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271.
Valentina Ferrari Alison Tarke Hannah Fields Luca Ferrari Trevor Conley Franco Ferrari Zeynep Koşaloğlu-Yalçın Alessandro Sette Bjoern Peters Colin L. McCarthy Asad Bashey Dimitrios Tzachanis Edward D. Ball Tiffany N. Tanaka Rafael Bejar Thomas A. Lane Antonella Vitiello 《Cytotherapy》2021,23(4):320-328
Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34+) and normal (CD3+) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4+ response and 11 (34%) induced a CD8+ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients. 相似文献
272.
Júlia R. de Rezende Thomas B. P. Oldenburg Tetyana Korin William D. L. Richardson Milovan Fustic Carolyn M. Aitken Bernard F. J. Bowler Angela Sherry Alexander Grigoryan Gerrit Voordouw Stephen R. Larter Ian M. Head Casey R. J. Hubert 《Environmental microbiology》2020,22(8):3049-3065
Most of the oil in low temperature, non-uplifted reservoirs is biodegraded due to millions of years of microbial activity, including via methanogenesis from crude oil. To evaluate stimulating additional methanogenesis in already heavily biodegraded oil reservoirs, oil sands samples were amended with nutrients and electron acceptors, but oil sands bitumen was the only organic substrate. Methane production was monitored for over 3000 days. Methanogenesis was observed in duplicate microcosms that were unamended, amended with sulfate or that were initially oxic, however methanogenesis was not observed in nitrate-amended controls. The highest rate of methane production was 0.15 μmol CH4 g−1 oil d−1, orders of magnitude lower than other reports of methanogenesis from lighter crude oils. Methanogenic Archaea and several potential syntrophic bacterial partners were detected following the incubations. GC–MS and FTICR–MS revealed no significant bitumen alteration for any specific compound or compound class, suggesting that the very slow methanogenesis observed was coupled to bitumen biodegradation in an unspecific manner. After 3000 days, methanogenic communities were amended with benzoate resulting in methanogenesis rates that were 110-fold greater. This suggests that oil-to-methane conversion is limited by the recalcitrant nature of oil sands bitumen, not the microbial communities resident in heavy oil reservoirs. 相似文献
273.
Ian Towle Joel D. Irish Kris H. Sabbi Carolina Loch 《American journal of primatology》2022,84(1):e23349
Dental caries has been reported in a variety of primates, although it is still considered rare in wild populations. In this study, 11 catarrhine primate taxa (n = 339 individuals; 7946 teeth) were studied for the presence of caries. A differential diagnosis of lesions in interproximal regions of anterior teeth was undertaken, since they had been previously described as both carious and non-carious in origin. Each permanent tooth was examined macroscopically, with severity and position of lesions recorded. Two specimens were examined further, using micro-CT scans to assess demineralization. Differential diagnosis confirmed the cariogenic nature of interproximal cavities on anterior teeth (ICATs). Overall results show 3.3% of all teeth (i.e., anterior and posterior teeth combined) were carious (n = 262), with prevalence varying among species from 0% to >7% of teeth affected. Those with the highest prevalence of ICATs include Pan troglodytes verus (9.8% of anterior teeth), Gorilla gorilla gorilla (2.6%), Cercopithecus denti (22.4%), Presbytis femoralis (19.5%), and Cercopithecus mitis (18.3%). ICATs make up 87.9% of carious lesions on anterior teeth. These results likely reflect dietary and food processing differences among species, but also between the sexes (e.g., 9.3% of all female P. troglodytes verus teeth were carious vs. 1.8% in males). Processing cariogenic fruits and seeds with the anterior dentition (e.g., wadging) likely contributes to ICAT formation. Further research is needed in living primate populations to ascertain behavioral/dietary influences on caries occurrence. Given the presence of ICATs in frugivorous primates, their diagnosis in archaeological and paleontological specimens may shed light on diet and food processing behaviors in fossil primates. 相似文献
274.
Sotiris Zartilas Nick Hadjiliadis Nikolaos Kourkoumelis Maciej Kubicki Ian S. Butler Jan Balzarini 《Inorganica chimica acta》2009,362(3):1003-121
Silver(I) halides react with tri(p-tolyl)phosphine (tptp, C21H21P) in MeOH/MeCN solutions in 1:1 or 1:3 molar ratios to give complexes of formulae {[AgCl(tptp)]4} (1) or [AgX(tptp)3] (X = Cl (2), Br (3), I (4)), respectively. The complexes were characterized by elemental analyses, and FT-IR far-IR, FT-Raman, TG and 1H, 13C, 31P NMR spectroscopic techniques. Crystal structures of complexes 2-4 were determined by X-ray diffraction at room temperature (rt). The crystal structure of 1 and 4 was also determined at 100(1) and 140(2) K (lt), respectively. In complex 1 four μ3-Cl ions are bonded with four Ag(I) ions forming a cubane while the coordination sphere of silver(I) ions is completed by one P atom from a terminal tri(p-tolyl)phosphine ligand. In complexes 2-3 one terminal halogen and three P atoms from phosphine ligands form a tetrahedral arrangement around the metal ion. Complexes 1-4 were tested for in vitro cytostatic activity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, polycyclic aromatic hydrocarbons (PAH, benzo[a]pyrene) carcinogenesis and against murine leukemia (L1210) and human T-lymphocyte (Molt4/C8 and CEM) cells. The silver(I) complexes 1-4 show strong activity. 相似文献
275.
Ann-Kathrin Oehme Asia N. Rashed Barbara Hefele Ian C. K. Wong Wolfgang Rascher Antje Neubert 《PloS one》2012,7(9)
Background
In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period.Methodology
Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis.Results
A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001).Conclusions
Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed. 相似文献276.
Evaluating the Ribosomal Internal Transcribed Spacer (ITS) as a Candidate Dinoflagellate Barcode Marker 总被引:4,自引:0,他引:4
RF Stern RA Andersen I Jameson FC Küpper MA Coffroth D Vaulot F Le Gall B Véron JJ Brand H Skelton F Kasai EL Lilly PJ Keeling 《PloS one》2012,7(8):e42780
Background
DNA barcoding offers an efficient way to determine species identification and to measure biodiversity. For dinoflagellates, an ancient alveolate group of about 2000 described extant species, DNA barcoding studies have revealed large amounts of unrecognized species diversity, most of which is not represented in culture collections. To date, two mitochondrial gene markers, Cytochrome Oxidase I (COI) and Cytochrome b oxidase (COB), have been used to assess DNA barcoding in dinoflagellates, and both failed to amplify all taxa and suffered from low resolution. Nevertheless, both genes yielded many examples of morphospecies showing cryptic speciation and morphologically distinct named species being genetically similar, highlighting the need for a common marker. For example, a large number of cultured Symbiodinium strains have neither taxonomic identification, nor a common measure of diversity that can be used to compare this genus to other dinoflagellates.Methodology/Principal Findings
The purpose of this study was to evaluate the Internal Transcribed Spacer units 1 and 2 (ITS) of the rDNA operon, as a high resolution marker for distinguishing species dinoflagellates in culture. In our study, from 78 different species, the ITS barcode clearly differentiated species from genera and could identify 96% of strains to a known species or sub-genus grouping. 8.3% showed evidence of being cryptic species. A quarter of strains identified had no previous species identification. The greatest levels of hidden biodiversity came from Scrippsiella and the Pfiesteriaceae family, whilst Heterocapsa strains showed a high level of mismatch to their given species name.Conclusions/Significance
The ITS marker was successful in confirming species, revealing hidden diversity in culture collections. This marker, however, may have limited use for environmental barcoding due to paralogues, the potential for unidentifiable chimaeras and priming across taxa. In these cases ITS would serve well in combination with other markers or for specific taxon studies. 相似文献277.
Understanding the factors contributing to expansion of nonnative populations is a critical step toward accurate risk assessment and effective management of biological invasions. Nevertheless, few studies have attempted explicitly to test hypotheses regarding factors driving invasive spread by seeking correlations between patterns of vector movement and patterns of genetic connectivity. Herein, we describe such an attempt for the invasive tunicate Styela clava in the northeastern Pacific. We utilized microsatellite data to estimate gene flow between samples collected throughout the known range of S. clava in the region, and assessed correlation of these estimates with patterns of intracoastal commercial vessel traffic. Our results suggest that recent shipping patterns have contributed to the contemporary distribution of genetic variation. However, the analysis also indicates that other factors—including a complex invasion history and the influence of other vectors—have partially obscured genetic patterns associated with intracoastal population expansion. 相似文献
278.
Objective
To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR) Profile for Respiratory Medicine.Design
Single-site parallel-arm pragmatic trial using stratified randomisation.Setting
Nurse-led respiratory outpatient clinic in general hospital in South Wales.Participants
54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists.Intervention
Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care (‘intervention arm’ with 26 participants); or usual care alone (‘control arm’ with 28 participants).Main Outcome Measures
Problems reported and actions taken.Results
We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR) 13–26], while that in the control arm was −1 [−3 to +2] [Mann-Whitney U test: z = 6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]–[4] while that in the control arm was 0 [−1.75 to +1] [Mann-Whitney U test: z = 4.40, p<0.001].Conclusion
When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management.Trial Registration
Controlled-trials.com ISRCTN10386209 相似文献279.
Maninder Kaur Kosuke Izumi Alisha B. Wilkens Kathryn C. Chatfield Nancy B. Spinner Laura K. Conlin Zhe Zhang Ian D. Krantz 《PloS one》2014,9(10)
Pallister Killian syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian syndrome probands and supportive evidence for a Pallister Killian syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian syndrome such as downregulation of ZFPM2, GATA6 and SOX9, and overexpression of IGFBP2. 相似文献
280.