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This study examines the relationships among friends and ethnicity of older adults. Friends includes friend numbers and their quality of relationships with friends of older adults in the current study. Data from the National Social Life, Health, and Aging Project (NSHAP) survey (Waite et al., 2020) were used. The NSHAP study sampled persons 57-85 years of age (n=3005). The respondents completed a telephone survey in which they reported their background information (e.g., income, gender, race, age, health, retirement status, and marital status) and social network characteristics. It was hypothesized that older adults’ ethnicity differentially influenced family relations. In comparison to Anglo older adults, African and Hispanic older adults have weaker (smaller number and less cohesive) family culture. In order to identify the associations between ethnicity and friend relations, multiple regression analysis was used. Results revealed that African American and Hispanic older adults reported larger numbers of close friends, higher quality of friend in general, and higher frequency of contact with them compared to Anglo older adults. The current study’s findings build on a convoy model to account for how older adults’ ethnicity is differentially associated with their quality and size in friend relationship for future research is to examine more diverse in friend and ethnicity variables which explain the dynamic relationships between older adults’ demographic factors and friend network.

This study investigated L1 interference in the perception of released word-final stops in English by performing perception experiments on Korean and English listeners. Stimuli with conflicting cues were used in experiments in which the ‘long CV’ and the ‘short vowel CV’ were rejoined with six silent closure duration intervals and two release bursts of [g] and two release bursts of [k]. The perception results show that Korean listeners perceived significantly more [k] compared to English listeners when ‘k’ release was attached to a ‘long CV.’ We suggest that this is due to different phonological systems in Korean and English. In Korean, a released stop occurs only in the onset position in which the VOT and the stop closure duration are important acoustic cues for the identity of a stop. Thus, the English coda [k] with voiceless release burst could be perceived as an onset with long VOT, namely [k], by Korean listeners. In contrast, English listeners mostly perceived a voiced stop due to the long preceding vowel (cf. Raphael, 1972). With the stimuli of ‘short CV’ with ‘g’ release, Korean listeners perceived significantly more [g] than NE listeners did. English coda [g] with a voiced release may be perceived as an onset [g] with a short VOT by Korean listeners. In contrast, English listeners perceived a voiceless stop [k] due to the preceding short vowel. This paper also showed that Korean listeners would perceive finer distinctions than two levels of release, ‘g’ release and ‘k’ release.

The aim of this study was to explore to what extent life styles, income, and health factors contribute to the life satisfaction of Hispanic older adults. A secondary data analysis from a national survey of Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE) (Markides, Ray, Angel, & Espino, 2012) was used. Subjects were Hispanic older adults (over 75 years, n = 1542). For this study, Hispanics and Latinos were considered as one and the same. A two-step hierarchical regression was conducted to address the research question. The results showed health status and income were unique predictors in the first step and (a) eating out with family, (b) eating out with friends, (c) spending time on cooking were unique predictors in the second step. It is culturally consistent that Hispanic older adults are more satisfied when they have time eating with people around them (e.g., family, friends) and spending time on cooking.

The objective of this study was to examine the breadth and depth of relationships with relatives and friends and the possible implications of those relationships with regards to life satisfaction to widowhood. Data from the National Social Life, Health, and Aging Project (NSHAP) survey were used, which sampled persons 57-85 years of age (N=3005). It was hypothesized that older widowed adults have greater quality of both family and friend relationships than do older married adults. Structural Equational Modeling analysis results supported these hypotheses, revealing that older widowed adults reported higher quality of engagement in family and friend relations compared to older married adults, possibly enabling greater life satisfaction to widowhood.

Glucose metabolism is an important metabolic pathway in the auditory system. Chronic alcohol exposure can cause metabolic dysfunction in auditory cells during hearing loss. While alcohol exposure has been linked to hearing loss, the mechanism by which impaired glycolysis promotes cytotoxicity and cell death in auditory cells remains unclear. Here, we show that the inhibition of epidermal growth factor receptor (EGFR)-induced glycolysis is a critical mechanism for alcohol exposure-induced apoptosis in HEI-OC1 cells. The cytotoxicity via apoptosis was significantly increased by alcohol exposure in HEI-OC1 cells. The glycolytic activity and the levels of hexokinase 1 (HK1) were significantly suppressed by alcohol exposure in HEI-OC1 cells. Mechanistic studies showed that the levels of EGFR and AKT phosphorylation were reduced by alcohol exposure in HEI-OC1 cells. Notably, HK1 expression and glycolytic activity was suppressed by EGFR inhibition in HEI-OC1 cells. These results suggest that impaired glycolysis promotes alcohol exposure-induced apoptosis in HEI-OC1 cells via the inhibition of EGFR signaling.

This study investigates alveolar nasal perception on various portions of two Korean [ni] sequences: one [ni] sequence in the suffix medial position of -mnita with L tone and the other [ni] sequence at the IP-final position -ni with H tone. The perception test results show that various portions of [ni] from the suffix-medial position induce significantly more errors than the corresponding portions of [ni] from the IP-final position in all three conditions (vowel, murmur-vowel, and the whole phrase). The test results also show that suffix-medial [ni] sequences of some speakers obtain near-perfect perception scores as [mi], showing that [n] has undergone the categorical change to [m]. This shows that unlike the traditional assumption, Korean may allow progressive place assimilation if the target is the least prominent segment in the environment, like an alveolar nasal [n] in the context of /nasal__i/.

The objective of this study was to examine the breadth and depth of relationships with retirement and health regarding older adults’ physical activities. In addition, the possible implication of the relationships is to examine better understanding of how to stay active after retirement. Data from the American Association of Retirement Persons (AARP, Montenegro, 2015) telephone survey were used, which sampled persons, age range was 60-89 years old (n=134). Result indicated that health and physical activity factors affected retired older life satisfaction. It is not surprising that retired older adults are less satisfied when they have decreased physical health, but more satisfied when they engage in diverse physical activities or exercise after retirement (USDHHS, 2018). Given that aerobic and muscle strengthening activities contributed to improving physical function and reducing the risk of falls (Chodzko-Zajko et al., 2009; Spark et al., 2018), this study also supported the findings that aerobic and muscle strengthening activities with relative intensity level positively influenced the satisfaction levels of participants (USDHHS, 2018).

Stem cell (SC) therapy has become a potential treatment modality for pulmonary artery hypertension (PAH), but the efficacy of human SC and priming effects have not yet been established. The mobilization and homing of hematopoietic stem cells (HSCs) are modulated by priming factors that include a bioactive lipid, sphingosine-1-phosphate (S1P), which stimulates CXCR4 receptor kinase signaling. Here, we show that priming human mesenchymal stem cells (MSCs) with S1P enhances their therapeutic efficacy in PAH. Human MSCs, similar to HSCs, showed stronger chemoattraction to S1P in transwell assays. Concomitantly, MSCs treated with 0.2 μM S1P showed increased phosphorylation of both MAPKp42/44 and AKT protein compared with nonprimed MSCs. Furthermore, S1P-primed MSCs potentiated colony forming unit-fibroblast, anti-inflammatory, and angiogenic activities of MSCs in culture. In a PAH animal model induced by subcutaneously injected monocrotaline, administration of human cord blood-derived MSCs (hCB-MSCs) or S1P-primed cells significantly attenuated the elevated right ventricular systolic pressure. Notably, S1P-primed CB-MSCs, but not unprimed hCB-MSCs, also elicited a significant reduction in the right ventricular weight ratio and pulmonary vascular wall thickness. S1P-primed MSCs enhanced the expression of several genes responsible for stem cell trafficking and angiogenesis, increasing the density of blood vessels in the damaged lungs. Thus, this study demonstrates that human MSCs have potential utility for the treatment of PAH, and that S1P priming increases the effects of SC therapy by enhancing cardiac and vascular remodeling. By optimizing this protocol in future studies, SC therapy might form a basis for clinical trials to treat human PAH.

Cisplatin-induced early-onset ototoxicity is linked to hearing loss. The mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase (RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in vitro and in vivo. Sprague&ndash, Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p.) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H &amp, E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. Inhibitor experiments with necrostatin 1 (Nec-1) and Z-VAD were also performed in HEI-OC1 cell line. H&amp, E stains revealed that the necroptotic changes were increased in the organ of Corti (OC) and spiral ganglion neurons (SGNs). Moreover, immunohistochemistry and western blot analysis showed that cisplatin treatment increased the protein levels of RIP3 in both OCs and SGNs. The treatment of Nec-1, a selective RIP1 inhibitor, resulted in markedly suppression of cisplatin-induced cell death in HEI-OC1 cells, whereas Z-VAD treatment did not change the cisplatin-induced cell death. Our results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity, inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

Aberrant activation of transglutaminase 2 (TGase2) contributes to a variety of protein conformational disorders such as neurodegenerative diseases and age-related cataracts. The accumulation of improperly folded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which promotes either repair or degradation of the damaged proteins. Inadequate UPR results in protein aggregation that may contribute to the development of age-related degenerative diseases. TGase2 is a calcium-dependent enzyme that irreversibly modifies proteins by forming cross-linked protein aggregates. Intracellular TGase2 is activated by oxidative stress which generates large quantities of unfolded proteins. However, the relationship between TGase2 activity and UPR has not yet been established. In the present study, we demonstrated that ER stress activated TGase2 in various cell types. TGase2 activation was dependent on the ER stress-induced increase in the intracellular calcium ion concentration but not on the TGase2 protein expression level. Enzyme substrate analysis revealed that TGase2-mediated protein modification promoted protein aggregation concurrently with decreasing water solubility. Moreover, treatment with KCC009, a TGase2 inhibitor, abrogated ER stress-induced TGase2 activation and subsequent protein aggregation. However, TGase2 activation had no effect on ER stress-induced cell death. These results demonstrate that the accumulation of misfolded proteins activates TGase2, which further accelerates the formation of protein aggregates. Therefore, we suggest that inhibition of TGase2 may be a novel strategy by which to prevent the protein aggregation in age-related degenerative diseases.

This study examined cross-generational changes in the vowel system of Seoul Korean. Acoustic analyses of the vowel formants of /o/ and /u/, and their Euclidean distances in the vowel space were undertaken to explore an on-going merger of these two vowels as proposed in previous acoustic studies and a phonological analysis by Chae (1999). A robust cross-generational change of /o/ and /u/ was found, more evident for female speakers than for male speakers. For female speakers, with each successive generation, /o/ became increasingly approximated with /u/, regardless of the syllable positions that the target vowels were posited, whereas the cross-generational differences in the Euclidean distances were only shown in the second syllable position for the male speakers. These results demonstrate that 1) women are more advanced than men in the on-going approximation of /o/ and /u/; 2) the approximation of /o/ and /u/ is common in the non-initial position. Taken together, the merger of /o/ and /u/ appears to be in progress in Seoul Korean.

This is a follow-up study on Han and Kang (2013) which argued that the Euclidean distances between /o/ and /u/ in Seoul Korean decreased in the first syllable position as speakers were among younger female speakers but not for male speakers, whereas in the second syllable position both gender groups showed a cross-generational decreasing effect of the Euclidean distance between /o/ and /u/. This study normalized the same data in Han and Kang (2013) which measured 12 speakers (six males and six females) for each Age group and investigated the spectral changes vowels /o/ and /u/ between age and gender, using the log-mean normalized statistical results. This study also examined overlap fraction values generated in SOAM 2D () (cf. Wassink, 2006), which may also indicate the proximity of two vowels in question. The results showed that /o/ and /u/ vowels were making closer with /o/ raising for female speakers in and positions but only in the position for male speakers. That is, females led the upward movement of peripheral /o/ vowel, just like the raising of `e` and `o` in New York City (Labov, 1991). The results also showed that younger speakers used a rather narrow vowel space for the vowels. This also contributed to the proximity of the vowels /o/ and /u/, resulting in rather large overlap fraction values for younger speakers between these two vowels.

This paper investigates acoustic characteristics of Korean /s/ before a high front segment and argues that Korean /s/ shows acoustic characteristics of a palatalized segment due to the coarticulation with the following high front segments. In Experiment, it is shown that the first 30 msec of /s/ before /i, ye, ya/ shows spectral peaks around 4 kHz whereas /s/ before open vowels like /e, a/ shows peaks around 6 kHz. We suggest that this is due to the tongue body position at the palatal area placed at the beginning of /s/ when it is followed by /i/ or /y/. Center of gravity frequency, and band energy difference also show differences of Korean /s/ in different contexts. Based on the results of this experiment, we argue that Korean /s/ is modified from its beginning due to the coarticulation with the following segments if articulators of /s/ are compatible with those of the following segments. Interestingly, this paper also shows that in case /s/ is followed by /yu/ or /yo/, its spectral shape shows significant differences from /s/ followed by /ya/ or /ye/. It raises the question that in Korean the domain of coarituclation may be larger than the target and its immediately surrounding segment.

Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague–Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC+MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC+MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology.

This study examined the relationship of family and friends to the resiliency of older widows. Data from the National Social Life, Health, and Aging Project (NSHAP) survey (Waite et al., 2007), which sampled persons 57-85 years of age (n = 3005), was used. It was hypothesized that older widows have greater breadth and depth of family and friend relationships than older married adults. Multiple regression analysis results revealed that older widows engaged more frequently in family and friend relations compared to older married adults, possibly enabling greater resilience to widowhood.

Davis and Shin (1999) recognize the importance of the Syllable Contact Law in Korean phonology and showed that by incorporating a syllable contact constraint many of the consonant alternations in Korean can be insightfully explained. However, their analysis is not complete in that they failed to recognize the importance of word structure or did not fully consider it. This is most relevant in accounting for the different alternations involving /nl/ and /ln/ sequences. There are certain alternations involving these sequences which occur but are not predicted under the Davis and Shin analysis. I will show that such alternations reflect the importance of word structure and can be accounted for by implementing output-to-output constraints in addition to the constraints and rankings posited by Davis and Shin.

Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (∼3-6 μm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells.

Tissue and organ rejuvenation and senescence/aging are closely related to the function of stem cells. Thus, stem cells have been considered as guardians for the homeostasis of tissue/organ throughout life span. Recently, we identified a population of pluripotent Oct4+ very small embryonic/epiblast-like stem cells (VSELs) residing in the adult murine bone marrow (BM) and human cord blood (CB). VSELs can differentiate into cells from all three germ layers in vitro culture condition and in vivo tissue regeneration animal models. VSELs express the gene-expression and epigenetic profiling, which are similar to germ-line stem cells including (i) open/active chromatin structure in Oct4 promoter, (ii) parent-of-origin-specific reprogramming of genomic imprinting, (iii) deoxyribonucleic acid (DNA) demethylation in the promoter of germ-line lineage genes, and (iv) reactivate the X chromosome (in female pluripotent stem cells, PSCs). The unique epigenetic reprogramming in VSELs suggest that they could developmentally originate from the migratory primordial germ cells (PGCs) and the proliferation of VSELs are negatively controlled by epigenetic changes of some imprinted genes that regulate insulin/insulin-like growth-factor (Ins/Igf) signaling (Igf2, H19, Igf2R, and Rasgrf1). Since the chronic exposure to Ins/Igf signaling negatively correlates with longevity, we propose that Ins/Igf signaling mediated decrease in the number of VSELs could be a novel explanation of ageing. Therefore, VSELs could play a pivotal role in maintaining the integrity of adult tissues and these cells could provide a therapeutic alternative to stem cells isolated from embryos. Therefore, the understanding the precise molecular signature of VSELs such as reprogrammed genomic imprints could increase the regenerative power of these cells.

It has been postulated that the most primitive population of stem cells, Oct4(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs), differentiate into tissue-committed stem cells in adult mice. However, Oct4(+) VSELs remain quiescent in adult tissues and do not form teratomas. In thi study, we report the characteristics of the VSEL transcriptome by gene set enrichment analysis employing a microarray database established from 20 murine bone marrow-derived, FACS-sorted VSELs in comparison with hematopoietic stem cells and embryonic stem cells. In the Oct4(+) VSELs, we observed the upregulation of tissue-specific gene sets and a gene set encoding the complement-coagulation cascade. By contrast, in the VSELs, we observed the downregulation of genes involved in the UV radiation response, mRNA processing and mitogenic growth factor signaling [e.g., insulin-like growth factor‑1 (IGF-1) and neurotrophic tyrosine kinase receptor A (TRKA), as well as the ERK and PI3K pathways]. Employing leading-edge subset analysis and real-time PCR assays, we observed that several genes, such as growth factor receptor-bound protein 2 (Grb2), son of sevenless homolog 1 (Sos1), SHC (Src homology 2 domain containing) transforming protein 1 (Shc1), mitogen-activated protein kinase kinase 1 (Map2k1), v-akt murine thymoma viral oncogene homolog 3 (Akt3), Elk1, ribosomal protein S6 kinase, 90 kDa, polypeptide 3 (Rps6kA3), glycogen synthase kinase 3β (Gsk3β) and casein kinase 2, alpha 1 polypeptide (Csnk2A1), which are involved in mitogenic growth factor signaling pathways, were commonly downregulated in the VSELs. Notably, this repression was reversed in the VSELs co-cultured over a C2C12 supportive cell-line, whereby they are induced to form VSEL-derived spheres (VSEL-DSs); thus, they are enriched, forming more differentiated stem cells. Therefore, we suggest that the repression of mitogenic growth factor signaling (e.g., through the IGF-1 receptor) may prevent uncontrolled Oct4(+) VSEL proliferation and teratoma formation. Thus, restoring the responsiveness to mitogenic growth factors may be a crucial step in employing these cells in regenerative medicine.