Disordered DNA repair in tumor cells as affected by sarcolysine

Sarcolysine-induced damaging and reparative processes in the primary structure of tumour cell DNA have been studied. The presence of low sarcolysine concentrations (1 mkM) in the cell culture during the first two hours of incubation caused suturing of DNA molecules. The increase of the incubation time from 4 to 18 hours and the rise in the drug concentration (by 10.20 times and more) resulted in intensive accumulation of one-strand breaks. However, we have not observed the appearance of high-molecular DNA, which is the evidence of the completion of the reparative process. The impulse treatment with sarcolysine (1 hour, 10 mkM) with subsequent drug removal caused the irreversible damage of DNA reparative processes at the stage of short fragments' suturing.     

Normal killer function in CBA mice as affected by long-term intake of tritium oxide

A study was made of the cytotoxic function of normal killers of CBA mice during long-term administration of tritium oxide in potable water (a cumulative absorbed dose of 8.7 Gy, dose-rate, 4.5 Gy/day) and at different times after termination of the radionuclide injection. A mean decrease of 20-30% in the lytic effect of the effectors from spleen of the experimental mice on cell-targets of K-562 human erythroleukosis was demonstrated by a 17-19-hour test with 51Cr. At later times after termination of action of tritium oxide, the cytotoxic effect of normal killers increased by 1.8 times as compared to intact controls of the same age.     

Impaired long-term potentiation and long-term memory deficits in xCT-deficient sut mice

xCT is the functional subunit of the cystine/glutamate antiporter system xc-, which exchanges intracellular glutamate with extracellular cystine. xCT has been reported to play roles in the maintenance of intracellular redox and ambient extracellular glutamate, which may affect neuronal function. To assess a potential role of xCT in the mouse hippocampus, we performed fear conditioning and passive avoidance for long-term memories and examined hippocampal synaptic plasticity in wild-type mice and xCT-null mutants, sut mice. Long-term memory was impaired in sut mice. Normal basal synaptic transmission and short-term presynaptic plasticity at hippocampal Schaffer collateral-CA1 synapses were observed in sut mice. However, LTP (long-term potentiation) was significantly reduced in sut mice compared with their wild-type counterparts. Supplementation of extracellular glutamate did not reverse the reduction in LTP. Taken together, our results suggest that xCT plays a role in the modulation of hippocampal long-term plasticity.     

Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice

Voltage-dependent N-type Ca(2+) channels, along with the P/Q-type, have a crucial role in controlling the release of neurotransmitters or neuromodulators at presynaptic terminals. However, their role in hippocampus-dependent learning and memory has never been examined. Here, we investigated hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses in mice deficient for the alpha(1B) subunit of N-type Ca(2+) channels. The mutant mice exhibited impaired learning and memory in the Morris water maze and the social transmission of food preference tasks. In particular, long-term memory was impaired in the mutant mice. Interestingly, among activity-dependent long-lasting synaptic changes, theta burst- or 200-Hz-stimulation-induced long-term potentiation (LTP) was decreased in the mutant, compared with the wild-type mice. This type of LTP is known to require brain-derived neurotrophic factor (BDNF). It was found that both BDNF-induced potentiation of field excitatory postsynaptic potentials and facilitation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) were reduced in the mutant. Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP.     

Antigen-nonspecific suppression of the immune response in mice as affected by pertussis vaccine

A study was made of the suppressorgenic action of killed whole-cell pertussis vaccine prepared from B. pertussis strains 475 and 305. Thymic and splenic lymphocytes of CBA mice 3-7 days following intraperitoneal or intravenous inoculation of pertussis vaccine were shown to inhibit in an antigen-nonspecific manner the plaque-forming cell (PFC) production in the adoptive transfer experiments. Suppression of graft-versus-host reaction was also observed, estimated by the survival of irradiated (CBA X C57BL/6) Fl mice, or by measuring the endogenous colony formation. Suppression-mediating cells were found to be susceptible to complement-dependent lysis by the anti-I-Jk alloantiserum against the specific marker of suppressor T cells, antigen I-J. Furthermore, thymocytes of pertussis vaccine-treated mice were shown to inhibit the endogenous colony formation in syngeneic mice irradiated in sublethal dose. Thus, B. pertussis vaccination of CBA mice resulted in appearance of suppressor T cells that exerted various inhibitory activities in several experimental test-systems.     

Colony-forming activity of hematopoietic stem cells in tolerant mice as affected by antigens

The effect of sheep red blood cells (SRBC) and human red blood cells (HRBC) on the amount of CFUs in the bone marrow and spleen of (CBA X C57BL/6) FI SRBC-tolerant mice was studied. The increase in the number of bone marrow and spleen CFUs was demonstrated in SRBC-tolerant mice injected with HRBC. Using SRBC test injection the increase in CFUs amount was observed in the spleen, but not the bone marrow, where the amount of CFUs remained unchanged.     

Dynamics of bacterial communities in rice field soils as affected by different long-term fertilization practices

Fertilization and the response of the soil microbial community to the process significantly affect crop yield and the environment. In this study, the seasonal variation in the bacterial communities in rice field soil subjected to different fertilization treatments for more than 50 years was investigated using 16S rRNA sequencing. The simultaneous application of inorganic fertilizers and rice straw compost (CAPK) maintained the species richness of the bacterial communities at levels higher than that in the case of non-fertilization (NF) and application of inorganic fertilizers only (APK) in the initial period of rice growth. The seasonal variation in the bacterial community structure in the NF and APK plots showed cyclic behavior, suggesting that the effect of season was important; however, no such trend was observed in the CAPK plot. In the CAPK plot, the relative abundances of putative copiotrophs such as Bacteroidetes, Firmicutes, and Proteobacteria were higher and those of putative oligotrophs such as Acidobacteria and Plactomycetes were lower than those in the other plots. The relative abundances of organotrophs with respiratory metabolism, such as Actinobacteria, were lower and those of chemoautotrophs that oxidize reduced iron and sulfur compounds were higher in the CAPK plot, suggesting greater carbon storage in this plot. Increased methane emission and nitrogen deficiency, which were inferred from the higher abundances of Methylocystis and Bradyrhizobium in the CAPK plot, may be a negative effect of rice straw application; thus, a solution for these should be considered to increase the use of renewable resources in agricultural lands.     

长期施肥对农田杂草的影响及其适应性进化研究进展

杂草一方面与作物竞争资源而造成作物减产,另一方面在维持农田生态平衡以及保持农田可持续利用方面起着不可或缺的作用.化学肥料的施用显著加快了农田土壤肥力演变的进程,也直接影响了农田杂草的生长、群落演替及遗传进化.因此,如何科学合理地制定农田养分管理对策是现代农业发展的现实问题.本文就长期施肥对农田杂草物种、群落结构的影响以及杂草的遗传与适应性进化三个方面的研究结果进行了收集整理;综合分析了杂草营养管理的薄弱环节,指出在治理杂草的同时也要考虑到保持杂草群落的生物多样性,提出加强对长期不同施肥方式下的杂草遗传多样性及其分子生态适应性方面的研究,以评价在土壤施肥选择压力下的杂草遗传多样性,评估杂草的生存与进化潜力及其适应性进化的分子机制,为科学制定杂草综合管理策略提供更广阔的思路.     

Biology and predatory efficiency of two phytoseiid mites as affected by long-term pollen feeding

The predatory mites,Amblyseius gossypi Elbadry andPhytoseius plumifer (Canestrini & Fanzago) successfully went through three generations on a diet of castor-oil pollen and were able to return to their natural prey,Tetranychus arabicus Attiah, apparently unaffected in a way except for a reduction in the predatory efficiency of adultA. gossypi.     

工作记忆的负荷影响心理旋转任务中的性别差异

目的:探讨心理旋转任务中的性别差异是否受工作记忆的负荷的影响。方法:采用先后呈现提示刺激和目标刺激的范式,任务分为三种:1.无效提示的数字旋转;2.有效提示的数字旋转;3.有效提示的PMA图形旋转。结果:重复测量的方差分析表明:对无效提示的数字旋转任务,男性和女性之间的反应时和正确率都无差异;对有效提示的数字旋转任务,男性和女性之间的正确率无差异,而反应时的差异边缘显著;对有效提示的PMA图形旋转任务,男性和女性之间的正确率无差异,而反应时有显著差异。结论:工作记忆的负荷可能会影响心理旋转任务中的性别差异。     

Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice

Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.     

Repertoire of antibody response in bone marrow and the memory response are differentially affected in aging mice

The primary burst of Ab and germinal center (GC) formation in response to T-dependent Ag is compromised in aging mice. Here we examine the effects of aging on the post-GC phase of memory B cell differentiation and the late Ab repertoire maturation in bone marrow (BM) in mice immunized with a hapten nitrophenyl coupled to chicken gamma-globulin. Specific Ab-forming cells (AFC) with mutated V(H) genes accumulated preferentially in the BM of aged mice, although the AFC numbers and average number of mutations per V(H) were lower, and the D gene usage was less restricted compared with those in the young animals. However, the repertoire of AFC after an Ag boost demonstrated the hallmarks of Ag selection, including the recurrent mutations and canonical VD rearrangements, similar to the late primary response in young animals. It is postulated that the Ab repertoire maturation in aged mice is delayed and may be notably improved by repeated immunizations.     

Sentence memory affected by vasopressin analog (DDAVP) in cross-over experiment

DDAVP has been shown to facilitate memory, especially retrieval, in humans. Healthy young male adult subjects received DDAVP (60 micrograms) in a cross-over design with a one-week interval between sessions. Results indicated that DDAVP improved immediate memory during the first but not the second testing session, particularly for low-verbal subjects. Treatment with DDAVP also facilitated delayed (one-week) recall in the opposite group, a cross-over interaction that suggests a retrieval locus for the DDAVP effect. Furthermore, since DDAVP improved immediate memory more for low-verbal subjects and delayed memory more for high-verbal subjects, it appears that individual difference factors will be important in understanding the effects of vasopressin on memory.     

Appearance of the signs of stress in mice as affected by lymphoid cells from syngeneic hypokinetic animals

Lymphoid cells of the spleen were transferred from F1(CBA X C57BL/6) mice exposed to hypokinesia for 17 hours to unoperated and partially hepatectomized syngeneic recipients. It caused (on days 2, 3 and 7) changes in the body weight, thymus, spleen, adrenals and in proliferative activity of hepatocytes in the intact and regenerating liver, with these changes being similar to those induced by stress alone.     

Multicompartmental LC-Q-TOF-based metabonomics as an exploratory tool to identify novel pathways affected by polyphenol-rich diets in mice

Metabonomics has recently been used to study the physiological response to a given nutritional intervention, but such studies have usually been restricted to changes in either plasma or urine. In the present study, we demonstrate that the use of LC-Q-TOF-based metabolome analyses (foodstuff, plasma, urine, and caecal content metabolomes) in mice offer higher order information, including intra- and intercompartment relationships. To illustrate this, we performed an intervention study with three different phenolic-rich extracts in mice over 3 weeks. Both unsupervised (PCA) and supervised (PLS-DA) multivariate analyses used for pattern recognition revealed marked effects of diet in each compartment (plasma, urine, and caecal contents). Specifically, dietary intake of phenolic-rich extract affects pathways such as bile acid and taurine metabolism. Q-TOF-based metabonomics demonstrated that the number of correlations is higher in caecal contents and urine than in plasma. Moreover, intercompartment correlations showed that caecal contents-plasma correlations are the most frequent in mice, followed by plasma-urine ones. The number of inter- and intracompartment correlations is significantly affected by diet. These analyses reveal the complexity of interorgan metabolic relationships and their sensitivity to dietary changes.     

Mycorrhizal fungal abundance is affected by long-term climatic manipulations in the field

Climate change treatments – winter warming, summer drought and increased summer precipitation – have been imposed on an upland grassland continuously for 7 years. The vegetation was surveyed yearly. In the seventh year, soil samples were collected on four occasions through the growing season in order to assess mycorrhizal fungal abundance. Mycorrhizal fungal colonisation of roots and extraradical mycorrhizal hyphal (EMH) density in the soil were both affected by the climatic manipulations, especially by summer drought. Both winter warming and summer drought increased the proportion of root length colonised (RLC) and decreased the density of external mycorrhizal hyphal. Much of the response of mycorrhizal fungi to climate change could be attributed to climate‐induced changes in the vegetation, especially plant species relative abundance. However, it is possible that some of the mycorrhizal response to the climatic manipulations was direct – for example, the response of the EMH density to the drought treatment. Future work should address the likely change in mycorrhizal functioning under warmer and drier conditions.     

2-Chloro-2'-deoxyadenosine synergistically enhances azidothymidine cytotoxicity in azidothymidine resistant T-lymphoid cells

This report presents quantitative analysis of the synergistic interaction of azidothymidine (AZT) and cladribine (CdA) in human H9-lymphoid cell lines sensitive and resistant to AZT (H9-araC cells). H9-araC cells obtained by cultivation of H9 cells in the presence of 0.5 microM arabinosyl-cytosine (araC) had lower deoxycytidine kinase and thymidine kinase (TK) activities and expressed cross-resistance to araC and AZT. The IC(50) values of AZT and CdA were calculated by using median-effect analysis and CalcuSyn software. The IC(50) values were 0.44 and 0.82 microM for CdA and 67.8 and 30,310 microM for AZT in H9 and H9-araC cells, respectively. However, when the drugs were used in combination the IC(50) values of CdA and AZT were reduced to 0.12 and 15.5 microM in H9 cells and to 0.19 and 24.9 microM in H9-araC cells, respectively. Calculation of dose reduction index (DRI) indicated that at 50-90% growth inhibition level, the combination of the drugs caused 3.6-5.8- and 4.1-11.5-fold reduction in the dose of CdA and 4.4-37.6- and > 1000-fold reduction in the dose of AZT in H9 and H9-araC cells, respectively. The combination index (CI) values simulated from these data suggested synergistic to very strong synergistic lymphocytotoxic effects of AZT combined with CdA. These findings suggest the potential usefulness of a double-targeted approach for designing efficacious therapeutics for the kinase deficient drug resistant tumors.     

Mechanisms of long-term memory

Long-term potentiation (LTP) of the hippocampus provides an excellent model on which to build hypotheses for the laying down of memories in the cerebral cortex. After repetitive activation, the primary happening seems to be the increase in transmitter sensitivity brought about by the increased Ca2+ in the recipient neurons. There may be secondary presynaptic changes. The extreme duration of the LTP may require structural changes of the synaptic spines. The hippocampus plays an essential role in the laying down of cognitive memories, the pathway to the frontal lobe being via the MD thalamus. The thalamo-cortical fibres activate stellate cells whose axons make climbing fibre-like ramifications up the apical dendrites of the pyramidal cells. On the Marr hypothesis repetitive conjunction of synaptic activation by these climbing fibres with synaptic activation by horizontal fibres on the apical dendrites produces prolonged potentiation of the horizontal fibre synapses, which is the neural basis of memory. Presumably this is a consequence of the raised Ca2+ of the apical dendrites, acting as it does on the hippocampal LTP. It will be considered how this elemental unit for cerebral memory can be developed into the varieties of cerebral memories that have been located by study of the regional cerebral blood flow during their retrieval. These sites for memory are in the frontal lobe, usually in the superior prefrontal area.