NUCLEAR-CYTOPLASMIC RELATIONS IN THE MITOSIS OF SEA URCHIN EGGS : III. γ-Ray-Induced Damage to Whole Eggs and Nucleate and Anucleate Half-Eggs

Sea urchin eggs were cut into halves. The nucleate and anucleate halves and whole eggs were irradiated with γ-rays and then fertilized with normal sperm. The first mitosis of the diploid half-egg was more delayed than the division of the whole egg. There was a small, but highly significant, delay of the mitosis of the haploid half-egg, thus demonstrating cytoplasmic sensitivity to ionizing radiation. Since the sensitivity of nucleate cells is influenced by cytoplasmic volume, the problem of the role of cytoplasm in repair is considered in relation to these data and other reports in the literature.     

Strategies for organ level tissue engineering

The field of tissue engineering has made considerable strides since it was first described in the late 1980s. The advent and subsequent boom in stem cell biology, emergence of novel technologies for biomaterial development and further understanding of developmental biology have contributed to this accelerated progress. However, continued efforts to translate tissue-engineering strategies into clinical therapies have been hampered by the problems associated with scaling up laboratory methods to produce large, complex tissues. The significant challenges faced by tissue engineers include the production of an intact vasculature within a tissue-engineered construct and recapitulation of the size and complexity of a whole organ. Here we review the basic components necessary for bioengineering organs-biomaterials, cells and bioactive molecules-and discuss various approaches for augmenting these principles to achieve organ level tissue engineering. Ultimately, the successful translation of tissue-engineered constructs into everyday clinical practice will depend upon the ability of the tissue engineer to "scale up" every aspect of the research and development process.     

From Transient to Steady-state Response of Ecosystems to Atmospheric CO2-enrichment and Global Climate Change: Conceptual Challenges and Need for an Integrated Approach

Evidence continues to accumulate that humans are significantly increasing atmospheric CO₂ concentrations, resulting in unprecedented changes in the global climate system. Experimental manipulations of terrestrial ecosystems and their components have greatly increased our understanding of short-term responses to these global perturbations and have provided valuable input to ecosystem, dynamic vegetation, and global scale models. However, concerns exist that these initial experimental responses may be transitory, thereby limiting our ability to extrapolate short-term experimental responses to infer longer-term effects. To do these extrapolations, it will be necessary to understand changes in response patterns over time, including alterations in the magnitude, direction, and rate of change of the responses. These issues represent one of our largest challenges in accurately predicting longer-term changes in ecosystems and associated feedbacks to the climate system. Key issues that need to be considered when designing future experiments or refining models include: linear vs. non-linear responses, direct vs. indirect effects, lags in response, acclimation, resource limitation, homeostasis, buffers, thresholds, ecosystem stoichiometry, turnover rates and times, and alterations in species composition. Although experimental and landscape evidence for these response patterns exist, extrapolating longer-term response patterns from short-term experiments will ultimately require a unified multidisciplinary approach, including better communication and collaboration between theoreticists, experimentalists and modelers.     

The distribution of DNA among dividing mitochondria of Tetrahymena pyriformis

A squash technique was developed for log phase Tetrahymena pyriformis which permitted the resolution of over 100 individual mitochondria from a single cell. Mitochondria incorporated thymidine at all stages of the cell cycle, even when nuclear DNA synthesis was not occurring. During the stage of macronuclear DNA synthesis, however, there was a significant increase in the extent of mitochondrial labeling. Low radioautograph background suggests that mitochondrial DNA is synthesized at the mitochondria themselves. All mitochondria incorporated thymidine-3H within one population-doubling time. Grain counts also showed that the amount of mitochondrial label was retained for four generations and that this label remained randomly distributed among all mitochondria during this time. The results are not consistent with any theory of de-novo or "microbody" origin of mitochondria, but do support the hypothesis that mitochondria are produced by the growth and division of preexisting mitochondria. The stability of the mitochondrial DNA and its distribution among daughter mitochondria satisfy two prerequisites for a genetic material. The possibility is discussed that some of the genetic information for the mitochondrion is contained in the DNA associated with this organelle.     

Forest biogeochemistry in response to drought

Trees alter their use and allocation of nutrients in response to drought, and changes in soil nutrient cycling and trace gas flux (N₂O and CH₄) are observed when experimental drought is imposed on forests. In extreme droughts, trees are increasingly susceptible to attack by pests and pathogens, which can lead to major changes in nutrient flux to the soil. Extreme droughts often lead to more common and more intense forest fires, causing dramatic changes in the nutrient storage and loss from forest ecosystems. Changes in the future manifestation of drought will affect carbon uptake and storage in forests, leading to feedbacks to the Earth's climate system. We must improve the recognition of drought in nature, our ability to manage our forests in the face of drought, and the parameterization of drought in earth system models for improved predictions of carbon uptake and storage in the world's forests.     

PDL1 Expression on Plasma and Dendritic Cells in Myeloma Bone Marrow Suggests Benefit of Targeted anti PD1-PDL1 Therapy

In this study we set out to investigate whether anti PDL1 or PD–1 treatment targeting the immune system could be used against multiple myeloma. DCs are important in regulating T cell responses against tumors. We therefore determined PDL1 and PDL2 expression on DC populations in bone marrow of patients with plasma cell disorders using multicolour Flow Cytometry. We specifically looked at CD141⁺ and CD141^- myeloid and CD303⁺ plasmacytoid DC. The majority of plasma cells (PC) and DC subpopulations expressed PDL1, but the proportion of positive PDL1+ cells varied among patients. A correlation between the proportion of PDL1⁺ PC and CD141⁺ mDC was found, suggesting both cell types could down-regulate the anti-tumor T cell response.