scholarly journals The Importation of Hematogenous Precursors by the Thymus Is a Gated Phenomenon in Normal Adult Mice

2001 ◽  
Vol 193 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Deborah L. Foss ◽  
Elina Donskoy ◽  
Irving Goldschneider
Keyword(s):  
Adult Life ◽  
Normal Adult ◽  
New Paradigm ◽  
Intravenous Injections ◽  
Adult Mice ◽  
Gate Opening ◽  
Age Dependent ◽  
Intrathymic Injection ◽  
Kinetics Of ◽  
Old Mice

Hematogenous precursors repopulate the thymus of normal adult mice, but it is not known whether this process is continuous or intermittent. Here, two approaches were used to demonstrate that the importation of prothymocytes in adult life is a gated phenomenon. In the first, age-dependent receptivity to thymic chimerism was studied in nonirradiated Ly 5 congenic mice by quantitative intrathymic and intravenous bone marrow (BM) adoptive transfer assays. In the second, the kinetics of importation of blood-borne prothymocytes was determined by timed separation of parabiotic mice. The results showed that >60% of 3–18-wk-old mice developed thymic chimerism after intrathymic injection of BM cells, and that the levels of chimerism (range, 5–90% donor-origin cells) varied cyclically (periodicity, 3 to 5 wk). In contrast, only 11–14% of intravenously injected recipients became chimeric, and chimerism occurred intermittently (receptive period ∼1 wk; refractory period ∼3 wk). In the intravenously injected mice, chimerism occurred simultaneously in both thymic lobes; gate opening occurred only after most intrathymic niches for prothymocytes had emptied; and the ensuing wave of thymocytopoiesis encompassed two periods of gating. These kinetics were confirmed in parabiotic mice, and in cohorts of mice in whom gating was synchronized by an initial intrathymic injection of BM cells. In addition, a protocol was developed by which sequential intravenous injections of BM cells over a 3 to 4 wk period routinely induces thymic chimerism in the apparent absence of stem cell chimerism. Hence, the results not only provide a new paradigm for the regulation of prothymocyte importation during adult life, but may also have applied implications for the selective induction of thymocytopoiesis in nonmyeloablated hosts.

scholarly journals Kinetics of alpha-synuclein depletion in three brain regions following conditional pan-neuronal inactivation of the encoding gene (Snca) by tamoxifen-induced Cre-recombination in adult mice

2021 ◽  
Author(s):  
Kirill D. Chaprov ◽  
Ekaterina A. Lysikova ◽  
Ekaterina V. Teterina ◽  
Vladimir L. Buchman
Keyword(s):  
Cerebral Cortex ◽  
Neuron Specific Enolase ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Tamoxifen Treatment ◽  
Adult Mice ◽  
Cre Recombination ◽  
Lag Period ◽  
Kinetics Of ◽  
Old Mice

AbstractConditional pan-neuronal inactivation of the Snca gene in 2-month old male and female mice causes dramatic decrease in the level of the encoded protein, alpha-synuclein, in three studied brain regions, namely cerebral cortex, midbrain and striatum, 12 weeks after the last injection of tamoxifen. Kinetics of alpha-synuclein depletion is different in these brain regions with a longer lag period in the cerebral cortex where this protein is normally most abundant. Our results suggest that efficient post-developmental pan-neuronal knockout of alpha-synuclein in adult, i.e. 5- to 6-month old, animals, could be achieved by tamoxifen treatment of 2-month old mice carrying loxP-flanked Snca gene and expressing inducible Cre-ERT2 recombinase under control of the promoter of neuron-specific enolase (NSE) gene.

scholarly journals Age-dependent intra-specific competition in pre-adult life stages and its effects on adult population dynamics

2015 ◽  
Vol 27 (1) ◽  
pp. 131-156
Author(s):  
RONGSONG LIU ◽  
GERGELY RÖST ◽  
STEPHEN A. GOURLEY
Keyword(s):  
Disease Transmission ◽  
Adult Population ◽  
Adult Life ◽  
Life Stages ◽  
Larval Competition ◽  
Amphibian Species ◽  
Age Dependent ◽  
Age Structured ◽  
Delay Differential ◽  
Boundedness And Persistence

Intra-specific competition in insect and amphibian species is often experienced in completely different ways in their distinct life stages. Competition among larvae is important because it can impact on adult traits that affect disease transmission, yet mathematical models often ignore larval competition. We present two models of larval competition in the form of delay differential equations for the adult population derived from age-structured models that include larval competition. We present a simple prototype equation that models larval competition in a simplistic way. Recognising that individual larvae experience competition from other larvae at various stages of development, we then derive a more complex equation containing an integral with a kernel that quantifies the competitive effect of larvae of ageāon larvae of agea. In some parameter regimes, this model and the famous spruce budworm model have similar dynamics, with the possibility of multiple co-existing equilibria. Results on boundedness and persistence are also proved.

scholarly journals Age-Dependent Resistance to Lethal Alphavirus Encephalitis in Mice: Analysis of Gene Expression in the Central Nervous System and Identification of a Novel Interferon-Inducible Protective Gene, Mouse ISG12

2002 ◽  
Vol 76 (22) ◽  
pp. 11688-11703 ◽  
Author(s):  
Lucia Labrada ◽  
Xiao Huan Liang ◽  
Wei Zheng ◽  
Christine Johnston ◽  
Beth Levine
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Virus Infection ◽  
Sindbis Virus ◽  
Expressed Sequence Tag ◽  
Severe Disease ◽  
Altered Expression ◽  
Age Dependent ◽  
Old Mice

ABSTRACT Several different mammalian neurotropic viruses produce an age-dependent encephalitis characterized by more severe disease in younger hosts. To elucidate potential factors that contribute to age-dependent resistance to lethal viral encephalitis, we compared central nervous system (CNS) gene expression in neonatal and weanling mice that were either mock infected or infected intracerebrally with a recombinant strain, dsTE12Q, of the prototype alphavirus Sindbis virus. In 1-day-old mice, infection with dsTE12Q resulted in rapidly fatal disease associated with high CNS viral titers and extensive CNS apoptosis, whereas in 4-week-old mice, dsTE12Q infection resulted in asymptomatic infection with lower CNS virus titers and undetectable CNS apoptosis. GeneChip expression comparisons of mock-infected neonatal and weanling mouse brains revealed developmental regulation of the mRNA expression of numerous genes, including some apoptosis regulatory genes, such as the proapoptotic molecules caspase-3 and TRAF4, which are downregulated during development, and the neuroprotective chemokine, fractalkine, which is upregulated during postnatal development. In parallel with increased neurovirulence and increased viral replication, Sindbis virus infection in 1-day-old mice resulted in both a greater number of host inflammatory genes with altered expression and greater changes in levels of host inflammatory gene expression than infection in 4-week-old mice. Only one inflammatory response gene, an expressed sequence tag similar to human ISG12, increased by a greater magnitude in infected 4-week-old mouse brains than in infected 1-day-old mouse brains. Furthermore, we found that enforced neuronal ISG12 expression results in a significant delay in Sindbis virus-induced death in neonatal mice. Together, our data identify genes that are developmentally regulated in the CNS and genes that are differentially regulated in the brains of different aged mice in response to Sindbis virus infection.

scholarly journals Age-dependent ribosomal DNA variations and their effect on cellular function in mammalian cells

2020 ◽  
Author(s):  
Eriko Watada ◽  
Sihan Li ◽  
Yutaro Hori ◽  
Katsunori Fujiki ◽  
Katsuhiko Shirahige ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Copy Number ◽  
Mammalian Cells ◽  
Bone Marrow Cells ◽  
Budding Yeast ◽  
Rdna Repeat ◽  
Age Dependent ◽  
Old Mice ◽  
Rdna Copy ◽  
Rdna Copy Number

AbstractThe ribosomal RNA gene, which consists of tandem repetitive arrays (rDNA repeat), is one of the most unstable regions in the genome. The rDNA repeat in the budding yeast is known to become unstable as the cell ages. However, it is unclear how the rDNA repeat changes in ageing mammalian cells. Using quantitative analyses, we identified age-dependent alterations in rDNA copy number and levels of methylation in mice. The degree of methylation and copy number of rDNA from bone marrow cells of 2-year-old mice were increased by comparison to 4-week-old mice in two mouse strains, BALB/cA and C57BL/6. Moreover, the level of pre-rRNA transcripts was reduced in older BALB/cA mice. We also identified many sequence variations among the repeats with two mutations being unique to old mice. These sequences were conserved in budding yeast and equivalent mutations shortened the yeast chronological lifespan. Our findings suggest that rDNA is also fragile in mammalian cells and alterations within this region have a profound effect on cellular function.Author SummaryThe ribosomal RNA gene (rDNA) is one of the most unstable regions in the genome due to its tandem repetitive structure. rDNA copy number in the budding yeast increases and becomes unstable as the cell ages. It is speculated that the rDNA produces an “aging signal” inducing senescence and death. However, it is unclear how the rDNA repeat changes during the aging process in mammalian cells. In this study, we attempted to identify the age-dependent alteration of rDNA in mice. Using quantitative single cell analysis, we show that rDNA copy number increases in old mice bone marrow cells. By contrast, the level of ribosomal RNA production was reduced because of increased levels of DNA methylation that represses transcription. We also identified many sequence variations in the rDNA. Among them, three mutations were unique to old mice and two of them were found in the conserved region in budding yeast. We then established a yeast strain with the old mouse-specific mutations and found this shortened the lifespan of the cells. These findings suggest that rDNA is also fragile in mammalian cells and alteration to this region of the genome affects cellular senescence.

scholarly journals OR28-01 Constitutive Activation of NRF2 Antioxidant Response Leads to Age-Dependent Goiter and Compensated Hypothyroidism in Male Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dionysios Chartoumpekis ◽  
Panos Ziros ◽  
Cédric Renaud ◽  
Massimo Bongiovanni ◽  
Ioannis Habeos ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Expression Profiles ◽  
Adult Life ◽  
Model Organisms ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Gene And Protein Expression ◽  
Age Dependent ◽  
Diffuse Goiter ◽  
Early Adult Life

Abstract Background: Familial non-toxic multinodular goiter (MNG) is a rare disease. KEAP1 gene (Kelch-like ECH-associated protein 1) that encodes the main inhibitor of nuclear factor erythroid 2-related transcription factor 2 (Nrf2), a central mediator of antioxidant responses, has been found to be one of the mutated genes that lead to familial MNG. The proposed association of KEAP1 with familial MNG is based on only two loss-of-function mutations in respective Japanese families, only one of which included proper phenotyping and demonstration of co-segregation of phenotype and mutation. To date, there is no experimental evidence from model organisms to support that decreased Keap1 levels can cause goiter. Hypothesis: We hypothesized that enhanced Nrf2 signaling induced by loss of Keap1 function in mice can lead to goiter. Methods: To this end, male Keap1 hypomorphic C57BL/6J mice that express ~80% less Keap1 in their tissues (Keap1 knockdown mice:“Keap1KD”) were studied at 3 and 12 months of age and compared to wild-type mice (WT). Plasma, thyroids and pituitary glands were collected for assessment of thyroid function by radioimmunoassays and for histology as well as gene and protein expression by quantitative PCR and immunoblotting respectively. Results: Keap1KD showed diffuse goiter that began to develop in early adult life and became highly prominent at the age of 12 months when the thyroids of Keap1KD were 6-fold heavier than WT. Histomorphometry assessment of thyroids showed that Keap1KD had ~3-fold larger follicle area and colloid compartment but no thyroid nodules or hyperplasia was detected. Keap1KD also showed primary hypothyroidism already in early adult life that was eventually well-compensated over time by increased TSH levels (at age of 12 months: WT TSH=47.7±9.1 mU/L, Keap1KD TSH=460±74 mU/L). This was also reflected in the pituitary gland of Keap1KD where Tshb mRNA was ~3-fold higher than WT. Despite a known stimulatory effect of Nrf2 on Tg gene transcription and Tg protein abundance, these measures were decreased in the thyroid of Keap1KD mice. No clear patterns were observed in the expression profiles of other thyroid hormone synthesis-specific factors, such as Duox1, Duoxa1, Duox2, Duoxa2, Tpo, Nis, Dio1, Dio2, Dehal1 mRNA levels, with the exception of Tg-processing and Tg-degrading cathepsins, including an increase in mature forms of cathepsins D, L and S. Conclusions: Keap1KD mice showed age-dependent diffuse goiter and compensated hypothyroidism. The precise mechanism accounting for the thyroidal phenotype remains to be elucidated, but it may involve enhanced Tg solubilization and excessive lysosomal Tg degradation. This study unravels novel roles of the druggable Keap1/Nrf2 pathway in thyroid function and economy. Subclinical hypothyroidism in Keap1KD mice may have broader implications regarding their use in metabolic research.

scholarly journals c-kit ligand reactivates fetal hemoglobin synthesis in serum-free culture of stringently purified normal adult burst-forming unit- erythroid

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 328-336 ◽  
Author(s):  
C Peschle ◽  
M Gabbianelli ◽  
U Testa ◽  
E Pelosi ◽  
T Barberi ◽  
...  
Keyword(s):  
Liquid Phase ◽  
Sharp Increase ◽  
Calf Serum ◽  
Adult Life ◽  
Fetal Hemoglobin ◽  
Normal Adult ◽  
Erythroid Progenitors ◽  
Gm Csf ◽  
Kit Ligand ◽  
F Cells

Abstract We have analyzed the reactivation of fetal hemoglobin (HbF) synthesis under rigorous in vitro conditions, ie, in mature erythroblasts generated by erythroid burst-forming units (BFU-E) stringently purified from normal adult peripheral blood and grown in fetal calf serum(FCS)- free semisolid or liquid phase culture. In clonogenetic dishes, graded amounts of c-kit ligand (KL) were added together with saturating levels of erythropoietin (Ep) and variable amounts of interleukin-3 and granulocyte-macrophage colony stimulating factor (IL-3/GM-CSF), ie, high or low level, or no IL-3/GM-CSF addition. In all conditions, KL induced a sharp, dose-dependent increase in the percentage of F cells and HbF content from nearly normal levels (< 10% and < 2.5%, respectively, at 0.1 and 1 ng/mL) up to 40% to 50% and 10% to 15% at 100 to 200 ng/mL. This increase was not associated with significant differences of burst number or stage of maturation at the time of analysis (as evaluated on the basis of percent mature erythroblasts and Hb content per cell). However, the KL-induced reactivation of HbF synthesis was strictly and directly correlated with a sharp increase of colony size, ie, cell number per burst. Addition of large amounts of IL- 3 and GM-CSF (10 to 100 U and 1 to 10 ng/mL, respectively) significantly potentiated the KL-induced reactivation of HbF, as compared with low levels (0.1 U and 0.01 to 0.1 ng) or no addition of these growth factors: this increase was highly significant at low KL doses (ie, 1 to 10 ng/mL). Single-burst analysis showed that the KL- induced HbF reactivation occurs homogeneously in the erythroid colonies within each of these culture conditions. We have analyzed the effect of KL in liquid phase BFU-E culture treated with the IL-3/GM-CSF/Ep combination at sequential times until terminal erythroid maturation: KL causes a sharp increase in the percentage of F cells and HbF content in all stages of maturation, whereas the IL-3/GM-CSF/Ep combination alone has a markedly lower effect. These results suggest that KL plays a key role in the reactivation of HbF synthesis in adult life, whereas IL- 3/GM-CSF potentiate this effect at low KL levels. The KL-induced HbF reactivation is seemingly related to an enhanced proliferation of erythroid progenitors in the erythropoietic differentiation pathway.

Passage rate of solids and fluids in the digestive tract of buffaloes, cattle and sheep: selection of non-linear model

1997 ◽  
Vol 64 (1) ◽  
pp. 63-69 ◽  
Author(s):  
A. Amici ◽  
S. Bartocci ◽  
S. Terramoccia ◽  
F. Martillotti
Keyword(s):  
Linear Models ◽  
Latin Square ◽  
Sums Of Squares ◽  
Passage Rate ◽  
Significant Difference ◽  
Age Dependent ◽  
Non Linear ◽  
Best Fitting ◽  
Kinetics Of ◽  
Selection Of

AbstractFive mathematical models were compared to select the most satisfactory model to describe digesta kinetics of solids and fluids in the gastrointestinal tract of buffaloes (Mediterranean bulls), cattle (Friesian bulls) and sheep (Delle Langhe rams) given food at maintenance level, according to a Latin-square arrangement for four consecutive periods of 21 days. Chromium mordanted alfalfa hay and cobalt-ethylenediamine tetraacetic acid were used as nonabsorbable markers and were administered through the rumen cannula in a single dose. Four different isonitrogenous diets (N × 6·25 = 140 g/kg dry matter) with different concentrate:forage ratios (12·5:87·5, 25:75, 37·5:62·5, 50:50) were used.Faecal chromium and cobalt concentration curves were fitted with five non-linear models: three gamma (G2, G3, G4) age-dependent one-compartment, one gamma age-dependent/age-independent two-compartment (G2G1) and one multicompartment (MC).Wilcoxon tests on residual sums of squares of the different models for solids showed that MC and G4 gave a better fit than G2G1, G2, G3 for all the data and within the species. The comparison of MC v. G4 did not show any significant difference (P > 0·05) for all the data computed together or within each species. Nevertheless, MC had a higher number of curves with lower residual sums of squares in comparison with G4 and was also able to produce estimates of digesta kinetics in the second compartment.The cobalt excretion curves for fluids, considering all the data, and only within sheep, showed G4 as the best fitting model. When G4 was compared with other models no significant differences were recorded either for cattle: G4 v. G2 (F = 0·6645), G4 v. G2G1 (P = 0·0620) and for buffalo: G4 v. G2 (P = 0·1575), G4 v.G3(P = 0·0796) and G4 v. G2G1 (P = 0·1641).It is concluded that the multicompartment model (MC) and G4 model were the best fits for solids and for fluids respectively.

scholarly journals Light-emitting Ga-oxide nanocrystals in glass: a new paradigm for low-cost and robust UV-to-visible solar-blind converters and UV emitters

Nanoscale ◽  
2014 ◽  
Vol 6 (3) ◽  
pp. 1763-1774 ◽  
Author(s):  
Vladimir N. Sigaev ◽  
Nikita V. Golubev ◽  
Elena S. Ignat'eva ◽  
Alberto Paleari ◽  
Roberto Lorenzi
Keyword(s):  
Light Emission ◽  
Low Cost ◽  
New Paradigm ◽  
Light Emitting ◽  
Solar Blind ◽  
Donor Acceptor ◽  
Uv Emitters ◽  
Kinetics Of

We demonstrate that nano-confinement of donor–acceptor recombination can force a nanophase to follow efficient bimolecular kinetics of light-emission, allowing Ga2O3 nanocrystals to work in glass as unprecedented solar-blind UV-to-visible converters.

scholarly journals AGE AND SUSCEPTIBILITY OF MICE TO COXSACKIE A VIRUSES

1962 ◽  
Vol 115 (4) ◽  
pp. 745-762 ◽  
Author(s):  
A. Martin Lerner ◽  
Howard S. Levin ◽  
Maxwell Finland
Keyword(s):  
Antibody Formation ◽  
Adult Mouse ◽  
Striated Muscle ◽  
Neutralizing Antibody ◽  
Subclinical Infection ◽  
Pathological Changes ◽  
Adult Mice ◽  
Hind Limbs ◽  
High Yields ◽  
Old Mice

Mice varying in age from 1 day to 8 months were inoculated intraperitoneally with Coxsackie A virus, type 9 and studies were made of the quantity of virus in striated muscle and myocardium, the presence of neutralizing antibody in the serum, and the pathological changes in the tissues. The hind limbs of young (1- to 20-day-old) mice yielded high titers of virus and showed diffuse myositis, whereas only low yields of virus and focal myositis were obtained in older mice. In the 20-day-old mice the skeletal lesions were not accompanied by manifest symptoms and histologically showed evidence of regeneration progressing from the 3rd to the 11th day after inoculation. Older mice showed no symptoms and only focal myositis and low yields of virus were found in their hind limbs. Coxsackie A9 virus replicated to relatively low titers in the hearts of young (1- to 40-day-old) mice without producing any demonstrable lesions whereas frank myocarditis with high yields of virus were demonstrated in mice infected at 8 months of age. The data suggest that at least for the 2 strains used, the adult mouse should be considered susceptible to subclinical infection with Coxsackie A9 virus. Neither subclinical infection, nor antibody formation was demonstrable in young adult mice inoculated with a strain of Coxsackie A4 virus.

Sign in / Sign up

Export Citation Format

Share Document