HLA-Ehigh /HLA-Ghigh /HLA-IIlow Human iPSC-Derived Cardiomyocytes Exhibit Low Immunogenicity for Heart Regeneration.

Although human pluripotent stem cells (hPSCs)-derived cardiomyocytes (hPSC-CMs) can remuscularize infarcted hearts and restore post-infarct cardiac function, post-transplant rejection resulting from human leukocyte antigen (HLA) mismatching is an enormous obstacle. It is crucial to identify hypoimmunogenic hPSCs for allogeneic cell therapy. This study is conducted to demonstrate the immune privilege of HLA-Ehigh /HLA-Ghigh /HLA-IIlow human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs). Ischemia-reperfusion surgery is done to create transmural myocardial infarction in rats. At post-infarct 4 days, hPSC-CMs (1.0×107 cells per kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), HLA-Elow/HLA-Glow/HLA-IIhigh hiPSC-CMs, and HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs, are injected into the infarcted myocardium. Under the treatment of very low dose cyclosporine A (CsA), only HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs survive in vivo and improved post-infarct cardiac function with infarct size reduction. HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs activate the SHP-1 signaling pathway of natural killer (NK) cells and cytotoxic T cells to evade attack by NK cells and cytotoxic T cells. Herein, it is demonstrated that using a clinically relevant CsA dose, HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs repair the infarcted myocardium and restore the post-infarct heart function. HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSCs are less immunogenic and may serve as platforms for regeneration medicine.

Tumor endothelial marker 1 is upregulated in heart after cardiac injury and participates in cardiac remodeling.

Tumor endothelial marker 1 (TEM1) is a transmembrane glycoprotein that appears on mesenchymal lineage-derived cells during embryogenesis, but its expression greatly reduces after birth. Re-upregulation of TEM1 is found in tumor angiogenesis, organ fibrosis and wound healing indicating its potential role in tissue remodeling and repair. The expression level and function of TEM1 in adult heart are unknown. In explanted hearts from heart failure (HF) patients received cardiac transplantation, immunofluorescence staining showed TEM1 was expressed in cardiomyocytes (CMs) and cardiac fibroblasts. Bioinformatics analysis showed TEM1 upregulation in mouse heart after coronary ligation. Cardiac TEM1 expression was reconfirmed in mouse HF induced by coronary ligation or doxorubicin injection. TEM1 expression increased in cultured CMs stimulated with mechanical stretch, doxorubicin and hypoxia. Further studies showed recombinant TEM1 (rTEM1) was a functional protein that influenced cell behaviors of CMs. It directly activated Erk and Akt through interaction with PDGF receptor. TEM1lacZ/lacZ mice had less collagen deposition and worse cardiac function than wild type mice. These results indicate that TEM1 expression increases in the heart after cardiac injury and works as a functional protein that participates in cardiac remodeling.

Does Prior Night's Sleep Impact Next Day's Executive Functioning? It Depends on an Individual's Average Sleep Quality.

Executive functioning (EF) is a series of fundamental goal-directed cognitive abilities that enable effective learning. Differences in daily sleep quality may covary with fluctuations in EF among youth. Most studies linking sleep to EF rely on between-person differences and average effects for the sample. This study employed an intensive longitudinal design and examined the within-person relations between self-reported prior night's sleep quality and next day's EF. Students from Grades 4 to 12 (M age= 14.60, SD = 2.53) completed three behavioral EF tasks repeatedly across approximately one semester. The final analytic sample included 2898 observations embedded in 73 participants. Although, on average, sleep did not significantly covary with EF, there was heterogeneity in within-person sleep-EF relations. Moreover, individuals' average sleep quality moderated within-person effects. For individuals with low mean sleep quality, a better-than-usual sleep quality was linked to better EF performance. However, for individuals with high mean sleep quality, better-than-usual sleep quality was linked to worse EF performance. Understanding person-specific relations between sleep and EF can help educators optimize EF and learning on a daily basis and produce positive academic outcomes across longer time periods.

Stressful Experiences, Connection, and Depressive Symptoms Among Taiwanese Han and Indigenous Youth.

This study examined Taiwanese Han and indigenous (Tayal) youth's experiences of stressful life events, the association between stressful experiences and depressive symptomology, and also the indirect and interactive effects of connection on the relationship between stressful experiences and depressive symptomology. Taiwanese Han (97%) is the majority group, whereas indigenous people make up 2.3% of Taiwan's population. Taiwanese indigenous people have experienced disparities across socio-historical, educational, and economic aspects of their lives. This study included 291 eighth-grade participants (40% from the Tayal tribe, 48.8% female, and M age = 13.44). The Han sample in this study all lived in cities, and the Tayal sample all lived in the tribal areas of the Northern Taiwan mountain regions. Person-centered (latent class analyses) and cumulative (sum of items) approaches were used to investigate family and school stressful events, respectively. Hierarchical regression analyses were conducted separately for the Han and Tayal participants to examine the role of family and school connection in relation to family and school stressors and depressive symptomology. Our results showed that stressful experiences are clearly linked to depressive symptomology and family connection was important to both Tayal and Han youth in supporting their coping with depressive symptoms. However, Tayal youth might be particularly vulnerable to family stressful events because family stressors disrupted their connection with their parents and thereby minimized the protective function of family relationships. To decrease the likely onset of depression during early adolescence, our results suggest that it is important for parents and other family members to monitor adolescents' daily experiences of stress and provide support when needed. Furthermore, mental health interventions need to be tailored specifically for youth in specific racial, social, and economic contexts. Tayal youth mental health might benefit particularly from increasing school connection and decreasing stresses experienced in family contexts. Implications, limitations, and recommendations for future research are discussed.

Intraindividual Fluctuations in Sleep Predict Subsequent Goal Setting in Adolescents.

The purpose of this study was to investigate within- and between-person associations between sleep and subsequent goal setting in adolescents. We conducted an intensive repeated measures longitudinal study to assess intra- and inter-individual associations between sleep and goal setting and potential moderators of such associations. Thirty-nine seventh through 12th graders reported on their sleep quality and propensity to set goals in their daily lives several times per week for approximately four months. We used a combination of multilevel modeling with time-varying covariates and centering techniques to partition within- and between-person variance. We found significant and positive associations between sleep and goal setting within individuals, but no such associations between individuals. That is, students were more likely to set goals for their work after getting a good night's sleep relative to their own average sleep quality, but getting good sleep on average relative to other individuals showed no association with average goal setting. These relationships were not moderated by participant age, gender, or sociodemographic status as indexed by maternal education. Differences in average sleep between adolescents matters less for their propensity to set goals than whether they experienced better- or worse-than-usual sleep the previous night given their own average. This finding represents the first evidence documenting effects of sleep on goal setting, which is an important psychological precursor to many youth behavioral and achievement outcomes. Our findings highlight the individuality of sleep needs and point to new directions for sleep-related practice and policy aimed at youth.

Progress and Challenges of Amniotic Fluid Derived Stem Cells in Therapy of Ischemic Heart Disease.

Cardiovascular disease is the leading cause of deaths worldwide, claiming an estimated total of 17.9 million lives each year, of which one-third of the people are under the age of 70 years. Since adult cardiomyocytes fail to regenerate, the heart loses the ability to repair itself after an injury, making patients with heart disease suffer from poor prognosis. Pluripotent stem cells have the ability to differentiate into cardiomyocytes in vitro through a well-established process, which is a new advancement in cardiac regeneration therapy. However, pluripotent stem cell-derived cardiomyocytes have certain drawbacks, such as the risk of arrhythmia and immune incompatibility. Thus, amniotic fluid stem cells (AFSCs), a relatively novel source of stem cells, have been exploited for their ability of pluripotent differentiation. In addition, since AFSCs are weakly positive for the major histocompatibility class II molecules, they may have high immune tolerance. In summary, the possibility of development of cardiomyocytes from AFSCs, as well as their transplantation in host cells to produce mechanical contraction, has been discussed. Thus, this review article highlights the progress of AFSC therapy and its application in the treatment of heart diseases in recent years.

Immunogenicity in Stem Cell Therapy for Cardiac Regeneration.

Despite enormous advances in the treatment of cardiovascular disease (CVD), heart disease remains the leading cause of mortality and morbidity worldwide. Thus, there is a need for novel CVD therapeutics. CVD appears to be a custom-made scenario for applying stem cell therapy. Although human pluripotent stem cells can differentiate into cardiomyocytes to regenerate injured heart tissue and restore post-myocardial infarction cardiac function, several obstacles need to be overcome before cell therapy can be applied in CVD patients. One of these major hurdles is the immunological barrier. Currently, long-term immunosuppressant treatment is necessary for allogenic stem cell or organ transplantation to prevent rejection. However, the long-term use of immunosuppressants may cause serious adverse events such as nephrotoxicity, severe infections and malignancy. Thus, overcoming this immunological hurdle is crucial for the clinical application of stem cell therapy in cardiac regeneration. This review summarizes the recent advances and challenges of immunogenicity in relation to stem cell therapy.

Efficient Cardiac Differentiation of Human Amniotic Fluid-Derived Stem Cells into Induced Pluripotent Stem Cells and Their Potential Immune Privilege.

Mature mammalian hearts possess very limited regenerative potential. The irreversible cardiomyocyte loss after heart injury can lead to heart failure and death. Pluripotent stem cells (PSCs) can differentiate into cardiomyocytes for cardiac repair, but there are obstacles to their clinical application. Among these obstacles is their potential for post-transplant rejection. Although human amniotic fluid-derived stem cells (hAFSCs) are immune privileged, they cannot induce cardiac differentiation. Thus, we generated hAFSC-derived induced PSCs (hAFSC-iPSCs) and used a Wnt-modulating differentiation protocol for the cardiac differentiation of hAFSC-iPSCs. In vitro studies using flow cytometry, immunofluorescence staining, and patch-clamp electrophysiological study, were performed to identify the characteristics of hAFSC-iPSC-derived cardiomyocytes (hAFSC-iPSC-CMs). We injected hAFSC-iPSC-CMs intramuscularly into rat infarcted hearts to evaluate the therapeutic potential of hAFSC-iPSC-CM transplantation. At day 21 of differentiation, the hAFSC-iPSC-CMs expressed cardiac-specific marker (cardiac troponin T), presented cardiomyocyte-specific electrophysiological properties, and contracted spontaneously. Importantly, these hAFSC-iPSC-CMs demonstrated low major histocompatibility complex (MHC) class I antigen expression and the absence of MHC class II antigens, indicating their low immunogenicity. The intramyocardial transplantation of hAFSC-iPSC-CMs restored cardiac function, partially remuscularized the injured region, and reduced fibrosis in the rat infarcted hearts. Therefore, hAFSC-iPSCs are potential candidates for the repair of infarcted myocardium.

Exploring Idiographic Approaches to Children's Executive Function Performance: An Intensive Longitudinal Study.

Traditional variable-centered research on executive functions (EFs) often infers intraindividual development using group-based averages. Such a method masks meaningful individuality and involves the fallacy of equating group-level data with person-specific changes. We used an intensive longitudinal design to study idiographic executive function fluctuation among ten boys from Grade 4. Each of the participants completed between 33 and 43 measurement occasions (M = 38.8) across approximately three months. Data were collected remotely using a computerized short version of the Dimensional Change Card Sort task. Multi-group analyses of three participant pairs (Participants 5 and 3, 5 and 2, and 5 and 6) demonstrated that Participant 5 differed from Participants 3 and 2 in different ways but Participants 5 and 6 were similar in all comparisons. Dynamic structural equation modeling demonstrated unique individual trajectories, which were not represented by the trajectory of group-averages. Although more than half of the participants showed a negative association between EFs and inattention, two participants showed a positive association between EF and inattention. This study demonstrated meaningful person-specific trajectories of EFs, suggesting that future study should undertake the analysis of individual development before data-aggregation or generalization from aggregate statistics to individuals.

Microdermal Grafting for Color Regeneration of White Scars.

White scars are defined in this study as mature hypopigmented surgical or traumatic scars whose color is much lighter than surrounding skin, to the extent that they appear white. These scars are often obvious and very difficult to treat or mask. This 3-year retrospective study reports the outcomes from 38 recipients of a new microdermal grafting surgery we developed, which introduces melanocytes into the white scar lesion to regenerate skin color. The study shares 18 years of experience with this procedure, describes the surgical steps, offers videos of the procedures, and presents 4 cases. Between September 2013 and December 2016, 38 patients (30 females; 8 males) underwent microdermal grafting for color regeneration of white scars in our plastic surgery clinic. Most patients, 78.9%, received 1 treatment, 15.8% received 2 treatments, and 5.3% received 3 treatments. Three lay judges were asked to assess percentage pigmentation recovery by comparing photographic images of patients' preoperative and postoperative scars. Patients were also asked to assess, via a questionnaire, satisfaction and percentage improvement 1 year after surgical treatment. Lay judges found an average of 49% improvement after 1 session, 75% after 2 sessions, and 90% after 3 sessions. In total, 71.1% of the patients completed the questionnaire 1 year after the surgery. Average subjective improvement was 55% after 1 session, 88% after 2 sessions, and 95% after 3 sessions. The patient satisfaction rate was high. Microdermal grafting provides adequate treatment of white scars by regenerating melanocytes, although more than 1 session treatment may be needed.

Clathrin-mediated endocytosis is required for ANE 30-100K-induced autophagy.

BACKGROUND: We identified an autophagy-inducing areca nut (AN) ingredient (AIAI) in the 30-100 kDa fraction of AN extract (ANE 30-100K). This study was to analyze the role of endocytosis in ANE 30-100K-induced autophagy. METHODS: We used benzyl alcohol, dynasore, and shRNA of clathrin and dynamin to assess whether ANE 30-100K-induced cytotoxicity and accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II were affected in oral (OECM-1) and esophageal (CE81T/VGH) carcinoma cells. RESULTS: Both benzyl alcohol and dynasore effectively reduced ANE 30-100K-induced cytotoxicity and LC3-II accumulation in OECM-1 and CE81T/VGH cells. Downregulated protein expression of both clathrin and dynamin by their shRNA also significantly attenuated ANE 30-100K-induced elevation of LC3-II levels in CE81T/VGH cells. CONCLUSIONS: These results indicate that AIAI may be engulfed by cells through clathrin-mediated endocytosis, which promotes the execution of the following autophagy program.

Hybrid proximal linearized algorithm for the split DC program in infinite-dimensional real Hilbert spaces.

To be the best of our knowledge, the convergence theorem for the DC program and split DC program are proposed in finite-dimensional real Hilbert spaces or Euclidean spaces. In this paper, to study the split DC program, we give a hybrid proximal linearized algorithm and propose related convergence theorems in the settings of finite- and infinite-dimensional real Hilbert spaces, respectively.

Synthesis and bioactivity of ß-(1→4)-linked oligomannoses and partially acetylated derivatives.

The synthesis of ß-(1→4)-linked hexa- to octamannoses and their partially acetylated derivatives was efficiently carried out by assembly of appropriate oligomeric fragments using ß-selective glucosylation followed by gluco to manno epimerization at a late stage of the synthetic pathway. In the course of this study, we also observed that 2-O-acetylated oligomannoses coexisted in equilibrium with the 3-O-acetylated isomers due to intramolecular migration of the acetyl group. Bioactivity of the synthetic oligomannoses and partially acetylated derivatives was investigated in order to identify the possible smallest oligomer for induction of cytokines as that shown in the polysaccharides extracted from Dendrobium huoshanense.

Do human figure diagrams help alleged victims of sexual abuse provide elaborate and clear accounts of physical contact with alleged perpetrators?

The present study examined whether the use of human figure diagrams within a well-structured interview was associated with more elaborate and clearer accounts about physical contact that had occurred in the course of an alleged abuse. The sample included investigative interviews of 88 children ranging from 4 to 13 years of age. Children were interviewed using the NICHD Investigative Interview Protocol, and were then asked a series of questions in association with unclothed gender-neutral outline diagrams of a human body. A new coding scheme was developed to examine the types and clarity of touch-related information. Use of the HFDs was associated with reports of new touches not mentioned before and elaborations regarding the body parts reportedly touched. The HFDs especially helped clarify reports by the oldest rather than the youngest children. The clarity of children's accounts of touch was also greater when details were sought using recall prompts.