Long Term Physiologic and Behavioural Effects of Housing Density and Environmental Resource Provision for Adult Male and Female Sprague Dawley Rats

There is considerable interest in refining laboratory rodent environments to promote animal well-being, as well as research reproducibility. Few studies have evaluated the long term impact of enhancing rodent environments with resources and additional cagemates. To that end, male and female Sprague Dawley (SD) rats were housed singly (n = 8/sex), in pairs (n = 16/sex), or in groups of four (n = 16/sex) for five months. Single and paired rats were housed in standard cages with a nylon chew toy, while group-housed rats were kept in double-wide cages with two PVC shelters and a nylon chew toy and were provided with food enrichment three times weekly. Animal behaviour, tests of anxiety (open field, elevated plus maze, and thermal nociception), and aspects of animal physiology (fecal corticoid levels, body weight, weekly food consumption, organ weights, and cerebral stress signaling peptide and receptor mRNA levels) were measured. Significant differences were noted, primarily in behavioural data, with sustained positive social interactions and engagement with environmental resources noted throughout the study. These results suggest that modest enhancements in the environment of both male and female SD rats may be beneficial to their well-being, while introducing minimal variation in other aspects of behavioural or physiologic responses

Assessing the Effectiveness of a Mathematics-Focused, Instructional Technology Program for Grades 6-8: A 5-Year Trend Analysis of NASA CONNECT(tm) Evaluation Data

NASA CONNECT is a research-, inquiry, and standards-based, integrated mathematics, science, and technology series of 30-minute instructional distance learning (television and web-based) programs for students in grades 6 8. Respondents who evaluated the programs in the series over the first five seasons (1998-99 through 2002-03) reported that (1) they used the programs in the series; (2) the goals and objectives for the series were met; (3) the programs were aligned with the national mathematics, science, and technology standards; (4) the program content was developmentally appropriate for the grade level; and (5) the programs in the series enhanced and enriched the teaching of mathematics, science, and technology

NASA/TM-2004-213242 Assessing the Effectiveness of a Mathematics- Focused, Instructional Technology Program for Grades 6–8: A 5-Year Trend Analysis of NASA CONNECT � Evaluation Data

Since its founding, NASA has been dedicated to the advancement of aeronautics and space science. The NASA Scientific and Technical Information (STI) Program Office plays a key part in helping NASA maintain this important role. The NASA STI Program Office is operated by Langley Research Center, the lead center for NASA’s scientific and technical information. The NASA STI Program Office provides access to the NASA STI Database, the largest collection of aeronautical and space science STI in the world. The Program Office is also NASA’s institutional mechanism for disseminating the results of its research and development activities. These results are published b

Evaluating the Effectiveness of the 2003-2004 NASA CONNECT(trademark)Program

NASA CONNECT is an Emmy-award-winning series of instructional (distance learning) programs for grades 6-8. Produced by the NASA Center for Distance Learning, the nine programs in the 2003-2004 NASA CONNECT series are research-, inquiry-, standards-, teacher-, and technology-based and include a 30-minute program, an educator guide containing a hands-on activity, and a web-based component. The 1,500 randomly selected NASA CONNECT registered users were invited to complete an electronic (self-reported) survey that employed a 5-point Likert-type scale. Regarding NASA CONNECT, respondents reported that the programs (1) enhance the teaching of mathematics, science, and technology (4.53); (2) are aligned with the national mathematics, science, and technology standards (4.52); (3) raise student awareness of careers requiring mathematics, science, and technology (4.48); (4) demonstrate the application of mathematics, science, and technology (4.47); and (5) present women and minorities performing challenging engineering and science tasks (4.50)

The POZ-ZF Transcription Factor Kaiso (ZBTB33) Induces Inflammation and Progenitor Cell Differentiation in the Murine Intestine

<div><p>Since its discovery, several studies have implicated the POZ-ZF protein Kaiso in both developmental and tumorigenic processes. However, most of the information regarding Kaiso’s function to date has been gleaned from studies in <i>Xenopus laevis</i> embryos and mammalian cultured cells. To examine Kaiso’s role in a relevant, mammalian organ-specific context, we generated and characterized a Kaiso transgenic mouse expressing a murine Kaiso transgene under the control of the intestine-specific <i>villin</i> promoter. Kaiso transgenic mice were viable and fertile but pathological examination of the small intestine revealed distinct morphological changes. Kaiso transgenics (<i>Kaiso^Tg/+</i>) exhibited a crypt expansion phenotype that was accompanied by increased differentiation of epithelial progenitor cells into secretory cell lineages; this was evidenced by increased cell populations expressing Goblet, Paneth and enteroendocrine markers. Paradoxically however, enhanced differentiation in <i>Kaiso^Tg/+</i> was accompanied by reduced proliferation, a phenotype reminiscent of Notch inhibition. Indeed, expression of the Notch signalling target HES-1 was decreased in <i>Kaiso^Tg/+</i> animals. Finally, our Kaiso transgenics exhibited several hallmarks of inflammation, including increased neutrophil infiltration and activation, villi fusion and crypt hyperplasia. Interestingly, the Kaiso binding partner and emerging anti-inflammatory mediator p120^ctn is recruited to the nucleus in <i>Kaiso^Tg/+</i> mice intestinal cells suggesting that Kaiso may elicit inflammation by antagonizing p120^ctn function.</p></div

Signaling through the inhibitory Fc receptor Fc gamma RIIB Induces CD8+ T Cell apoptosis to limit T Cell immunity

Effector CD8+ T cells are important mediators of adaptive immunity, and receptor-ligand interactions that regulate their survival may have therapeutic potential. Here, we identified a subset of effector CD8+ T cells that expressed the inhibitory fragment crystallizable (Fc) receptor FcγRIIB following activation and multiple rounds of division. CD8+ T cell-intrinsic genetic deletion of Fcgr2b increased CD8+ effector T cell accumulation, resulting in accelerated graft rejection and decreased tumor volume in mouse models. Immunoglobulin G (IgG) antibody was not required for FcγRIIB-mediated control of CD8+ T cell immunity, and instead, the immunosuppressive cytokine fibrinogen-like 2 (Fgl2) was a functional ligand for FcγRIIB on CD8+ T cells. Fgl2 induced caspase-3/7-mediated apoptosis in Fcgr2b+, but not Fcgr2b-/-, CD8+ T cells. Increased expression of FcγRIIB correlated with freedom from rejection following withdrawal from immunosuppression in a clinical trial of kidney transplant recipients. Together, these findings demonstrate a cell-intrinsic coinhibitory function of FcγRIIB in regulating CD8+ T cell immunity

Secretory cell lineages are expanded in the intestines of <i>Kaiso^Tg</i>^/+ mice.

<p>(<b>A</b>) PAS stain for Goblet cells (black arrowheads) revealed increased numbers of Goblet cells in both the villi and crypts of <i>Kaiso^Tg</i>^/+ intestines, p = 0.011 & 0.002. (<b>B</b>) Lysozyme staining revealed increased Paneth cell numbers in <i>Kaiso^Tg</i>^/+ mice, p = 0.017. (<b>C</b>) Synaptophysin positive enteroendocrine cells (arrowheads) are increased in <i>Kaiso^Tg</i>^/+ mice, p = 0.031. n = 3 mice/genotype; measurements performed by two independent blind observers; T-test used for p-value. ** represents significance.</p

<i>Kaiso^Tg</i>^/+ mice display decreased HES-1 expression in the small intestine.

<p>Both Non-Tg and <i>Kaiso^Tg</i>^/+ tissues displayed nuclear HES-1 expression in the crypts of the small intestine, however <i>Kaiso^Tg</i>^/+ tissue displays significantly decreased HES-1 expression in the villi. Quantitative RT-PCR showed a significant decrease in HES-1 expression in <i>Kaiso^Tg</i>^/+ mice. Values were first normalized to the GAPDH housekeeping gene, followed by normalizing to non-Tg HES-1 expression (** represents p<0.05).</p

Generation of transgenic mouse lines ectopically expressing <i>villin</i>-Kaiso.

<p>(<b>A</b>) Myc-tagged murine <i>Kaiso</i> cDNA was cloned downstream of the 9 kb v<i>illin</i> promoter sequence. (<b>B</b>) The transgene copy number in each transgenic line was evaluated via PCR. Line A transgenic animals have the greatest copy number. (<b>C</b>) RT-PCR confirmed expression of the Kaiso transgene in <i>villin</i>-expressing tissues of transgenic mice, <i>i.e.</i> the small intestine, large intestine, and kidneys. (<b>D</b>) Immunoblot analysis shows increased Kaiso expression in both small and large intestines in Kaiso transgenic (<i>Kaiso^Tg</i>^/+) Line A mice compared to non-transgenic (Non-Tg) siblings.</p

Kaiso transgenic mice exhibit inflammation of the intestinal mucosa.

<p>(<b>A</b>) <b><u>H</u></b>ematoxylin and <b><u>e</u></b>osin (H&E) stained sections were used to measure villi length (red bracket; ∼80 villi/mouse) and crypt depth (black bracket; ∼800 open crypts/mouse). <i>Kaiso^Tg</i>^/+ display increased crypt depth compared to their Non-Tg siblings, p = 0.001. (<b>B</b>) <i>Kaiso^Tg</i>^/+ mice exhibit increased immune cell infiltration of the lamina propria (yellow demarcated area) accompanied by increased MPO activity compared to their Non-Tg siblings, p = 0.014. (<b>C</b>) Line B mice do not exhibit immune cell infiltration or enhanced MPO activity compared to Non-Tg siblings. ** represents significance.</p