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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.
Lauge Hjorth Mikkelsen Frederik Holm Erik Clasen-Linde Pernille Engraff Steffen Heegaard 《Acta veterinaria Scandinavica》2018,60(1):79
Background
Eyelid tumours are frequently found in dogs, most of these being benign. In case of an ulcerating eyelid tumour, malignancy must be considered. We report a unique case of a low-grade peripheral T-cell lymphoma in the eyelid of a 9-year-old English Setter.Case presentation
A 9-year-old Setter presented with a 6-month history of an eyelid ulcer. A malignant eyelid neoplasm was suspected, and the lesion was surgically excised. No other treatment was applied, and 19 months after excision the dog was still well. Histopathology revealed a diffuse lymphocytic infiltrate in the eyelid skin. Ulceration of the epithelium was seen, and the underlying tumour was composed of round and poorly demarcated pleomorphic tumour cells. The cytoplasm was pale and the nuclei heterogeneous. Numerous mitoses were present. The tumour cells stained strongly for CD3. The final diagnosis was a peripheral T-cell lymphoma not otherwise specified (NOS).Conclusions
This is the first described case of a solitary T-cell lymphoma NOS in the haired eyelid skin in a dog. Lymphoma should be considered in case of a persistent eyelid ulcer and a biopsy should be performed. T-cell lymphoma is generally an aggressive disease; however, indolent cases are well known, and as this case shows, complete excision of a solitary T-cell lymphoma can be curable. Canine cutaneous epitheliotropic T-cell lymphoma is an important differential diagnosis, which must be recognized as the prognosis is very poor and systemic treatment is mandatory. The sub-classification of canine lymphoma is not complete, and further studies are needed to identify lymphoma subgroups and provide treatment guidelines.3.
Kyle Devins Stephen J. Schuster Gabriel C. Caponetti Agata M. Bogusz 《Diagnostic pathology》2018,13(1):92
Background
Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), is a rare aggressive subtype of non-Hodgkin lymphoma characterized by angioinvasion, angiodestruction, necrosis and strong association with Epstein-Barr virus (EBV). ENKTCL-NT occurs worldwide and is more prevalent in Asian and the Native American populations of Mexico, Central and South America. It represents approximately 10% of all peripheral T-cell lymphomas worldwide. The aim of this report is to present a rare case of ENKTCL-NT with an unusually indolent clinical course and low-grade histopathologic features.Case presentation
A 71-year-old Asian woman with a long-standing history of seasonal rhinosinusitis presented with persistent nasal congestion, cough, and fever unresponsive to antihistamines and antibiotics. Histopathological evaluation of a polypoid nasal mass revealed an atypical infiltrate with predominantly small lymphoid cells that were CD2+, surface CD3-, cytoplasmic CD3+, CD5(dim)+, CD7(dim)+, cytotoxic markers (granzyme B and perforin)+, EBER+ and CD56-. The Ki-67 proliferative index was very low (<?1%). T-cell receptor gamma gene rearrangement studies were positive for a monoclonal rearrangement, and sequencing studies identified a novel KIT mutation (p. K167 M, c. 500 A?>?T). A diagnosis of low-grade ENKTCL-NT was rendered.Conclusions
Our case of ENKTCL-NT is unusual due to (1) an indolent clinical course (2) low-grade histopathologic features including a low proliferative index (3) lack of CD56 expression and (4) a novel KIT mutation. This case raises awareness of the existence of a subset of cases of ENKTCL-NT that can potentially be misdiagnosed as a reactive process, particularly in patients with recurrent chronic rhinosinusitis.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.
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.6.
7.
Pengcheng Zhou Ning Zhou Li Shao Jianzhou Li Sidi Liu Xiujuan Meng Juping Duan Xinrui Xiong Xun Huang Yuhua Chen Xuegong Fan Yixiang Zheng Shujuan Ma Chunhui Li Anhua Wu 《Metabolomics : Official journal of the Metabolomic Society》2018,14(8):102
Introduction
The fecal metabolome of Clostridium difficile (CD) infection is far from being understood, particularly its non-volatile organic compounds. The drawbacks of current tests used to diagnose CD infection hinder their application.Objective
The aims of this study were to find new characteristic fecal metabolites of CD infection and develop a metabolomics model for the diagnosis of CD infection.Methods
Ultra-performance liquid chromatography-mass spectrometry (UPLC–MS) was used to characterize the fecal metabolome of CD positive and negative diarrhea and healthy control stool samples.Results
Diarrhea and healthy control samples showed distinct clusters in the principal components analysis score plot, and CD positive group and CD negative group demonstrated clearer separation in a partial least squares discriminate analysis model. The relative abundance of sphingosine, chenodeoxycholic acid, phenylalanine, lysophosphatidylcholine (C16:0), and propylene glycol stearate was higher, and the relative abundance of fatty amide, glycochenodeoxycholic acid, tyrosine, linoleyl carnitine, and sphingomyelin was lower in CD positive diarrhea groups, than in the CD negative group. A linear discriminant analysis model based on capsiamide, dihydrosphingosine, and glycochenodeoxycholic acid was further constructed to identify CD infection in diarrhea. The leave-one-out cross-validation accuracy and area under receiver operating characteristic curve for the training set/external validation set were 90.00/78.57%, and 0.900/0.7917 respectively.Conclusions
Compared with other hospital-onset diarrhea, CD diarrhea has distinct fecal metabolome characteristics. Our UPLC–MS metabolomics model might be useful tool for diagnosing CD diarrhea.8.
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.9.
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.10.
Background
Psoriasis is one of the most common, immune-mediated, chronic inflammatory skin diseases. Proinflammatory cytokines play an important pathogenetic role at a local level.Objective
To assess whether the proinflammatory cytokines IL-1β, IL-6, IL-17, IL-22 and TNF-α are released systemically during psoriasis.Methods
Peripheral blood mononuclear cells (PBMCs) were isolated from 30 patients with psoriasis and 30 healthy volunteers. Cytokine production was assessed in supernatants using an enzyme immunoassay after stimulation of PBMCs with microbial stimuli. In addition, flow cytometry was used to determine the subsets of monocytes involved and the intracellular TNF-α production in monocytes.Results
IL-17 levels were significantly higher in the supernatants of PBMCs from psoriatic patients after stimulation with phytohemagglutinin. TNF-α production was also significantly higher in cells from psoriatic patients after stimulation with all stimuli, as compared with health volunteers. Similar changes were not found for the other cytokines. A statistically significant difference was observed between patients and controls for inflammatory CD14+/CD16+ monocytes (p<0.0001) and patrolling CD14-/CD16+ monocytes.Conclusion
Hyper-production of TNF-α is documented in psoriasis. These results support the concept that there is a systemic, proinflammatory component in psoriasis.11.
Background
Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alpha L beta 2) is required for many cellular adhesive interactions during the immune response.Results
The Capra hircus CD11a-encoding cDNA was sequenced and compared with its human, murine, rat, bovine and ovine counterparts. Despite some focal differences, it shares all the main characteristics of its known mammalian homologues.Conclusion
Therefore, along with the caprine CD18-encoding cDNA, which has been available for a few months, the sequence data revealed here will allow the Capra hircus LFA-1 expression in vitro as a tool to explore the specificities of inflammation in the caprine species.12.
Narasimhulu?Simma Tanima?Bose Sascha?Kahlfu? Judith?Mankiewicz Theresa?Lowinus Fred?Lühder Thomas?Schüler Burkhart?Schraven Martin?Heine Ursula?Bommhardt
Background
B cells are important effectors and regulators of adaptive and innate immune responses, inflammation and autoimmunity, for instance in anti-NMDA-receptor (NMDAR) encephalitis. Thus, pharmacological modulation of B-cell function could be an effective regimen in therapeutic strategies. Since the non-competitive NMDAR antagonist memantine is clinically applied to treat advanced Alzheimer`s disease and ketamine is supposed to improve the course of resistant depression, it is important to know how these drugs affect B-cell function.Results
Non-competitive NMDAR antagonists impaired B-cell receptor (BCR)- and lipopolysaccharide (LPS)-induced B-cell proliferation, reduced B-cell migration towards the chemokines SDF-1α and CCL21 and downregulated IgM and IgG secretion. Mechanistically, these effects were mediated through a blockade of Kv1.3 and KCa3.1 potassium channels and resulted in an attenuated Ca2+-flux and activation of Erk1/2, Akt and NFATc1. Interestingly, NMDAR antagonist treatment increased the frequency of IL-10 producing B cells after BCR/CD40 stimulation.Conclusions
Non-competitive NMDAR antagonists attenuate BCR and Toll-like receptor 4 (TLR4) B-cell signaling and effector function and can foster IL-10 production. Consequently, NMDAR antagonists may be useful to target B cells in autoimmune diseases or pathological systemic inflammation. The drugs’ additional side effects on B cells should be considered in treatments of neuronal disorders with NMDAR antagonists.13.
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.14.
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
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.15.
Sonia Liggi Christine Hinz Zoe Hall Maria Laura Santoru Simone Poddighe John Fjeldsted Luigi Atzori Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):52
Introduction
Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.Objectives
Merge in the same platform the steps required for metabolomics data processing.Methods
KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.Results
The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.Conclusion
KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.16.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.17.
Nadine Strehmel David Strunk Veronika Strehmel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):135
Introduction
Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.Objectives
To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.Methods
The extracted compounds were analyzed by LC/MS and GC/MS.Results
The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.Conclusion
From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.18.
Yun Yang Rui Guo Qi Chen Youxun Liu Pengfei Zhang Ziheng Zhang Xi Chen Tianyun Wang 《Biotechnology letters》2018,40(5):789-795
Objective
To promote targeting specificity of anti-CD47 agents, we have constructed a novel bispecific antibody fusion protein against EGFR and CD47, which may minimize the “off-target” effects caused by CD47 expression on red blood cells.Results
The novel bispecific antibody fusion protein, denoted as Bi-SP could simultaneously bind to EGFR and CD47 and exhibited potent phagocytosis-stimulation effects in vitro. Bi-SP treatment with a low dose more effectively inhibited tumor growth than either EGFR-targeting antibody, Pan or the SIRPα variant-Fc (SIRPαV-Fc) in the A431 xenograft tumor model. In addition, the treatment with Bi-SP produced less red blood cell (RBC) losses than the SIRPαV-Fc treatment, suggesting its potential use for minimizing RBC toxicity in therapy.Conclusions
Bi-SP with improved therapeutic index has the potential to treat CD47+ and EGFR+ cancers in clinics.19.
Thijs Welle Anna T. Hoekstra Ineke A. J. J. M. Daemen Celia R. Berkers Matheus O. Costa 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):83
Introduction
Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.Objective
The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.Methods
Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.Results
Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.Conclusions
The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.20.
Elizabeth A. Scoville Margaret M. Allaman Caroline T. Brown Amy K. Motley Sara N. Horst Christopher S. Williams Tatsuki Koyama Zhiguo Zhao Dawn W. Adams Dawn B. Beaulieu David A. Schwartz Keith T. Wilson 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):17