Effect of total lymphoid irradiation (TLI) on the primary and secondary antibody response to sheep red blood cells.

The effect of total lymphoid irradiation (TLI) on the primary and secondary hemagglutinin response to sheep red blood cells (SRBC) was studied in BALB/c mice. The primary response was eliminated for 1 month and began to return by Day 44. The latter response was IgM, and the IgG response did not return until approximately 200 days after TLI. The prolonged immunosuppression required inclusion of the thymus in the radiation field. Mice treated with single-dose whole-body irradiation (WBI) regained a normal IgG response within 28 days after irradiation. Immunization of mice prior to treatment with TLI or WBI resulted in a vigorous IgG response when mice were boosted 1 month after irradiation.     

Stabilization of Silver Chromate Golgi Impregnation in Rat Central Nervous System Neurons Using Photographic Developers. II. Electron Microscopy

The silver chromate precipitate present in neurons impregnated according to the Golgi-rapid and Golgi-Kopsch procedures can be stabilized by treatment with a photographic developer. In a complementary light microscopic study the stabilizing properties of various photographic developers were tested. Kodalith, Elon-ascorbic acid, HC-110, D-19 and Neutol proved to be the most successful. In the present electron microscopic study, we studied the distribution, shape and size of the particles found in Golgi-rapid and Golgi-Kopsch-impregnated neurons by treatment with each of these developers and, simultaneously, the effect of the developer on the preservation of the ultrastructural details. The reaction product after developer-treatment of Golgi-rapid material is sufficiently stable to withstand embedding and thin sectioning, whereas in Golgi-Kopsch material additional gold chloride “Honing” is necessary. In Golgi-impregnated, Kodalith-, Elon-ascorbic acid-, or HC-110-treated material the formed particles are small and located in the cytoplasm, limited by the plasma membranes of the impregnated profiles. In Golgi-impregnated, D-19 treated neurons, the formed particles are relatively coarse. The majority of these particles are within cytoplasm, but particles may also lie either across or entirely outside the plasma membranes of the impregnated profiles. A large number of the small particles in Golgi impregnated, Neutol-stabilized neurons can be seen partly or entirely outside the plasma membranes of the impregnated profiles. Good original ultrastructural preservation seems to be unaffected by developer treatment. Treatment of Golgi material with sodium bromide before stabilization (bromide substitution) results in the formation of small silver particles both inside and outside the impregnated profiles. The sodium bromide step of this procedure has an adverse effect on the preservation of ultrastructural detail.     

Natural regulatory T cells: mechanisms of suppression

Natural FOXP3+CD25+CD4+ regulatory T cells (Tregs) actively suppress pathological and physiological immune responses, contributing to the maintenance of immunological self-tolerance and immune homeostasis. Various molecular and cellular events have been described to explain the mechanism(s) of Treg-mediated suppression. However, none of the proposed mechanisms can explain all aspects of suppression. It is probable that various combinations of several mechanisms are operating, depending on the milieu and the type of immune responses, although there might be a single key mechanism that has a predominant role. Further studies of suppression and search for Treg-specific cell surface molecules are required for potential clinical application to treat and prevent immunological diseases and to control immune responses for the benefit of the host.     

Phenotypic plasticity and water flux rates of Citrus root orders under salinity

Knowledge about the root system structure and the uptake efficiency of root orders is critical to understand the adaptive plasticity of plants towards salt stress. Thus, this study describes the phenological and physiological plasticity of Citrus volkameriana rootstocks under severe NaCl stress on the level of root orders. Phenotypic root traits known to influence uptake processes, for example frequency of root orders, specific root area, cortical thickness, and xylem traits, did not change homogeneously throughout the root system, but changes after 6 months under 90 mM NaCl stress were root order specific. Chloride accumulation significantly increased with decreasing root order, and the Cl(-) concentration in lower root orders exceeded those in leaves. Water flux densities of first-order roots decreased to <20% under salinity and did not recover after stress release. The water flux densities of higher root orders changed marginally under salinity and increased 2- to 6-fold in second and third root orders after short-term stress release. Changes in root order frequency, morphology, and anatomy indicate rapid and major modification of C. volkameriana root systems under salt stress. Reduced water uptake under salinity was related to changes of water flux densities among root orders and to reduced root surface areas. The importance of root orders for water uptake changed under salinity from root tips towards higher root orders. The root order-specific changes reflect differences in vulnerability (indicated by the salt accumulation) and ontogenetic status, and point to functional differences among root orders under high salinity.     

T-cell receptor signaling and the pathogenesis of autoimmune arthritis: insights from mouse and man

The immune system has evolved to survey and respond appropriately to the universe of foreign pathogens, while at the same time deploying an intricate repertoire of mechanisms that keep responses to host tissues in check. For the adaptive immune system, specificity and sensitivity are provided by a large repertoire of antigen T-cell receptors (TCRs) constructed in their extracellular domain to recognize antigenic peptide fragments restricted and presented by histocompatibility complex molecules, and coupled through intracellular domains to signal transduction modules that serve to transmit environmental cues inside the cell. In this review we consider recent evidence that has provided insight into how altered TCR signaling thresholds could contribute to human autoimmune arthritis, including rheumatoid arthritis (RA), and the spondyloarthropathies (SpA). We also discuss mechanistic studies that demonstrate how perturbations of T-cell antigen receptor signaling in the SKG mouse model can promote systemic autoimmunity and the intersection with essential innate immune pathways that lead to the development of chronic inflammatory phenotypes.     

Survival of Schismus arabicus seedlings exposed to desiccation depends on annual periodicity

Schismus arabicus, a desert annual grass, is one of the most common pasture annuals in the deserts of Israel and Asia. S. arabicus exhibits a unique set of adaptations and survival strategies, which enable it to germinate, develop and produce seeds even in years with annual rainfall of less than 100 mm. The current study examined whether an annual rhythm exists in the survival ability of S. arabicus seedlings exposed to desiccation. Our results indicate that survival of S. arabicus seedlings after six different periods of 7 to 42 days of desiccation depended on the month of germination of the caryopses (seeds). Seed germination was 80–100% in all experiments, regardless the month of germination; however, seedlings that germinated in different months varied in their root and shoot elongation rates. None of about 2,500 seedlings that germinated in July (in each of the 4 years) survived the desiccation treatment. The percentages of surviving seedlings in each month of June from 2002 to 2005 were less than 40%. In contrast, over 80% of the seedlings that germinated in each of the months of December and January survived after the desiccation periods of 7–42 days. Seedlings that survived were transferred to 5 L soil pots in which the seedlings developed into mature plants, completed their life cycle and produced seeds that germinated well. The current study demonstrated a novel phenomenon indicating that seedling survival in plants may depend on an annual periodicity according to the date of germination.     

Telomere Shortening Sensitizes Cancer Cells to Selected Cytotoxic Agents: In Vitro and In Vivo Studies and Putative Mechanisms

Background

Telomere/telomerase system has been recently recognized as an attractive target for anticancer therapy. Telomerase inhibition results in tumor regression and increased sensitivity to various cytotoxic drugs. However, it has not been fully established yet whether the mediator of these effects is telomerase inhibition per se or telomere shortening resulting from inhibition of telomerase activity. In addition, the characteristics and mechanisms of sensitization to cytotoxic drugs caused by telomerase inhibition has not been elucidated in a systematic manner.

Methodology/Principal Findings

In this study we characterized the relative importance of telomerase inhibition versus telomere shortening in cancer cells. Sensitization of cancer cells to cytotoxic drugs was achieved by telomere shortening in a length dependent manner and not by telomerase inhibition per se. In our system this sensitization was related to the mechanism of action of the cytotoxic drug. In addition, telomere shortening affected also other cancer cell functions such as migration. Telomere shortening induced DNA damage whose repair was impaired after administration of cisplatinum while doxorubicin or vincristine did not affect the DNA repair. These findings were verified also in in vivo mouse model. The putative explanation underlying the phenotype induced by telomere shortening may be related to changes in expression of various microRNAs triggered by telomere shortening.

Conclusions/Significance

To our best knowledge this is the first study characterizing the relative impact of telomerase inhibition and telomere shortening on several aspects of cancer cell phenotype, especially related to sensitivity to cytotoxic drugs and its putative mechanisms. The microRNA changes in cancer cells upon telomere shortening are novel information. These findings may facilitate the development of telomere based approaches in treatment of cancer.     

Molecular imaging strategies for drug discovery and development

Recent advances in non-invasive molecular imaging provide exciting opportunities for discovery, validation and development of novel therapeutics. As the arsenal of detection devices and strategies, injectable probes, genetically encoded reporters and animal models rapidly expands, molecular imaging is becoming indispensable for drug discovery and development. Not only do such strategies reduce the time, cost and workload associated with conventional destructive end-point assays, but they also enable spatial and temporal monitoring of in vivo gene expression, signaling pathways, biochemical reactions and targets as they relate to the pharmacokinetics and pharmacodynamics of novel drugs.