MyMedR

Displaying publications 1 - 20 of 135 in total

Abstract:

Sort:

Fulltext Relative Validity and Reproducibility of a Food Frequency Questionnaire for Assessing Dietary Intakes in a Multi-Ethnic Asian Population Using 24-h Dietary Recalls and Biomarkers

Whitton C, Ho JCY, Tay Z, Rebello SA, Lu Y, Ong CN, et al.

Nutrients, 2017 Sep 25;9(10).
PMID: 28946670 DOI: 10.3390/nu9101059

The assessment of diets in multi-ethnic cosmopolitan settings is challenging. A semi-quantitative 163-item food frequency questionnaire (FFQ) was developed for the adult Singapore population, and this study aimed to assess its reproducibility and relative validity against 24-h dietary recalls (24 h DR) and biomarkers. The FFQ was administered twice within a six-month interval in 161 adults (59 Chinese, 46 Malay, and 56 Indian). Fasting plasma, overnight urine, and 24 h DR were collected after one month and five months. Intra-class correlation coefficients between the two FFQ were above 0.70 for most foods and nutrients. The median correlation coefficient between energy-adjusted deattenuated FFQ and 24 h DR nutrient intakes was 0.40 for FFQ1 and 0.39 for FFQ2, highest for calcium and iron, and lowest for energy and carbohydrates. Significant associations were observed between urinary isoflavones and soy protein intake (r = 0.46), serum carotenoids and fruit and vegetable intake (r = 0.34), plasma eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and fish/seafood intake (r = 0.36), and plasma odd chain saturated fatty acids (SFA) and dairy fat intake (r = 0.25). Associations between plasma EPA + DHA and fish/seafood intake were consistent across ethnic groups (r = 0.28-0.49), while differences were observed for other associations. FFQ assessment of dietary intakes in modern cosmopolitan populations remains feasible for the purpose of ranking individuals' dietary exposures in epidemiological studies.
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
Occurrence of microplastics in the seawater and atmosphere of the South China Sea: Pollution patterns and interrelationship

Liu B, Lu Y, Deng H, Huang H, Wei N, Jiang Y, et al.

Sci Total Environ, 2023 Sep 01;889:164173.
PMID: 37201824 DOI: 10.1016/j.scitotenv.2023.164173

Microplastic (MP) pollution is a serious global environmental problem, particularly in marine ecosystems. However, the pollution patterns of MPs in the ocean and atmosphere, particularly the sea-air interrelationship, remain unclear. Therefore, the abundance, distribution patterns, and sources of MPs in the seawater and atmosphere of the South China Sea (SCS) were comparatively investigated. The results showed that MPs were prevalent in the SCS with an average abundance of 103.4 ± 98.3 items/m3 in the seawater and 4.62 ± 3.60 items/100 m3 in the atmosphere. The spatial analysis indicated that the pollution patterns of seawater MPs were mainly determined by land-based discharge and sea surface currents, whereas atmospheric MPs were predominantly determined by air parcel trajectory and wind conditions. The highest MP abundance of 490 items/m3 in seawater was found at a station near Vietnam with current vortices. However, the highest MP abundance of 14.6 items/100 m3 in the atmosphere was found in air parcels with low-speed southerly winds from Malaysia. Similar MP compositions (e.g., polyethylene terephthalate, polystyrene, and polyethylene) were observed in the two environmental compartments. Furthermore, similar MP characteristics (e.g., shape, color, and size) in the seawater and atmosphere of the same region suggested a close relationship between the MPs in the two compartments. For this purpose, cluster analysis and calculation of the MP diversity integrated index were performed. The results showed an obvious dispersion between the two compartment clusters and a higher diversity integrated index of MPs in seawater than in the atmosphere, thus implying higher compositional diversity and more complex sources of MPs in seawater relative to the atmosphere. These findings deepen our understanding of MP fate and patterns in the semi-enclosed marginal sea environment and highlight the potential interrelationship of MPs in the air-sea system.
COVID-19 vaccination intention and vaccine characteristics influencing vaccination acceptance: a global survey of 17 countries

Wong LP, Alias H, Danaee M, Ahmed J, Lachyan A, Cai CZ, et al.

Infect Dis Poverty, 2021 Oct 07;10(1):122.
PMID: 34620243 DOI: 10.1186/s40249-021-00900-w

BACKGROUND: The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines present a dilemma in vaccination choices, which may result in individuals refusing a particular COVID-19 vaccine offered, hence presenting a threat to immunisation coverage and reaching herd immunity. The study aimed to assess global COVID-19 vaccination intention, vaccine characteristics influencing vaccination acceptance and desirable vaccine characteristics influencing the choice of vaccines.
METHODS: An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 countries worldwide. Proportions and the corresponding 95% confidence intervals (CI) of COVID-19 vaccine acceptance and vaccine characteristics influencing vaccination acceptance were generated and compared across countries and regions. Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy.
RESULTS: Of the 19,714 responses received, 90.4% (95% CI 81.8-95.3) reported likely or extremely likely to receive COVID-19 vaccine. A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia (96.4%), China (95.3%) and Norway (95.3%), while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan (34.6%), the U.S. (29.4%) and Iran (27.9%). Males, those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy. Less than two-thirds (59.7%; 95% CI 58.4-61.0) reported only being willing to accept a vaccine with an effectiveness of more than 90%, and 74.5% (95% CI 73.4-75.5) said they would accept a COVID-19 vaccine with minor adverse reactions. A total of 21.0% (95% CI 20.0-22.0) reported not accepting an mRNA vaccine and 51.8% (95% CI 50.3-53.1) reported that they would only accept a COVID-19 vaccine from a specific country-of-origin. Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology. The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries. The foremost important vaccine characteristic influencing vaccine choice is adverse reactions (40.6%; 95% CI 39.3-41.9) of a vaccine and effectiveness threshold (35.1%; 95% CI 33.9-36.4).
CONCLUSIONS: The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efficient plan for the delivery of interventions dynamically tailored to the local population.
Genotyping and characterization of Toxoplasma gondii strain isolated from pigs in Hubei province, central China

Xia NB, Lu Y, Zhao PF, Wang CF, Li YY, Tan L, et al.

Trop Biomed, 2020 Jun 01;37(2):489-498.
PMID: 33612818

Toxoplasma gondii, a ubiquitous pathogen that infects nearly all warm-blooded animals and humans, can cause severe complications to the infected people and animals as well as serious economic losses and social problems. Here, one local strain (TgPIG-WH1) was isolated from an aborted pig fetus, and the genotype of this strain was identified as ToxoDB #3 by the PCR RFLP typing method using 10 molecular markers (SAG1, SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, C22-8, C29-2 and Apico). A comparison of the virulence of this isolate with other strains in both mice and piglets showed that TgPIG-WH1 was less virulent than type 1 strain RH and type 2 strain ME49 in mice, and caused similar symptoms to those of ME49 such as fever in piglets. Additionally, in piglet infection with both strains, the TgPIG-WH1 caused a higher IgG response and more severe pathological damages than ME49. Furthermore, TgPIG-WH1 caused one death in the 5 infected piglets, whereas ME49 did not, suggesting the higher virulence of TgPIG-WH1 than ME49 during piglet infection. Experimental infections indicate that the virulence of TgPIG-WH1 relative to ME49 is weaker in mice, but higher in pigs. This is probably the first report regarding a ToxoDB #3 strain from pigs in Hubei, China. These data will facilitate the understanding of genetic diversity of Toxoplasma strains in China as well as the prevention and control of porcine toxoplasmosis in the local region.
Batch and continuous enzymatic interesterification of beef tallow: Interesterification degree, reaction relationship, and physicochemical properties

Yang D, Zhang Y, Lee YY, Lu Y, Wang Y, Zhang Z

Food Chem, 2024 Feb 02;444:138635.
PMID: 38325087 DOI: 10.1016/j.foodchem.2024.138635

The relationship between batch and continuous enzymatic interesterification was studied through enzymatic interesterification of beef tallow. The interesterification degree (ID) during the batch reaction was monitored based on triacylglycerol composition, sn-2 fatty acid composition, solid fat content, and melting profile and was described by an exponential model. A relationship equation featuring reaction parameters of the two reations was established to predict the ID and physicochemical characteristics in continuous interesterification. The prediction of the ID based on triacylglycerol composition was reliable, with an R2 value greater than 0.85. Interesterification produced more high-melting-point components for both reactions, but the acyl migration in the batch-stirring reactor was much greater, resulting in faster crystallization, a more delicate crystal network, and lower hardness. The relationship equation can be employed to predict the ID, but the prediction of physicochemical properties was constrained by the difference in acyl migration degree between the two reactions.
Fulltext Ratiometric Detection of Zn2+ Using DNAzyme-Based Bioluminescence Resonance Energy Transfer Sensors

Wu Y, Lewis W, Wai JL, Xiong M, Zheng J, Yang Z, et al.

Chemistry (Basel), 2023 Sep;5(3):1745-1759.
PMID: 38371491 DOI: 10.3390/chemistry5030119

While fluorescent sensors have been developed for monitoring metal ions in health and diseases, they are limited by the requirement of an excitation light source that can lead to photobleaching and a high autofluorescence background. To address these issues, bioluminescence resonance energy transfer (BRET)-based protein or small molecule sensors have been developed; however, most of them are not highly selective nor generalizable to different metal ions. Taking advantage of the high selectivity and generalizability of DNAzymes, we report herein DNAzyme-based ratiometric sensors for Zn2+ based on BRET. The 8-17 DNAzyme was labeled with luciferase and Cy3. The proximity between luciferase and Cy3 permiQed BRET when coelenterazine, the substrate for luciferase, was introduced. Adding samples containing Zn2+ resulted in a cleavage of the substrate strand, causing dehybridization of the DNAzyme construct, thus increasing the distance between Cy3 and luciferase and changing the BRET signals. Using these sensors, we detected Zn2+ in serum samples and achieved Zn2+ detection with a smartphone camera. Moreover, since the BRET pair is not the component that determines the selectivity of the sensors, this sensing platform has the potential to be adapted for the detection of other metal ions with other metal-dependent DNAzymes.
Associations of unprocessed and processed meat intake with mortality and cardiovascular disease in 21 countries [Prospective Urban Rural Epidemiology (PURE) Study]: a prospective cohort study

Iqbal R, Dehghan M, Mente A, Rangarajan S, Wielgosz A, Avezum A, et al.

Am J Clin Nutr, 2021 09 01;114(3):1049-1058.
PMID: 33787869 DOI: 10.1093/ajcn/nqaa448

BACKGROUND: Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent.
OBJECTIVE: The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD.
METHODS: The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts.
RESULTS: In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs. <50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004).
CONCLUSIONS: In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.
The discovery of 1, 3-diamino-7H-pyrrol[3, 2-f]quinazoline compounds as potent antimicrobial antifolates

Li Y, Ouyang Y, Wu H, Wang P, Huang Y, Li X, et al.

Eur J Med Chem, 2022 Jan 15;228:113979.
PMID: 34802838 DOI: 10.1016/j.ejmech.2021.113979

The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.
Fulltext Host genetic variants of ABCB1 and IL15 influence treatment outcome in paediatric acute lymphoblastic leukaemia

Lu Y, Kham SK, Ariffin H, Oei AM, Lin HP, Tan AM, et al.

Br. J. Cancer, 2014 Mar 18;110(6):1673-80.
PMID: 24434428 DOI: 10.1038/bjc.2014.7

Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL.
Identifying IGH disease clones for MRD monitoring in childhood B-cell acute lymphoblastic leukemia using RNA-Seq

Li Z, Jiang N, Lim EH, Chin WHN, Lu Y, Chiew KH, et al.

Leukemia, 2020 09;34(9):2418-2429.
PMID: 32099036 DOI: 10.1038/s41375-020-0774-4

Identifying patient-specific clonal IGH/TCR junctional sequences is critical for minimal residual disease (MRD) monitoring. Conventionally these junctional sequences are identified using laborious Sanger sequencing of excised heteroduplex bands. We found that the IGH is highly expressed in our diagnostic B-cell acute lymphoblastic leukemia (B-ALL) samples using RNA-Seq. Therefore, we used RNA-Seq to identify IGH disease clone sequences in 258 childhood B-ALL samples for MRD monitoring. The amount of background IGH rearrangements uncovered by RNA-Seq followed the Zipf's law with IGH disease clones easily identified as outliers. Four hundred and ninety-seven IGH disease clones (median 2, range 0-7 clones/patient) are identified in 90.3% of patients. High hyperdiploid patients have the most IGH disease clones (median 3) while DUX4 subtype has the least (median 1) due to the rearrangements involving the IGH locus. In all, 90.8% of IGH disease clones found by Sanger sequencing are also identified by RNA-Seq. In addition, RNA-Seq identified 43% more IGH disease clones. In 69 patients lacking sensitive IGH targets, targeted NGS IGH MRD showed high correlation (R = 0.93; P = 1.3 × 10-14), better relapse prediction than conventional RQ-PCR MRD using non-IGH targets. In conclusion, RNA-Seq can identify patient-specific clonal IGH junctional sequences for MRD monitoring, adding to its usefulness for molecular diagnosis in childhood B-ALL.
Fulltext Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia

Li Z, Lee SHR, Chin WHN, Lu Y, Jiang N, Lim EH, et al.

Blood Adv, 2021 12 14;5(23):5226-5238.
PMID: 34547766 DOI: 10.1182/bloodadvances.2021004895

Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
Taxonomic notes on eleven species of the subfamily Cteninae (Araneae, Ctenidae) from Asia

Chu C, Lu Y, Li S, Yao Z

Biodivers Data J, 2022;10:e96003.
PMID: 36761640 DOI: 10.3897/BDJ.10.e96003

BACKGROUND: The spider family Ctenidae Keyserling, 1877 has a worldwide distribution with 584 species belonging to 49 genera. Amongst these, 141 species are from Asia, including 130 species assigned to Cteninae Keyserling, 1877.
NEW INFORMATION: Nine new species belonging to three genera of Cteninae are reported from Asia: Amauropelmakrabi sp. n. (female; Krabi, Thailand), Am.phangnga sp. n. (male; Phang Nga, Thailand), Am.saraburi sp. n. (male and female; Saraburi, Thailand); Anahitamedog sp. n. (male and female; Tibet, China); Bowieninhbinh sp. n. (male; Ninh Binh, Vietnam) and B.vinhphuc sp. n. (male and female; Vinh Phuc, Vietnam) from the robustus-species group; B.borneo sp. n. (male; Sabah, Malaysia) from the chinagirl-species group; B.engkilili sp. n. (female; Engkilili, Malaysia); B.sabah sp. n. (male and female; Sabah, Malaysia) from the scarymonsters-species group. The male of An.popa Jäger & Minn, 2015 and the female of B.fascination Jäger, 2022 (robustus-species group) are described for the first time. B.fascination Jäger, 2022 is reported from China for the first time. In addition, the DNA barcodes of all the species in this study were obtained, except for B.vinhphuc sp. n.
Fulltext Whole-transcriptome sequencing identifies a distinct subtype of acute lymphoblastic leukemia with predominant genomic abnormalities of EP300 and CREBBP

Qian M, Zhang H, Kham SK, Liu S, Jiang C, Zhao X, et al.

Genome Res, 2017 02;27(2):185-195.
PMID: 27903646 DOI: 10.1101/gr.209163.116

Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54.1% of patients (n = 125), 31 of which have not been reported previously. In particular, we described a distinct ALL subtype with a characteristic gene expression signature predominantly driven by chromosomal rearrangements of the ZNF384 gene with histone acetyltransferases EP300 and CREBBP ZNF384-rearranged ALL showed significant up-regulation of CLCF1 and BTLA expression, and ZNF384 fusion proteins consistently showed higher activity to promote transcription of these target genes relative to wild-type ZNF384 in vitro. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro. EP300- and CREBBP-ZNF384 fusions resulted in loss of histone lysine acetyltransferase activity in a dominant-negative fashion, with concomitant global reduction of histone acetylation and increased sensitivity of leukemia cells to histone deacetylase inhibitors. In conclusion, our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting.
Association of CYP24A1 with survival and drug resistance in clinical cancer patients: a meta-analysis

Zeng R, Li H, Jia L, Lee SH, Jiang R, Zhang Y, et al.

BMC Cancer, 2022 Dec 16;22(1):1317.
PMID: 36527000 DOI: 10.1186/s12885-022-10369-x

BACKGROUND: Acquired chemo-drug resistance constantly led to the failure of chemotherapy for malignant cancers, consequently causing cancer relapse. Hence, identifying the biomarker of drug resistance is vital to improve the treatment efficacy in cancer. The clinical prognostic value of CYP24A1 remains inconclusive, hence we aim to evaluate the association between CYP24A1 and the drug resistance in cancer patients through a meta-analysis approach.
METHOD: Relevant studies detecting the expression or SNP of CYP24A1 in cancer patients up till May 2022 were systematically searched in four common scientific databases including PubMed, EMBASE, Cochrane library and ISI Web of Science. The pooled hazard ratios (HRs) indicating the ratio of hazard rate of survival time between CYP24A1high population vs CYP24A1low population were calculated. The pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were used to explore the association between CYP24A1's expression or SNP with survival, metastasis, recurrence, and drug resistance in cancer patients.
RESULT: Fifteen studies were included in the meta-analysis after an initial screening according to the inclusion and exclusion criteria. There was a total of 3784 patients pooled from all the included studies. Results indicated that higher expression or SNP of CYP24A1 was significantly correlated with shorter survival time with pooled HRs (95% CI) of 1.21 (1.12, 1.31), metastasis with pooled ORs (95% CI) of 1.81 (1.11, 2.96), recurrence with pooled ORs (95% CI) of 2.14 (1.45, 3.18) and drug resistance with pooled HRs (95% CI) of 1.42 (1.17, 1.68). In the subgroup analysis, cancer type, treatment, ethnicity, and detection approach for CYP24A1 did not affect the significance of the association between CYP24A1 expression and poor prognosis.
CONCLUSION: Findings from our meta-analysis demonstrated that CYP24A1's expression or SNP was correlated with cancer progression and drug resistance. Therefore, CYP24A1 could be a potential molecular marker for cancer resistance.
Fulltext A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence

Lou H, Lu Y, Lu D, Fu R, Wang X, Feng Q, et al.

Am J Hum Genet, 2015 Jul 02;97(1):54-66.
PMID: 26073780 DOI: 10.1016/j.ajhg.2015.05.005

Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1.
Fulltext Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia

Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.

Mol Biol Evol, 2022 Feb 03;39(2).
PMID: 34940850 DOI: 10.1093/molbev/msab361

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.
Fulltext PGG.SNV: understanding the evolutionary and medical implications of human single nucleotide variations in diverse populations

Zhang C, Gao Y, Ning Z, Lu Y, Zhang X, Liu J, et al.

Genome Biol, 2019 10 22;20(1):215.
PMID: 31640808 DOI: 10.1186/s13059-019-1838-5

Despite the tremendous growth of the DNA sequencing data in the last decade, our understanding of the human genome is still in its infancy. To understand the implications of genetic variants in the light of population genetics and molecular evolution, we developed a database, PGG.SNV ( https://www.pggsnv.org ), which gives much higher weight to previously under-investigated indigenous populations in Asia. PGG.SNV archives 265 million SNVs across 220,147 present-day genomes and 1018 ancient genomes, including 1009 newly sequenced genomes, representing 977 global populations. Moreover, estimation of population genetic diversity and evolutionary parameters is available in PGG.SNV, a unique feature compared with other databases.
Fulltext Safrana l Prevents Prostate Cancer Recurrence by Blocking the Re-activation of Quiescent Cancer Cells via Downregulation of S-Phase Kinase-Associated Protein 2

Jiang X, Li Y, Feng JL, Nik Nabil WN, Wu R, Lu Y, et al.

Front Cell Dev Biol, 2020;8:598620.
PMID: 33392189 DOI: 10.3389/fcell.2020.598620

The re-proliferation of quiescent cancer cells is considered to be the primary contributor to prostate cancer (Pca) recurrence and progression. In this study, we investigated the inhibitory effect of safranal, a monoterpene aldehyde isolated from Crocus sativus (saffron), on the re-proliferation of quiescent Pca cells in vitro and in vivo. The results showed that safranal efficiently blocked the re-activation of quiescent Pca cells by downregulating the G0/G1 cell cycle regulatory proteins CDK2, CDK4, CDK6, and phospho-Rb at Ser807/811 and elevating the levels of cyclin-dependent kinase inhibitors, p21 and p27. Further investigation on the underlying mechanisms revealed that safranal suppressed the mRNA and protein expression levels of Skp2, possibly through the deregulation of the transcriptional activity of two major transcriptional factors, E2F1 and NF-κB subunits. Moreover, safranal inhibited AKT phosphorylation at Ser473 and deregulated both canonical and non-canonical NF-κB signaling pathways. Safranal suppressed the tumor growth of quiescent Pca cell xenografts in vivo. Furthermore, safranal-treated tumor tissues exhibited a reduction in Skp2, E2F1, NF-κB p65, p-IκBα (Ser32), c-MYC, p-Rb (Ser807), CDK4, CDK6, and CDK2 and an elevation of p27 and p21 protein levels. Therefore, our findings demonstrate that safranal suppresses cell cycle re-entry of quiescent Pca cells in vitro and in vivo plausibly by repressing the transcriptional activity of two major transcriptional activators of Skp2, namely, E2F1 and NF-κB, through the downregulation of AKT phosphorylation and NF-κB signaling pathways, respectively.
Monkeypox virus 2022, gene heterogeneity and protein polymorphism

Li Y, Hou J, Sun Z, Hu J, Thilakavathy K, Wang Y, et al.

Signal Transduct Target Ther, 2023 Jul 17;8(1):278.
PMID: 37460567 DOI: 10.1038/s41392-023-01540-2

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links