis confirmed the credibility of all of the variables. The correlation and regression analyses supported the hypotheses. Thus, job satisfaction has a negative relationship with turnover intention, work stress has a positive relationship with turnover intention and organizational commitment has a negative relationship with turnover intention.  Originality: multiple regression analysis showed that the variables ranked in the following order of decreasing importance: organizational commitment > job satisfaction > work stress. To reduce the turnover rate among CMPs, industry management must increase organizational commitment with some efforts to enhance job satisfaction and reduce work stress.

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