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1.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.2.
Background
An influenza H3N2 epidemic occurred throughout Southern China in 2012.Methods
We analyzed the hemagglutinin (HA) and neuraminidase (NA) genes of influenza H3N2 strains isolated between 2011–2012 from Guangdong. Mutation sites, evolutionary selection, antigenic sites, and N-glycosylation within these strains were analyzed.Results
The 2011–2012 Guangdong strains contained the HA-A214S, HA-V239I, HA-N328S, NA-L81P, and NA-D93G mutations, similar to those seen in the A/ Perth/16/2009 influenza strain. The HA-NSS061–063 and NNS160–162 glycosylation sites were prevalent among the 2011–2012 Guangdong strains but the NA-NRS402–404 site was deleted. Antigenically, there was a four-fold difference between A/Perth/16/2009 -like strains and the 2011–2012 Guangdong strains.Conclusion
Antigenic drift of the H3N2 subtype contributed to the occurrence of the Southern China influenza epidemic of 2012.3.
Swee Ling Lim Zhunan Jia Yonghai Lu Hui Zhang Cheng Teng Ng Boon Huat Bay Han Ming Shen Choon Nam Ong 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):118
Introduction
Histologically lung cancer is classified into four major types: adenocarcinoma (Ad), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and small cell lung cancer (SCLC). Presently, our understanding of cellular metabolism among them is still not clear.Objectives
The goal of this study was to assess the cellular metabolic profiles across these four types of lung cancer using an untargeted metabolomics approach.Methods
Six lung cancer cell lines, viz., Ad (A549 and HCC827), SqCC (NCl-H226 and NCl-H520), LCC (NCl-H460), and SCLC (NCl-H526), were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry, with normal human small airway epithelial cells (SAEC) as the control group. The principal component analysis (PCA) was performed to identify the metabolic signatures that had characteristic alterations in each histological type. Further, a metabolite set enrichment analysis was performed for pathway analysis.Results
Compared to the SAEC, 31, 27, 34, 34, 32, and 39 differential metabolites mainly in relation to nucleotides, amino acid, and fatty acid metabolism were identified in A549, HCC827, NCl-H226, NCl-H520, NCl-H460, and NCl-H526 cells, respectively. The metabolic signatures allowed the six cancerous cell lines to be clearly separated in a PCA score plot.Conclusion
The metabolic signatures are unique to each histological type, and appeared to be related to their cell-of-origin and mutation status. The changes are useful for assessing the metabolic characteristics of lung cancer, and offer potential for the establishment of novel diagnostic tools for different origin and oncogenic mutation of lung cancer.4.
Objectives
To study the binding of pranlukast to hRKIP and its regulatory role in the Raf1/MEK/ERK signal pathway.Results
NMR and fluorescence experiments demonstrated hRKIP could bind pranlukast with a binding constant of 1016 mM?1. Residues (Y81, S109 and Y181) on the conserved ligand-binding pocket of hRKIP played a crucial role in binding pranlukast, and their mutations reduced the binding affinity more than 85 %. Furthermore, 25 μM pranlukast could up-regulate the ERK phosphorylation by about 17 %.Conclusion
Pranlukast may be used as a potential drug precursor for treating hRKIP involved diseases.5.
Marieke?Pingen Ramin?Sarrami-Forooshani Annemarie?MJ?Wensing Petra?van Ham Agata?Drewniak Charles?AB?Boucher Teunis?BH?Geijtenbeek
Background
Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.Results
In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5+ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.Conclusions
Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.6.
Objective
To re-engineer the active site of proteins for non-natural substrates using a position-based prediction method (PBPM).Results
The approach has been applied to re-engineer the E. coli glutamate dehydrogenase to alter its substrate from glutamate to homoserine for a de novo 1,3-propanediol biosynthetic pathway. After identification of key residues that determine the substrate specificity, residue K92 was selected as a candidate site for mutation. Among the three mutations (K92V, K92C, and K92M) suggested by PBPM, the specific activity of the best mutant (K92 V) was increased from 171 ± 35 to 1328 ± 71 μU mg?1.Conclusion
The PBPM approach has a high efficiency for re-engineering the substrate specificity of natural enzymes for new substrates.7.
Sayaka Okuzono Masataka Ishimura Shunsuke Kanno Motoshi Sonoda Noriyuki Kaku Yoshitomo Motomura Hisanori Nishio Utako Oba Masuo Hanada Jun-ichi Fukushi Michiyo Urata Dongchon Kang Hidetoshi Takada Shouichi Ohga 《Annals of clinical microbiology and antimicrobials》2018,17(1):31
Background
Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-purpura fulminans with literature review of the disease.Case presentation
A 3-year-old boy showed limping, lethargy and acral gangrene within 24 h. A diagnosis of S. pyogenes-purpura fulminans was made for bacterial isolation from throat and peripheral blood. Intensive therapy led to a survival with amputation of the left distal metatarsal bone, and normal development. The isolated M12 carried no mutation of csrS/R or rgg. Thrombophilia or immunodeficiency was excluded.Discussion
Twelve-reported cases (9 pediatric and 3 elderly) of S. pyogenes-purpura fulminans started with shock and coagulopathy. Five patients age <?8 years had no underlying disease and survived. One youngest and two immunocompromised patients died.Conclusion
Streptococcus pyogenes-acute infectious purpura fulminans is a distinctive rare form of aggressive GAS infections.8.
Li Li Chang-Sheng Wu Guan-Mei Hou Ming-Zhe Dong Zhen-Bo Wang Yi Hou Heide Schatten Gui-Rong Zhang Qing-Yuan Sun 《Reproductive biology and endocrinology : RB&E》2018,16(1):110
Background
Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.Methods
We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques.Results
T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations.Conclusions
T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring.9.
Yan Xu Rui Bi Yaoxing Xiao Xiaoyu Tu Ming Li Anqi Li Ling Shan Shuling Zhou Wentao Yang 《Diagnostic pathology》2017,12(1):87
Background
Mounting evidence has shown that KRAS and BRAF are somatic mutations associated with low grade serous carcinoma (LGSC) of the ovary. However, the frequency of KRAS or BRAF mutation was variable in literatures, with a frequency of 16–54% for KRAS mutation and 2–33% for BRAF mutation. Meanwhile, the prognostic significance of KRAS or BRAF mutation remains controversial.Methods
Codons 12 and 13 of exon 2 of KRAS gene and exon 15 of BRAF gene were analyzed using direct Sanger sequencing in 32 cases of LGSC of the ovary. The associations between KRAS or BRAF mutation and clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) were statistically analyzed.Results
KRAS mutation was observed in nine cases (9/32, 28%) and BRAF mutation in two cases (2/32, 6%). KRAS and BRAF mutations were mutually exclusive. Neither KRAS nor BRAF mutation was statistically associated with OS or DFS in our cohort, although there was a favorable prognostic trend in patients with KRAS G12D mutation than those with KRAS G12 V mutation or wild-type KRAS for OS.Conclusions
The present study indicated a low frequency of BRAF or KRAS mutation in Chinese patients with LGSC of the ovary, and neither KRAS nor BRAF mutation is a prognostic factor.10.
Background
The influenza matrix protein (M1) layer under the viral membrane plays multiple roles in virus assembly and infection. N-domain and C-domain are connected by a loop region, which consists of conserved RQMV motif.Methods
The function of the highly conserve RQMV motif in the influenza virus life cycle was investigated by site-directed mutagenesis and by rescuing mutant viruses by reverse genetics. Co-localization of M1 with nucleoprotein (NP), clustered mitochondria homolog protein (CLUH), chromosome region maintenance 1 protein (CRM1), or plasma membrane were studied by confocal microscopy.Results
Mutant viruses containing an alanine substitution of R163, Q164 and V166 result in the production of the virus indistinguishable from the wild type phenotype. Single M165A substitution was lethal for rescuing infection virus and had a striking effect on the distribution of M1 and NP proteins. We have observed statistically significant reduction in distribution of both M165A (p?0,05) and NP (p?0,001) proteins to the nucleus in the cells transfected with the reverse –genetic system with mutated M1. M165A protein was co-localized with CLUH protein in the cytoplasm and around the nucleus but transport of M165-CLUH complex through the nuclear membrane was restricted.Conclusions
Our finding suggest that methionine 165 is essential for virus replication and RQMV motif is involved in the nuclear import of viral proteins.11.
Seyed Mehdi Sajjadi Abbas Khosravi Jalil Pakravesh Zahra-soheila Soheili Shahram Samiei Saeed Mohammadi Mohammad Ali Jalali far 《生物学前沿》2016,11(6):471-475
BACKGROUND
Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.OBJECTIVE
The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.METHODS
A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.RESULTS
Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.CONCLUSION
These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.12.
Background
Nitrous oxide (N2O), a long-standing anesthetic, is also neurotoxic by interfering with the bioavailability of vitamin B12 if abused. A few case studies have reported the neurological and psychiatric complications of N2O.Case presentation
Here, we reported a patient of N2O induced subacute combined degeneration (SCD) with longitudinally extensive myelopathy with inverted V-sign exhibiting progressive limb paresthesia and unsteady gait.Conclusions
This case raises the awareness of an important mechanism of neural toxicity of N2O, and clinical physicians should be well recognized this in the field of substance-related disorders.13.
Maé Guinet Bernard Nicolardot Cécile Revellin Vincent Durey Georg Carlsson Anne-Sophie Voisin 《Plant and Soil》2018,432(1-2):207-227
Aims
A better understanding of how plant growth, N nutrition and symbiotic nitrogen fixation (SNF) are influenced by soil inorganic N availability, for a wide range of legume species, is crucial to optimise legume productivity, N2 fixation, while limiting environmental risks such as N leaching.Methods
A comparative analysis was performed for ten legume crops, grown in a field experiment and supplied with four N fertiliser rates. Dry matter, N concentration and SNF were measured. In parallel, root elongation rates were studied in a greenhouse experiment.Results
For most species, N fertilisation had little effect on plant growth and N accumulation. SNF was reduced by soil inorganic N available at sowing but with large differences in the magnitude of the response among species. The response varied according to plant N requirements for growth and plant ability to retrieve inorganic N. Accordingly, root lateral expansion rate measured in RhizoTubes was highly correlated with plant ability to retrieve inorganic N measured in the field experiment.Conclusion
Combining SNF response to soil inorganic N, shoot N and plant ability to retrieve inorganic N, allowed a robust evaluation of differential response to soil inorganic N among a wide range of legume species.14.
15.
Background
End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed.Results
A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) – IgG serostatus matched healthy individuals (31.4 %, P?<?0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8+ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing.Conclusions
ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity.16.
Timothy Sakellaridis Stavros Mathioulakis Christos Antiochos 《International Seminars in Surgical Oncology : ISSO》2005,2(1):19
Background
Synchronous early primary cancers are rare and in addition synchronous adenocarcinoma of both rectum and gallbladder is extremely rare.Case report
We report an unusual case of synchronous early primary adenocarcinoma of rectum and gallbladder. The patient was a 72-year-old woman with complaints of bloody stools and constipation. An endoscopy revealed adenocarcinoma of the lower rectum. A through preoperative investigation showed also cholelithiasis. The patient underwent abdominoperineal resection and cholecystectomy. The histopathological diagnosis was well to middle differentiate adenocarcinoma of the gallbladder (T2, N0, M0; stage II) and middle differentiate adenocarcinoma of the rectum (T2, N0, M0; stage II).Conclusion
For the cases of extracolonic primary cancer associated with colorectal primary carcinoma, Warren and Gates' diagnostic criteria are used. All patients with colorectal carcinoma, should undergo a throughout preoperative examination to exclude the possibility of synchronous early primary cancers.17.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.18.
Background
Long-term exposure to drugs of abuse causes an upregulation of the cAMP-signaling pathway in the nucleus accumbens and other forebrain regions, this common neuroadaptation is thought to underlie aspects of drug tolerance and dependence. Phosphodiesterase 4 (PDE4) is an enzyme that the selective hydrolyzes intracellular cAMP. It is expressed in several brain regions that regulate the reinforcing effects of drugs of abuse.Objective
Here, we review the current knowledge about central nervous system (CNS) distribution of PDE4 isoforms and the effects of systemic and brain-region specific inhibition of PDE4 on behavioral models of drug addiction.Methods
A systematic literature search was performed using the Pubmed.Results
Using behavioral sensitization, conditioned place preference and drug self-administration as behavioral models, a large number of studies have shown that local or systemic administration of PDE4 inhibitors reduce drug intake and/or drug seeking for psychostimulants, alcohol, and opioids in rats or mice.Conclusions
Preclinical studies suggest that PDE4 could be a therapeutic target for several classes of substance use disorder. We conclude by identifying opportunities for the development of subtype-selective PDE4 inhibitors that may reduce addiction liability and minimize the side effects that limit the clinical potential of non-selective PDE4 inhibitors. Several PDE4 inhibitors have been clinically approved for other diseases. There is a promising possibility to repurpose these PDE4 inhibitors for the treatment of drug addiction as they are safe and well-tolerated in patients.19.