Modification of radiation-induced genetic damage in Drosophila melanogaster male germ cells with nucleic acid precursors II. Effects on post-meiotic cells

Following the observation that the nucleoside pre-treatment reduced the radiation-induced dominant lethality in the post-meiotic germ cells, similar experiments were conducted using the same treatment conditions to study the influence of the nucleoside(s) pre-treatment on the radiation-induced (1.2 kR) incidence of sex-linked recessive lethals and translocation events in the post-meiotic male germ cells of 1-day-old D. melanogaster. The nucleoside pre-treatment reduced the translocation frequency (not statistically significant) and the lethal mutation frequency (statistically significant) in the post-meiotic cells (pre-injection DNA synthesis cells) especially in the mature sperms sampled in brood a (br a). The radio-protective effect of the nucleosides on the mature sperms was confirmed using 7-day-old virgin males and different radiation doses (2.4 kR and 3.6 kR).The frequency of lethal mutation was lowest when irradiation was preceded by the injection of an equimolar solution of thymidine (TdR), deoxyadenosine (AdR), deoxycytidine (CdR) and deoxyguanosine (GdR). However, when the nucleosides were injected after irradiation (within 10–30 min) there was no change in the yield of radiation-induced lethals.The possible mechanisms for the radioprotective action of the nucleosides in the post-meiotic germ cells such as (a) “protection” by a radiochemical action of nucleosides competing for short-lived radicals that might otherwise cause damage to DNA and (b) biochemical-physiological mechanisms such as metabolic events increasing the radioresistance of the cells, providing excess energy for repair or favoring and partaking in the DNA repair synthesis were discussed. Further studies were felt necessary to elucidate this phenomenon.     

Adaptability evaluation of switchgrass (Panicum virgatum L.) cultivars on the Loess Plateau of China

In the study, the growth traits, photosynthesis and morphology characteristics of several cultivars of switchgrass (Panicum virgatum L.) have been assessed the yield potential and adaptability in diverse environments (Yangling, Dingbian of Shaanxi province, Guyuan of Ningxia) on the Loess Plateau of China. Alamo was the best adapted switchgrass cultivar for biomass production in Yangling with dry matter (DM) yields of 44.22 t/ha; Illinois USA and Cave-in-Rock grown at Guyuan had DM yield of 10.59 t/ha and 9.36 t/ha, respectively. Similarly, Cave-in-Rock in Dingbian performed better than others except the lowland cultivars (Alamo and Kanlow), which could not overcome cold stress at Guyuan and Dingbian. Moreover, Cave-in-Rock and Nebraska 28 has the highest photosynthesis rate which reflects its high productivity. Nebraska 28 and Pathfinder shown strong drought tolerance due to their higher WUE. It appears that the upland cultivars with high ploidy (e.g. 8n) would have better establishment than lowland varieties there. Optimal mown management seems to enhance the growth and productivity of switchgrass. Morphological characteristics were further studied using light-and scanning electron microscopy (SEM). Silica particles, vacuole size and other traits in switchgrass tissues (stem, leaf and root), as well as trichomes (leaf) showed that Cave-in-Rock and Pathfinder had larger stoma area, up to 824.4 μm² and 770.1 μm², respectively. Silica particle length was the longest in Pathfinder and shortest in Cave-in-Rock. There was a highest density of silica particles in cv. Forestberg, and lowest in Cave-in-Rock and Pathfinder. The morphological characters seemed to be associated with their ploidy levels and the arid habitat from which they were selected. Therefore, if switchgrass is to be introduced and extended on the Loess Plateau of China, Cave-in-Rock and other upland cultivars with a high chromosome ploidy might be optimal choices for biomass plants.     

Waldenstr?m macroglobulinemia – immunophenotype and natural history

Despite encouraging progress in recent years, our knowledge of the natural history of Waldenström macroglobulinemia (WM), a low-grade LPL (lymphoplasmacytic lymphoma) of mature IgM⁺ B-lymphocytes, remains superficial. This is particularly true of the etiology of WM (tumor causation and initiation) and the sequence of events that underlie the malignant transformation of precursor B cells (tumor progression). Here we briefly review the epidemiology of and genetic predisposition to WM and consider the role of autoimmunity and chronic inflammation in related tumor development. We discuss the immunophenotypic features of WM, including the immunological specificity of WM-associated IgM paraproteins. The proclivity of patients with WM to develop the rare immunoglobulin autoantibody syndromes mixed IgM-IgG cryoglobulinemia, chronic cold agglutinin disease, and IgM neuropathy will also be discussed. We conclude with a call for additional research to elucidate outstanding questions, such as the role of T cell-dependent vs. –independent immune responses in the pathophysiology of WM.     

BAX insertion, oligomerization, and outer membrane permeabilization in brain mitochondria: Role of permeability transition and SH-redox regulation

BAX cooperates with truncated BID (tBID) and Ca²⁺ in permeabilizing the outer mitochondrial membrane (OMM) and releasing mitochondrial apoptogenic proteins. The mechanisms of this cooperation are still unclear. Here we show that in isolated brain mitochondria, recombinant BAX readily self-integrates/oligomerizes in the OMM but produces only a minuscule release of cytochrome c, indicating that BAX insertion/oligomerization in the OMM does not always lead to massive OMM permeabilization. Ca²⁺ in a mitochondrial permeability transition (mPT)-dependent and recombinant tBID in an mPT-independent manner promoted BAX insertion/ oligomerization in the OMM and augmented cytochrome c release. Neither tBID nor Ca²⁺ induced BAX oligomerization in the solution without mitochondria, suggesting that BAX oligomerization required interaction with the organelles and followed rather than preceded BAX insertion in the OMM. Recombinant Bcl-xL failed to prevent BAX insertion/oligomerization in the OMM but strongly attenuated cytochrome c release. On the other hand, a reducing agent, dithiothreitol (DTT), inhibited BAX insertion/oligomerization augmented by tBID or Ca²⁺ and suppressed the BAX-mediated release of cytochrome c and Smac/DIABLO but failed to inhibit Ca²⁺-induced swelling. Altogether, these data suggest that in brain mitochondria, BAX insertion/oligomerization can be dissociated from OMM permeabilization and that tBID and Ca²⁺ stimulate BAX insertion/oligomerization and BAX-mediated OMM permeabilization by different mechanisms involving mPT induction and modulation of the SH-redox state.     

Natural CD825 regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

Natural CD4⁺25⁺ and CD8⁺25⁺ regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8⁺25⁺ Tr cells from C57BL/6 mouse naive CD8⁺ T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO_Tr) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO_Tr had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC_OVA) plus Tr cells or EXO_Tr, and then assessed OVA-specific CD8⁺ T cell responses using PE-H-2K^b/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10_OVA melanoma cells. We demonstrated that DC_OVA-stimulated CD8⁺ T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC_OVA (p < 0.05) in immunized mice with co-injection of Tr cells and EXO_Tr, respectively. Our results indicate that natural CD8⁺25⁺ Tr cell-released EXOs, alike CD8⁺25⁺ Tr cells, can inhibit CD8⁺ T cell responses and antitumor immunity. Therefore, EXOs derived from natural CD4⁺25⁺ and CD8⁺25⁺ Tr cells may become an alternative for immunotherapy of autoimmune diseases.     

Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents

The interactions of the T cell receptor (TCR) with cognate MHC-peptide and co-stimulatory molecules expressed at surface of antigen presenting cells (APC) leads to activation or tolerance of T cells. The development of molecular biological tools allowed for the preparation of soluble MHC-peptide molecules as surrogate for the APC. A decade ago a monomeric class II MHC molecule in which the peptide was covalently linked to β-chain of class II molecule was generated. This type of molecule had a low-binding affinity and did not cause the multimerization of TCR. The requirement of multimerization of TCR led to development of a new class of reagents, chimeric peptides covalently linked to MHC that was dimerized via Fc fragment of an immunoglobulin and linked to 3' end of the β-chain of MHC class II molecule. These soluble dimerized MHC-peptide chimeric molecules display high affinity for the TCR and caused multimerization of TCR without processing by an APC. Because dimeric molecules are devoid of co-stimulatory molecules interacting with CD28, a second signal, they induce anergy rather the activation of T cells. In this review, we compare the human and murine dimerized MHC class II-peptides and their effect on CD4(+) T cells, particularly the generation of T regulatory cells, which make these chimeric molecules an appealing approach for the treatment of autoimmune diseases.     

中国陕西中三叠世直脉蝎蛉科和新直脉蝎蛉科新属、种(昆虫纲,长翅目)(英文)

记述直脉蝎蛉科两亚属的两新种和新直脉蝎蛉科1新属、种,并讨论其分类位置.这些新属种是本区独特的地方性类群,对地层划分与对比有一定的意义.化石标本采自陕西铜川中三叠统铜川组下段上部的灰绿色泥页岩.这些新属种也是铜川昆虫组合的新成员,属陕西昆虫群(系陕西生物群的一个化石类别).根据陕西生物群的特征,其时代相当欧洲中三叠世拉丁期(Ladinian Stage).