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Acute Toxicity Study and the In Vitro Cytotoxicity of a Black Lingzhi Medicinal Mushroom, Amauroderma rugosum (Agaricomycetes), from Malaysia

Fung SY, Tan NH, Kong BH, Lee SS, Tan YS, Sabaratnam V

Int J Med Mushrooms, 2017;19(12):1093-1099.
PMID: 29431070 DOI: 10.1615/IntJMedMushrooms.2017024550

Amauroderma rugosum is a wild medicinal mushroom also known as budak cendawan sawan. Members of the indigenous Malaysian Temuan community wear the fresh stipes as a necklace to prevent epileptic seizure and unremitting crying by babies. In our previous studies, A. rugosum exhibited significant antioxidant and anti-inflammatory activities. The aim of this study was to determine the toxicity (in the event that a stipe is accidentally bitten) and cytotoxicity of this mushroom on Sprague-Dawley rats and selected cell lines. A. rugosum was orally administered to test chemicals according to Organisation for Economic and Co-operation and Development guidelines (TG 425, adopted October 3, 2008). Blood samples were hematologically and biochemically analyzed and multiple tissue sections from each organ were examined using light microscopy. Cytotoxicity of various A. rugosum extracts was also determined against MCF-7 and A-549 cell lines. Our results showed that oral administration of a single dose of mycelial powder (2000 mg/kg) had no adverse effect on the growth rate or hematological and clinical biochemical parameters. Histological studies showed that the treatments did not induce any pathological changes in the organs of the tested animals. All the treated rats survived beyond the 14-day observation period. Methanol and cold and hot water extracts of the freeze-dried mycelial culture of A. rugosum exhibited no or little cytotoxic effect against the MCF-7 and A-549 cell lines.
Fulltext Inadequate vitamin D intake among pregnant women in Malaysia based on revised recommended nutrient intakes value and potential dietary strategies to tackle the inadequacy

Lee SS, Subramaniam R, Tusimin M, Ling KH, Rahim KF, Loh SP

Nutr Res Pract, 2021 Aug;15(4):492-503.
PMID: 34349882 DOI: 10.4162/nrp.2021.15.4.492

BACKGROUND/OBJECTIVES: Recently, the recommended nutrient intakes (RNI) for vitamin D for Malaysian aged 1-70 yrs has been revised from 5 µg/day to 15 µg/day. This study is aimed to assess the adequacy of vitamin D intake based on revised RNI and to recommend several dietary strategies to increase total vitamin D intake.
SUBJECTS/METHODS: Vitamin D intake from both food and supplement of 217 pregnant women was assessed using a validated food frequency questionnaire. Hypothetical effect of expanded supplementation and food fortifications strategies were modelled using the consumption data.
RESULTS: The results revealed that more than half (67.7%) of pregnant women had inadequate vitamin D intake (RNI < 15 µg/day). The modelling results demonstrated the potential of universal provision of 10 µg/day of multivitamins supplements in increasing vitamin D intake. Moreover, mandatory fortification of both milk and malted drink at single level of 5 µg/serving would lead to increase in vitamin D intake of Malaysians, particularly pregnant women.
CONCLUSIONS: The outcome of this study can be used as a reference for public health professionals to re-evaluate the existing Malaysian food fortification policies and supplementation recommendation for vitamin D for pregnant women.
Fulltext Multilocus phylogenetic analyses reveal unexpected abundant diversity and significant disjunct distribution pattern of the Hedgehog Mushrooms (Hydnum L.)

Feng B, Wang XH, Ratkowsky D, Gates G, Lee SS, Grebenc T, et al.

Sci Rep, 2016 May 06;6:25586.
PMID: 27151256 DOI: 10.1038/srep25586

Hydnum is a fungal genus proposed by Linnaeus in the early time of modern taxonomy. It contains several ectomycorrhizal species which are commonly consumed worldwide. However, Hydnum is one of the most understudied fungal genera, especially from a molecular phylogenetic view. In this study, we extensively gathered specimens of Hydnum from Asia, Europe, America and Australasia, and analyzed them by using sequences of four gene fragments (ITS, nrLSU, tef1α and rpb1). Our phylogenetic analyses recognized at least 31 phylogenetic species within Hydnum, 15 of which were reported for the first time. Most Australasian species were recognized as strongly divergent old relics, but recent migration between Australasia and the Northern Hemisphere was also detected. Within the Northern Hemisphere, frequent historical biota exchanges between the Old World and the New World via both the North Atlantic Land Bridge and the Bering Land Bridge could be elucidated. Our study also revealed that most Hydnum species found in subalpine areas of the Hengduan Mountains in southwestern China occur in northeastern/northern China and Europe, indicating that the composition of the mycobiota in the Hengduan Mountains reigion is more complicated than what we have known before.
Differential capacity of phragmites ecotypes in remediation of inorganic contaminants in coastal ecosystems: Implications for climate change

Akhter N, Aqeel M, Shazia, Irshad MK, Shehnaz MM, Lee SS, et al.

Environ Res, 2024 Apr 15;247:118127.
PMID: 38220075 DOI: 10.1016/j.envres.2024.118127

Remediating inorganic pollutants is an important part of protecting coastal ecosystems, which are especially at risk from the effects of climate change. Different Phragmites karka (Retz) Trin. ex Steud ecotypes were gathered from a variety of environments, and their abilities to remove inorganic contaminants from coastal wetlands were assessed. The goal is to learn how these ecotypes process innovation might help reduce the negative impacts of climate change on coastal environments. The Phragmites karka ecotype E1, found in a coastal environment in Ichkera that was impacted by residential wastewater, has higher biomass production and photosynthetic pigment content than the Phragmites karka ecotypes E2 (Kalsh) and E3 (Gatwala). Osmoprotectant accumulation was similar across ecotypes, suggesting that all were able to successfully adapt to polluted marine environments. The levels of both total soluble sugars and proteins were highest in E2. The amount of glycine betaine (GB) rose across the board, with the highest levels being found in the E3 ecotype. The study also demonstrated that differing coastal habitats significantly influenced the antioxidant activity of all ecotypes, with E1 displaying the lowest superoxide dismutase (SOD) activity, while E2 exhibited the lowest peroxidase (POD) and catalase (CAT) activities. Significant morphological changes were evident in E3, such as an expansion of the phloem, vascular bundle, and metaxylem cell areas. When compared to the E3 ecotype, the E1 and E2 ecotypes showed striking improvements across the board in leaf anatomy. Mechanistic links between architectural and physio-biochemical alterations are crucial to the ecological survival of different ecotypes of Phragmites karka in coastal environments affected by climate change. Their robustness and capacity to reduce pollution can help coastal ecosystems endure in the face of persistent climate change.
Fulltext BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history

Toh GT, Kang P, Lee SS, Lee DS, Lee SY, Selamat S, et al.

PLoS One, 2008;3(4):e2024.
PMID: 18431501 DOI: 10.1371/journal.pone.0002024

BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised.
METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (
Fulltext Admission policies and methods at crossroads: a review of medical school admission policies and methods in seven Asian countries

Soemantri D, Karunathilake I, Yang JH, Chang SC, Lin CH, Nadarajah VD, et al.

Korean J Med Educ, 2020 Sep;32(3):243-256.
PMID: 32723988 DOI: 10.3946/kjme.2020.169

Selecting the right applicants is an important part of medical student admission. While one universally accepted selection criterion is academic capacity, there are other criteria such as communication skills and local criteria (e.g., socio-cultural values) that are no less important. This article reviews the policies and methods of selection to medical schools in seven countries with varying socio-economic conditions and healthcare systems. Senior academics involved in medical education in Indonesia, Japan, Malaysia, the Philippines, Singapore, Sri Lanka, and Taiwan completed a pre-agreed pro-forma per each country to describe the country's admission policies and methods. The details were then compared and contrasted. This review identifies tension between many of the policies and methods used in medical school admissions, such as between the need to assess non-cognitive abilities and widen access, and between the need for more medical professionals and the requirement to set high entry standards. Finding the right balance requires careful consideration of all variables, including the country's human resource needs; socio-economic status; graduates' expected competencies; and the school's vision, mission, and availability of resources.
Fulltext Characterisation of a New Fungal Immunomodulatory Protein from Tiger Milk mushroom, Lignosus rhinocerotis

Pushparajah V, Fatima A, Chong CH, Gambule TZ, Chan CJ, Ng ST, et al.

Sci Rep, 2016 07 27;6:30010.
PMID: 27460640 DOI: 10.1038/srep30010

Lignosus rhinocerotis (Tiger milk mushroom) is an important folk medicine for indigenous peoples in Southeast Asia. We previously reported its de novo assembled 34.3 Mb genome encoding a repertoire of proteins including a putative bioactive fungal immunomodulatory protein. Here we report the cDNA of this new member (FIP-Lrh) with a homology range of 54-64% to FIPs from other mushroom species, the closest is with FIP-glu (LZ-8) (64%) from Ganoderma lucidum. The FIP-Lrh of 112 amino acids (12.59 kDa) has a relatively hydrophobic N-terminal. Its predicted 3-dimensional model has identical folding patterns to FIP-fve and contains a partially conserved and more positively charged carbohydrates binding pocket. Docking predictions of FIP-Lrh on 14 glycans commonly found on cellular surfaces showed the best binding energy of -3.98 kcal/mol to N-acetylgalactosamine and N-acetylglucosamine. Overexpression of a 14.9 kDa soluble 6xHisFIP-Lrh was achieved in pET-28a(+)/BL21 and the purified recombinant protein was sequence verified by LC-MS/MS (QTOF) analysis. The ability to haemagglutinate both mouse and human blood at concentration ≥0.34 μM, further demonstrated its lectin nature. In addition, the cytotoxic effect of 6xHisFIP-Lrh on MCF-7, HeLa and A549 cancer cell lines was detected at IC50 of 0.34 μM, 0.58 μM and 0.60 μM, respectively.
The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia

Samson KLI, Loh SP, Lee SS, Sulistyoningrum DC, Khor GL, Mohd Shariff ZB, et al.

J Nutr, 2021 Aug 07;151(8):2264-2270.
PMID: 33978167 DOI: 10.1093/jn/nxab115

BACKGROUND: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anemia prevalence is ≥20%; however, it is unknown whether the inclusion of folic acid in weekly IFA supplements reduces anemia.
OBJECTIVES: We examined whether the inclusion of folic acid in weekly IFA supplements conferred any benefit on hemoglobin (Hb) concentration, anemia reduction, or iron status [ferritin and soluble transferrin receptor (sTfR)], over iron alone.
METHODS: In this secondary analysis of a randomized controlled trial in Malaysia, n = 311 nonpregnant women (18-45 y old) received 60 mg Fe with either 0, 0.4, or 2.8 mg folic acid once-weekly for 16 wk. Fasting blood was collected at baseline and 16 wk. A generalized linear model (normal distribution with identity link) was used to assess Hb concentration at 16 wk (primary outcome).
RESULTS: At baseline, 84% of women had low folate status (plasma folate 0.05). Baseline plasma folate concentration did not modify the effect of treatment on Hb concentration at 16 wk. Among all women, the risks of anemia [risk ratio (RR): 0.65; 95% CI: 0.45, 0.96; P = 0.03] and iron deficiency based on ferritin (RR: 0.30; 95% CI: 0.20, 0.44; P
Fulltext Notes on Amanita section Validae in Hainan Island, China

Huang T, Su LJ, Zeng NK, Lee SML, Lee SS, Thi BK, et al.

Front Microbiol, 2022;13:1087756.
PMID: 36741898 DOI: 10.3389/fmicb.2022.1087756

Hainan is the second largest island in China with the most extensive and well-preserved tropical forests and is also the largest island of the Indo Burma Biodiversity Hotspot. It provides in situ conservation for the unique ecosystem of the island. Recent studies have shown that there are diverse fungal species in Hainan. In this study, about 40 collections of the genus Amanita have been studied based on the morphology and molecular systematics, including 35 Chinese specimens (24 from Hainan, and eleven from other regions) and three specimens from other countries (Singapore and Malaysia). In total, five new species belonging to Amanita section Validae are described: A. cacaina, A. parvigrisea, A. pseudofritillaria, A. pseudosculpta, and A. yangii. Amanita parvifritillaria is recorded for the first time in Hainan. It is also the first report of this fungus occurring, outside Yunnan Province, China. Among the five new species, two are unique in this section because of the appendiculate pileus margin and the absence of an annulus. Based on these new findings, the diagnosis of the section Validae should be slightly modified to include a few species with appendiculate margin and the lack of annulus.
Fulltext Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia

Samson KLI, Loh SP, Lee SS, Sulistyoningrum DC, Khor GL, Shariff ZBM, et al.

BMJ Glob Health, 2020 12;5(12).
PMID: 33272946 DOI: 10.1136/bmjgh-2020-003897

INTRODUCTION: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk.
METHODS: We conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks.
RESULTS: At 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group.
CONCLUSION: Weekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed.
TRAIL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).
Fulltext Lazertinib Versus Gefitinib Tyrosine Kinase Inhibitors in Treatment-Naíve Patients With EGFR-Mutated Advanced NSCLC: Analysis of the Asian Subpopulation in LASER301

Reungwetwattana T, Cho BC, Lee KH, Pang YK, Fong CH, Kang JH, et al.

J Thorac Oncol, 2023 Oct;18(10):1351-1361.
PMID: 37702629 DOI: 10.1016/j.jtho.2023.06.016

INTRODUCTION: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients.
METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety.
RESULTS: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively.
CONCLUSIONS: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile.
Fulltext Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis

Soo RA, Cho BC, Kim JH, Ahn MJ, Lee KH, Zimina A, et al.

J Thorac Oncol, 2023 Dec;18(12):1756-1766.
PMID: 37865896 DOI: 10.1016/j.jtho.2023.08.017

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.
METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
Fulltext High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry

Sun C, Molineros JE, Looger LL, Zhou XJ, Kim K, Okada Y, et al.

Nat Genet, 2016 Mar;48(3):323-30.
PMID: 26808113 DOI: 10.1038/ng.3496

Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.
Fulltext Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians

Molineros JE, Looger LL, Kim K, Okada Y, Terao C, Sun C, et al.

PLoS Genet, 2019 04;15(4):e1008092.
PMID: 31022184 DOI: 10.1371/journal.pgen.1008092

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.
Precessing jet nozzle connecting to a spinning black hole in M87

Cui Y, Hada K, Kawashima T, Kino M, Lin W, Mizuno Y, et al.

Nature, 2023 Sep;621(7980):711-715.
PMID: 37758892 DOI: 10.1038/s41586-023-06479-6

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356

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