Distraction during Deployment: Marital Relationship Associations with Spillover for Deployed Army Soldiers.

Military spouses often have concerns regarding the impact of their communication on soldiers during deployment. However, literature is mixed regarding how communication between soldiers and spouses may impact soldiers' self-reported work functioning during deployment, suggesting the need to evaluate moderating factors. In the current study, three relationship factors (marital satisfaction, conflictual communication, and proportion of conversation focused on problems) were tested as moderators of communication frequency and negative marriage-to-work spillover for soldiers. Whereas the three relationship factors were independently related to negative spillover, none significantly moderated the relationship between communication frequency and spillover. The overall pattern of results suggests that (a) lower marital satisfaction, a focus on problems during communication, and conflictual communication are each strongly linked to spillover for deployed soldiers, and (b) military couples may be self-restricting deployment communication frequency when experiencing less marital satisfaction and higher rates of negative communication. Implications for communication during deployment are discussed.

Sensitive response of the Greenland Ice Sheet to surface melt drainage over a soft bed.

The dynamic response of the Greenland Ice Sheet (GrIS) depends on feedbacks between surface meltwater delivery to the subglacial environment and ice flow. Recent work has highlighted an important role of hydrological processes in regulating the ice flow, but models have so far overlooked the mechanical effect of soft basal sediment. Here we use a three-dimensional model to investigate hydrological controls on a GrIS soft-bedded region. Our results demonstrate that weakening and strengthening of subglacial sediment, associated with the seasonal delivery of surface meltwater to the bed, modulates ice flow consistent with observations. We propose that sedimentary control on ice flow is a viable alternative to existing models of evolving hydrological systems, and find a strong link between the annual flow stability, and the frequency of high meltwater discharge events. Consequently, the observed GrIS resilience to enhanced melt could be compromised if runoff variability increases further with future climate warming.

Vaccination against tuberculosis in badgers and cattle: an overview of the challenges, developments and current research priorities in Great Britain.

Bovine tuberculosis (TB) is a significant threat to the cattle industry in England and Wales. It is widely acknowledged that a combination of measures targeting both cattle and wildlife will be required to eradicate bovine TB or reduce its prevalence until European official freedom status is achieved. Vaccination of cattle and/or badgers could contribute to bovine TB control in Great Britain, although there are significant gaps in our knowledge regarding the impact that vaccination would actually have on bovine TB incidence. Laboratory studies have demonstrated that vaccination with BCG can reduce the progression and severity of TB in both badgers and cattle. This is encouraging in terms of the prospect of a sustained vaccination programme achieving reductions in disease prevalence; however, developing vaccines for tackling the problem of bovine TB is challenging, time-consuming and resource-intensive, as this review article sets out to explain.

Heterogeneity in the risk of Mycobacterium bovis infection in European badger (Meles meles) cubs.

The behaviour of certain infected individuals within socially structured populations can have a disproportionately large effect on the spatio-temporal distribution of infection. Endemic infection with Mycobacterium bovis in European badgers (Meles meles) in Great Britain and Ireland is an important source of bovine tuberculosis in cattle. Here we quantify the risk of infection in badger cubs in a high-density wild badger population, in relation to the infection status of resident adults. Over a 24-year period, we observed variation in the risk of cub infection, with those born into groups with resident infectious breeding females being over four times as likely to be detected excreting M. bovis than cubs from groups where there was no evidence of infection in adults. We discuss how our findings relate to the persistence of infection at both social group and population level, and the potential implications for disease control strategies.

Study of lithium absorption by users of spas treated with lithium ion.

This study examines the possible dermal absorption of lithium ion into the blood serum of spa/hot tub bathers. Fifty-three participants (28 males and 25 females) spent 20 minutes per day, 4 days per week for 2 consecutive weeks in one of two assigned spas. The participants were randomly assigned to one of the two spas after matching based on sex, age, and use of oral contraceptives. The test spa contained 40 +/- 5 ppm lithium ion, while the control spa contained no additional lithium ion above the background levels of approximately 0.02 ppm. The exposure in the spa treated with lithium ion (from lithium chloride) simulated the maximum exposure that would be expected in a spa sanitized with lithium hypochlorite. The two spas were maintained at 101 +/- 2 degrees F. Serum lithium ion levels before and after spa use were determined using graphite-furnace atomic absorption spectroscopy with a minimum detectable level of lithium ion in serum of 2 micrograms l-1 (ppb). There was no statistically significant difference in serum lithium levels between the control and treatment group at any stage. We conclude that dermal exposure to lithium ion (as would be present after treatment of a spa with lithium hypochlorite) did not result in a detectable increase in the serum lithium ion level.

Effect of derivatives of chrysophanol, a new type of potential antitumor agents of anthraquinone family, on growth and cell cycle of L1210 leukemic cells.

The new C-methyl modified derivatives of the anthraquinones chrysophanol and emodin, recently synthesized by us, are potentially bifunctional agents having the ability to intercalate to nucleic acids and also having alkylating properties. Two of these compounds, namely 3-(N,N-bis(2-chloroethyl)-amino)methyl-1,8-dihydroxy-9,10-anthraquinone (Compound 31.662) and its 1,8-di-O-methylated analog (Compound 31.655) have been presently tested on murine leukemic L1210 cells in vitro with respect to their cell cycle specificity. During the initial 24 h of treatment the cytostatic effects of the drugs predominated, manifesting as suppression of cell progression through S (especially through the early portion of S phase) and G2. After 24 h, the cytotoxic effects became apparent, and there was also the appearance of cells with doubled DNA content suggestive of either endoreduplication or impairment of cytokinesis; these cells at higher ploidy level were progressing through S and G2. The observed effects were time- and dose-dependent, occurring at 0.1-0.4 micrograms/ml concentration of 31.662 and 2.0-10.0 micrograms/ml of its methylated analog, either during continuous- or after a 4-h pulse-treatment. Modulation of the cell cycle by the studied drugs is similar to that generally caused by intercalators as well as alkylating agents. However, because no positive evidence of intercalation of the studied drugs to nucleic acids was found, it is possible that alkylation of DNA or other cell constituents may be the primary lesion(s) leading to perturbation of the cell cycle.

Thermal stability of nucleosomes studied in situ by flow cytometry: effect of ionic strength and n-butyrate.

Heating of cells permeabilized with ethanol and resuspended in aqueous media increases accessibility of DNA to intercalating dyes such as acridine orange (AO). The curves, representing increase in binding of AO as a function of rise in temperature, indicate that the transitions are cooperative. The transitions are sensitive to ionic strength and occur at lower temperatures when cells are suspended in media of increasing ionic strength. Extraction of histones raises accessibility of DNA to intercalators at room temperature, and heating has little effect on additional binding. The results are interpreted as indicating thermal destruction of nucleosomal structure in nuclear chromatin; dissociation of DNA from core histones results in its increasing ability to intercalate AO, most likely due to increased topological freedom to undergo unwinding and elongation following binding of the intercalator. Preincubation of cells with n-butyrate, known to induce histone hyperacetylation, lowers the heat stability of nucleosomes by about 5 degrees C. On the other hand, no differences are observed between chromatin of mitotic vs interphase cells tested over a wide range of ionic strengths (0.1-0.7 N NaCl). The method appears to be useful as a probe of chromatin structure at the nucleosomal level.

Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent.

P-30 Protein is a novel protein, of molecular weight approximately 15 KD, obtained from the extract of a vertebrate tissue showing in vivo antitumour activity. Cytostatic and cytotoxic effects of this product in its purified form (P-30 Protein) or in partially purified extracts (Pannon) were studied in vitro on human leukaemic HL-60, human submaxillary carcinoma A-253, human colon adenocarcinoma Colo 320 CM and murine erythroleukaemia (Friend leukaemia) cell lines. Of these cells, HL-60, A-253 and Colo 320 CM were sensitive and Friend leukaemia resistant to this agent. The effects were time- and concentration-dependent. During the initial 24-48 h of treatment, a slowdown in cell proliferation was apparent but cell death was not extensive. After 24-48 h, there was a reduction in the proportion of cells in S phase of the cell cycle and the cells became preferentially arrested in G1 phase. The G1 cells showed high heterogeneity with respect to RNA content and some cells were characterized by very low RNA content. Progressive cell death occurred in cultures maintained with Pannon for up to 7 d in proportion to its concentration. Reductions of 50 and 90% in clonogenicity of A-253 cells were observed during their growth in the presence of 0.13 and 1.5 micrograms/ml of this protein, respectively. Exponentially growing cells were more sensitive to Pannon compared with cells from confluent cultures. Colonies of A-253 cells growing in the presence of Pannon were much smaller in size compared with control colonies, indicating that the rate of proliferation of clonogens is reduced by this agent. It appears that P-30 Protein induces cytostatic effects via modulation of cell transition to quiescence or differentiation. The mechanism of its cytotoxic activity is unclear.

Photosensitizing effects of the tricyclic heteroaromatic cationic dyes pyronin Y and toluidine blue O (tolonium chloride).

Pyronin Y [3,6-bis(dimethylamino)xanthylium chloride; PY] and toluidine blue O [tolonium chloride; 3-amino-7-(dimethylamino)-2-methyl phenothiazin-5-ium chloride; TB] are cationic dyes commonly used in cytochemistry that have affinity to nucleic acids, predominantly to RNA. In live cells these dyes accumulate in mitochondria and sensitize the cells to light. The photosensitizing effects of PY and TB were compared with those of another mitochondrial cationic dye, rhodamine 123, and a noncationic dye, merocyanine 540, which binds to the cell membrane. Ninety % reduction of clonogenicity of human epidermoid carcinoma (A-253) cells pretreated with 3.3 microM PY, 0.67 microM TB, 13 microM rhodamine 123, or 18 microM merocyanine 540 was achieved by cell exposure to 0.7, 1.0, 1.2, or 1.5 J/cm2 doses of white light, respectively. The above concentrations of PY, TB, or merocyanine 540 represent the maximal ones at which the effect of each of these dyes alone, in the dark, in reducing cell clonogenicity was less than 12%. Exposure of A-253 cells to light at doses reducing clonogenicity by 50% caused a transient (24 h) arrest of the surviving cell population in the G1 phase of the cell cycle. In contrast to A-253 cells, Chinese hamster ovary cells were highly resistant to the photosensitizing effects of each of the four dyes. Also, the normal human lung fibroblasts (WI-38) were highly resistant to photosensitization by PY, whereas the simian virus 40-transformed WI-38 cells and another carcinoma line (OV-3) were sensitive. The data suggest that PY and TB, like other mitochondrial dyes, may have a selective antitumor photosensitizing activity.

In situ factors affecting stability of the DNA helix in interphase nuclei and metaphase chromosomes.

The data from earlier cytochemical studies, in which the metachromatic fluorochrome acridine orange (AO) was used to differentially stain single vs double-stranded DNA, suggested that DNA in situ in intact metaphase chromosomes or in condensed chromatin of G0 cells is more sensitive to denaturation, induced by heat or acid, than DNA in decondensed chromatin of interphase nuclei. Present studies show that, indeed, DNA in permeabilized metaphase cells, in contrast to cells in interphase, when exposed to buffers of low pH (1.5-2.8) becomes digestible with the single-strand-specific S1 or mung bean nucleases. A variety of extraction procedures and enzymatic treatments provided evidence that the presence of histones, HMG proteins, and S-S bonds in chromatin, as well as phosphorylation or poly(ADP)ribosylation of chromatin proteins, can be excluded as a factor responsible for the differential sensitivity of metaphase vs interphase DNA to denaturation. Cell treatment with NaCl at a concentration of 1.2 N and above abolished the difference between interphase and mitotic cells, rendering DNA in mitotic cells less sensitive to denaturation; such treatment also resulted in decondensation of chromatin visible by microscopy. The present data indicate that structural proteins extractable with greater than or equal to 1.2 N NaCl may be involved in anchoring DNA to the nuclear matrix or chromosome scaffold and may be responsible for maintaining a high degree of chromatin compaction in situ, such as that observed in metaphase chromosomes or in G0 cells. Following dissociation of histones, the high spatial density of the charged DNA polymer may induce topological strain on the double helix, thus decreasing its local stability; this can be detected by metachromatic staining of DNA with AO or digestion with single-strand-specific nucleases.

Effect of recombinant tumor necrosis factor on HL-60 cells: cell-cycle specificity and synergism with actinomycin D.

The tumor necrosis factor (TNF) exhibits a multitude of activities depending on the type of target cells. We characterized the cytostatic and cytotoxic effects of recombinant TNF, alone and in combination with actinomycin D (AMD), on the human leukemic cell line HL-60. Because HL-60 cells, when triggered to monocytic differentiation by phorbol esters, are known to produce and secrete TNF, their sensitivity to the factor could indicate an autocrine function of TNF in this cell system. Indeed, HL-60 cells were affected by TNF; their doubling time was increased by about 50% and progression through the cell cycle was perturbed. Initially, (up to 8 h) TNF induced a temporary arrest in G2 while later (24-48 h) it delayed progression through the G1 phase. Also, a transient increase in RNA content peaking at 6-8 h was apparent. The cytotoxicity of TNF alone was low. Thus, TNF may be involved in the regulation of the cell cycle of HL-60 cells during early stages of their differentiation. The cytotoxicity of TNF was markedly potentiated in the presence of AMD; the effect was AMD but not TNF concentration-dependent. Whereas at 20 and 50 ng/ml of AMD alone nonviable cells did not exceed 20% during the first 24 h of treatment, their proportion increased to 80 and 90%, respectively, in the presence of TNF. The most sensitive were cells in the S phase of the cell cycle. The observed synergistic effect of TNF and AMD does not appear to be caused by the action of TNF increasing the permeability of the cell membrane to AMD. The results indicate that HL-60 cells, ordinarily resistant to the cytotoxic action of TNF, can be rendered sensitive by treatment with AMD. This implies that a combination of TNF and AMD may be considered in oncology for treatment of tumors otherwise nonresponding to TNF alone.

Cytostatic and cytotoxic properties of pyronin Y: relation to mitochondrial localization of the dye and its interaction with RNA.

Pyronin Y (PY) is an intercalating cationic dye that shows specificity towards RNA. In viable cells this dye also accumulates in mitochondria. The cytostatic and cytotoxic effects of PY on L1210 and Chinese hamster ovary cells were studied in relation to its intracellular localization and compared with the affinity of PY to bind to double-stranded DNA and RNA and its propensity to condense single-stranded DNA and RNA. Antitumor properties of PY were tested on L1210 leukemia and Sarcoma 180 ascites in mice. At a concentration of 1.7 to 3.3 microM, PY was localized almost exclusively in mitochondria of cultured cells, similar to another mitochondrial probe, rhodamine 123. At that concentration PY was not toxic but suppressed cell growth, arresting cells in G1. At a concentration of 6.7 to 33.0 microM, PY was also localized in nucleoli and uniformly in cytoplasm, bound to the RNase-sensitive material therein. At that high concentration PY induced cell arrest in G2 and S and was cytotoxic. The dye exhibited a propensity to bind and condense (precipitate) single-stranded nucleic acids, and condensation could be measured by the appearance of light-scattering products. Among a variety of natural and synthetic nucleic acids the most sensitive were the RNA polymer, polyriboadenylate, and the copolymer, polyriboadenylate and polyriboguanylate, which underwent condensation at a PY concentration of 6.6 to 10.0 microM. Natural and synthetic DNA polymers were resistant to condensation. The data suggest that the cytostatic (G2 and S arrest) and cytotoxic (inability to exclude trypan blue, loss of clonogenicity) effects of PY seen at 6.7 to 33.0 microM concentration may be a consequence of the dye binding to RNA. PY may intercalate to double-stranded RNA and/or cause the specific condensation of single-stranded RNA; the polyadenylated sections of mRNA appear to be the most sensitive cellular targets to undergo condensation. PY showed antitumor properties extending survival of L1210 leukemic mice by 50% and slowing growth of Sarcoma 180 ascites tumor. The possibility that certain antitumor drugs, generally believed to act via intercalation to DNA, may exert chemotherapeutic effects via their interactions with RNA is discussed.

Ganglioside profiles of metastases and of metastasizing and nonmetastasizing rat primary mammary carcinomas.

The possible relationship between ganglioside levels and ganglioside profiles in malignant tumors and the formation of metastasis was investigated by the analysis of gangliosides in metastasizing SMT-2A and nonmetastasizing MT-W9a mammary carcinomas as well as in metastases formed from SMT-2A tumors. The extracted lipid of SMT-2A tumors contained 3.3-fold more lipid-bound sialic acid than did that of MT-W9a tumors. THe differences were also substantial in the ganglioside profiles in these 2 tumors. Plasma membranes isolated from SMT-2A tumors also contained 1.8-fold more lipid-bound sialic acid than did plasma membranes from MT-W9a tumors. Ganglioside profiles in two types of SMT-2A secondary tumors were investigated. The lipid-bound sialic acid content was 1.5-fold higher in tumor nodules in the lung and 1.9-fold higher in axillary lymph node tumors than it was in primary SMT-2A tumors. The ganglioside pattern in these 2 secondary tumors generally reflected that found in SMT-2A: high levels of gangliosides containing three or four sialic acid molecules. The lung nodule retained its specificity with respect to lipid-bound sialic acid content and ganglioside pattern after the lung nodule was sequentially transplanted three times to the site of the original SMT-2A tumor growth.