De Novo Missense Variations of ATP8B2 Impair Its Phosphatidylcholine Flippase Activity.

P4-ATPases comprise a family of lipid flippases that translocate lipids from the exoplasmic (or luminal) to the cytoplasmic leaflet of biological membranes. Of the 14 known human P4-ATPases, ATP8B2 is a phosphatidylcholine flippase at the plasma membrane, but its physiological function is not well understood. Although ATP8B2 could interact with both CDC50A and CDC50B, it required only the CDC50A interaction for its exit from the endoplasmic reticulum and subsequent transport to the plasma membrane. Three de novo monoallelic missense variations of ATP8B2 were found in patients with intellectual disability. None of these variations affected the interaction of ATP8B2 with CDC50A or its localization to the plasma membrane. However, variations of either of two amino acid residues, which are conserved in all P4-ATPases, significantly reduced the phosphatidylcholine flippase activity of ATP8B2. Furthermore, mutations in the corresponding residues of ATP8B1 and ATP11C were found to decrease their flippase activities toward phosphatidylcholine and phosphatidylserine, respectively. These results indicate that the conserved amino acid residues are crucial for the enzymatic activities of the P4-ATPases.

Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane.

Phosphatidylinositol is a precursor of various phosphoinositides, which play crucial roles in intracellular signaling and membrane dynamics and have impact on diverse aspects of cell physiology. Phosphoinositide synthesis and turnover occur in the cytoplasmic leaflet of the organellar and plasma membranes. P4-ATPases (lipid flippases) are responsible for translocating membrane lipids from the exoplasmic (luminal) to the cytoplasmic leaflet, thereby regulating membrane asymmetry. However, the mechanism underlying phosphatidylinositol translocation across cellular membranes remains elusive. Here, we discovered that the phosphatidylcholine flippases ATP8B1, ATP8B2, and ATP10A can also translocate phosphatidylinositol at the plasma membrane. To explore the function of these phosphatidylinositol flippases, we used cells depleted of CDC50A, a protein necessary for P4-ATPase function and ATP8B1 and ATP8B2, which express in HeLa cells. Upon activation of the Gq-coupled receptor, depletion of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was accelerated in CDC50A knockout (KO) and ATP8B1/8B2 double KO cells compared with control cells, suggesting a decrease in PtdIns(4,5)P2 levels within the plasma membrane of the KO cells upon stimulation. These findings highlight the important role of P4-ATPases in maintaining phosphoinositide homeostasis and suggest a mechanism for asymmetry of phosphatidylinositol in the cytoplasmic leaflet of the plasma membrane.

Community recruitment of underrepresented populations to the AHEAD 3-45 preclinical AD trial using novel partnerships with nursing and community-based organizations: Lessons and outcomes.

INTRODUCTION: Alzheimer's disease (AD) disproportionately affects minoritized populations who remain underrepresented in AD trials. METHODS: We partnered with local nursing community-based organizations to implement a culturally tailored educational intervention and recruit Hispanic/Latino American, Filipino American, and Korean American adults aged 55 to 80 for the AHEAD study, a preclinical AD trial, at the University of California, Irvine. RESULTS: We engaged 654 individuals across 21 events, leading to 71 prescreenings: 21.1% Filipino, 11.2% Hispanic/Latino, and 67.6% Korean adults. Ineligibility due to age and language barriers was common among Hispanic/Latino and Korean adults, respectively. Filipino adults often withdrew interest or were lost to follow-up. Ultimately, 25 participants enrolled: eight Filipino, two Hispanic/Latino, and 15 Korean adults. Tailored, culturally relevant content significantly contributed to the engagement success. DISCUSSION: This study demonstrates the value and impact of novel partnerships with health-related provider organizations that provide trusted care and access to underrepresented communities. HIGHLIGHTS: Six hundred and fifty four underrepresented individuals were reached, and 25 enrolled in the AHEAD 3-45 trial. Twenty-one community events were held via partnerships with nursing and community organizations. The study engaged 21% Filipino, 11% Hispanic/Latino, 68% Korean adults. Community-Based Participatory Research (CBPR) principles enhanced the recruitment process. Transparent communication and joint planning were key.

Feasibility of density-based separation of Ce and Hf intermetallics in liquid Bi.

Efficient separation of actinide elements from molten salts employed in pyroprocessing can significantly diminish the radiological hazards and oversight duration associated with spent nuclear fuel storage. The lanthanum content of waste salts is very high compared to actinides, leading to the co-electrodeposition of both groups of elements for conventional electrochemical techniques. Due to the difficulty in separating the two groups of elements, the feasibility of the density-based separation using liquid bismuth and intermetallics was explored. Hafnium was used as a stand-in for actinide elements with physical properties mirroring those of actinide-laden Bi-Hf intermetallics. Conversely, cerium was chosen to represent lanthanides. This study delved into the formation and spatial distribution of bismuth intermetallics under varying concentration ratios and cooling durations. Comprehensive characterization was achieved using scanning electron microscopy and energy-dispersive spectrometry. The analysis showed that Bi-Ce particles were formed and distributed in the upper layer of the Bi ingot, and Bi-(Ce, Hf) particles containing both Ce and Hf in the lower layer. The findings underscore the viability of density-based separation while highlighting the intricacies related to intermetallic coprecipitation. Continued investigations are essential to fully harness the potential of density-based separation.

Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

A facile method for monitoring sphingomyelin synthase activity in HeLa cells using liquid chromatography/mass spectrometry.

Sphingomyelin synthase (SMS) is a sphingolipid-metabolizing enzyme involved in the de novo synthesis of sphingomyelin (SM) from ceramide (Cer). Recent studies have indicated that SMS is a key therapeutic target for metabolic diseases such as fatty liver, type 2 diabetes, atherosclerosis, and colorectal cancer. However, very few SMS inhibitors have been identified because of the limited sensitivity and selectivity of the current fluorescence-based screening assay. In this study, we developed a simple cell-based assay coupled with liquid chromatography/tandem mass spectrometry (LC-MS/MS) to screen for SMS inhibitors. HeLa cells stably expressing SMS1 or SMS2 were used for the screening. A non-fluorescent unnatural C6-Cer was used as a substrate for SMS to produce C6-SM. C6-Cer and C6-SM levels in the cells were monitored and quantified using LC-MS/MS. The activity of ginkgolic acid C15:1 (GA), a known SMS inhibitor, was measured. GA had half-maximal inhibitory concentrations of 5.5 µM and 3.6 µM for SMS1 and SMS2, respectively. To validate these findings, hSMS1 and hSMS2 proteins were optimized for molecular docking studies. In silico analyses were conducted to assess the interaction of GA with SMS1 and SMS2, and its binding affinity. This study offers an analytical approach for screening novel SMS inhibitors and provides in silico support for the experimental findings.

Glucosylceramide flippases contribute to cellular glucosylceramide homeostasis.

Lipid transport is an essential cellular process with importance to human health, disease development, and therapeutic strategies. Type IV P-type ATPases (P4-ATPases) have been identified as membrane lipid flippases by utilizing nitrobenzoxadiazole (NBD)-labeled lipids as substrates. Among the 14 human type IV P-type ATPases, ATP10D was shown to flip NBD-glucosylceramide (GlcCer) across the plasma membrane. Here, we found that conversion of incorporated GlcCer (d18:1/12:0) to other sphingolipids is accelerated in cells exogenously expressing ATP10D but not its ATPase-deficient mutant. These findings suggest that 1) ATP10D flips unmodified GlcCer as well as NBD-GlcCer at the plasma membrane and 2) ATP10D can translocate extracellular GlcCer, which is subsequently converted to other metabolites. Notably, exogenous expression of ATP10D led to the reduction in cellular hexosylceramide levels. Moreover, the expression of GlcCer flippases, including ATP10D, also reduced cellular hexosylceramide levels in fibroblasts derived from patients with Gaucher disease, which is a lysosomal storage disorder with excess GlcCer accumulation. Our study highlights the contribution of ATP10D to the regulation of cellular GlcCer levels and maintaining lipid homeostasis.

Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease.

Gaucher disease (GD) is a recessively inherited lysosomal storage disorder characterized by a deficiency of lysosomal glucocerebrosidase (GBA1). This deficiency results in the accumulation of its substrate, glucosylceramide (GlcCer), within lysosomes. Here, we investigated lysosomal abnormalities in fibroblasts derived from patients with GD. It is noteworthy that the cellular distribution of lysosomes and lysosomal proteolytic activity remained largely unaffected in GD fibroblasts. However, we found that lysosomal membranes of GD fibroblasts were susceptible to damage when exposed to a lysosomotropic agent. Moreover, the susceptibility of lysosomal membranes to a lysosomotropic agent could be partly restored by exogenous expression of wild-type GBA1. Here, we report that the lysosomal membrane integrity is altered in GD fibroblasts, but lysosomal distribution and proteolytic activity is not significantly altered.Key words: glucosylceramide, lysosome, Gaucher disease, lysosomotropic agent.

Examining Utilization of Formal Supports and Related Impacts on Overall Well-Being Among East Asian American Family Caregivers of Persons With Dementia: A Mixed-Methods Study.

BACKGROUND AND OBJECTIVES: Although East Asian American family caregivers are known to underutilize formal support services, there is a lack of evidence regarding the associations of formal service utilization with caregivers' well-being. This study examined the prevalence of different types of home-and community-based formal service utilization among Korean and Chinese American family caregivers of persons with dementia and how utilization of such services was associated with their well-being. We also explored their overall experience in accessing and utilizing formal dementia support services and programs. RESEARCH DESIGN AND METHODS: We employed a convergent mixed-methods study design. In a convenience sampling method, we recruited 62 family caregivers. Logistic regression and thematic analysis were utilized to analyze data. RESULTS: The results showed in-home services were mostly utilized among family caregivers of these ethnic groups. Out of 9 different support services, those who utilized nutrition programs and case management were more likely to report higher overall well-being. Four themes were developed: (1) awareness of formal support services but uncertainty on how to access them, (2) language barriers imposing additional challenges in accessing formal support services, (3) traveling to access culturally appropriate services, and (4) desire for culturally tailored medical and long-term care services. DISCUSSION AND IMPLICATIONS: Findings from this study suggest the importance of case management services to overcome barriers to accessing and utilizing a wide range of formal support services and provision of culturally appropriate food in formal support services to increase East Asian American family caregivers' utilization of long-term care services.

Asian Americans' and Pacific Islanders' preferences in recruitment strategies and messaging for participation in the CARE registry: A discrete choice experiment.

INTRODUCTION: This discrete choice experiment (DCE) identified Asian American and Pacific Islander (AAPI) adults' preferences for recruitment strategies/messaging to enroll in the Collaborative Approach for AAPI Research and Education (CARE) registry for dementia-related research. METHODS: DCE recruitment strategy/messaging options were developed in English, Chinese, Korean, and Vietnamese. AAPI participants 50 years and older selected (1) who, (2) what, and (3) how they would prefer hearing about CARE. Analyses utilized conditional logistic regression. RESULTS: Participants self-identified as Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, or Vietnamese (N = 356). Overall, they preferred learning about CARE from the healthcare community (vs. community champions and faith-based organizations), joining CARE to advance research (vs. personal experiences), and hearing about CARE through social media/instant messaging (vs. flyer or workshop/seminar). Preferences varied by age, ethnic identity, and survey completion language. DISCUSSION: DCE findings may inform tailoring recruitment strategies/messaging to engage diverse AAPI in an aging-focused research registry.

A scoping review of dementia caregiving for Korean Americans and recommendations for future research.

OBJECTIVES: This scoping review aims to examine the caregiving experiences of Korean American caregivers of persons with dementia. METHODS: A comprehensive electronic search was conducted within 5 databases (PubMed, CINAHL, Web of Science, Embase, PsycINFO-ProQuest) for papers published from 01/01/00 -01/24/22. Seventeen articles met the inclusion criteria. Thematic analysis was used to summarize key findings from these papers. RESULTS: Most Korean American dementia caregivers were immigrants and wives/daughters/daughters-in-law. Two themes emerged: 1) how Korean American caregivers perceived their caregiving experiences, and 2) how Korean American caregivers perceived their caregiving support services. Korean American caregivers often experience poor mental health and burden. Social support and familism were found to be two of the most important factors that determine their attitudes toward caregiving. Most reported barriers to utilizing public services. Challenges in finding culturally relevant resources were common. CONCLUSIONS: Dementia caregiving is a significant public health problem facing Korean Americans. Recommendations for future research are provided.

Economic hardships of Korean American family caregivers of persons with dementia: a mixed-methods study.

Objectives. This study examined the relationships between economic hardships (i.e. perceived financial hardship and job interference) and caregiver burden among Korean American family caregivers of persons with dementia and explored their lived experience caring for their loved ones.Methods. Using a mixed-methods research design, we first conducted a survey with 36 Korean American family caregivers. We also conducted semi-structured, in-depth, individual interviews (n = 33) and subsequently compared the results.Results. Cohabiting with their loved ones, the total duration of caregiving, and financial hardship were statistically significant predictors of higher levels of caregiver burden. Our thematic analysis resulted in four themes: (1) financial hardship, (2) early retirement, (3) dual responsibilities contributing to physical and emotional challenges, and (4) a lack of caregiver support.Conclusion. Our findings suggest the importance of developing culturally appropriate interventions that are affordable and accessible to Korean American family caregivers of persons with dementia.

Experience of operating a medical humanities course at one medical school during the COVID-19: a retrospective study.

BACKGROUND: This study summarizes the experience of operating a 'Medical Humanities' course, which was taught remotely to maintain activities and discussions at medical schools in Daegu, Korea during the sudden and unexpected coronavirus disease 2019 (COVID-19). METHODS: The subjects of this study were 73 first- and 79 second-grade medical students who took the medical humanities (1) and (2) courses among first- and second-grade students of Yeungnam University College of Medicine in 2020. Of the 152 students who agreed to the online survey, 123 completed the survey. Self-, environmental, and program evaluations were conducted on the study subjects, and differences according to grade and gender were analyzed. RESULTS: As a result of the study, a significant difference between self-evaluation and environmental evaluation was confirmed. Self-evaluation was determined to be higher in the first grade than in the second grade. The environmental evaluation showed that male students were more satisfied than female students and students generally had difficulties in the classroom environment. Of the applications used in class, the highest satisfaction was observed with KakaoTalk (Kakao Corp.) and Zoom (Zoom Video Communications Inc.). At the end of COVID-19, the students preferred online classes. CONCLUSION: If the learning environment for online classes is well prepared and systematic provisions are made, such as class operations that are suitable for the subject, effective education and learning can be achieved by taking advantage of both face-to-face and online classes.

Comparing the demographics and laboratory biomarkers of the COVID-19 Omicron wave and the Alpha wave in a predominantly Afro-Caribbean patient population in New York City.

BACKGROUND: There is a knowledge gap of specific characteristics linked to disease severity of the different COVID-19 waves, especially in underserved populations. We compared the demographic and clinical factors associated with SARS-CoV-2-infected patients admitted to the intensive care unit (ICU) during the Omicron and Alpha waves. METHODS: An observational study comparing two COVID-19 waves was conducted in Brooklyn, NY. Twenty-seven ICU admitted patients with a positive COVID-19 test result during the period of November 1, 2021, to January 31, 2022, ("Omicron wave") were compared to 271 COVID-19 patients who received ICU consults during the Alpha wave, the period from March 28, 2020, to April 30, 2020. RESULTS: The Omicron wave had a 55.6% mortality rate compared to a 67.2% mortality rate in the Alpha wave. For the non-survivors, there were more females (66.7%) in the Omicron wave, while the trend was reversed in the Alpha wave (38.5%). Most of the patients seen were Black (> 85%) in both waves. A bivariate comparison of the two waves found that patients in the Omicron wave had overall significantly lower ALT levels (p = 0.03) and higher monocyte % (p = 0.005) compared to the patients in the Alpha wave. In the multivariate analysis, adjusting for age and sex, increasing levels of HCO3- were significantly associated with reduced mortality in the Omicron wave (OR: 0.698; 95% CI: 0.516 - 0.945; p = 0.02). Also, multivariable analyses using both waves combined found that neutrophil % was significantly associated with increased mortality (OR: 1.05; 95% CI: 1.02 - 1.09; p = 0.006) while lymphocyte % was significantly associated with reduced mortality (OR: 0.946; 95% CI: 0.904 - 0.990; p = 0.018). CONCLUSIONS: The COVID-19-positive ICU patients in the Omicron wave experienced less severe outcomes than those of the Alpha wave. In contrast to the Alpha variant, the Omicron variant exhibited enhanced infectivity and disease severity in females.

Phosphatidylserine exposure modulates adhesion GPCR BAI1 (ADGRB1) signaling activity.

Brain-specific angiogenesis inhibitor 1 (BAI1; also called ADGRB1 or B1) is an adhesion G protein-coupled receptor known from studies on macrophages to bind to phosphatidylserine (PS) on apoptotic cells via its N-terminal thrombospondin repeats. A separate body of work has shown that B1 regulates postsynaptic function and dendritic spine morphology via signaling pathways involving Rac and Rho. However, it is unknown if PS binding by B1 has any effect on the receptor's signaling activity. To shed light on this subject, we studied G protein-dependent signaling by B1 in the absence and presence of coexpression with the PS flippase ATP11A in human embryonic kidney 293T cells. ATP11A expression reduced the amount of PS exposed extracellularly and also strikingly reduced the signaling activity of coexpressed full-length B1 but not a truncated version of the receptor lacking the thrombospondin repeats. Further experiments with an inactive mutant of ATP11A showed that the PS flippase function of ATP11A was required for modulation of B1 signaling. In coimmunoprecipitation experiments, we made the surprising finding that ATP11A not only modulates B1 signaling but also forms complexes with B1. Parallel studies in which PS in the outer leaflet was reduced by an independent method, deletion of the gene encoding the endogenous lipid scramblase anoctamin 6 (ANO6), revealed that this manipulation also markedly reduced B1 signaling. These findings demonstrate that B1 signaling is modulated by PS exposure and suggest a model in which B1 serves as a PS sensor at synapses and in other cellular contexts.

Effectiveness of an integrative medicine approach to improve cognitive dysfunction and dementia: An observational study.

Despite the urgent need to control dementia, an effective treatment has yet to be developed. Along with the Korean government's policy of cooperation between conventional medicine (CM) and Korean medicine (KM), integrative medical services for dementia patients are being provided. This study aimed to compare the integrative medical clinic (IMC) for dementia used by Dongguk University Hospitals (DUH) with other service models and to review the characteristics and treatment outcomes of patients who had visited DUH over the past 5 years. Patients' electronic medical records from May 2015 to June 2020 were searched and their data were analyzed to evaluate the IMC's service model. Patient demographic and clinical characteristics, diagnostic tests, and treatment patterns for CM and KM were collected. The proportion of patients who did not show worsening cognitive function was described in detail. A strength of the DUH integrative medicine clinic is its ability to manage both KM and CM patients in the same space at the same time. Among the 82 patients who visited the clinic during our study period, 56 remained for data analysis after we excluded patients who met the exclusion criteria; nineteen patients had diagnoses of mild cognitive impairment. Among collaboration patterns, the first visit to the IMC had the highest proportion (55.4%). Among diagnosed tests in CM, laboratory tests and neuropsychological tests were used the most. In KM, a heart rate variability test was frequently used. The most common CM treatment prescribed was anticonvulsants, with 22 patients (39.2%) receiving donepezil, whereas the most frequent KM treatments were acupuncture (82.1%) and herbal medicine (78.6%). Twelve patients were followed up with the Mini-Mental State Examination, and 8 demonstrated either no worsening or improved cognition (baseline Mini-Mental State Examination range: 21-26). All 8 patients had mild cognitive impairment including 6 with amnestic, multidomain impairment. This study searched for a way to improve cognitive dysfunction and dementia using an integrative approach, and it shows promising results for mild cognitive impairment. However, more precisely designed follow-up studies are needed to address the present work's limitations of a retrospective study design and a small sample size.

Identifying the white matter structural network of motor reserve in early Parkinson's disease.

INTRODUCTION: Motor reserve refers to the individual capacity to cope with nigrostriatal dopamine depletion in Parkinson's disease (PD). This study aimed to explore the white matter structural network associated with motor reserve in patients with newly diagnosed PD. METHODS: A total of 238 patients with early-stage drug-naïve PD who underwent 18F-FP-CIT PET and brain MRI scans at initial assessment were enrolled. We estimated individual motor reserve based on the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores and dopamine transporter availability in the posterior putamen using a residual model. Then, we performed threshold-free network-based statistics (TFNBS) analysis to identify the structural brain network associated with the estimated motor reserve. We also assessed the effect of the network connectivity strength on the longitudinal increase in levodopa-equivalent dose (LED). RESULTS: The mean age at PD symptom onset was 69.10 ± 9.03 years and the mean UPDRS-III score at the time of PD diagnosis was 22.44 ± 9.72. TFNBS analysis identified a motor reserve-associated structural network whose nodes were mainly in the frontal region and cerebellum. Higher network strength (i.e., greater motor reserve) was associated with a slower longitudinal increase in LED during a 3-year follow-up period. CONCLUSION: The structural brain network is associated with motor reserve in patients with PD. Connectivity strength within the identified network indicates the individual's capacity to tolerate PD-related pathologies, which is maintained with disease progression and affects the long-term motor prognosis of PD.

Postoperative propofol bolus treatment did not affect recovery time in patients with emergence agitation after sevoflurane anesthesia in pediatric patients undergoing strabismus surgery: Prospective nonrandomized case-control study.

BACKGROUND: The incidence of emergence agitation (EA) after sevoflurane anesthesia is high, especially in pediatric strabismus surgery. However, research thus far has focused on the pharmacological prophylaxis of EA and administering drugs to pediatric patients without EA is problematic. The purpose of this study was to determine whether the use of propofol after sevoflurane anesthesia affects recovery time in patients with EA. METHODS: After obtaining informed written consent, 113 children (aged 2-12 years) with the American Society of Anesthesiologists physical status of I or II who underwent strabismus surgery were enrolled. Patients were divided into 2 groups; upon arrival at the postanesthetic care unit (PACU), patients who had EA (pediatric anesthesia emergence delirium [PAED] scale score ≥14) were treated with 1.0 mg/kg 1% propofol (group P: n = 30). Patients who did not have EA (PAED scale score <14, group C: n = 83) were taken care of in the PACU without propofol administration. RESULTS: There was no difference in the PAED scale scores between the 2 groups from 10 minutes to discharge from the PACU (P > .05). There was no difference in PACU stay time between the 2 groups (P > .05). CONCLUSIONS: We concluded that propofol administration for intense EA alleviated EA symptoms and prevented an increase in the duration of PACU stay due to EA in children undergoing strabismus surgery under sevoflurane anesthesia.

Regulatory Roles of N- and C-Terminal Cytoplasmic Regions of P4-ATPases.

P4-ATPases, which are subfamily members of P-type ATPase superfamily, translocate membrane lipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet, thus regulating trans-bilayer lipid asymmetry. Mammalian P4-ATPases localize to the specific subcellular organelles or the plasma membrane where they translocate the specific lipids. Although recent advances in the structural analysis of P4-ATPases have improved our understanding of lipid transporting machinery, the mechanism of substrate specificity and the regulatory mechanism of the enzymes remain largely unknown. Recent studies have uncovered several specific localization and regulatory mechanisms of P4-ATPases. Here, we review the current understanding of the regulatory mechanism of P4-ATPase activity and localization in mammalian cells.

Risk Assessment and Evaluation of Analytical Method of Polycyclic Aromatic Hydrocarbons (PAHs) for Deep-Fat Fried Pork Products in Korea.

Polycyclic aromatic hydrocarbons (PAHs) are produced during incomplete combustion of organic matter. Many of them are likely to be carcinogenic and cause mutations. In this study, the PAH4 (benzo[a]pyrene (BaP), benz[a]anthracene (BaA), chrysene (CHR), benzo[b]fluoranthene (BbF)) content in deep-fat fried pork was evaluated according to temperature and time, and a risk assessment was conducted. The high performance liquid chromatography-fluorescence detection (HPLC-FLD) method for PAH4 analysis was validated by determining linearity (R2), recovery, limit of detection (LOD), and limit of quantitation (LOQ). The linearity was R2 ≥ 0.99. The PAH4 level was dependent on the temperature, time, and nature of the edible oil. Before heat treatment, the PAH4 content of pork was 0.38 µg/kg. The PAH4 content of deep-fat fried pork ranged from 0.86 to 6.86 µg/kg according to temperature (160, 180, 200 °C) and time (3, 6, 9 min). Exposure to PAH4 via the consumption of deep-fat fried pork for different age groups among the Korean population was 0.01-0.89 µg-TEQBaP/kg/day, with the margin of exposure calculated as 7.88 × 104-5.22 × 106. The PAH4 content and risk of exposure increased proportionally with the heat treatment temperature and time. The survey provided important information in terms of evaluating the health risks that PAH compounds can cause in people's diets due to the heat treatment of pork.