2,312 research outputs found
Thymic Involution in Viable Motheaten (meĻ ) Mice is Associated with a Loss of Intrathymic Precursor Activity
Mice homozygous for the viable motheaten (meĻ
) allele manifest abnormalities in
thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders
early in life. Premature thymic involution occurs in meĻ
/meĻ
mice, and their bone marrow
prothymocytes are unable to repopulate the thymus of adoptive recipients following
intravenous (i.v.) transfer. However, analysis of thymocytopoiesis following intrathymic
(i.t.) adoptive transfer of bone marrow from meĻ
/meĻ
mice demonstrates the presence of
normal numbers of prothymocytes. To investigate intrathymic development in meĻ
/meĻ
mice, we determined intrathymic precursor cell number and activity. Dual labeling
analyses showed that an involuted meĻ
/meĻ
thymus is relatively enriched (fivefold) in
CD4ā CD8ā thymocytes (intrathymic precursor phenotype) compared with wild-type
(+/+) thymus. However, thymocytes from meĻ
/meĻ
mice were deficient in precursor
activity when adoptively transferred i.t. into irradiated recipients. Thymocytes
recovered from the involuted thymus of aged or steroid-treated normal mice also
displayed reduced precursor activity. However, the phenotypic profile of thymocyte
subsets from steroid-treated mice was enriched in single positive cells (mature
phenotype) and was distinctly different from the subset distribution of thymocytes in
meĻ
/meĻ
and aged mice. These results suggest that intrathymic precursor activity in
meĻ
/meĻ
mice is decreased, and may be reflective of decreased prothymocyte seeding to
the thymus in vivo, In addition, the results suggest that the thymic involution in meĻ
/meĻ
mice is not due solely to effects of corticosteroids
Lack of Peripherally Induced Tolerance to Established Skin Allografts in Immunologically Reconstituted Scid Mice
The mechanism by which the antigen-specific immune system distinguishes between
foreign antigens (toward which it mounts an immune response) and self-antigens (of
which it is tolerant) is not completely understood. Studies using āsuperantigensā and
transgenic mice have allowed investigations into some of the mechanisms of clonal
deletion, anergy, and peripheral tolerance. In the present report, we have attempted to
develop a new model system to investigate the possible mechanism(s) of peripheral
tolerance to allografts. In this system, skin grafts from C57BL/6J (B6; H-2b mice are
grafted onto T- and B-lymphocyte-deficient C.B-17-scid/scid (H-2d; hereafter referred to
as scid) mice. Because of their lack of functional lymphocytes, the scid mice readily
accept the allogeneic skin grafts. After the allografts healed, the scid mice were
reconstituted with T-cell-deficient fetal liver from coisogeneic C.B-17-ā¤/ā¤ mice or bone
marrow from weanling congenitally athymic BALB/c-nu/nu (H-2d; hereafter referred to
as nude) mice. Upon immunological reconstitution, the scid mice reiected the established
B6 skin allografts, suggesting that an immune system developing in the presence of an
intact peripheral skin allograft fails to develop tolerance to the peripheral allograft. This
model system may be useful for the study of the mechanisms required for the induction
of peripheral tolerance
A sequence based synteny map between soybean and Arabidopsis thaliana
BACKGROUND: Soybean (Glycine max, L. Merr.) is one of the world's most important crops, however, its complete genomic sequence has yet to be determined. Nonetheless, a large body of sequence information exists, particularly in the form of expressed sequence tags (ESTs). Herein, we report the use of the model organism Arabidopsis thaliana (thale cress) for which the entire genomic sequence is available as a framework to align thousands of short soybean sequences. RESULTS: A series of JAVA-based programs were created that processed and compared 341,619 soybean DNA sequences against A. thaliana chromosomal DNA. A. thaliana DNA was probed for short, exact matches (15 bp) to each soybean sequence, and then checked for the number of additional 7 bp matches in the adjacent 400 bp region. The position of these matches was used to order soybean sequences in relation to the A. thaliana genome. CONCLUSION: Reported associations between soybean sequences and A. thaliana were within a 95% confidence interval of e(-30 )ā e(-100). In addition, the clustering of soybean expressed sequence tags (ESTs) based on A. thaliana sequence was accurate enough to identify potential single nucleotide polymorphisms (SNPs) within the soybean sequence clusters. An EST, bacterial artificial chromosome (BAC) end sequence and marker amplicon sequence synteny map of soybean and A. thaliana is presented. In addition, all JAVA programs used to create this map are available upon request and on the WEB
Thymic involution in viable motheaten (me(v)) mice is associated with a loss of intrathymic precursor activity
Mice homozygous for the viable motheaten (me(v)) allele manifest abnormalities in thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders early in life. Premature thymic involution occurs in me(v)/me(v) mice, and their bone marrow prothymocytes are unable to repopulate the thymus of adoptive recipients following intravenous (i.v.) transfer. However, analysis of thymocytopoiesis following intrathymic (i.t.) adoptive transfer of bone marrow from me(v)/me(v) mice demonstrates the presence of normal numbers of prothymocytes. To investigate intrathymic development in me(v)/me(v) mice, we determined intrathymic precursor cell number and activity. Dual labeling analyses showed that an involuted me(v)/me(v) thymus is relatively enriched (fivefold) in CD4-CD8- thymocytes (intrathymic precursor phenotype) compared with wild-type (+/+) thymus. However, thymocytes from me(v)/me(v) mice were deficient in precursor activity when adoptively transferred i.t. into irradiated recipients. Thymocytes recovered from the involuted thymus of aged or steroid-treated normal mice also displayed reduced precursor activity. However, the phenotypic profile of thymocyte subsets from steroid-treated mice was enriched in single positive cells (mature phenotype) and was distinctly different from the subset distribution of thymocytes in me(v)/me(v) and aged mice. These results suggest that intrathymic precursor activity in me(v)/me(v) mice is decreased, and may be reflective of decreased prothymocyte seeding to the thymus in vivo. In addition, the results suggest that the thymic involution in me(v)/me(v) mice is not due solely to effects of corticosteroids
Investigating the Magnetospheres of Rapidly Rotating B-type Stars
Recent spectropolarimetric surveys of bright, hot stars have found that ~10%
of OB-type stars contain strong (mostly dipolar) surface magnetic fields (~kG).
The prominent paradigm describing the interaction between the stellar winds and
the surface magnetic field is the magnetically confined wind shock (MCWS)
model. In this model, the stellar wind plasma is forced to move along the
closed field loops of the magnetic field, colliding at the magnetic equator,
and creating a shock. As the shocked material cools radiatively it will emit
X-rays. Therefore, X-ray spectroscopy is a key tool in detecting and
characterizing the hot wind material confined by the magnetic fields of these
stars. Some B-type stars are found to have very short rotational periods. The
effects of the rapid rotation on the X-ray production within the magnetosphere
have yet to be explored in detail. The added centrifugal force due to rapid
rotation is predicted to cause faster wind outflows along the field lines,
leading to higher shock temperatures and harder X-rays. However, this is not
observed in all rapidly rotating magnetic B-type stars. In order to address
this from a theoretical point of view, we use the X-ray Analytical Dynamical
Magnetosphere (XADM) model, originally developed for slow rotators, with an
implementation of new rapid rotational physics. Using X-ray spectroscopy from
ESA's XMM-Newton space telescope, we observed 5 rapidly rotating B-type stars
to add to the previous list of observations. Comparing the observed X-ray
luminosity and hardness ratio to that predicted by the XADM allows us to
determine the role the added centrifugal force plays in the magnetospheric
X-ray emission of these stars.Comment: IAUS Conference Proceeding
ADAM17 is essential for ectodomain shedding of the EGF-receptor ligand amphiregulin.
The epidermal growth factor (EGF)-receptor ligand amphiregulin (AREG) is a potent growth factor implicated in proliferative skin diseases and in primary and metastatic epithelial cancers. AREG, synthesized as a propeptide, requires conversion to an active peptide by metalloproteases by a process known as ectodomain shedding. Although (ADAM17) a disintegrin and metalloprotease 17 is a key sheddase of AREG, ADAM8-, ADAM15-, and batimastat (broad metalloprotease inhibitor)-sensitive metalloproteases have also been implicated in AREG shedding. In the present study, using a curly bare (Rhbdf2cub ) mouse model that shows loss-of-hair, enlarged sebaceous gland, and rapid cutaneous wound-healing phenotypes mediated by enhanced Areg mRNA and protein levels, we sought to identify the principal ectodomain sheddase of AREG. To this end, we generated Rhbdf2cub mice lacking ADAM17 specifically in the skin and examined the above phenotypes of Rhbdf2cub mice. We find that ADAM17 deficiency in the skin of Rhbdf2cub mice restores a full hair coat, prevents sebaceous gland enlargement, and impairs the rapid wound-healing phenotype observed in Rhbdf2cub mice. Furthermore, in vitro, stimulated shedding of AREG is abolished in Rhbdf2cub mouse embryonic keratinocytes lacking ADAM17. Thus, our data support previous findings demonstrating that ADAM17 is the major ectodomain sheddase of AREG. FEBS Open Bio 2018; 8(4):702-710
Research in and application of modern automatic control theory to nuclear rocket dynamics and control, volume I Semiannual status report
Linear optimal feedback control theory for nuclear rocket dynamics and control problem
Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics
There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an allogenized mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts
Sediment-to-water partition coefficients: the influence of physicochemical and seasonal factors in eastern Ontario
RHBDF2-regulated growth factor signaling in a rare human disease tylosis with esophageal cancer: What can we learn from murine models?
Tylosis with esophageal cancer syndrome (TOC) is a rare autosomal dominant proliferative skin disease caused by missense mutations in the rhomboid 5 homolog 2 (RHBDF2) gene. TOC is characterized by thickening of the skin in the palms and feet and is strongly linked with the development of esophageal squamous cell carcinoma. Murine models of human diseases have been valuable tools for investigating the underlying genetic and molecular mechanisms of a broad range of diseases. Although current mouse models do not fully recapitulate all aspects of human TOC, and the molecular mechanisms underlying TOC are still emerging, the available mouse models exhibit several key aspects of the disease, including a proliferative skin phenotype, a rapid wound healing phenotype, susceptibility to epithelial cancer, and aberrant epidermal growth factor receptor (EGFR) signaling. Furthermore, we and other investigators have used these models to generate new insights into the causes and progression of TOC, including findings suggesting a tissue-specific role of the RHBDF2-EGFR pathway, rather than a role of the immune system, in mediating TOC; and indicating that amphiregulin, an EGFR ligand, is a functional driver of the disease. This review highlights the mouse models of TOC available to researchers for use in investigating the disease mechanisms and possible therapies, and the significance of genetic modifiers of the disease identified in these models in delineating the underlying molecular mechanisms
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