scholarly journals Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells

2021 ◽  
Author(s):  
Dehao Huang ◽  
Jianhuan Li ◽  
Fangxiao Hu ◽  
Qitong Weng ◽  
Tongjie Wang ◽  
...  

ABSTRACTHuman pluripotent stem cell (hPSC)-induced NK (iNK) cells are a promising “off-the-shelf” cell product for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryonic body-formation and feeder-based expansion steps, which bring instability, time-consuming, and high costs for manufacture. In this study, we develop an embryonic body-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time window of 27-day induction, millions of hPSC input can produce over billions of iNK cells without the necessity of NK cell-expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells by mechanisms of direct cytotoxity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.

2011 ◽  
Vol 19 ◽  
pp. S113
Author(s):  
M.E. van Meegeren ◽  
N.W. Jansen ◽  
G. Roosendaal ◽  
S.C. Mastbergen ◽  
F.P. Lafeber

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S293-S293
Author(s):  
Jonathan Altamirano ◽  
Grace Tam ◽  
Marcela Lopez ◽  
India Robinson ◽  
Leanne Chun ◽  
...  

Abstract Background While pediatric cases of COVID-19 are at low risk for adverse events, schoolchildren should be considered for surveillance as they can become infected at school and serve as sources of household or community transmission. Our team assessed the feasibility of young children self-collecting SARS-CoV-2 samples for surveillance testing in an educational setting. Methods Students at a K-8 school were tested weekly for SARS-CoV-2 from September 2020 - June 2021. Error rates were collected from September 2020 - January 2021. Clinical staff provided all students with instructions for anterior nares specimen self-collection and then observed them to ensure proper technique. Instructions included holding the sterile swab while making sure not to touch the tip, inserting the swab into their nostril until they start to feel resistance, and rubbing the swab in four circles before repeating the process in their other nostril. An independent observer timed random sample self-collections from April - June 2021. Results 2,590 samples were collected from 209 students during the study period when data on error rates were collected. Errors occurred in 3.3% of all student encounters (n=87). Error rates over time are shown in Figure 1, with the highest rate occurring on the first day of testing (n=20/197, 10.2%) and the lowest in January 2021 (n=1/202, 0.5%). 2,574 visits for sample self-collection occurred during the study period when independent timing data was collected (April - June 2021). Of those visits, 7.5% (n=193) were timed. The average duration of each visit was 70 seconds. Figure 1. Swab Error Rates Over Time Conclusion Pediatric self-collected lower nasal swabs are a viable and easily tolerated specimen collection method for SARS-CoV-2 surveillance in school settings, as evidenced by the low error rate and short time window of sample self-collection during testing. School administrators should expect errors to drop quickly after implementing testing. Disclosures All Authors: No reported disclosures


Development ◽  
2002 ◽  
Vol 129 (20) ◽  
pp. 4785-4796 ◽  
Author(s):  
Jean-Baptiste Charrier ◽  
Françoise Lapointe ◽  
Nicole M. Le Douarin ◽  
Marie-Aimée Teillet

Molecular analysis carried out on quail-chick chimeras, in which quail Hensen’s node was substituted for its chick counterpart at the five- to six-somite stage (ss), showed that the floor plate of the avian neural tube is composed of distinct areas: (1) a median one (medial floor plate or MFP) derived from Hensen’s node and characterised by the same gene expression pattern as the node cells (i.e. expression of HNF3β and Shh to the exclusion of genes early expressed in the neural ectoderm such as CSox1); and (2) lateral regions that are differentiated from the neuralised ectoderm (CSox1 positive) and form the lateral floor plate (LFP). LFP cells are induced by the MFP to express HNF3β transiently, Shh continuously and other floor-plate characteristic genes such as Netrin. In contrast to MFP cells, LFP cells also express neural markers such as Nkx2.2 and Sim1. This pattern of avian floor-plate development presents some similarities to floor-plate formation in zebrafish embryos. We also demonstrate that, although MFP and LFP have different embryonic origins in normal development, one can experimentally obtain a complete floor plate in the neural epithelium by the inductive action of either a notochord or a MFP. The competence of the neuroepithelium to respond to notochord or MFP signals is restricted to a short time window, as only the posterior-most region of the neural plate of embryos younger than 15 ss is able to differentiate a complete floor plate comprising MFP and LFP. Moreover, MFP differentiation requires between 4 and 5 days of exposure to the inducing tissues. Under the same conditions LFP and SHH-producing cells only induce LFP-type cells. These results show that the capacity to induce a complete floor plate is restricted to node-derived tissues and probably involves a still unknown factor that is not SHH, the latter being able to induce only LFP characteristics in neuralised epithelium.


2020 ◽  
Vol 12 (22) ◽  
pp. 3720 ◽  
Author(s):  
Francesca Giannetti ◽  
Raffaello Pegna ◽  
Saverio Francini ◽  
Ronald E. McRoberts ◽  
Davide Travaglini ◽  
...  

A Landsat time series has been recognized as a viable source of information for monitoring and assessing forest disturbances and for continuous reporting on forest dynamics. This study focused on developing automated procedures for detecting disturbances in Mediterranean coppice forests which are characterized by rapid regrowth after a cut. Specifically, new methods specific to Mediterranean coppice forests are needed for mapping clearcut disturbances over time and for estimating related indicators in the context of Sustainable Forest Management and Biodiversity International monitoring frameworks. The aim of this work was to develop a new change detection algorithm for mapping clearcut disturbances in Mediterranean coppice forests with Landsat time series (LTS) using a short time window. Accuracy for the new algorithm, characterized as the Two Thresholds Method (TTM), was evaluated using an independent clearcut reference dataset over a temporal period of the 13 years between 2001 and 2013. TTM was also evaluated against two benchmark approaches: (i) LandTrendr, and (ii) the forest loss category of the Global Forest Change Map. Overall Accuracy for LandTrendr and TTM were greater than 0.94. Meanwhile, smaller accuracies were always obtained for the GFC. In particular, Producer’s Accuracy ranged between 0.45 and 0.84 for TTM and between 0.49 and 0.83 for LT, while for the GFC, PA ranged between 0 and 0.38. User’s Accuracy ranged between 0.86 and 0.96 for TTM and between 0.73 and 0.91 for LT, while for the GFC UA ranged between 0.19 and 1.00. Moreover, to illustrate the utility of TTM for mapping clearcut disturbances in Mediterranean coppice forests, we applied TTM to a Landsat scene that covered almost the entirety of the Tuscany region in Italy.


2008 ◽  
Vol 20 (5) ◽  
pp. 1325-1343 ◽  
Author(s):  
Zbyněk Pawlas ◽  
Lev B. Klebanov ◽  
Martin Prokop ◽  
Petr Lansky

We study the estimation of statistical moments of interspike intervals based on observation of spike counts in many independent short time windows. This scenario corresponds to the situation in which a target neuron occurs. It receives information from many neurons and has to respond within a short time interval. The precision of the estimation procedures is examined. As the model for neuronal activity, two examples of stationary point processes are considered: renewal process and doubly stochastic Poisson process. Both moment and maximum likelihood estimators are investigated. Not only the mean but also the coefficient of variation is estimated. In accordance with our expectations, numerical studies confirm that the estimation of mean interspike interval is more reliable than the estimation of coefficient of variation. The error of estimation increases with increasing mean interspike interval, which is equivalent to decreasing the size of window (less events are observed in a window) and with decreasing the number of neurons (lower number of windows).


2011 ◽  
Vol 390 (20) ◽  
pp. 3444-3453 ◽  
Author(s):  
Paulo S.G. de Mattos Neto ◽  
David A. Silva ◽  
Tiago A.E. Ferreira ◽  
George D.C. Cavalcanti

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e103269 ◽  
Author(s):  
Sarah E. Marsh ◽  
Michael Poulsen ◽  
Adrián Pinto-Tomás ◽  
Cameron R. Currie

2020 ◽  
Author(s):  
Gwen Brekelmans ◽  
Claudia Bruns ◽  
Vanessa Meitanis ◽  
Michael Coleman ◽  
Vitor Zimmerer

Research into human language processing is challenged by its implicit nature of processes, the short time-window in which they take place, and heterogeneity within the population. We used a word monitoring task to measure implicit sensitivity to grammar, semantics, and the strength of word collocations, when listening to natural spoken sentences. We report substantial and novel adjustments to the paradigm, which allowed a participant to be tested in about three minutes, and data from a proof-of-concept study for which we recruited 125 visitors of different backgrounds to a science event. Linear mixed-effects models suggest that participants’ response time to target words was 45ms slower when words were less predictable in their grammatical, semantic, or collocational context (p = .034). There was no significant difference between language conditions. However, in non-native speakers, grammatical manipulation was less effective than manipulations of semantics and word collocations (p < .08), which is consistent with theories of shallow language processing in non-native speakers. There was no significant effect of age on language sensitivity. Effects generally replicated findings based on standard word-monitoring methods, suggesting that the novel adjustments can be applied in situations where participants’ time is limited, e.g. at events, in schools or online.


2015 ◽  
Vol 210 (2) ◽  
pp. 287-301 ◽  
Author(s):  
Yvonne Nyathi ◽  
Martin R. Pool

The ribosome exit site is a focal point for the interaction of protein-biogenesis factors that guide the fate of nascent polypeptides. These factors include chaperones such as NAC, N-terminal-modifying enzymes like Methionine aminopeptidase (MetAP), and the signal recognition particle (SRP), which targets secretory and membrane proteins to the ER. These factors potentially compete with one another in the short time-window when the nascent chain first emerges at the exit site, suggesting a need for regulation. Here, we show that MetAP contacts the ribosome at the universal adaptor site where it is adjacent to the α subunit of NAC. SRP is also known to contact the ribosome at this site. In the absence of NAC, MetAP and SRP antagonize each other, indicating a novel role for NAC in regulating the access of MetAP and SRP to the ribosome. NAC also functions in SRP-dependent targeting and helps to protect substrates from aggregation before translocation.


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