NEXUS/Physics: An interdisciplinary repurposing of physics for biologists

In response to increasing calls for the reform of the undergraduate science curriculum for life science majors and pre-medical students (Bio2010, Scientific Foundations for Future Physicians, Vision & Change), an interdisciplinary team has created NEXUS/Physics: a repurposing of an introductory physics curriculum for the life sciences. The curriculum interacts strongly and supportively with introductory biology and chemistry courses taken by life sciences students, with the goal of helping students build general, multi-discipline scientific competencies. In order to do this, our two-semester NEXUS/Physics course sequence is positioned as a second year course so students will have had some exposure to basic concepts in biology and chemistry. NEXUS/Physics stresses interdisciplinary examples and the content differs markedly from traditional introductory physics to facilitate this. It extends the discussion of energy to include interatomic potentials and chemical reactions, the discussion of thermodynamics to include enthalpy and Gibbs free energy, and includes a serious discussion of random vs. coherent motion including diffusion. The development of instructional materials is coordinated with careful education research. Both the new content and the results of the research are described in a series of papers for which this paper serves as an overview and context.Comment: 12 page

Bridging The Gaps: How Students Seek Disciplinary Coherence In Introductory Physics For Life Science

Students in one discipline often receive their scientific training from faculty in other disciplines. As a result of tacit disciplinary differences, especially as implemented in courses at the introductory college level, such students can have difficulty in understanding the nature of the knowledge they are learning in a discipline that they do not identify as their own. We developed a course in introductory physics for life science (IPLS) students that attempts to help them cross disciplinary boundaries. By analyzing student reasoning during recitation sections and interviews, we identified three broad ways in which students in our course meaningfully crossed boundaries: (i) by unpacking biochemical heuristics in terms of underlying physical interactions, (ii) by locating both biochemical and physical concepts within a mathematical bridging expression, and (iii) by coordinating functional and mechanistic explanations for the same biological phenomenon. Drawing on episodes from case-study interviews and in-class problem-solving sessions, we illustrate how each of these types of boundary crossing involves the coordination of students’ conceptual and epistemological resources from physics, chemistry, and biology in distinct but complementary ways. Together, these boundary crossing categories form a theoretical framework for classifying student coherence seeking. We explore how the IPLS course helps our life science students fill in the gaps that exist between traditional introductory courses, by finding and exploring questions that might otherwise fall through disciplinary cracks. By identifying these types of explanatory coherence, we hope to suggest ways of inviting life science students to participate in physics and see physics as a tool for making sense of the living world

Use of RIP to inactivate genes in Neurospora crassa.

About two years ago we suggested that a novel genetic mechanism, operating in the period between fertilization and nuclear fusion in Neurospora, scans the genome for sequence dupliations and alters them (Selker E. et al. 1987 Cell 51:741-752)

Focal therapy for prostate cancer: revolution or evolution?

The face of prostate cancer has been dramatically changed since the late 1980s when PSA was introduced as a clinical screening tool. More men are diagnosed with small foci of cancers instead of the advanced disease evident prior to PSA screening. Treatment options for these smaller tumors consist of expectant management, radiation therapy (brachytherapy and external beam radiotherapy) and surgery (cryosurgical ablation and radical prostatectomy). In the highly select patient, cancer specific survival employing any of these treatment options is excellent, however morbidity from these interventions are significant. Thus, the idea of treating only the cancer within the prostate and sparing the non-cancerous tissue in the prostate is quite appealing, yet controversial. Moving forward if we are to embrace the focal treatment of prostate cancer we must: be able to accurately identify index lesions within the prostate, image cancers within the prostate and methodically study the litany of focal therapeutic options available

Analysis of hemopoietic lineage of accessory cells in the developing thymus of Xenopus laevis.

Abstract The developmental history of accessory cells in the thymus was studied by grafting hemopoietic stem cells into cytogenetically distinct frog embryos (diploid-2N or triploid-3N) before the establishment of circulation and overt differentiation and colonization of the thymus. The DNA content of cortical thymocytes and circulating erythrocytes was quantified by staining with propidium iodide and measuring the amount of red fluorescence emitted by individual nuclei with the use of flow cytometry. Accessory cells from thymic medulla were separated by incubating for 2 hr on glass slides. For comparison, the developmental history of peritoneal macrophages was examined as representative, myeloid-derived phagocytic cells. DNA content of adherent cells was quantified by staining with the DNA-specific Feulgen reaction and measuring light absorption of individual nuclei by microdensitometry. Thymic accessory cells were subdivided into phagocytic and nonphagocytic phenotypes on the basis of latex bead ingestion. Phagocytic cells in the thymus were usually nonspecific esterase positive and phenotypically resembled peritoneal macrophages. Nonphagocytic cells from the thymus were usually esterase negative and had a dendritic morphology characterized by branched cytoplasmic extensions. Nonphagocytic cells were positive for cytoplasmic RNA based on staining with methyl green-pyronin Y. Phagocytic cells from both the thymus and the peritoneal cavity had no levels of cytoplasmic RNA detectable by this method. Analysis of the embryonic derivation of thymic accessory cells, based on the proportion of cells carrying the cytogenetic marker, demonstrated that thymic lymphocytes and thymic accessory cells were a concordant pair of cells, distinct from myeloid-derived erythrocytes and possibly macrophages. These experiments provide circumstantial evidence suggesting thymocytes and thymic accessory cells could arise from a bipotential precursor that diverges into these separate lineages after colonization of the epithelial thymic rudiment during early development.</jats:p

Precursor immigration and thymocyte succession during larval development and metamorphosis in Xenopus.

Abstract The developing thymus in Xenopus was examined at four different levels: 1) precursor immigration of cytogenetically distinct embryonic stem cells; 2) waves of colonization during tadpole life and metamorphosis; 3) inter-thymic exchange of cells between separate lobes; and 4) development of cortical and medullary thymocytes. Based on the flow cytometric analysis of cytogenetically distinct thymocytes, there were at least two periods of stem cell immigration into the thymus, one during early larval life and the second before or during metamorphosis. Within the thymus, cohorts of cells derived from the first wave of immigration expanded at different times. The initial expansion occurred before 35 days of development. Cells involved in the second period of expansion were also derived from the initial immigrants, expanded after 35 days, and resulted in a turnover of thymocytes during the larval period. Precursor cells entering the thymus during metamorphosis expanded and resulted in an additional replacement of thymocytes. Cortical and medullary thymocytes were isolated from animals that received embryonic stem cell grafts. No differences in the presence or absence, or in the percentages, of donor thymocytes in these different fractions were observed. When limiting numbers of stem cells were transplanted, several cases of asymmetrical thymic lobe colonization were observed. These data suggested that an inter-thymic exchange of cells did not occur during larval life.</jats:p

Location of hemopoietic stem cells influences frequency of lymphoid engraftment in Xenopus embryos.

Abstract The first hemopoietic stem cells to differentiate in Xenopus embryos arise from ventral blood island (VBI) mesoderm. Progeny of these stem cells contribute to larval E, macrophage, thymocyte, and B lymphocyte populations. When small pieces of mesoderm are transplanted to a central location within the VBI, the contribution of this mesoderm is predominantly to erythropoiesis and engraftment of lymphoid populations is minimal. The present experiments examined the influence of position within the VBI on the contribution of single stem cells to lymphoid populations. Pieces of diploid VBI mesoderm, containing an average of one hemopoietic stem cell, were transplanted to either a central or a peripheral location within the defined boundaries of the VBI of triploid, stage matched embryos. The number of animals with donor-derived cells in lymphoid populations was markedly increased when stem cells were grafted to a peripheral position. In three cases, stem cells contributed to lymphoid populations at the exclusion of erythroid populations. These data were consistent with the notion of either a lymphoid stem cell or restricted B and T lymphocyte precursors. These data also suggested that during embryogenesis, stochastic differentiation of hemopoietic stem cells was influenced by regional differences in the VBI microenvironment.</jats:p

Intraembryonic origin of hepatic hematopoiesis in Xenopus laevis.

Abstract The liver is a major site of hematopoietic stem cell differentiation during vertebrate development. Hepatic hematopoiesis is dependent on colonization of the organ by extrinsically derived stem cells which, in mammals, are thought to originate only in the yolk sac. However, in birds and amphibians two distinct embryonic stem cell sources have been identified. The yolk sac or extraembryonic compartment is associated with the developing vitelline veins, and the para-aortic or intraembryonic compartment is associated with the dorsal aortae and postcardinal veins. The homologous compartments in the Xenopus embryo are the ventral blood island (extraembryonic) and dorsal lateral plate (intraembryonic) mesoderms, which contribute to primitive larval erythrocyte and definitive late larval and adult erythroid populations, respectively. The role of these embryonic stem cell sources in hepatic hematopoiesis has not been determined. We have examined the development of hepatic hematopoiesis in Xenopus 2N/3N stem cell chimeras using two-color FACS analysis. DNA content was determined using Hoechst 33342, and subpopulations of hematopoietic cells were identified with specific mAbs. Here we show that hepatic erythrocytes, leukocytes, and B lymphocytes in the liver of Xenopus larvae were derived from stem cells that originated from the intraembryonic mesoderm.</jats:p

Dual contribution of embryonic ventral blood island and dorsal lateral plate mesoderm during ontogeny of hemopoietic cells in Xenopus laevis.

Abstract The early embryonic development of hemopoietic cells in Xenopus laevis was examined. Either dorsal lateral plate (DLP) or ventral blood island (VBI) mesoderm was reciprocally transplanted between cytogenetically distinct (2N or 3N) stage 14 to 19 (neural fold) embryos. F-DNA content of circulating erythrocytes was assayed at stages 40, 41, 43, 45, and 49. The F-DNA content of cells in the thymus and mesonephros was assayed at stage 49. F-DNA values were used to distinguish between donor or host origin of hemopoietic cells in individual animals. The results demonstrated that DLP mesoderm gave rise to a population of stem cells that colonized the thymus and mesonephros, but not the blood. VBI mesoderm gave rise to a population of stem cells that colonized the blood and thymus, but not the mesonephros. These experiments show that there are two stem cell compartments in the amphibian embryo, separated in both space and time.</jats:p