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1.
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.2.
Background
CD90 (Thy-1) is a small glycoprotein that is particularly abundant on the surface of mouse thymocytes and peripheral T cells, and is often used as a marker in adoptive transfer experiments to distinguish donor and recipient T cells with different CD90 subtypes. We have performed adoptive transfer experiments with T cell receptor transgenic (TCR Tg) mice to study the impaired CD8 T cell response with aging.Findings
After stimulation with a CD8 T cell epitope, HA518-524, the response of TCR Tg CD8 T cells from aged mice was decreased compared to the response of TCR Tg T cells from young mice. CD90 expression was also substantially decreased on the TCR Tg CD8 T cells of aged mice. However, the responses of CD90hi and CD90low CD8 T cells of the aged mice were similar in both early activation and proliferation, demonstrating that the impaired Tg T cell response with aging is not associated with the altered CD90 expression on CD8 T cells.Conclusions
The impaired Tg CD8 T cell response in aged mice is not due to age-associated changes in CD90 expression on Tg CD8 T cells.3.
Hong-Bin?Cheng Rong-Yi?Chen Jing-Ping?Wu Li?Chen Yan-Hua?Liang Hai-Feng?Pan Zi-Feng?Pan Qing-Hua?Zhang Qing?Li Tian-Xi?Du Yong-Mei?Lv
Background
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation.Methods
Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs.Results
Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R2 = 0.5907, p < 0.001) and TGFβ concentration (R2 = 0.5641, p < 0.001) in SLE patients. Different concentrations of C4 had no effect on T cells differentiation. Co-incubated T cells with DCs and C4 for 7 days, the Treg percentage and TGF-β concentration were significantly elevated. In addition, pre-treated DCs (from healthy subjects or SLE patients) with C4 and then co-incubated with T cells, the increases of Treg percentage and TGF-β concentration were also observed.Conclusion
C4 takes part in T cells differentiation to Treg cells via DCs.4.
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.5.
Peilin Han Qingbo Cui Shulong Yang Hao Wang Peng Gao Zhaozhu Li 《Biotechnology letters》2017,39(5):711-719
Objectives
To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) on the proliferation and differentiation of tendon-derived stem cells (TDSC).Results
TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-β1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased. During these processes, Smad2/3 and Smad1/5/8 were highly phosphorylated, meaning that the TGF-β and BMP signaling pathways were highly activated. Further study revealed that the expression of Inhibitor-Smad appeared to be negatively correlated to the proliferation and differentiation of TDSC.Conclusions
Combining the use of TNF-α and TGF-β1 could improve the proliferation and differentiation of TDSC in vitro, and the expression of I-Smad is negatively correlated with TDSC proliferation and differentiation.6.
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.7.
Background
The heme-protein interactions are essential for various biological processes such as electron transfer, catalysis, signal transduction and the control of gene expression. The knowledge of heme binding residues can provide crucial clues to understand these activities and aid in functional annotation, however, insufficient work has been done on the research of heme binding residues from protein sequence information.Methods
We propose a sequence-based approach for accurate prediction of heme binding residues by a novel integrative sequence profile coupling position specific scoring matrices with heme specific physicochemical properties. In order to select the informative physicochemical properties, we design an intuitive feature selection scheme by combining a greedy strategy with correlation analysis.Results
Our integrative sequence profile approach for prediction of heme binding residues outperforms the conventional methods using amino acid and evolutionary information on the 5-fold cross validation and the independent tests.Conclusions
The novel feature of an integrative sequence profile achieves good performance using a reduced set of feature vector elements.8.
Objective
To investigate the relationship between the response to influenza vaccination and the ability to produce proinflamatory cytokines in elderly subjects.Methods
Whole blood samples from 25 elderly subjects collected before influenza vaccination were stimulated with the influenza vaccine in order to evaluate the secretion of five specific cytokines: TNFα, IFNα, IFNγ, IL2 and IL10. The results were correlated with the increased HAI antibody titres two weeks after vaccination.Results
Only 30% of elderly individuals seroconverted after vaccination. Although 50 to 70% of the cohort did not produce TNFα, IFNα, IFNγ, IL2 or IL10, all of the individuals who seroconverted were able to produceTNFα. Furthermore production of IFNγ, with or without production of IFNα/β, was not associated with a better response to the vaccine.Conclusion
Production of TNFα appears to be primordial for an efficient vaccine response, and may provide a predictive marker for the humoral response to vaccination. It may also provide the basis for evaluating agents designed to rescue TNFα-producing cells. This study emphasises a need to rescue TNF-producing cell function.9.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.10.
Background
Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1β production by macrophages from aged mice. We examined the production of pro-IL-1β and its conversion into IL-1β as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6–8 weeks) and aged (18–24 months) C57BL/6 mice.Findings
Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1β after TLR4 stimulation with LPS. However upon activation of the NLRP3 inflammasome with ATP, macrophages from young and aged mice were able to efficiently convert and secrete intracellular pro-cytokines as functional cytokines.Conclusions
Lower levels of IL-1β production are a result of slower and lower overall production of pro-IL-1β in macrophages from aged mice.11.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.12.
Wojciech Bobela Sameer Nazeeruddin Graham Knott Patrick Aebischer Bernard L. Schneider 《Molecular neurodegeneration》2017,12(1):80
Background
Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson’s disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration.Methods
Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo.Results
Both AMPKα1 and α2 subunits have neuroprotective effects against human α-synuclein toxicity in nigral dopaminergic neurons. Remarkably, a modified variant of AMPKα1 (T172Dα1) with constitutive low activity most effectively prevents the loss of dopamine neurons, as well as the motor impairments caused by α-synuclein accumulation. In the striatum, T172Dα1 decreases the formation of dystrophic axons, which contain aggregated α-synuclein. In primary cortical neurons, overexpression of human α-synuclein perturbs mitochondrial and lysosomal activities. Co-expressing AMPKα with α-synuclein induces compensatory changes, which limit the accumulation of lysosomal material and increase the mitochondrial mass.Conclusions
Together, these results indicate that modulating AMPK activity can mitigate α-synuclein toxicity in nigral dopamine neurons, which may have implications for the development of neuroprotective treatments against PD.13.
Guifang Zhong Fangfang Wang Jianhong Sun Jianbin Ye Duobin Mao Ke Ma Xuepeng Yang 《Biotechnology letters》2017,39(7):1019-1024
Objectives
To investigate the final product of the bioconversion of lutein by a novel lutein-degrading bacterium, Enterobacter hormaechei A20, and the kinetics of the process.Results
A new product, 8-methyl-α-ionone, was resolved by GC–MS. The compound was further identified by NMR. A conversion yield of 90% was achieved by E. hormaechei in 36 h with 10 g lutein l?1.Conclusions
This is the first report of the bioconversion of lutein to form 8-methyl-α-ionone. A degradation pathway is proposed.14.
Zhiqiang?Xu Na?Xiao Yali?Chen Huang?Huang Charles?Marshall Junying?Gao Zhiyou?Cai Ting?Wu Gang?Hu Ming?Xiao
Background
Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent.Results
Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples.Conclusions
These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD.15.
P.-J. Royer K. Henrio M. Pain J. Loy A. Roux A. Tissot P. Lacoste C. Pison S. Brouard the COLT consortium 《Respiratory research》2017,18(1):208
Background
Airway epithelial cells (AEC) act as the first line of defence in case of lung infections. They constitute a physical barrier against pathogens and they participate in the initiation of the immune response. Yet, the modalities of pathogen recognition by AEC and the consequences on the epithelial barrier remain poorly documented.Method
We investigated the response of primary human AEC to viral (polyinosinic-polycytidylic acid, poly(I:C)) and bacterial (lipopolysaccharide, LPS) stimulations in combination with the lung remodeling factor Transforming Growth Factor-β (TGF-β).Results
We showed a strong production of pro-inflammatory cytokines (Interleukin (IL)-6, Tumor Necrosis Factor α, TNFα) or chemokines (CCL2, CCL3, CCL4, CXCL10, CXCL11) by AEC stimulated with poly(I:C). Cytokine and chemokine production, except CXCL10, was Toll Like Receptor (TLR)-3 dependent and although they express TLR4, we found no cytokine production after LPS stimulation. Poly(I:C), but not LPS, synergised with TGF-β for the production of matrix metalloproteinase-9 (MMP-9) and fibronectin. Mechanistic analyses suggest the secretion of Wnt ligands by AEC along with a degradation of the cellular junctions after poly(I:C) exposure, leading to the release of β-catenin from the cell membrane and stimulation of the Wnt/β-catenin pathway.Conclusion
Our results highlight the cross talk between TGF-β and TLR signaling in bronchial epithelium and its impact on the remodeling process.16.
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.17.
Latifu?A?Sanni Catherine?EM?Allsopp Lieke?Reubsaet Ambaliou?Sanni Chris?Newbold Virander?S?Chauhan Jean?Langhorne
Background
Plasmodium falciparum erythrocyte membrane protein-1, a variant antigen of the malaria parasite, is potentially a target for the immune response. It would be important to determine whether there are CD4 T cells that recognise conserved regions. However, within the relatively conserved region, there is variation. It is not possible to test T cell responses from small field samples with all possible peptides.Methods
We have aligned sequences that are relatively conserved between several PfEMP1 molecules, and chosen a representative sequence similar to most of the PfEMP1 variants. Using these peptides as pools representing CIDRα, CIDRβ and DBLβ-δ domains, DBLα domain, and EXON 2 domain of PfEMP1, we measured the CD4 T cell responses of malaria-exposed donors from Benin, West Africa by a FACS based assay.Results
All the three peptide pools elicited a CD4 T cell response in a proportion of malaria-exposed and non-exposed donors. CD4 T cell proliferation occurs at a relatively higher magnitude to peptide pools from the DBLα and EXON 2 in the malaria-exposed donors living in Benin than in the UK malaria-unexposed donors.Conclusions
These findings suggest that an immunological recall response to conserved peptides of a variant antigen can be measured. Further testing of individual peptides in a positive pool will allow us to determine those conserved sequences recognised by many individuals. These types of assays may provide information on conserved peptides of PfEMP1 which could be useful for stimulating T cells to provide help to P. falciparum specific B cells.18.
Jamie V. de Seymour Stephanie Tu Xiaoling He Hua Zhang Ting-Li Han Philip N. Baker Karolina Sulek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):79
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.Objective
Investigate the maternal hair metabolome for predictive biomarkers of ICP.Methods
The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.Results
Of 105 metabolites detected in hair, none were significantly associated with ICP.Conclusion
Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.19.
Kai Yang Fan Zhang Peng Han Zhuo-zhong Wang Kui Deng Yuan-yuan Zhang Wei-wei Zhao Wei Song Yu-qing Cai Kang Li Bin-bin Cui Zheng-Jiang Zhu 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):110
Introduction
Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT).Objectives
An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes.Methods
In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n?=?30) and response (n?=?27) patients to NACT were studied using UHPLC–quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods.Results
The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199).Conclusion
These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.20.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35