scholarly journals Kinetics of Steady-state Differentiation and Mapping of Intrathymic-signaling Environments by Stem Cell Transplantation in Nonirradiated Mice

2003 ◽  
Vol 198 (6) ◽  
pp. 957-962 ◽  
Author(s):  
Helen E. Porritt ◽  
Kristie Gordon ◽  
Howard T. Petrie
Keyword(s):  
Stem Cells ◽  
Steady State ◽  
Gene Rearrangement ◽  
New Wave ◽  
Regulatory Cells ◽  
Narrow Region ◽  
Cortical Regions ◽  
First Time ◽  
Kinetics Of ◽  
Outer Half

Upon thymus entry, thymic-homing progenitors undergo distinct phases of differentiation as they migrate through the cortex to the capsule, suggesting that the signals that induce these differentiation steps may be stratified in corresponding cortical regions. To better define these regions, we transplanted purified stem cells into nonirradiated congenic recipients and followed their differentiation with respect to both tissue location and time. The earliest progenitors (DN1) remained confined to a very narrow region of the cortex for about the first 10 d of intrathymic residence; this region virtually overlaps the sites of thymic entry, suggesting that DN1 cells move very little during this lengthy period of proliferation and lineage commitment. Movement out of this region into the deeper cortex is asynchronous, and corresponds to the appearance of DN2 cells. Differentiation to the DN3 stage correlates with movement across the midpoint of the cortex, indicating that stromal signals that induce functions such as TCR gene rearrangement reside mainly in the outer half of the cortex. The minimum time to reach the capsule, and thus transit to the DP stage, is ∼13 d, with the average time a few days longer. These findings reveal for the first time the kinetics of steady-state progenitor differentiation in the thymus, as well as defining the boundaries of cortical regions that support different phases of the differentiation process. We also show that the first lineage-positive progeny of transplanted stem cells to appear in the thymus are dendritic cells in the medulla, suggesting that each new wave of new T cell production is preceded by a wave of regulatory cells that home to the medulla and ensure efficient tolerance and selection.

scholarly journals Mapping Precursor Movement through the Postnatal Thymus Reveals Specific Microenvironments Supporting Defined Stages of Early Lymphoid Development

2001 ◽  
Vol 194 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Evan F. Lind ◽  
Susan E. Prockop ◽  
Helen E. Porritt ◽  
Howard T. Petrie
Keyword(s):  
Steady State ◽  
Lineage Specification ◽  
Temporal Separation ◽  
Tissue Mass ◽  
Narrow Region ◽  
Complex Process ◽  
Undifferentiated State ◽  
Postnatal Differentiation ◽  
Cortical Regions ◽  
Outward Migration

Cellular differentiation is a complex process involving integrated signals for lineage specification, proliferation, endowment of functional capacity, and survival or cell death. During embryogenesis, spatially discrete environments regulating these processes are established during the growth of tissue mass, a process that also results in temporal separation of developmental events. In tissues that undergo steady-state postnatal differentiation, another means for inducing spatial and temporal separation of developmental cues must be established. Here we show that in the postnatal thymus, this is achieved by inducing blood-borne precursors to enter the organ in a narrow region of the perimedullary cortex, followed by outward migration across the cortex before accumulation in the subcapsular zone. Notably, blood precursors do not transmigrate the cortex in an undifferentiated state, but rather undergo progressive developmental changes during this process, such that defined precursor stages appear in distinct cortical regions. Identification of these cortical regions, together with existing knowledge regarding the genetic potential of the corresponding lymphoid precursors, sets operational boundaries for stromal environments that are likely to induce these differentiative events. We conclude that active cell migration between morphologically similar but functionally distinct stromal regions is an integral component regulating differentiation and homeostasis in the steady-state thymus.

FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3453-3460 ◽  
Author(s):  
Natalija Buza-Vidas ◽  
Min Cheng ◽  
Sara Duarte ◽  
Hojjatollah Nozad Charoudeh ◽  
Sten Eirik W. Jacobsen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Steady State ◽  
Ex Vivo ◽  
Fetal Liver ◽  
Functional Evaluation ◽  
Hematopoietic Stem ◽  
First Time ◽  
Deficient Mice

Abstract Originally cloned from hematopoietic stem cell (HSC) populations and its ligand being extensively used to promote ex vivo HSC expansion, the FMS-like tyrosine kinase 3 (FLT3; also called FLK2) receptor and its ligand (FL) were expected to emerge as an important physiologic regulator of HSC maintenance and expansion. However, the role of FLT3 receptor and ligand in HSC regulation remains unclear and disputed. Herein, using Fl-deficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Flk2−/− mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative ligands might potentially interact directly or indirectly with FLT3 receptor, we here also characterized HSCs in Flk2−/− mice. Advanced phenotypic as well as functional evaluation of Flk2−/− HSCs showed that the FLT3 receptor is dispensable for HSC steady-state maintenance and expansion after transplantation. Taken together, these studies show that the FLT3 receptor and ligand are not critical regulators of mouse HSCs, neither in steady state nor during fetal or posttransplantation expansion.

Zeolites Fit For A Crown: Probing Host-Guest Interactions with Thermogravimetric Methods

2018 ◽  
Author(s):  
Asel Sartbaeva ◽  
Paul R. Raithby ◽  
Remi Castaing ◽  
Antony Nearchou
Keyword(s):  
Mass Spectrometry ◽  
Thermal Analysis ◽  
Differential Thermal Analysis ◽  
Petrochemical Industry ◽  
Rational Use ◽  
New Methodologies ◽  
First Time ◽  
Kinetics Of

Through a combination of thermogravimetry, mass spectrometry and differential thermal analysis, we demonstrate for the first time that all four zeolites show experimental differences in their host-guest interactions with 18C6. In addition, we have estimated the kinetics of 18C6 decomposition, which is a technique that has not been applied to zeolites previously. Using these findings as a toolkit, a more rational use of OSDAs can be utilised to prepare designer zeolites. Furthermore, the new methodologies presented herein can be applied to current zeolites, such as MFI-type zeolites used in the petrochemical industry.

Kinetic analysis of mechanism of intestinal Na+-dependent sugar transport

1985 ◽  
Vol 248 (5) ◽  
pp. C498-C509 ◽  
Author(s):  
D. Restrepo ◽  
G. A. Kimmich
Keyword(s):  
Experimental Data ◽  
Steady State ◽  
Sugar Transport ◽  
Enzyme Kinetic ◽  
Steady State Distribution ◽  
State Distribution ◽  
Least Squares Fit ◽  
Coupling Stoichiometry ◽  
Rate Limiting ◽  
Kinetics Of

Zero-trans kinetics of Na+-sugar cotransport were investigated. Sugar influx was measured at various sodium and sugar concentrations in K+-loaded cells treated with rotenone and valinomycin. Sugar influx follows Michaelis-Menten kinetics as a function of sugar concentration but not as a function of Na+ concentration. Nine models with 1:1 or 2:1 sodium:sugar stoichiometry were considered. The flux equations for these models were solved assuming steady-state distribution of carrier forms and that translocation across the membrane is rate limiting. Classical enzyme kinetic methods and a least-squares fit of flux equations to the experimental data were used to assess the fit of the different models. Four models can be discarded on this basis. Of the remaining models, we discard two on the basis of the trans sodium dependence and the coupling stoichiometry [G. A. Kimmich and J. Randles, Am. J. Physiol. 247 (Cell Physiol. 16): C74-C82, 1984]. The remaining models are terter ordered mechanisms with sodium debinding first at the trans side. If transfer across the membrane is rate limiting, the binding order can be determined to be sodium:sugar:sodium.

scholarly journals Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Olav Sundnes ◽  
William Ottestad ◽  
Camilla Schjalm ◽  
Peter Lundbäck ◽  
Lars la Cour Poulsen ◽  
...  
Keyword(s):  
High Resolution ◽  
Prospective Observational Study ◽  
Tissue Injury ◽  
Trauma Patients ◽  
Decoy Receptor ◽  
Interleukin 33 ◽  
Injured Patients ◽  
First Time ◽  
Kinetics Of ◽  
Insight Into

Abstract Background Alarmins are considered proximal mediators of the immune response after tissue injury. Understanding their biology could pave the way for development of new therapeutic targets and biomarkers in human disease, including multiple trauma. In this study we explored high-resolution concentration kinetics of the alarmin interleukin-33 (IL-33) early after human trauma. Methods Plasma samples were serially collected from 136 trauma patients immediately after hospital admission, 2, 4, 6, and 8 h thereafter, and every morning in the ICU. Levels of IL-33 and its decoy receptor sST2 were measured by immunoassays. Results We observed a rapid and transient surge of IL-33 in a subset of critically injured patients. These patients had more widespread tissue injuries and a greater degree of early coagulopathy. IL-33 half-life (t1/2) was 1.4 h (95% CI 1.2–1.6). sST2 displayed a distinctly different pattern with low initial levels but massive increase at later time points. Conclusions We describe for the first time early high-resolution IL-33 concentration kinetics in individual patients after trauma and correlate systemic IL-33 release to clinical data. These findings provide insight into a potentially important axis of danger signaling in humans.

scholarly journals Nanoliposomal Cercodemasoide A and Its Improved Activities Against NTERA-2 Cancer Stem Cells

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098210
Author(s):  
Nguyen Thi Nga ◽  
Do Thi Phuong ◽  
Nguyen Thi Cuc ◽  
Trieu Ha Phuong ◽  
Pham Thi Mai Huong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Drug Carrier ◽  
Free Form ◽  
Cancer Therapies ◽  
3 Dimensional ◽  
Novel Target ◽  
Average Size ◽  
Biopharmaceutical Properties ◽  
First Time

Recently, saponins derived from marine sources have received much attention because of their promising bioactivities, such as anticancer, anti-angiogenesis, and anti-inflammation. In particular, a triterpene saponin from the sea cucumber Cercodemas anceps Selenka, cercodemasoide A (CAN1), showed potent cytotoxicity against various cancer cell lines. Recent evidence has indicated that cancer stem cells (CSCs) could be a novel target for efficient cancer therapies. In order to improve the biopharmaceutical properties of CAN1, the compound was loaded into nanoliposomes as an ideal drug carrier. CAN1 was successfully incorporated into nanoliposomes as small unilamellar liposome vesicles with an average size of 73.39 ± 1.57 nm, zeta potential of −0.299 ± 0.046 mV, polydispersity index of 0.336 ± 0.038, and with an encapsulation efficiency of up to 62.9%. For the first time, CAN1 and its nanoliposomal forms have been shown to have a promising cytotoxic activity against NTERA-2 CSCs, with half-maximal inhibitory concentration (IC50) =1.03 ± 0.04 and 0.41 ± 0.03 µM, respectively. The CAN1 nanoliposomes also presented significantly improved activities in suppressing the growth of NTERA-2 3-dimensional tumorspheres (IC50 = 1.71 ± 0.06 µM) in comparison with the free form ( P < .05). The anti-CSC effects of CAN1 nanoliposomes on NTERA-2 cells were due to their apoptotic induction through enhancing caspase-3 activity (more than 2-fold) and arresting the cell cycle at the S phase ( P < .05). The obtained CAN1-encapsulated nanoliposomes suggest valuable applications in CSC-targeting treatment for more efficient clinical therapy.

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