speCombined estradiol and lithium increase ER-α mRNA in embryonic C57BL/6J primary hippocampal cultures

Estrogen replacement therapy (ERT) is commonly prescribed during menopause. Post-menopausal women also tend to suffer from bipolar disorders and as a result are prescribed mood stabilizers – in addition to ERT. There is a paucity of data on how combined hormones and mood stabilizers interact in regulating gene expression that led us to hypothesize that in primary cultures of mixed brain cells predominated by glia, combined 17β-estradiol (E2) and lithium chloride (LiCl) (E2/LiCl) will alter estrogen receptor-alpha (ER-α) mRNA expression. We quantified mRNA expression of ER-α using the cDNA of treated primary cultures of mixed brain cells from a previous study. Our results indicate that hippocampal cultures predominated by glia increase in ER-α mRNA expression when treated for 48 h with combined E2/LiCl. Our findings may encourage further investigation on the molecular mechanisms involved in combined estrogen and lithium treatment

Confluence: A Seminar Series as a Teaching Tool ?

In 2007 Florida International University (FIU) received NIH, NSF, and internal support to create a curriculum that was quantitative in nature, and that incorporated some of the most contemporary approaches to the classroom. The QBIC (Quantifying Biology In the Classroom; http://qbic. fiu.edu) Program is a specialized program in the Department of Biology specifically set up to implement ‘vision and change’ principles in the department’s overall approach to students. It is now an optional track within the Department of Biological Sciences. We discuss the major objectives of this series, the affect areas that it addresses, as well as how students incorporate the series’ lessons for their own professional development. It became apparent to us anecdotally that our undergraduates were making career choices without the awareness of the many other viable career options in biology. This is not an issue unique to our institution and other authors (1) have discussed steps to address career choice and exposure. At our institution, we created a number of career development initiatives, one of which was a seminar series called “Confluence: where life and science meet.” For this series we invite science professionals from around the country to give a seminar, mostly to undergraduates, not only on the technical specifics of their field, but also on their personal life story, and how that story informed their career choice. After the seminar, the speaker sits down with a QBIC faculty member for a half-hour interview where he or she is able to go into more specifics about the themes from the seminar. The interview is videotaped in front of a live student-only audience in a film studio on campus. The recording is published on the series’ website (http://qbic.fiu. edu/confluence). In this article we discuss using the series to address issues of identity, and how our video blog can be used in other classrooms to achieve similar objectives for science students nationally

Lithium enhances cortical mRNA expression in ovariectomized C57BL/6J mice

The hippocampus and cortex of the mammalian brain are regions involved in learning and long-term memory. Estrogen and lithium affect similar learning and memory molecular processes. We hypothesized that in ovariectomized mice lithium treatment will enhance genetic factors in the brain that are involved in neuroprotection, learning and memory. Our study used bilaterally ovariectomized (bOVX) C57BL÷6J mice treated for one month with 14.2 mM LiCl in their drinking water. Results indicate that LiCl-treated bOVX mice show enhanced cortical increases in mRNA expression of ER-alpha, NR1, Bcl-2, BDNF, and CaMkII-alpha; hippocampal mRNA showed no changes. Our results indicate that in bOVX C57BL÷6J mice, lithium enhances the expression of specific cortical genes coded for proteins involved in learning, memory and neuroprotection

Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice

ASXL1 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies, and its alterations are associated with poor prognosis. De novo ASXL1 mutations cause Bohring-Opitz syndrome characterized by multiple congenital malformations. We show that Asxl1 deletion in mice led to developmental abnormalities including dwarfism, anophthalmia, and 80% embryonic lethality. Surviving Asxl1(-/-) mice lived for up to 42 days and developed features of myelodysplastic syndrome (MDS), including dysplastic neutrophils and multiple lineage cytopenia. Asxl1(-/-) mice had a reduced hematopoietic stem cell (HSC) pool, and Asxl1(-/-) HSCs exhibited decreased hematopoietic repopulating capacity, with skewed cell differentiation favoring granulocytic lineage. Asxl1(+/-) mice also developed mild MDS-like disease, which could progress to MDS/myeloproliferative neoplasm, demonstrating a haploinsufficient effect of Asxl1 in the pathogenesis of myeloid malignancies. Asxl1 loss led to an increased apoptosis and mitosis in Lineage(-)c-Kit(+) (Lin(-)c-Kit(+)) cells, consistent with human MDS. Furthermore, Asxl1(-/-) Lin(-)c-Kit(+) cells exhibited decreased global levels of H3K27me3 and H3K4me3 and altered expression of genes regulating apoptosis (Bcl2, Bcl2l12, Bcl2l13). Collectively, we report a novel ASXL1 murine model that recapitulates human myeloid malignancies, implying that Asxl1 functions as a tumor suppressor to maintain hematopoietic cell homeostasis. Future work is necessary to clarify the contribution of microenvironment to the hematopoietic phenotypes observed in the constitutional Asxl1(-/-) mice

Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells

TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2?/? mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2?/? tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies. Single-cell-targeted sequencing of wild-type and premalignant Tet2?/? Lin?c-Kit+ cells shows higher mutation frequencies in Tet2?/? cells. We further show that the increased mutational burden is particularly high at genomic sites that gained 5-hydroxymethylcytosine, where TET2 normally binds. Furthermore, TET2-mutated myeloid malignancy patients have significantly more mutational events than patients with wild-type TET2. Thus, Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated mechanism of haematological malignancy pathogenesis

Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells

TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2-/- mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2-/- tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies. Single-cell-targeted sequencing of wild-type and premalignant Tet2-/- Lin-c-Kit+ cells shows higher mutation frequencies in Tet2-/- cells. We further show that the increased mutational burden is particularly high at genomic sites that gained 5-hydroxymethylcytosine, where TET2 normally binds. Furthermore, TET2-mutated myeloid malignancy patients have significantly more mutational events than patients with wild-type TET2. Thus, Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated mechanism of haematological malignancy pathogenesis

Science café course: an innovative means of improving communication skills of undergraduate biology majors

To help bridge the increasing gap between scientists and the public, we developed an innovative two-semester course called Science Café. In this course, undergraduate biology majors learn to develop communication skills to be better able to explain science concepts and current developments in science to non-scientists. Students develop and host outreach events on various topics relevant to the community, thereby increasing interactions between budding scientists and the public. Such a Science Café course emphasizes development of science communication skills early, at the undergraduate level, and empowers students to use their science knowledge in everyday interactions with the public to increase science literacy, get involved in the local community and engage the public in a dialogue on various pressing science issues. We believe that undergraduate science majors can be great ambassadors for science and are often overlooked since many aspire to go on to medical/veterinary/pharmacy schools. However, science communication skills are especially important for these types of students because when they become healthcare professionals, they will interact with the public as part of their everyday jobs and can thus be great representatives for the field

Science Café Course: An Innovative Means of Improving Communication Skills of Undergraduate Biology Majors

To help bridge the increasing gap between scientists and the public, we developed an innovative two-semester course, called Science Café. In this course undergraduate biology majors learn to develop communication skills to be better able to explain science concepts and current developments in science to non-scientists. Students develop and host outreach events on various topics relevant to the community, thereby increasing interactions between budding scientists and the public. Such a Science Cafe course emphasizes development of science communication skills early, at the undergraduate level and empowers students to use their science knowledge in every day interactions with the public to increase science literacy, get involved in the local community and engage the public in a dialogue on various pressing science issues. We believe that undergraduate science majors can be great ambassadors for science and are often overlooked since many aspire to go on to medical/veterinary/pharmacy schools. However, science communication skills are especially important for these types of students because when they become healthcare professionals, they will interact with the public as part of their everyday jobs and can thus be great representatives for the field