The CTSA Consortium's Catalog of Assets for Translational and Clinical Health Research (CATCHR).

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortium's effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open-access, searchable database of consortium resources to support multisite clinical and translational research studies.

Effects of fenbendazole on the murine humoral immune system.

Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment.

Accelerated Notch-dependent degradation of E47 proteins in aged B cell precursors is associated with increased ERK MAPK activation.

The transcriptional regulator E47, encoded by the E2A gene, is crucial to B lymphopoiesis. In BALB/c senescent mice (approximately 2 years old), the incidence of E47-expressing pro-B cells in vivo and E47 protein steady state levels in B cell precursors in vitro were reduced. Poor expression of E47 protein was a consequence of accelerated proteasome-mediated turnover and was associated with heightened ubiquitin modification of E2A-encoded proteins in aged B cell precursors.

RNA stability of the E2A-encoded transcription factor E47 is lower in splenic activated B cells from aged mice.

We have demonstrated previously that DNA binding and protein expression of the E2A-encoded transcription factor E47 are lower in nuclear extracts of activated splenic B cells from old mice. In the present study, we address how E47 protein expression is regulated in aging. Results herein show that E2A mRNA levels were decreased in stimulated splenic B cells from old as compared with young mice.

Deficient B lymphopoiesis in murine senescence: potential roles for dysregulation of E2A, Pax-5, and STAT5.

B lymphopoiesis in senescent mice is typically diminished and characterized by low pre-B cell numbers. The transcription factors E2A, Pax-5, and STAT5 have been implicated in the differentiation, proliferation, and survival of B cell precursors. In this review, we discuss the impairment of B lymphopoiesis during old age in the context of mechanisms at the molecular level responsible for the handling and turnover of these key transcriptional proteins.

Decreased E47 in senescent B cell precursors is stage specific and regulated posttranslationally by protein turnover.

The E2A-encoded transcription factor E47 is crucial to B lymphopoiesis. Senescent BALB/c mice ( approximately 2 years old) had reduced pre-B cells ex vivo. Pro-B/early pre-B cells from these aged mice, both ex vivo and in vitro, were deficient in E47 protein.

Age-related differences in the E2A-encoded transcription factor E47 in bone marrow-derived B cell precursors and in splenic B cells.

We have investigated the effects of aging on the E2A-encoded transcription factor E47, a key regulator of B cell functions, in B cell precursors and in splenic B cells. Here, we show that old mice can be classified as severely depleted, moderately depleted or not depleted mice, according to the percentage of pre-B cells in their bone marrow. IL-7-expanded populations of pro-B/early pre-B cells from bone marrow of both severely depleted and moderately depleted old mice exhibit a reduced E47 DNA-binding and expression compared to young mice, and this defect in severely depleted old mice is more dramatic than that in moderately depleted old mice.

Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase.

The capacity to class switch the IgH chain is critical to the effectiveness of humoral immune responses. We show that in vitro-stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes (IgG1, G2a, G3, and E), class switch recombination (CSR), and induction of the E2A-encoded transcription factor E47. E47 has previously been shown to be required for CSR, at least in part via expression of the activation-induced cytidine deaminase.

Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis.

Senescence in murine models is associated with a reduction, albeit heterogeneous, in bone marrow pre-B cells. We have categorized aged BALB/c mice into two phenotypes based on their patterns of pre-B/pro-B cell loss. Each phenotype is characterized by distinct responses to the growth cytokine IL-7 and capacity for survival in vitro.

The age-related decrease in E47 DNA-binding does not depend on increased Id inhibitory proteins in bone marrow-derived B cell precursors.

Our previous results showed that decreased numbers of pre-B cells in aged mice were associated with decreases in surrogate light chain, lambda5, and transcription factors E47/E12. In the present paper, we have analyzed IL-7-expanded populations of pro-B/early pre-B cells to evaluate whether the age-related reduction in E47 DNA-binding could be attributed to reduced E47 expression and/or increased Id expression. According to the percentage of pre-B cells present in their bone marrow, old mice were classified as severely depleted (>80% loss in pre-B cells, 50% loss in pro-B cells), or moderately depleted (20-80% loss in pre-B cells).