Tumor immunity in vitro: destruction of a mouse ascites tumor through a cycling pathway

Lymphocytes in peritoneal exudate from BALB/(c) mice immunized against ascites leukemia EL4 are uniquely efficient at destroying (51)chromiumlabeled EL4 cells in vitro. The lytic process depends upon the number of lymphocyte-tumor cell interactions. Efector lymphocytes are not inactivated as a result of lethal contact but can interact repeatedly with tumor cells.     

Effects of dietary fiber and feeding frequency on ruminal fermentation, digesta water-holding capacity, and fractional turnover of contents.

To determine the effects of different sources of fiber and feeding frequency on digesta water-holding capacity (WHC; g H2O/g DM) and ruminal liquid contents, four ruminally fistulated Jersey steers were fed a 60:40 roughage-concentrate diet at 1.5 times NEm. Diets contained either sorghum silage (SS) or a 67:33 mixture of SS and soyhulls (SH) as roughage and were fed either once or 12 times daily, in a 2 x 2 factorial experiment with 15-d periods. Ruminal fluid was sampled at 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after a dose of Co-EDTA on d 10 and analyzed for Co, VFA, ammonia, buffering capacity, and osmolality. Ruminal WHC, NDF, ADF, lignin, and starch were measured in samples obtained by ruminal evacuation at 3, 6, 12, and 24 h after feeding on d 11, 12, 14, and 15, respectively. Substitution of SH for SS decreased ruminal pH .32 units and dilution rate by 26.8% but increased total VFA by 10.9%, osmolality by 13.6%, and the fractional turnover rate (FTR) of ADF by 22.5% (P less than .05). Frequent feeding resulted in 4.7, 21.9, and 74.4% increases in total VFA and FTR of ruminal DM and starch (P less than .05), respectively. Interactions (P less than .05) were observed between dietary fiber source and feeding frequency for ruminal fluid molar percentage acetate to propionate ratio (A/P), liquid volume (evacuated), and WHC (kilograms). Substituting SH for SS decreased ruminal WHC (kilograms), liquid volume, and A/P only in steers fed once daily. Ruminal WHC (kilograms) was correlated positively with ruminal liquid volume but negatively with DM FTR. The dynamics of digesta WHC (kilograms) associated with dietary fiber source and feeding frequency suggest that it may influence the contribution of water and salivary secretions to ruminal liquid contents.     

The Marine-Derived Macrolactone Mandelalide A Is an Indirect Activator of AMPK

The mandelalides are complex macrolactone natural products with distinct macrocycle motifs and a bioactivity profile that is heavily influenced by compound glycosylation. Mandelalides A and B are direct inhibitors of mitochondrial ATP synthase (complex V) and therefore more toxic to mammalian cells with an oxidative metabolic phenotype. To provide further insight into the pharmacology of the mandelalides, we studied the AMP-activated protein kinase (AMPK) energy stress pathway and report that mandelalide A is an indirect activator of AMPK. Wild-type mouse embryonic fibroblasts (MEFs) and representative human non-small cell lung cancer (NSCLC) cells showed statistically significant increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in response to mandelalide A. Mandelalide L, which also harbors an A-type macrocycle, induced similar increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in U87-MG glioblastoma cells. In contrast, MEFs co-treated with an AMPK inhibitor (dorsomorphin), AMPKα-null MEFs, or NSCLC cells lacking liver kinase B1 (LKB1) lacked this activity. Mandelalide A was significantly more cytotoxic to AMPKα-null MEFs than wild-type cells, suggesting that AMPK activation serves as a protective response to mandelalide-induced depletion of cellular ATP. However, LKB1 status alone was not predictive of the antiproliferative effects of mandelalide A against NSCLC cells. When EGFR status was considered, erlotinib and mandelalide A showed strong cytotoxic synergy in combination against erlotinib-resistant 11-18 NSCLC cells but not against erlotinib-sensitive PC-9 cells. Finally, prolonged exposures rendered mandelalide A, a potent and efficacious cytotoxin, against a panel of human glioblastoma cell types regardless of the underlying metabolic phenotype of the cell. These results add biological relevance to the mandelalide series and provide the basis for their further pre-clinical evaluation as ATP synthase inhibitors and secondary activators of AMPK.     

Geography limits island small‐scale fishery production

Interacting social and ecological processes shape productivity and sustainability of island small‐scale fisheries (SSF). Understanding limits to productivity through historical catches help frame future expectations and management strategies, but SSF are dispersed and unaccounted, so long‐term standardized data are largely absent for such analyses. We analysed 40 years of trade statistics of a SSF product that enter international markets (sea cucumber) from 14 Pacific Island Countries and Territories (PICT) against response variables to test predictors of fishery production: (i) scale, (ii) productivity and (iii) socio‐economics. Combined production in PICT peaked over 20 years ago, driven by exploitation trends in Melanesia that accounted for 90% of all production since 1971. The size of island fisheries (as measured by total exports), and the duration and magnitude of fishery booms were most influenced by ungovernable environmental variables, in particular land area. The large and high islands of Melanesia sustained larger booms over longer periods than atoll nations. We hypothesize that land area is a proxy for land‐based nutrient availability and habitat diversity, and therefore the productivity of the shallow water areas where SSF are operating. PICT need to tailor management based on the intrinsic productivity of shallow inshore habitats: harvests from atoll nations will need to be smaller per unit area than at the high islands. Particularly countries with low productivity fisheries must consider the crucial economic “safety nets” that export SSF make up for dispersed island populations and incorporate them into broader development and island resilience strategies.     

The effects of photoperiod and water exchange rate on growth and survival of gilthead sea bream (Sparus aurata, Linnaeus; Sparidae) from hatching to metamorphosis in mass rearing systems

The effects of photoperiod and water exchange rate on the larvae of gilthead sea bream, Sparus aurata, from hatching to metamorphosis, 60–70 days later, were tested. Survival, growth rate and condition factor were determined with photoperiods of 12 and 24 h, and water exchange rates of 0 and 25%/day.Continuous light supported the highest mean survival (3.25%), with a maximum of 7.8% from hatching to metamorphosis. Growth rate in dry weight was best under continuous light in a water system with no exchange, up to 20 days post-hatching. Highest growth rates of larvae 40–60 days old were obtained in tanks with 25% of their water exchanged daily, along with a 12-h photoperiod. Condition factor was directly correlated with larval age. For the first 30 days after hatching, condition factor was affected by photoperiod and was highest for larvae exposed to continuous light.     

PCR-based detection of blood parasites in cattle and adult Rhipicephalus appendiculatus ticks

To ascertain the infection rate for tick-borne pathogens in Zambia, an epidemiological survey of Theileria parva, Babesia bigemina and Anaplasma marginale in traditionally managed Sanga cattle was conducted using PCR. Of the 71 native Zambian cattle, 28 (39.4%) were positive for T. parva, 16 (22.5%) for B. bigemina and 34 (47.9%) for A. marginale. The mixed infection rate in cattle was 8.5% (6/71), 16.9% (12/71), 7.0% (5/71) and 2.8% (2/71) for T. parva/B. bigemina, T. parva/A. marginale, B. bigemina/A. marginale and T. parva/B. bigemina/A. marginale, respectively.To predict the risk for transmission of tick-borne pathogens from ticks to cattle, a total of 74 Rhipicephalus appendiculatus ticks were collected from a location where cattle had been found positive for T. parva. Of the ticks collected, 10 (13.5%) were found to be PCR-positive for T. parva. The results suggest that the infection rate for tick-borne pathogens was relatively high in Sanga cattle and that adult R. appendiculatus ticks were highly infected with T. parva.     

Alfalfa saponins and microbial transformations of nitrogen in peat

Alfalfa saponins, their sugar fraction or glucose, but not their sapogenin fraction, favored nitrogen immobilization and denitrification and inhibited proteolysis and ammonification in both peatinoculated and Pseudomonas sp.-inoculated media. Alfalfa root saponins and sapogenins significantly reduced the fungal peat population, but did not affect the bacterial population. The inhibition of N mineralization in peat by saponins and by their sapogenin fraction during dry and wet cycles was mostly due to their fungistatic activity. The inhibitory effect of the sugar fraction of alfalfa roots on mineral-N accumulation in peat is mainly under moist conditions.     

Effect of dietary energy source and level on serum growth hormone, insulin-like growth factor 1, growth and body composition in beef heifers

Effects of fiber vs starch energy supplements on endogenous growth hormone (GH), insulin-like growth factor (IGF-1) and animal performance from weaning to breeding age were evaluated in 18, 9-mo-old beef heifers. Heifers had ad libitum access to wheat silage plus an average daily supplement intake of 1) 4.08 kg corn-soybean meal (SBM) (high energy-starch, HS), 2) 4.54 kg soyhulls (SH)-SBM (high energy-fiber, HF) or 3) 1.36 kg SH-SBM (low energy-fiber, LE). Serum samples were collected via jugular puncture every 10 d and were analyzed for IGF-1 by RIA. On d 45 and d 176, four heifers per treatment were fasted 18 h and serial blood samples collected via jugular cannulas every 15 min for 6.5 h. Arginine (.5 g/kg BW) was administered intravenously (ARG) to induce release of GH, and four additional samples of blood were collected. Samples were analyzed by RIA for GH. Mean fasted GH (6.4 +/- .4, 8.3 +/- .4 and 13.8 +/- .4 ng/ml for HS, HF and LE, respectively) varied with energy source and level (P less than .01). Mean GH following ARG was higher (P less than .01) in heifers receiving LE (46.2 +/- 4.7) than in those receiving HS and HF (23.5 +/- 4.4 and 24.1 +/- 4.6 ng/ml). Basal GH concentration and peak amplitude were higher (P less than .05) in LE than in HS and HF treatments. Diet did not influence number or frequency of GH peaks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bacillus thuringiensis insecticides in crop protection — reality and prospects

Bacillus thuringiensis (Bt) has been the leading biopesticide against lepidopterous pests since 1959. In the 1990 s the following developments contributed to increased rational uses of Bt: (1) natural and recombinant Bt products were developed to broaden the insect host range in pest management programs; (2) new formulations based on conventional or genetically engineered encapsulation of the toxins and/or feeding stimulants to increase ingestion and, in turn, the efficacy of the microbe; (3) screening of the interactions of Bt with insect herbivores and plant allelochemicals or natural enemies of the pests, to aid the formulation of biological control strategies; and (4) knowledge and management of insect resistance to Bt. The prospects for Bt insecticides will be described and discussed.