Human vs. machine-like representation in chatbot mental health counseling: the serial mediation of psychological distance and trust on compliance intention.

This study examined a serial mediation mechanism to test the effect of chatbots' human representation on the intention to comply with health recommendations through psychological distance and trust towards the chatbot counselor. The sample of the study comprised 385 adults from the USA. Two artificial intelligence chatbots either with human or machine-like representation were developed. Participants had a short conversation with either of the chatbots to simulate an online mental health counseling session and reported their experience in an online survey. The results showed that participants in the human representation condition reported a higher intention to comply with chatbot-generated mental health recommendations than those in the machine-like representation condition. Furthermore, the results supported that both psychological distance and perceived trust towards the chatbot mediated the relationship between human representation and compliance intention, respectively. The serial mediation through psychological distance and trust in the relationship between human representation and compliance intention was also supported. These findings provide practical guidance for healthcare chatbot developers and theoretical implications for human-computer interaction research.

Effect of AI chatbot emotional disclosure on user satisfaction and reuse intention for mental health counseling: a serial mediation model.

This study explored the effect of chatbot emotional disclosure on user satisfaction and reuse intention for a chatbot counseling service. It also examined the independent and sequential mediation roles of user emotional disclosure intention and perceived intimacy with a chatbot on the relationship between chatbot emotional disclosure, user satisfaction, and reuse intention for chatbot counseling. In total, 348 American adults were recruited to participate in a mental health counseling session with either of the two types of artificial intelligence-powered mental health counseling chatbots. These included a chatbot disclosing factual information only or a chatbot disclosing humanlike emotions. The results revealed that chatbot emotional disclosure significantly increased user satisfaction and reuse intention for a chatbot counseling service. The results further revealed that user emotional disclosure intention and perceived intimacy with a chatbot independently and serially mediates the effect of chatbot emotional disclosure on user satisfaction and chatbot counseling service reuse intention. The results indicate positive effects of artificial emotions and their disclosure in the context of chatbot moderated mental health counseling. Practical implications and psychological mechanisms are discussed.

APP overexpression in the absence of NPC1 exacerbates metabolism of amyloidogenic proteins of Alzheimer's disease.

Amyloid-ß (Aß) peptides originating from ß-amyloid precursor protein (APP) are critical in Alzheimer's disease (AD). Cellular cholesterol levels/distribution can regulate production and clearance of Aß peptides, albeit with contradictory outcomes. To better understand the relationship between cholesterol homeostasis and APP/Aß metabolism, we have recently generated a bigenic ANPC mouse line overexpressing mutant human APP in the absence of Niemann-Pick type C-1 protein required for intracellular cholesterol transport. Using this unique bigenic ANPC mice and complementary stable N2a cells, we have examined the functional consequences of cellular cholesterol sequestration in the endosomal-lysosomal system, a major site of Aß production, on APP/Aß metabolism and its relation to neuronal viability. Levels of APP C-terminal fragments (α-CTF/ß-CTF) and Aß peptides, but not APP mRNA/protein or soluble APPα/APPß, were increased in ANPC mouse brains and N2a-ANPC cells. These changes were accompanied by reduced clearance of peptides and an increased level/activity of γ-secretase, suggesting that accumulation of APP-CTFs is due to decreased turnover, whereas increased Aß levels may result from a combination of increased production and decreased turnover. APP-CTFs and Aß peptides were localized primarily in early-/late-endosomes and to some extent in lysosomes/autophagosomes. Cholesterol sequestration impaired endocytic-autophagic-lysosomal, but not proteasomal, clearance of APP-CTFs/Aß peptides. Moreover, markers of oxidative stress were increased in vulnerable brain regions of ANPC mice and enhanced ß-CTF/Aß levels increased susceptibility of N2a-ANPC cells to H2O2-induced toxicity. Collectively, our results show that cellular cholesterol sequestration plays a key role in APP/Aß metabolism and increasing neuronal vulnerability to oxidative stress in AD-related pathology.

Elevated TRAF2/6 expression in Parkinson's disease is caused by the loss of Parkin E3 ligase activity.

Parkinson's disease (PD) is the second leading neurodegenerative disease, and is known to be induced by environmental factors or genetic mutations. Among the verified genetic mutations of PD, Parkin, isolated from the PARK2 locus, shows an autosomal recessive inheritance pattern and is known to be an E3 ligase. However, the physiological target of Parkin and the molecular mechanism of Parkin-deficiency-induced PD have not been clearly demonstrated until now. It has recently been proposed that inflammation, suggesting as a causal factor for PD, is enhanced by Parkin deficiency. Thus, we examined the relationship between inflammation-related factors and Parkin. Here, we provide the evidence that Parkin suppresses inflammation and cytokine-induced cell death by promoting the proteasomal degradation of TRAF2/6 (TNF-α receptor-associated factor 2/6). Overexpression of Parkin can reduce the half-lives of TRAF2 and TRAF6, whereas si-Parkin can extend them. However, mutant Parkins did not alter the expression of TRAF2/6. Thus, loss of Parkin enhances sensitivity to TNF-α- or IL-1ß-induced JNK activation and NF-κB activation. Indeed, si-Parkin-induced apoptosis is suppressed by the knockdown of TRAF6 or TRAF2. We also observed elevated expression levels of TRAF6 and a reduction of IκB in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model. Moreover, elevated expression levels or aggregation of TRAF6 were detected in approximately half of the human PD tissues (7/15 cases) and 2 cases, respectively. In addition, TRAF6 and Parkin expression levels show a reverse relationship in human PD tissues. Our results strongly suggest that the reduction of Parkin or overexpression of TRAF2/6 by chronic inflammation would be the reason for occurrence of PD.

Do Anthropomorphic Chatbots Increase Counseling Satisfaction and Reuse Intention? The Moderated Mediation of Social Rapport and Social Anxiety.

The growing demand for mental health services and artificial intelligence chatbots to replace human agents have led to increased attention to chatbot anthropomorphizing. This study explored the effect of anthropomorphism on counseling satisfaction and reuse intention for chatbot-led mental health counseling and the mediating role of social rapport in the relationship. This study also examined the interaction effect of anthropomorphism and social anxiety on counseling satisfaction and reuse intention. A total of 374 U.S. adults were recruited from an online crowdsourcing company to simulate user-chatbot interactions in the context of mental health counseling. Two chatbots either with a high anthropomorphic design (i.e., human face) or low anthropomorphic design (i.e., robot face) were developed through Dialogflow-a natural language processing engine-to examine the hypotheses. The results revealed that the high anthropomorphic design produced higher counseling satisfaction and reuse intention than the low anthropomorphic design, while this relationship is mediated by the perceived social rapport between chatbot counselors and users. The results further revealed a significant interaction effect of anthropomorphism and social anxiety on counseling satisfaction and reuse intention. The findings of this study are expected to (a) enhance the understanding of the effect of anthropomorphic chatbots on counseling satisfaction and reuse intention, (b) clarify moderating effects of social rapport and social anxiety, and (c) help mental health practitioners and chatbot designers by providing a psychological mechanism of how anthropomorphism functions in the context of human-chatbot interaction.

Direct interaction of α-synuclein and AKT regulates IGF-1 signaling: implication of Parkinson disease.

Genetic mutation of α-synuclein (α-SYN) is clearly verified as the causal factor of human and mouse Parkinson's disease. However, biological function of α-SYN has not been clearly demonstrated until now. In this investigation, we reveal that α-SYN is a co-regulator of growth factor-induced AKT activation. Elimination of SYN reduces the IGF-1-mediated AKT activation. Similarly, mutant SYN suppresses the IGF-1-induced AKT activation. Wild-type SYN can interact with AKT and enhance the solubility and plasma localization of AKT in response to IGF-1, whereas mutant α-SYNs do not interact with AKT. In addition, elevated expression of SYN blocks the AKT activation. We also find that si-RNA against α-SYN abolished the protective effect of IGF-1 against DNA damage-induced apoptosis. Our result strongly indicates that Parkinson's disease, induced by α-SYN mutation, is evoked by deregulation of the AKT-signaling cascade.

Loss of VHL promotes progerin expression, leading to impaired p14/ARF function and suppression of p53 activity.

Renal cell carcinomas (RCCs) are frequently occurring genitourinary malignancies in the aged population. A morphological characteristic of RCCs is an irregular nuclear shape, which is used to index cancer grades. Other features of RCCs include the genetic inactivation of the von Hippel-Lindau gene, VHL, and p53 genetic-independent inactivation. An aberrant nuclear shape or p53 suppression has not yet been demonstrated. We examined the effect of progerin (an altered splicing product of the LMNA gene linked to Hutchinson Gilford progeria syndrome; HGPS) on the nuclear deformation of RCCs in comparison to that of HGPS cells. In this study, we showed that progerin was suppressed by pVHL and was responsible for nuclear irregularities as well as p53 inactivation. Thus, progerin suppression can ameliorate nuclear abnormalities and reactivate p53 in response to genotoxic addition. Furthermore, we found that progerin was a target of pVHL E3 ligase and suppressed p53 activity by p14/ARF inhibition. Our findings indicate that the elevated expression of progerin in RCCs results from the loss of pVHL and leads to p53 inactivation through p14/ARF suppression. Interestingly, we showed that progerin was expressed in human leukemia and primary cell lines, raising the possibility that the expression of this LMNA variant may be a common event in age-related cancer progression.

Slug, mammalian homologue gene of Drosophila escargot, promotes neuronal-differentiation through suppression of HEB/daughterless.

At the neuron developmental stage, neuron-precursor cells can be differentiated into neuron or glia cells. However, precise molecular mechanism to determine the cell fate has not been clearly demonstrated. In this study, we reveal that Drosophila esgarcot and its mammalian homologue genes, Snail and Slug, play a key role in neuronal differentiation. In Drosophila model system, overexpression of Esg, like as Wingless, suppresses the bristle formation. In contrast, elimination of Esg though RNAi promotes double bristle phenotype. We can also observe the similar phenotype in Snail-overexpression system. In mammalian system, overexpression of Slug or Snail can induce neuronal differentiation. Esg and its mammalian homologue gene Slug directly interact with Daughtherless and its mammalian homologue HEB and eliminate them through siah-1 mediated protein degradation. Thus, overexpression of siah-1 can promote neuron cell differentiation, whereas si-siah-1 blocks the Slug-induced HEB suppression. In fact, Drosophila SINA, Siah-1 homologue, has been also known to be involved in bristle formation and Neuronal differentiation. In addition, it has been revealed that CK1 is involved in Esg or Snail stability and Neuronal differentiation. However, Snail is regulated only by CK1 but not by Siah. Considering the fact that Slug mutations have been found in human genetic disease, waardenberg syndrome, major symptoms of which is loss of hearing neuron and odd eye, our result implies that slug/Snail system is required for proper neuronal differentiation, like as Esg in Drosophila.