Novel Role of Prostate Apoptosis Response-4 Tumor Suppressor in B-Cell Chronic Lymphocytic Leukemia

Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition. Lack of Par-4 also increased the expression of p21 and delayed CLL growth in Eμ-Tcl1 mice. Par-4 expression in CLL cells required constitutively active B-cell receptor (BCR) signaling, as inhibition of BCR signaling with US Food and Drug Administration (FDA)–approved drugs caused a decrease in Par-4 messenger RNA and protein, and an increase in apoptosis. In particular, activities of Lyn, a Src family kinase, spleen tyrosine kinase, and Bruton tyrosine kinase are required for Par-4 expression in CLL cells, suggesting a novel regulation of Par-4 through BCR signaling. Together, these results suggest that Par-4 may play a novel progrowth rather than proapoptotic role in CLL and could be targeted to enhance the therapeutic effects of BCR-signaling inhibitors

Active Amplification of the Terrestrial Albedo to Mitigate Climate Change: An Exploratory Study

This study explores the potential to enhance the reflectance of solar insolation by the human settlement and grassland components of the Earth's terrestrial surface as a climate change mitigation measure. Preliminary estimates derived using a static radiative transfer model indicate that such efforts could amplify the planetary albedo enough to offset the current global annual average level of radiative forcing caused by anthropogenic greenhouse gases by as much as 30 percent or 0.76 W/m2. Terrestrial albedo amplification may thus extend, by about 25 years, the time available to advance the development and use of low-emission energy conversion technologies which ultimately remain essential to mitigate long-term climate change. However, additional study is needed to confirm the estimates reported here and to assess the economic and environmental impacts of active land-surface albedo amplification as a climate change mitigation measure.Comment: 21 pages, 3 figures. In press with Mitigation and Adaptation Strategies for Global Change, Springer, N

Interleukin-10 Mediated Autoregulation of Murine B-1 B-Cells and Its Role in Borrelia hermsii Infection

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-κB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10−/− mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B-1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity

Radiation Induced Apoptosis of Murine Bone Marrow Cells is Independent of Early Growth Response 1 (EGR1)

An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis—p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA) nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies

Effects of Soil Water and Nitrogen on Growth and Photosynthetic Response of Manchurian Ash (Fraxinus mandshurica) Seedlings in Northeastern China

Soil water and nitrogen (N) are considered to be the main environmental factors limiting plant growth and photosynthetic capacity. However, less is known about the interactive effects of soil water and N on tree growth and photosynthetic response in the temperate ecosystem. seedlings. The seedlings were exposed to three water regimes including natural precipitation (CK), higher precipitation (HW) (CK +30%) and lower precipitation (LW) (CK −30%), and both with and without N addition for two growing seasons. We demonstrated that water and N supply led to a significant increase in the growth and biomass production of the seedlings. LW treatment significantly decreased biomass production and leaf N content, but they showed marked increases in N addition. N addition could enhance the photosynthetic capability under HW and CK conditions. Leaf chlorophyll content and the initial activity of Rubisco were dramatically increased by N addition regardless of soil water condition. The positive relationships were found between photosynthetic capacity, leaf N content, and SLA in response to water and N supply in the seedling. Rubisco expression was up-regulated by N addition with decreasing soil water content. Immunofluorescent staining showed that the labeling for Rubisco was relatively low in leaves of the seedlings under LW condition. The accumulation of Rubisco was increased in leaf tissues of LW by N addition. seedlings, which may provide novel insights on the potential responses of the forest ecosystem to climate change associated with increasing N deposition

Loss of rachis cell viability is associated with ripening disorders in grapes

Rachises of grape (Vitis vinifera L.) clusters that appeared healthy or displayed symptoms of the ripening disorders berry shrivel (BS) or bunch-stem necrosis (BSN) were treated with the cellular viability stain fluorescein diacetate and examined by confocal microscopy. Clusters with BS and BSN symptoms experienced a decrease of cell viability throughout the rachis, and their berries contained 70-80% less sugar than healthy berries. The xylem-mobile dye basic fuchsin, infiltrated via the cut base of shoots with one healthy and one BS cluster, moved to all berries on the healthy cluster but generally failed to move into the peduncle of the BS cluster. Peduncle girdling did not interrupt dye movement in the xylem, but stopped solute accumulation in berries and led to berry shrinkage. In contrast, surgically destroying the peduncle xylem at the onset of ripening did not affect berry growth and solute accumulation. These results indicate that cessation of sugar and water accumulation in BS and BSN is associated with phloem death in the rachis. Although xylem flow to the berries may also cease, a functional xylem connection to the shoot may not be required for normal ripening, while water loss from berries by transpiration and xylem efflux may explain the characteristic berry shrinkage that is associated with these ripening disorders. The similarity of internal tissue breakdown in BS and BSN rachises and the correlation observed here between the proportion of shrinking berries on a cluster and the severity of rachis necrosis suggest that there may be a gradual transition between the two ripening disorders. Seeds from healthy and BS clusters showed no differences in colour, morphology, weight, viability, and ability to germinate, which indicates that the disorder may not appear until seeds are mature