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Background The genetic interactions in the circadian rhythm biological system are promising as a source of pathophysiology in mood disorder. We examined the role of the gene–gene interactions of clock genes in mood disorder. Methods We included 413 patients with mood disorder and 1294 controls. The clock genes investigated were BHLHB2, CLOCK, CSNK1E, NR1D1, PER2, PER3, and TIMELESS. Allele, genotype, and haplotype associations were tested. Gene–-gene interactions were analyzed using the non-parametric model-free multifactor-dimensionality reduction (MDR) method. Results TIMELESS rs4630333 and CSNK1E rs135745 were significantly associated with both major depressive disorder and bipolar disorder. The CLOCK haplotype was also strongly associated. The genetic roles of these SNPs were consistent from the allele and genotypic associations to the MDR interaction results. In MDR analysis, the combination of TIMELESS rs4630333 and CSNK1E rs135745 exhibited the most significant association with mood disorders in the two-locus model. BHLHB2 rs2137947 for major depressive disorder and CLOCK rs12649507 for bipolar disorder were the most significant third loci in the three-locus combination model. The four-locus SNP combination model showed the best balanced accuracy (BA), but its cross-validation consistency (CVC) was unsatisfactory. Limitations We included only 17 SNPs for seven circadian genes due to our limited resources; all subjects were ethnically Korean. Conclusions Our results suggest significant single-gene associations and gene–gene interactions of circadian genes with mood disorder. Gene–gene interactions play a crucial role in mood disorder, even when individual clock genes do not have significant roles.

The multi-band UWAS communication techniques are effective in terms of performance and throughput efficiency. However, the multi-band configuration in a particular band affects the output from the entire bands. This problem can be solved through a receiving end that analyzes error rates of each band. In this paper, we proposed an estimation BER algorithm which get the reliability of received data to set the weighting value to each band. Therefore, we analyzed the efficiency of multi-band transmission scheme with estimation BER and 3 [dB] performance gain is obtained.

Ginsenoside Re (G-Re) is a panaxatriol saponin and one of the pharmacologically active natural constituents of ginseng (Panax ginseng C.A. Meyer). G-Re has antioxidant, anti-inflammatory and antidiabetic effects. The present study aimed to investigate the effects of G-Re on neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated microglia and its protective effects on hippocampal neurons. Cytokine levels were measured using ELISA and reactive oxygen species (ROS) levels were assessed using flow cytometry and fluorescence microscopy. Protein levels of inflammatory molecules and kinase activity were assessed by western blotting. Cell viability was assessed by MTT assay; apoptosis was estimated by Annexin V apoptosis assay. The results revealed that G-Re significantly inhibited the production of IL-6, TNF-α, nitric oxide (NO) and ROS in BV2 microglial cells, and that of NO in mouse primary microglia, without affecting cell viability. G-Re also inhibited the nuclear translocation of NF-κB, and phosphorylation and degradation of IκB-α. In addition, G-Re dose-dependently suppressed LPS-mediated phosphorylation of Ca2+/calmodulin-dependent protein kinase (CAMK)2, CAMK4, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK). Moreover, the conditioned medium from LPS-stimulated microglial cells induced HT22 hippocampal neuronal cell death, whereas that from microglial cells incubated with both LPS and G-Re ameliorated HT22 cell death in a dose-dependent manner. These results suggested that G-Re suppressed the production of pro-inflammatory mediators by blocking CAMK/ERK/JNK/NF-κB signaling in microglial cells and protected hippocampal cells by reducing these inflammatory and neurotoxic factors released from microglial cells. The present findings indicated that G-Re may be a potential treatment option for neuroinflammatory disorders and could have therapeutic potential for various neurodegenerative diseases.

Sarcopenia, defined as loss of muscle mass and strength with age, becomes a public health concern as the elderly population increases. This study aimed to determine whether the mixture of soluble whey protein hydrolysate (WPH) andIn the first experiment, C57BL/6 mice were hindlimb immobilized for one-week and then administered WPH 800 mg/kg, GBE 100 mg/kg, WPH 800 mg/kg+ GBE 100 mg/kg mixture, andIn the first experiment, we confirmed the synergetic effect of WPH and GBE on muscle mass and identified that GBE was more effective on the protein synthesis side, and WPH tended to be slightly more effective for protein degradation. In the second experiment, among three different ratios, the WPH 800 mg/kg+ GBE 100 mg/kg was most effective for muscle mass and strength. The mixtures activated muscle protein synthesis via PI3K/Akt/mTORc1 pathway and inhibited muscle protein degradation via suppressing ubiquitin-proteasome system (UPS) and autophagy-lysosome system (ALS), and these effects were more GBE dose-dependent than WPH.The WPH and GBE mixture having a synergetic effect is a potential agent to prevent sarcopenia.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractable Drosophila model and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment of Drosophila larvae with paclitaxel caused degeneration and altered the branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We further found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-induced cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. Paclitaxel-induced changes in recycling endosomes precede morphological degeneration of nociceptive neuron arbors, which could be prevented by integrin overexpression. We used primary dorsal root ganglia (DRG) neuron cultures to test conservation of integrin-mediated protection. We show that transduction of a human integrin β-subunit 1 also prevented degeneration following paclitaxel treatment. Furthermore, endogenous levels of surface integrins were decreased in paclitaxel-treated mouse DRG neurons, suggesting that paclitaxel disrupts recycling in vertebrate sensory neurons. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring neuronal interactions with the extracellular environment to antagonize paclitaxel-induced toxicity in sensory neurons.

Mutations in Fms-like tyrosine kinase 3 (FLT3) have been implicated in the pathogenesis of acute myeloid leukemia (AML) by affecting the proliferation and differentiation of hematopoietic stem and progenitor cells. Although several FLT3 inhibitors have been developed, the occurrence of secondary TKD mutations of FLT3 such FLT3/D835Y and FLT3/F691L lead to drug resistance and has become a key area of unmet medical needs. To overcome the obstacle of secondary TKD mutations, a new series of indirubin-3'-aminooxy-acetamide derivatives was discovered as potent and selective FLT3 and FLT3/D835Y inhibitors that were predicted to bind at the DFG-in active conformation of FLT3 in molecular docking studies. Through structure-activity relationship studies, the most optimized compound 13a was developed as a potent inhibitor at FLT3 and FLT3/D835Y with IC

The pathogenesis of chemotherapy-induced peripheral neuropathy (CIPN) is poorly understood. Here, we report that the CIPN-causing drug bortezomib (Bort) promotes delta 2 tubulin (D2) accumulation while affecting microtubule stability and dynamics in sensory neurons in vitro and in vivo and that the accumulation of D2 is predominant in unmyelinated fibers and a hallmark of bortezomib-induced peripheral neuropathy (BIPN) in humans. Furthermore, while D2 overexpression was sufficient to cause axonopathy and inhibit mitochondria motility, reduction of D2 levels alleviated both axonal degeneration and the loss of mitochondria motility induced by Bort. Together, our data demonstrate that Bort, a compound structurally unrelated to tubulin poisons, affects the tubulin cytoskeleton in sensory neurons in vitro, in vivo, and in human tissue, indicating that the pathogenic mechanisms of seemingly unrelated CIPN drugs may converge on tubulin damage. The results reveal a previously unrecognized pathogenic role for D2 in BIPN that may occur through altered regulation of mitochondria motility.

Sarcopenia and obesity are serious health problems that are highly related to several metabolic diseases. Sarcopenic obesity, a combined state of sarcopenia and obesity, results in higher risks of metabolic diseases and even mortality than sarcopenia or obesity alone. Therefore, the development of therapeutic agents for sarcopenic obesity is crucial. C57BL/6 mice were fed with a high-fat diet (HFD) for 9 weeks. Then, mice were administered with Panax ginseng berry extract (GBE) for an additional 4 weeks, with continuous HFD intake. GBE significantly decreased the food efficiency ratio, serum lipid and insulin levels, adipose tissue weights, and adipocyte size. It significantly increased the grip strength, muscle masses, and myofiber cross-sectional area. It deactivated the protein kinase C (PKC) theta and zeta, resulting in activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is known to regulate muscle synthesis and degradation. Furthermore, it inhibited the production of inflammatory cytokines in the muscle tissue. GBE attenuated both obesity and sarcopenia. Thus, GBE is a potential agent to prevent or treat sarcopenic obesity.

This study was conducted to assess the changes in the annual incidence of adult asthma in Korea where the prevalence of asthma had increased steadily in recent decades. A population-based cohort study was conducted using the National Health Insurance Service–National Sample Cohort (NHIS-NSC), which consisted of 746,816 adults aged >20 years between 2004 and 2012. Asthma was defined by two or more physician claims on the basis of a primary diagnostic code for asthma and administration of asthma medications within 1 year. The incidence rates and annual percent change were calculated, and the influence of age and sex on the incidence rates was studied. The annual asthma incidence increased from 3.63 in 2004 to 6.07 per 1,000 person-years in 2008. Since 2008, the asthma incidence did not change significantly. The asthma incidence was higher in women than in men throughout the study periods (p

BACKGROUND/AIM Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. PATIENTS AND METHODS Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. RESULTS Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). CONCLUSION Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those

Physical attractiveness (PAT), despite its allure in everyday life, has been an inconsistent predictor of happiness in past studies. In this research, we find that a lay belief about the locus of a person's “essence” moderates the PAT and happiness link. Specifically, we measured how strongly one believes in the diagnostic value of the visible (e.g., status, appearance) over the invisible (e.g., mood, thoughts) aspects of a person in understanding who s/he is. As expected, the more one believed in the value of the visible features, the more central PAT was in the person's overall life, and appearance was compared more often with others (Study 1). More importantly, PAT and well-being correlated significantly only among those who strongly endorsed the visible selfhood belief (Study 2). Compared to past studies on PAT that relied heavily on self-reports, a highly objective measure of attractiveness (waist-to-hip ratio) was employed in this research. Our research uncovers a novel individual difference factor that helps to clarify why PAT predicts the happiness of some, but not of others. Whether one thinks a person's essence can be judged by one's “cover” seems to matter in the PAT and happiness link.

The present study examined cultural differences in the act of sharing positive events with others, called capitalization attempts. The first three studies tested whether capitalization attempts differ between two cultures using multiple methods: self-reports (Study 1), children’s storybooks (Study 2), and Facebook (Study 3). We found that Koreans are less likely to share their positive events with others than European Americans. Study 4 further examined the antecedents and consequences of capitalization attempts. We replicated the earlier findings that Koreans are hesitant to share their positive events and demonstrated that this is because Koreans are more concerned about the potential negative consequences for social relationships. Moreover, we found that the cultural differences in capitalization attempts partly account for mean-level differences in well-being between cultures. Implications for capitalization, culture, and well-being are discussed.

L’objectif de cet article est de comprendre les caracteristiques du don d’organes post mortem en termes d’unilateralite, de dette et de rapport a autrui. En partant de l’analyse du don d’organes dans la perspective de l’echange asymetrique de la vie et de la mort, cet article commence par examiner la specificite des sentiments de dette et de culpabilite que certains receveurs ont vecus apres la transplantation d’organes. Dans un deuxieme temps, il propose une analyse critique des discours mecaniste et utilitariste qui visent a reduire les organes humains a une substance sans âme. Ensuite, nous montrerons comment un receveur tente de se lier avec son donneur mort par le biais d’une parente fictive. En examinant ce temoignage, nous pourrons voir dans quelle mesure le receveur arrive enfin a accepter l’organe du donneur et a etablir un rapport imaginaire avec lui.

How the brain makes trillions of synaptic connections using a genome of only 20,000 genes is a major question in modern neuroscience. Alternative splicing is one mechanism that can increase the number of proteins produced by each gene, but its role in regulating synapse formation is poorly understood. In Drosophila, photoreceptors form a synapse with multiple postsynaptic elements including lamina neurons L1 and L2. L1 and L2 express distinct isoforms of the homophilic repulsive protein Dscam2, and since these isoforms cannot bind to each other, cell-specific expression has been proposed to be necessary for preventing repulsive interactions that could disrupt the synapse. Here, we show that the number of synapses are reduced in flies that express only one isoform, and L1 and L2 dendritic morphology is perturbed. We propose that these defects result from inappropriate interactions between L1 and L2 dendrites. We conclude that regulated Dscam2 alternative splicing is necessary for the proper assembly of photoreceptor synapses.

This experiment was conducted to investigate the effect of dietary Ca concentrations in phytase-containing diets on growth performance, bone mineralization, litter quality, and footpad dermatitis (FPD) score in broiler chickens. A total of 2100 1-d-old Ross 308 broiler chicks was used and allotted to 1 of 5 dietary treatments with 6 replicates consisting of 70 birds in a completely randomized design. Five commercial-type diets were formulated to contain increasing Ca concentrations of 6.0, 7.0, 8.0, 9.0, or 10.0 g/kg. All diets contained 3.5 g/kg nonphytate phosphorus and 1000 FTU/kg phytase. Diets were fed to birds for 21 d. At the end of the experiment, birds were sacrificed for tibia sampling and litter samples were collected. The FPD score was measured visually based on a 6-point scale scoring system. Results indicated that increasing Ca concentrations in phytase-containing diets decreased (linear, P 0.01) body weight gain, feed intake, and feed efficiency of broiler chickens. The concentrations of ash, Ca, and P in the tibia, and tibia breaking strength were not affected by dietary Ca concentrations. Dietary Ca concentrations had no effect on litter quality including pH and moisture and nitrogen contents. A tendency (linear, P = 0.10) for increased FPD score was observed as dietary Ca concentrations were increased. In conclusion, increasing Ca concentrations from 6.0 to 10.0 g/kg in phytase-containing diets have negative effects on growth performance of broiler chickens during 21 d posthatch, possibly due to decreased FI and subsequent phytase intake. Increasing Ca concentrations in phytase-containing diets have little impact on litter quality but tend to increase FPD incidence in broiler chickens.

La figure de flâneur montre que le desir de nomadisme persiste fermement encore dans notre societe postmoderne. Cet article propose d’examiner comment lorsque les flâneurs desordonnes s’ordonnent en mouvement circulaire, ils se transforment en organisation tourbillonnaire. La force y declenche la (re)organisation et le mouvement sociaux. Il est evident que l’anomie et l’effervescence sont donc des fondations solides de structuration nouvelle. Cela nous permet de critiquer les theories du comportement collectif de la foule, et de chercher de nouvelles expressions et notions plus adequates pour expliquer la possibilite d’explosion sociale dans notre societe postmoderne. L’eros effect est manifeste dans des rassemblements des flâneurs, e.g. flashmobs. Il remet en question les divisions definitives entre le politique et l’erotique, le travail et les passions.

Lonely individuals are sensitive to negative social information. Past evidence for this finding comes mostly from research on visual cues (e.g., facial expression); less is known whether a parallel pattern occurs for auditory cues (e.g., voice). Using a vocal emotional Stroop task, we examined whether loneliness heightens attention to other's vocal tone. Compared to less lonely individuals, lonely participants' reaction time during the Stroop task was significantly slower when a positive (vs. negative) semantic word was presented via a negative vocal tone. It appears that lonely individuals, compared to others, are more distracted by the negative emotionality of a voice tone, which might signal social threats. This attentional bias remained when controlling for neuroticism, and was more pronounced when social, rather than nonsocial words were presented.

Can people make valid inferences about the person's mate value by a glance of his/her face? Eighty-seven independent coders rated how attractive neutral facial pictures of 297 (152 males) undergraduate students were, after viewing each image for 3 s. The facial attractiveness rating significantly correlated with important sex-specific mate qualities. In case of female targets, facial attractiveness predicted their body shape (waist-to-hip ratio; WHR), whereas among males, it correlated with their household income. The results remained after controlling for the positive affectivity reflected in the facial image. It appears that sex-specific markers of mate value are implicitly ingrained in attractive facial features.

SummaryChemotherapy induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN primarily affects unmyelinated nociceptive sensory terminals. Despite the high prevalence of CIPN, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractableDrosophilamodel and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment ofDrosophilalarvae with paclitaxel caused sensory neuron degeneration, altered the terminal branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-mediated cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. We used primary dorsal root ganglia neuron cultures to test conservation of integrin-mediated protection. We show that overexpression of a human integrin β subunit 1 (ITGB1) also prevented degeneration following paclitaxel treatment. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring integrin levels to antagonize paclitaxel-mediated toxicity in sensory neurons.

In this study, we examined loneliness and hope components as predictors of unhappy conditions (viz., anxious symptoms, depressive symptoms, & suicidal ideation) in young adults. The sample was comprised of 489 Hungarian college students. Results of conducting hierarchical regression analyses indicated that loneliness and hope pathways (but not hope agency) were important unique predictors of anxious symptoms, depressive symptoms, and suicidal ideation. Moreover, in part, consistent with the notion that hope might buffer the negative effects of loneliness on unhappy conditions, evidence for a significant Loneliness × Hope Pathways interaction effect in predicting each of the three indices of unhappy conditions was found. In contrast, the Loneliness × Hope Agency interaction effect was not found to be significant. Some implications of the present findings for the study and treatment of unhappy conditions in adults are discussed

Dscam2 is a cell recognition molecule involved in many aspects of neurodevelopment. Here, Odierna et al. identify a new function for this protein in regulating synaptic strength., Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous to motor neurons. We link the PI3K enhancer, Centaurin gamma 1A, to the Dscam2-dependent regulation of synaptic strength and show that changes in phosphoinositide levels correlate with changes in endosomal compartments that have previously been associated with synaptic strength. Using transmission electron microscopy, we find an increase in synaptic vesicles at Dscam2 mutant active zones, providing a rationale for the increase in synaptic strength. Our study provides the first evidence that Dscam2 can regulate synaptic physiology and highlights how diverse roles of alternative protein isoforms can contribute to unique aspects of brain development and function.

FMS-like receptor tyrosine kinase-3 (FLT3) is expressed on acute leukemia cells and is implicated in the survival, proliferation and differentiation of hematopoietic cells in most acute myeloid leukemia (AML) patients. Despite recent achievements in the development of FLT3-targeted small-molecule drugs, there are still unmet medical needs related to kinase selectivity and the progression of some mutant forms of FLT3. Herein, we describe the discovery of novel orally available type 1 FLT3 inhibitors from structure-activity relationship (SAR) studies for the optimization of indirubin derivatives with biological and pharmacokinetic profiles as potential therapeutic agents for AML. The SAR exploration provided important structural insights into the key substituents for potent inhibitory activities of FLT3 and in MV4-11 cells. The profile of the most optimized inhibitor (36) showed IC50 values of 0.87 and 0.32 nM against FLT3 and FLT3/D835Y, respectively, along with potent inhibition against MV4-11 and FLT3/D835Y expressed MOLM14 cells with a GI50 value of 1.0 and 1.87 nM, respectively. With the high oral bioavailability of 42.6%, compound 36 displayed significant in vivo antitumor activity by oral administration of 20 mg/kg once daily dosing schedule for 21 days in a mouse xenograft model. The molecular docking study of 36 in the homology model of the DFG-in conformation of FLT3 resulted in a reasonable binding mode in type 1 kinases similar to the reported type 1 FLT3 inhibitors Crenolanib and Gilteritinib.

Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal–regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

What three words come to your mind in association with “happiness”? We analyzed the 1563 words reported by 521 Korean and American participants in this free association task. The most frequently endorsed word was “family” in Korea, whereas the most popular word among Americans was “smile.” The overall frequency of social words (e.g., relationships, social emotions) reported by Koreans was higher, and the most often mentioned relationship type differed between the two groups (family in Korea; friend in the US). Nonetheless, both in Korea and the US, individuals who mentioned more social words were significantly more satisfied with their lives. The amount of social support provision mediated the link between the number of reported social words and experienced happiness. Regardless of culture, a simple count of social words associated with happiness appears to offer a reasonably good clue for how happy the person actually is.

YAP/TAZ, the transcriptional coactivators of TEAD and major transducers of the Hippo pathway, has been studied only in solid tumors. Interestingly, YAP/TAZ are consistently upregulated in adherent tumor cell lines, but hardly expressed in hematologic malignancies including lymphoma and leukemia. However, we identified significant upregulation of TAZ in specific leukemia mouse models driven by FLT3 (AML) or Bcr-Abl (blast crisis-CML; bc-CML). We observed strong correlation between TAZ and FLT3 induction in bc-CML patients as well as leukemia cells, which led us to investigate the role of FLT3-TAZ signaling in imatinib-induced drug resistance in CML. FLT3 expression induced imatinib resistance (IR) in K562 CML cells. In K562-IR cells, transcription of TAZ mRNA is significantly increased, but not YAP. Our data show that target gene induction by TAZ-TEAD interaction promotes imatinib resistance. Importantly, inhibition of FLT3-TAZ signaling resensitized K562-IR cell to imatinib treatment and caused cell death. Therefore, we propose that combination therapy targeting both FLT3-TAZ and Bcr/abl signaling could trigger synthetic lethality in bc-CML cells. Citation Format: Ji Eun Shin, Hyun Woo Park. FLT3-TAZ signaling induces drug resistance in leukemia [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B35.

What three words come to your mind in response to “happiness”? Using a free-association task [cf. Nelson, D. L., McEvoy, C. L., & Dennis, S. (2000). What is free association and what does it measure? Memory and Cognition, 28, 887–899], this research finds that the number of social words (e.g. family, love) provided in link to happiness predicts people’s actual life satisfaction level. However, this association was significantly moderated by the person’s self-perceived financial state. The contingency between holding a socially-oriented belief about happiness and experienced life satisfaction was significant among members of low socioeconomic status (SES), but not among the high SES group. This pattern was replicated across two divergent samples (Asian college students, Study 1; American adults, Study 2), regardless of one’s extraversion level (Studies 1, 2) and availability of social support (number of friends, Study 2). Given the overlapping function of money and social relationships (instrumental in promoting survival), believing in the social nature of happiness seems to be more central in the life satisfaction of those with less financial resource.

This study aimed to investigate the efficacy of the transplantation of autologous adipose-derived stromal vascular fraction (AD-SVF) containing adipose stem cells (ASCs) in regenerating functional endometrium in patients with severe Asherman’s syndrome (AS). This was a prospective clinical study involving six infertile women aged 20–44 years who were diagnosed with severe AS by hysteroscopy. Autologous AD-SVF were isolated from patient’s adipose tissue obtained by liposuction and then transplanted into uterus by transcervical instillation using an embryo transfer catheter followed by estrogen hormone therapy. Endometrial growth and pregnancy outcomes were assessed after fresh or frozen embryo transfer. Of the five patients who remained in the study, two women who had amenorrhea resumed their menstruation with irregular scant bleeding. Three women with oligomenorrhea had increased menstrual amount. Before therapy, the maximum EMT measured ultrasonographically was 3.0 ± 1.0 mm (range: 1.7 to 4.4 mm), which significantly increased to 6.9 ± 2.9 mm (range: 5.2 to 12.0 mm, p = 0.043) after cell transplantation and hormone therapy. Five women had embryo transfer after therapy: one fresh and four frozen-thawed. One woman conceived but aborted spontaneously at 9-week gestation. AD-SVF is a safe and easily available cell product containing adipose-derived stem cells. Autologous transplantation of AD-SVF may regenerate damaged human endometrium and increase endometrial receptivity. Our study showed the feasibility of AD-SVF in restoring endometrial function and increasing endometrial thickness. This cell therapy may become a promising treatment for infertile women with endometrial dysfunction and needs further investigation.

Objective: Thin or damaged endometrium remains to be an unsolved problem in the treatment of patients with infertility. The empirical preference for endometrial thickness (EMT) among clinicians is >7 mm, and the refractory thin endometrium, which doesn't respond to standard medical therapies, can be the etiology of recurrent implantation failure (RIF). Autologous platelet-rich plasma (PRP) is known to help tissue regeneration and is widely used in various fields. In the present study, we conducted PRP treatment and investigated its effect on the refractory thin endometrium.Design: Prospective interventional study (https://cris.nih.go.kr/cris, clinical trial registration number: KCT0003375).Methods: Women who had a history of two or more failed IVF cycles and refractory thin endometrium were enrolled in this study. The main inclusion criteria were EMT of

To prevent perinatal morbidity and mortality of high-order multiple pregnancy (HOMP), multifetal pregnancy reduction (MPR) is offered to some patients. In this study, we investigated whether twin pregnancies derived from MPRs carry a higher adverse obstetrical outcome compared to non-reduced control group of twins. We retrospectively analyzed the data from HOMPs on which transvaginal ER (n = 153) at a mean gestational age of 7.6 weeks or transabdominal FR (n = 59) at a mean gestational age of 12.4 weeks was performed between December 2006 and January 2018. The risk of each procedure was evaluated by comparing obstetrical outcome with that of a control population of 157 non-reduced twins conceived by infertility treatment. The mean gestational ages at delivery were 35.2 weeks in the ER group, 35.7 weeks in the FR group, and 34.1 weeks in the control group (P = NS). Compared with those in the control group, the ER group had higher miscarriage (1.3% vs. 6.5%; P = 0.047; OR 0.21; 95% CI 0.45–0.898) and higher overall fetal loss (3.8% vs. 14.4%; P = 0.003; OR 0.24; 95% CI 0.09–0.60) rates. Differently compared with those in the control group, the FR group had no statistical difference in miscarriage (2.5% vs. 1.7%; P=NS) and overall fetal loss (3.8% vs. 6.8%; P=NS) rates. Compared with the control group, ER in twins had a higher miscarriage and fetal loss rate, whereas FR in twins was similar to the control group. So, the FR procedure is overall a better and safer approach of MPR in reducing morbidity and mortality in HOMPs.

Sleep, although a vital aspect of human functioning, has received scant attention in happiness research. This research examines the effect of sleep quality on life satisfaction, and one possible mechanism that bridges the two. One cognitive factor that might tie the relationship between sleep and life satisfaction is a belief about the (in) finite nature of happiness (zero-sum belief about happiness; ZBH), a mindset that occurs more under conditions of scarcity. Given the interconnections among experiences prompted by various types of scarcity (e.g., financial and calorie), we predicted that deprived cognitive resource caused by poor sleep may activate the ZBH, thereby hurting one's life satisfaction. As expected, we found that sleep quality predicted the participants' life satisfaction, even controlling for baseline variables. More importantly, this relationship was partially mediated by ZBH. This study opens interesting questions on a relatively unexamined role of non-social predictors, such as sleep, in well-being.

Objective : This study compares sensory processing ability of children with and without spastic diplegia. In addition, it investigates characteristics of sensory processing differentiated by developmental phase such as pre-school age versus school age. Methods : Participants in this study are ordinal children without specific condition and children with spastic diplegia who are aged 3 to 10 years olds. Using Short Sensory Profile (SSP), sensory processing function of the participants was measured. The survey was distributed to caregivers of the children from November, 2013 to February, 2014, and it was suggested that the caregivers to record the questionnaire directly after approval from a rehabilitation hospital, a university hospital, welfare center, day care center, preschool and elementary school to participate in our study. Results : Group of children with spastic diplegia showed lower score than group of children with no special condition in the total score and the each score of all items of Short Sensory Profile. There was significant difference between the two groups in terms of the total score of sensory processing and the 5 factors except tactile sensitiveness and taste/smell sensitiveness among the 7 factors of test. In the comparison of different age groups, pre-school age group showed lower total score than school age group. Conclusion : This study provides a foundational evidence that can be used when therapist evaluate sensory processing function of children with spastic diplegia. There is need for more study about sensory processing functions of various types of children with cerebral palsy.