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Discovery of an Abundant Viral Genus in Polar Regions through the Isolation and Genomic Characterization of a New Virus against Oceanospirillaceae

Zhang W, Liu Y, Zheng K, Xing J, Li Q, Gu C, et al.

Appl Environ Microbiol, 2023 Mar 28.
PMID: 36975807 DOI: 10.1128/aem.01896-22

The marine bacterial family Oceanospirillaceae, is well-known for its ability to degrade hydrocarbons and for its close association with algal blooms. However, only a few Oceanospirillaceae-infecting phages have been reported thus far. Here, we report on a novel Oceanospirillum phage, namely, vB_OsaM_PD0307, which has a 44,421 bp linear dsDNA genome and is the first myovirus infecting Oceanospirillaceae. A genomic analysis demonstrated that vB_OsaM_PD0307 is a variant of current phage isolates from the NCBI data set but that it has similar genomic features to two high-quality, uncultured viral genomes identified from marine metagenomes. Hence, we propose that vB_OsaM_PD0307 can be classified as the type phage of a new genus, designated Oceanospimyovirus. Additionally, metagenomic read mapping results have further shown that Oceanospimyovirus species are widespread in the global ocean, display distinct biogeographic distributions, and are abundant in polar regions. In summary, our findings expand the current understanding of the genomic characteristics, phylogenetic diversity, and distribution of Oceanospimyovirus phages. IMPORTANCE Oceanospirillum phage vB_OsaM_PD0307 is the first myovirus found to infect Oceanospirillaceae, and it represents a novel abundant viral genus in polar regions. This study provides insights into the genomic, phylogenetic, and ecological characteristics of the new viral genus, namely Oceanospimyovirus.
A deep convolutional neural network for the automatic segmentation of glioblastoma brain tumor: Joint spatial pyramid module and attention mechanism network

Liu H, Huang J, Li Q, Guan X, Tseng M

Artif Intell Med, 2024 Feb;148:102776.
PMID: 38325925 DOI: 10.1016/j.artmed.2024.102776

This study proposes a deep convolutional neural network for the automatic segmentation of glioblastoma brain tumors, aiming sat replacing the manual segmentation method that is both time-consuming and labor-intensive. There are many challenges for automatic segmentation to finely segment sub-regions from multi-sequence magnetic resonance images because of the complexity and variability of glioblastomas, such as the loss of boundary information, misclassified regions, and subregion size. To overcome these challenges, this study introduces a spatial pyramid module and attention mechanism to the automatic segmentation algorithm, which focuses on multi-scale spatial details and context information. The proposed method has been tested in the public benchmarks BraTS 2018, BraTS 2019, BraTS 2020 and BraTS 2021 datasets. The Dice score on the enhanced tumor, whole tumor, and tumor core were respectively 79.90 %, 89.63 %, and 85.89 % on the BraTS 2018 dataset, respectively 77.14 %, 89.58 %, and 83.33 % on the BraTS 2019 dataset, and respectively 77.80 %, 90.04 %, and 83.18 % on the BraTS 2020 dataset, and respectively 83.48 %, 90.70 %, and 88.94 % on the BraTS 2021 dataset offering performance on par with that of state-of-the-art methods with only 1.90 M parameters. In addition, our approach significantly reduced the requirements for experimental equipment, and the average time taken to segment one case was only 1.48 s; these two benefits rendered the proposed network intensely competitive for clinical practice.
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
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Fulltext Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations

Liu L, Mo Z, Liang Z, Zhang Y, Li R, Ong KC, et al.

BMC Med, 2015;13:226.
PMID: 26381232 DOI: 10.1186/s12916-015-0448-7

To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy.
Molecular mechanisms underlying lignocellulose degradation and antibiotic resistance genes removal revealed via metagenomics analysis during different agricultural wastes composting

Ma C, Lo PK, Xu J, Li M, Jiang Z, Li G, et al.

Bioresour Technol, 2020 Oct;314:123731.
PMID: 32615447 DOI: 10.1016/j.biortech.2020.123731

In this study, the differences on the physico-chemical parameters, lignocellulose degradation, dynamic succession of microbial community, gene expression of carbohydrate-active enzymes and antibiotics resistance genes were compared during composting systems of bagasse pith/pig manure (BP) and manioc waste/pig manure (MW). The results revealed that biodegradation rates of organic matter, cellulose, hemicellulose and lignin (29.14%, 17.53%,45.36% and 36.48%) in BP were higher than those (15.59%, 16.74%, 41.23% and 29.77%) in MW. In addition, the relative abundance of Bacillus, Luteimonas, Clostridium, Pseudomonas, Streptomyces and expression of genes encoding carbohydrate- active enzymes in BP were higher than those in MW based on metagenomics sequencing. During composting, antibiotics and antibiotic resistance genes were substantially reduced, but the removal efficiency was divergent in the both samples. Taken together, metagenomics analysis was a potential method for evaluating lignocellulose's biodegradation process and determining the elimination of antibiotic and antibiotic resistance genes from different composting sources of biomass.
An interdigitated aptasensor to detect interleukin-6 for diagnosing rheumatoid arthritis in serum

Chen N, Yang H, Li Q, Song L, Gopinath SCB, Wu D

Biotechnol Appl Biochem, 2021 Dec;68(6):1479-1485.
PMID: 33244818 DOI: 10.1002/bab.2068

Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation in the small joints of the articular bone and destruction of articular cartilage. RA causes stiffness, pain, joint destruction, substantial comorbidity, and functional disability. Early-stage diagnosis of RA can help in the treatment of the disease and expand the patient life span. Interleukins are a group of inflammatory cytokines; in particular, an abundance of interleukin-6 (IL-6) was found in the synovial fluid and serum. In RA patients, the levels of IL-6 have been found to be correlated with the disease, and this work focused on detecting IL-6 by its aptamer with the help of a biotin-streptavidin strategy on an interdigitated electrode. A sensitivity of 1 fM (0.021 pg/mL) and a limit of detection of 10 fM (0.21 pg/mL) were found by a linear regression [y = 0.6413x - 0.6249; R² = 0.952] of the linear range from 1 fM to 100 pM. This method enhanced the immobilization of higher aptamer molecules for recognizing RA in serum-containing samples and is applicable to other diseases.
Fulltext Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, et al.

Cancer Discov, 2016 Sep;6(9):1052-67.
PMID: 27432226 DOI: 10.1158/2159-8290.CD-15-1227

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.
SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
Fulltext Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Kar SP, Tyrer JP, Li Q, Lawrenson K, Aben KK, Anton-Culver H, et al.

Cancer Epidemiol Biomarkers Prev, 2015 Oct;24(10):1574-84.
PMID: 26209509 DOI: 10.1158/1055-9965.EPI-14-1270

BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.
METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).
RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.
CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.
IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.
Fulltext Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, et al.

Carcinogenesis, 2015 Nov;36(11):1341-53.
PMID: 26424751 DOI: 10.1093/carcin/bgv138

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
Influences of metal ions on microcystin-LR degradation capacity and dynamics in microbial distribution of biofilm collected from water treatment plant nearby Kasumigaura Lake

Wang X, Utsumi M, Gao Y, Li Q, Tian X, Shimizu K, et al.

Chemosphere, 2016 Mar;147:230-8.
PMID: 26766360 DOI: 10.1016/j.chemosphere.2015.12.067

Microcystins-LR (MC-LR) which is a kind of potent hepatotoxin for humans and wildlife can be biodegraded by microbial community. In this study, the capacity of biofilm in degrading MC-LR was investigated with and without additional metal ions (Mn(2+), Zn(2+) and Cu(2+)) at the concentration of 1 mg L(-1). The results indicated that the degradation rate of MC-LR by biofilm was inhibited by introduced Mn(2+) and Cu(2+) during the whole culture period. MC-LR cannot be degraded until a period of culture time passed both in the cases with Zn(2+) and Cu(2+) (2 and 8 days for Zn(2+) and Cu(2+), respectively). The results of mlrA gene analysis showed that the abundance of MC-LR degradation bacteria (MCLDB) in the microbial community under Mn(2+) condition was generally lower than that under no additional metal ion condition. Meanwhile, a two days lag phase for the proliferation of MCLDB occurred after introducing Zn(2+). And a dynamic change of MCLDB from Cu(2+) inhibited species to Cu(2+) promoted species was observed under Cu(2+) condition. The maximum ratio of MCLDB to overall bacteria under various conditions during culture process was found to follow the tendency as: Cu(2+) > Zn(2+) ≈ no additional metal ion (Control) > Mn(2+), suggesting the adverse effect of Mn(2+), no obvious effect of Zn(2+) and positive effect of Cu(2+) on the distribution ratio of MCLDB over the biofilm.
Three dimensional quantification of mandibular bone remodeling using standard tessellation language registration based superimposition

Ahmad R, Abu-Hassan MI, Li Q, Swain MV

Clin Oral Implants Res, 2013 Nov;24(11):1273-9.
PMID: 22862429 DOI: 10.1111/j.1600-0501.2012.02566.x

The aim of this study was to evaluate a new method to quantify longitudinal mandibular bone remodeling three-dimensionally by superimposition of cone beam computed tomography images.
Pharmacokinetics of artemisinin-type compounds

Navaratnam V, Mansor SM, Sit NW, Grace J, Li Q, Olliaro P

Clin Pharmacokinet, 2000 Oct;39(4):255-70.
PMID: 11069212

Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.
Fulltext Evaluation of the Pharmacokinetics and Exposure-Response Relationship of Dapagliflozin in Patients without Diabetes and with Chronic Kidney Disease

van der Aart-van der Beek AB, Koomen JV, Dekkers CCJ, Barbour SJ, Boulton DW, Gansevoort RT, et al.

Clin Pharmacokinet, 2021 04;60(4):517-525.
PMID: 33587286 DOI: 10.1007/s40262-020-00956-1

BACKGROUND AND OBJECTIVE: Dapagliflozin, a sodium-glucose co-transporter inhibitor, was originally developed as an oral glucose-lowering drug for the treatment of type 2 diabetes mellitus. Emerging data suggest that cardiovascular and kidney benefits extend to patients without diabetes. Limited pharmacological data are, however, available in patients without diabetes. We aimed to characterise the pharmacokinetic profile of dapagliflozin in patients with chronic kidney disease without type 2 diabetes.
METHODS: Plasma samples were collected in a randomised, placebo-controlled, double-blind, cross-over trial (DIAMOND, NCT03190694, n = 53) that assessed the effects of 10 mg of dapagliflozin in patients with a glomerular filtration rate ≥ 25 mL/min/1.73 m2 and proteinuria > 500 mg/day. Mixed-effects models were used to develop a pharmacokinetic model and to evaluate the association between plasma exposure and response.
RESULTS: Plasma concentrations (n = 430 observations) from 48 patients (mean age 50.8 years, mean glomerular filtration rate 57.9 mL/min/1.73 m2, median proteinuria 1115 mg/24 h) were best described using a two-compartment model with first-order elimination. Apparent clearance and volume of distribution were 11.7 (95% confidence interval 10.7-12.7) L/h and 44.9 (95% confidence interval 39.0-50.9) L, respectively. Median dapagliflozin plasma exposure was 740.9 ng h/mL (2.5th-97.5th percentiles: 434.0-1615.3). Plasma exposure increased with decreasing kidney function. Every 100-ng h/mL increment in dapagliflozin plasma exposure was associated with a decrease in the urinary albumin:creatinine ratio (β = - 2.8%, p = 0.01), glomerular filtration rate (β = - 0.5 mL/min/1.73 m2, p
Fulltext A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution

Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.

Comput Softw Big Sci, 2020;4(1):10.
PMID: 33196702 DOI: 10.1007/s41781-020-00041-z

We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯ .
Fulltext The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

Hudson LN, Newbold T, Contu S, Hill SL, Lysenko I, De Palma A, et al.

Ecol Evol, 2017 Jan;7(1):145-188.
PMID: 28070282 DOI: 10.1002/ece3.2579

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
Robot-assisted Cavectomy Versus Thrombectomy for Level II Inferior Vena Cava Thrombus: Decision-making Scheme and Multi-institutional Analysis

Shi T, Huang Q, Liu K, Du S, Fan Y, Yang L, et al.

Eur Urol, 2020 10;78(4):592-602.
PMID: 32305170 DOI: 10.1016/j.eururo.2020.03.020

BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described.
OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT.
DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019.
SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals.
MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed.
RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed.
CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation.
PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.
Fulltext Induction of Apoptosis in HeLa Cells by a Novel Peptide from Fruiting Bodies of Morchella importuna via the Mitochondrial Apoptotic Pathway

Xiong C, Li P, Luo Q, Phan CW, Li Q, Jin X, et al.

Evid Based Complement Alternat Med, 2021;2021:5563367.
PMID: 34394384 DOI: 10.1155/2021/5563367

Morels (Morchella spp.) are a genus of edible fungi with important economic and medicinal value. In this study, a novel peptide (MIPP) was extracted from the fruiting bodies of Morchella importuna using gel filtration chromatography. Structural analysis showed that the molecular mass of MIPP is 831 Da, and it has a simple amino acid sequence: Ser-Leu-Ser-Leu-Ser-Val-Ala-Arg. To explore the antitumor activity of MIPP, the effect of MIPP on HeLa cell apoptosis and the underlying preventative mechanisms were investigated. Results showed that MIPP reduced the viability of HeLa cells in a concentration-dependent manner. TUNEL analysis and flow cytometric examination showed that MIPP decreased cell proliferation via a mitochondrial-dependent pathway, as manifested by downregulation of Bcl-2/Bax, promotion of the movement of cytochrome C from the mitochondria to the cytoplasm, and triggering of caspase-9 and caspase-3. Therefore, MIPP may be a promising tumor-preventive agent, especially in human cervical cancer.
Fulltext Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

Luk ADW, Lee PP, Mao H, Chan KW, Chen XY, Chen TX, et al.

Front Immunol, 2017;8:808.
PMID: 28747913 DOI: 10.3389/fimmu.2017.00808

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis.
OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID.
METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study.
RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 10(9)/L with over 88% patients below 3 × 10(9)/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis.
CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 10(9)/L.
Fulltext A comparison of 25 complete chloroplast genomes between sister mangrove species Kandelia obovata and Kandelia candel geographically separated by the South China Sea

Xu X, Shen Y, Zhang Y, Li Q, Wang W, Chen L, et al.

Front Plant Sci, 2022;13:1075353.
PMID: 36684775 DOI: 10.3389/fpls.2022.1075353

In 2003, Kandelia obovata was identified as a new mangrove species differentiated from Kandelia candel. However, little is known about their chloroplast (cp) genome differences and their possible ecological significance. In this study, 25 whole cp genomes, with seven samples of K. candel from Malaysia, Thailand, and Bangladesh and 18 samples of K. obovata from China, were sequenced for comparison. The cp genomes of both species encoded 128 genes, namely 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes, but the cp genome size of K. obovata was ~2 kb larger than that of K. candle due to the presence of more and longer repeat sequences. Of these, tandem repeats and simple sequence repeats exhibited great differences. Principal component analysis based on indels, and phylogenetic tree analyses constructed with homologous protein genes from the single-copy genes, as well as 38 homologous pair genes among 13 mangrove species, gave strong support to the separation of the two species within the Kandelia genus. Homologous genes ndhD and atpA showed intraspecific consistency and interspecific differences. Molecular dynamics simulations of their corresponding proteins, NAD(P)H dehydrogenase chain 4 (NDH-D) and ATP synthase subunit alpha (ATP-A), predicted them to be significantly different in the functions of photosynthetic electron transport and ATP generation in the two species. These results suggest that the energy requirement was a pivotal factor in their adaptation to differential environments geographically separated by the South China Sea. Our results also provide clues for future research on their physiological and molecular adaptation mechanisms to light and temperature.

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