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Using a friendship framework, we explored interactions between a multi-functional companion robot and older adults residing in a low-resource community in South Korea.We conducted in-depth interviews with 12 older adults who kept a doll-shaped companion robot called Hyodol for 18 months on average. We applied the Framework Analysis Method to explore three types of friendship (i.e., friendships of utility, pleasure, and the good) that participants cultivated with the robot.The most common aspect of utility companionship reported by all participants was Hyodol's role as their health coach who reminded them to take medication and to exercise. Participants also found pleasure in playing with Hyodol and reported reduced feelings of loneliness. In the absence of other social supports, all participants also regarded Hyodol as a surrogate family member or human-friend, and interacted with Hyodol as such.Findings illustrated high acceptability of Hyodol among these socially isolated older adults especially during the global COVID-19 pandemic, suggesting that a humanoid like Hyodol could be complementary to homecare services for solo-living older adults.Well-designed robot interventions, as complements to existing aging service and clinical interventions, have a potential to improve health behaviors among socially isolated older adults.

Smartphone-based ECG analyzer using camera input can be useful as everyone have it. The purpose of this study was to evaluate whether such a system can outperform clinicians in detecting ST-elevation myocardial infarction (STEMI) regardless of image acquisition conditions.We retrospectively enrolled suspected STEMI patients in an emergency department from January to October 2021. A multifaceted cardiovascular assessment system (Quantitative ECG, QCG™) using ECG images to produce a quantitative score (QCG score, ranging from 0 to 100) was compared to human experts of 7 emergency physicians and 3 cardiologists. Voting scores (number of participants answering "yes" for STEMI) were calculated for comparison. The system's robustness was evaluated using an equivalence test where we prove its performance metric (area under the curve of the receiver operating characteristic curve, AUC-ROC) changes within a predetermined equivalence range (-0.01 to 0.01) in 6 different environments (A combination of three different smartphones and two image sources including computer screen and paper).187 patients (96 STEMI, 51.3%) were analyzed. AUC-ROC of QCG score was 0.919 (0.880-0.957). AUC-ROCs of voting scores, 0.856 (0.799-0.913) for all clinicians, 0.843 (0.786-0.900) for emergency physicians, 0.817 (0.756-0.877) for cardiologists, and 0.848 (0.790-0.905) for high-performance group were significantly lower compared to that of QCG score. The change in AUC-ROC by image acquisition condition was negligible with a narrow confidence interval within -0.01 to 0.01 confirming the equivalence.Image-based AI system can outperform clinicians in STEMI diagnosis and its performance was robust to change in image acquisition conditions.

Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.

Rare earth elements induce ER membrane remodeling and increase ER–PM connectivity in a process that involves phosphoinositide-associated reorganization of synaptotagmin-tethering complexes., In plant cells, environmental stressors promote changes in connectivity between the cortical endoplasmic reticulum (ER) and the plasma membrane (PM). Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in interorganelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+- and lipid-binding protein 1 (CLB1/SYT7). This complex is enriched at ER–PM contact sites (EPCSs), has slow responses to changes in extracellular Ca2+, and displays severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositide species at the PM.

The interorganelle communication mediated by membrane contact sites (MCSs) is an evolutionary hallmark of eukaryotic cells. MCS connections enable the nonvesicular exchange of information between organelles and allow them to coordinate responses to changing cellular environments. In plants, the importance of MCS components in the responses to environmental stress has been widely established, but the molecular mechanisms regulating interorganelle connectivity during stress still remain opaque. In this report, we use the model plant Arabidopsis thaliana to show that ionic stress increases endoplasmic reticulum (ER)-plasma membrane (PM) connectivity by promoting the cortical expansion of synaptotagmin 1 (SYT1)-enriched ER-PM contact sites (S-EPCSs). We define differential roles for the cortical cytoskeleton in the regulation of S-EPCS dynamics and ER-PM connectivity, and we identify the accumulation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the PM as a molecular signal associated with the ER-PM connectivity changes. Our study highlights the functional conservation of EPCS components and PM phosphoinositides as modulators of ER-PM connectivity in eukaryotes, and uncovers unique aspects of the spatiotemporal regulation of ER-PM connectivity in plants.

BACKGROUND The number of older adults with vision impairment (VI) is growing. As health care services increasingly call for patients to use technology, it is important to examine internet/health information technology (HIT) use among older adults with VI. OBJECTIVE This study aimed to examine (1) the rates of internet/HIT use among older adults with VI compared with a matched sample of their peers without VI, (2) associations of VI with internet/HIT use, and (3) association of HIT use with psychological distress, assessed with the Kessler-6 screen. METHODS Data were obtained from the 2013 to 2018 US National Health Interview Survey. Older adults (aged ≥65 years) with self-reported VI were matched with older adults without VI, in a 1:1 ratio, based on age, sex, number of chronic medical conditions, and functional limitations (N=2866). Descriptive statistics and multivariable logistic regression models, with sociodemographic factors, health conditions, health insurance type, and health care service use as covariates, were used to examine the research questions. RESULTS In total, 3.28% of older adults (compared with 0.84% of those aged 18-64 years) reported VI, and 25.7% of them were aged ≥85 years. Those with VI were significantly more socioeconomically disadvantaged than those without VI and less likely to use the internet (adjusted odds ratio [aOR] 0.64, 95% CI0.49-0.83) and HIT (aOR 0.74, 95% CI 0.56-0.97). However, among internet users, VI was not associated with HIT use. HIT use was associated with lower odds of mild/moderate or serious psychological distress (aOR 0.62, 95% CI 0.43-0.90), whereas VI was associated with greater odds of mild/moderate or serious distress (aOR 1.84, 95% CI 1.36-2.49). Health care provider contacts were also associated with higher odds of internet or HIT use. CONCLUSIONS Compared with their matched age peers without VI, older adults with VI are less likely to use HIT because they are less likely to use the internet. Socioeconomically disadvantaged older adults experiencing a digital divide need help to access information and communication technologies through a fee waiver or subsidy to cover internet equipment and subscription and ensure continuous connectivity. Older adults with VI who do not know how to use the internet/HIT but want to learn should be provided instruction, with special attention to accessibility features and adaptive devices. Older adults with a low income also need better access to preventive eye care and treatment of VI as well as other health care services.

Computational thinking (CT), which is the core of the Computer Science field, is an essential thinking process to solve problems effectively and efficiently using computing systems. Learners must be able to design algorithms, identify the appropriate algorithm design skill for a specific problem, and apply it to the problem. Aiming to stimulate learners' interest in learning algorithm design skills, we developed puzzle-based algorithm learning program that has a user-friendly format tailored to real-world scenario. We investigated the effect of this puzzle-based algorithm learning program on learners' CT abilities. The results provide evidence that puzzle based algorithm learning program is effective for developing learners' CT. The study suggests that puzzle based algorithm learning is worth as a learning model for improving CT of learners.

In plant cells, environmental stressors induce changes in the cytosolic concentration of calcium ([Ca2+]cyt) that are transduced by Ca2+-sensing proteins. To confer specificity to the stress signaling response, [Ca2+]cytsensing must be tightly regulated in space and time; the molecular mechanisms that restrict the localization and dynamics of Ca2+sensors in plants, however, are largely unknown. In this report, we identify a putative Ca2+-sensitive complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+-dependent lipid binding protein (CLB1), which is enriched at ER-PM contact sites (EPCS) and relocalizes in response to Rare Earth Elements (REEs)-induced endocytosis. Our results show that endocytosed REEs influence cytosolic Ca2+signaling, as indicated by the activation of the Ca2+/Calmodulin-based ratiometric sensor GCaMP3, and promote the cytoskeleton-dependent accumulation of ER-PM contact sites at the cell cortex. Based on these results, we propose that the EPCS-localized SYT1/SYT5/CLB1 complex is part of an evolutionarily conserved and spatially regulated Ca2+-responsive mechanism that control cER-PM communication during stress episodes.

The interorganelle communication mediated by membrane contact sites (MCSs) is an evolutionary hallmark of eukaryotic cells. MCS connections enable the nonvesicular exchange of information between organelles and allow them to coordinate responses to changing cellular environments. In plants, the importance of MCS components in the responses to environmental stress has been widely established, but the molecular mechanisms regulating interorganelle connectivity during stress still remain opaque. In this report, we use the model plant Arabidopsis thaliana to show that ionic stress increases endoplasmic reticulum (ER)–plasma membrane (PM) connectivity by promoting the cortical expansion of synaptotagmin 1 (SYT1)-enriched ER–PM contact sites (S-EPCSs). We define differential roles for the cortical cytoskeleton in the regulation of S-EPCS dynamics and ER–PM connectivity, and we identify the accumulation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] at the PM as a molecular signal associated with the ER–PM connectivity changes. Our study highlights the functional conservation of EPCS components and PM phosphoinositides as modulators of ER–PM connectivity in eukaryotes, and uncovers unique aspects of the spatiotemporal regulation of ER–PM connectivity in plants.

Premise of the study The FOUR LIPS (FLP) and MYB88 transcription factors, which are closely related in structure and function, control the development of stomata, as well as entry into megasporogenesis in Arabidopsis thaliana. However, other locations where these transcription factors are expressed are poorly described. Documenting additional locations where these genes are expressed might define new functions for these genes. Methods Expression patterns were examined throughout vegetative and reproductive development. The expression from two transcriptional-reporter fusions were visualized with either β-glucuronidase (GUS) or green fluorescence protein (GFP). Key results Both flp and myb88 genes were expressed in many, previously unreported locations, consistent with the possibility of additional functions for FLP and MYB88. Moreover, expression domains especially of FLP display sharp cutoffs or boundaries. Conclusions In addition to stomatal and reproductive development, FLP and MYB88, which are R2R3 MYB transcription factor genes, are expressed in many locations in cells, tissues, and organs.

(180 words)Stomatal guard cells are formed through a sequence of asymmetric and symmetric divisions in the epidermis of the sporophyte of most land plants. We show that several D-type cyclins are consecutively activated in the stomatal linage in the epidermis of Arabidopsis thaliana. Whereas CYCD2;1 and CYCD3;2 are activated in the meristemoids early in the lineage, CYCD7;1 is activated before the final division. CYCD7;1 expression peaks in the guard mother cell, where its transcription is modulated by the FOUR-LIPS/MYB88 transcription factor. FOUR-LIPS/MYB88 interacts with the CYCD7;1 promoter and represses CYCD7;1 transcription. CYCD7;1 stimulates the final symmetric division in the stomatal lineage, since guard cell formation is delayed in the cycd7;1 mutant epidermis and guard mother cell (GMC) divisions in four-lips mutant guard mother cells are limited by loss of function of CYCD7;1. Hence, the precise activation of a specific D-type cyclin, CYCD7;1, is required for correct timing of the last symmetric division that creates the stomatal guards cells, and CYCD7;1 expression is regulated by the FLP/MYB pathway that ensures cell cycle arrest in the stomatal guard cells.Summary StatementThe formation of paired guard cells in the epidermis of the Arabidopsis thaliana shoot, requires the activity of the D-type cyclin CYCD7;1 for the normal timing of the final division.

The initiation of stomatal lineage and subsequent asymmetric divisions in Arabidopsis require the activity of the basic helix-loop-helix transcription factor SPEECHLESS (SPCH). It has been shown that SPCH controls entry into the stomatal lineage as a substrate either of the MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) cascade or GSK3-like kinase BRASSINOSTEROID INSENSITIVE 2 (BIN2). Here we show that three serine residues of SPCH appear to be the primary phosphorylation targets of Cyclin-Dependent Kinases A;1 (CDKA;1) in vitro , and among them Serine 186 plays a crucial role in stomatal formation. Expression of an SPCH construct harboring a mutation that results in phosphorylation deficiencies on Serine 186 residue failed to rescue stomatal defects in spch null mutants. Expression of a phosphorylation-mimic mutant SPCH S186D complemented stomatal production defects in the transgenic lines harboring the targeted expression of dominant-negative CDKA;1.N146 . Therefore, in addition to MAPK- and BIN2-mediated phosphorylation on SPCH, phosphorylation at Serine 186 is positively required for SPCH function in regulating stomatal development.

Eukaryotic endoplasmic reticulum (ER)-plasma membrane (PM) contact sites are evolutionarily conserved microdomains that have important roles in specialized metabolic functions such as ER-PM communication, lipid homeostasis, and Ca2+ influx. Despite recent advances in knowledge about ER-PM contact site components and functions in yeast (Saccharomyces cerevisiae) and mammals, relatively little is known about the functional significance of these structures in plants. In this report, we characterize the Arabidopsis (Arabidopsis thaliana) phospholipid binding Synaptotagmin1 (SYT1) as a plant ortholog of the mammal extended synaptotagmins and yeast tricalbins families of ER-PM anchors. We propose that SYT1 functions at ER-PM contact sites because it displays a dual ER-PM localization, it is enriched in microtubule-depleted regions at the cell cortex, and it colocalizes with Vesicle-Associated Protein27-1, a known ER-PM marker. Furthermore, biochemical and physiological analyses indicate that SYT1 might function as an electrostatic phospholipid anchor conferring mechanical stability in plant cells. Together, the subcellular localization and functional characterization of SYT1 highlights a putative role of plant ER-PM contact site components in the cellular adaptation to environmental stresses.

Moebius syndrome is a rare, congenital neurological disease involving facial paralysis and limitation of eye movements. It results from maldevelopment of the sixth and seventh cranial nerves. Dental features of this syndrome include micrognathia, microstomia, tongue deformity, cleft palate, hypoplasia of the teeth, and congenital missing teeth. A 7-year-old female with Moebius syndrome was referred from a local dental clinic for caries treatment. She presented with facial paralysis and microstomia. Oral findings included multiple caries with enamel hypoplasia, congenital missing teeth, and tongue deformity. Dental treatments including restorative and preventive procedures were performed. Oral findings and management aspects of Moebius syndrome for this case are discussed. Early evaluation and multidisciplinary care are needed for children with Moebius syndrome. (J Korean Dis Oral Health Vol.10, No.2: 101-105, December 2014) Abstract

Functional redundancy arises between gene paralogs as well as non-homologous genes that play a common role at a shared node. The bHLH transcription factor FAMA, along with the paralogous MYB genes, FOUR LIPS (FLP) and MYB88 all ensure that Arabidopsis stomata contain just two guard cells (GCs) by enforcing a single symmetric precursor cell division before stomatal maturity. Consistent with this function, FLP and FAMA exhibit the same expression pattern in which both translational GFP fusions emit fluorescence just before and after symmetric division; however, FAMA but not FLP is required to confer GC fate. Strikingly, swapping the genes and promoters of the FLP and FAMA genes results in the reciprocal complementation of respective loss-of-function mutants. Thus, an FLP transgene can restore GC fate to a fama mutant background. FAMA, FLP and the FLP paralog MYB88 were previously shown to influence higher order functions in stomatal development, including maintaining and stabilizing stomatal fate. Here we show that these overlapping functions are likely to also involve interactions between FLP and FAMA with the RETINOBLASTOMA-RELATED (RBR) protein.