Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Monocyte function in rhesus monkeys with simian acquired immune deficiency syndrome

Monocyte function in rhesus monkeys with simian acquired immune deficiency syndrome (SAIDS) was compared with that in age-matched normal juvenile rhesus monkeys. The functional tests were 1) chemotaxis, 2) phagocytosis of opsonized Candida albicans, 3) killing and/or growth inhibition of Candida albicans, 4) generation of respiratory burst, and 5) monocyte-derived macrophage response (morphology and/or respiratory burst) to stimulating agents such as lymphokines, gamma interferon, endotoxin, and phorbol myristate acetate. The monkeys tested had either clinical SAIDS (alive with lymphadenopathy, splenomegaly, and lymphopenia or neutropenia) or had terminal SAIDS (moribund due to the disease). Responses of monocytes from 14 monkeys with clinical SAIDS were indistinguishable from those of 9 normal juvenile rhesus monkeys, whereas monocytes from 3 monkeys with terminal SAIDS had enhanced phagocytosis and respiratory burst capacity. Chemotaxis, candidacidal/stasis activity, and response to stimulating agents were normal in these terminal cases. Plasma from the SAIDS monkeys was as capable of opsonizing yeasts and of being able to generate chemotactic factors by endotoxin as was control plasma. SAIDS retrovirus (SRV) was detected by co-cultivation of pure monocyte-derived macrophage cultures with Raji cells, an indicator cell line which forms syncytia in the presence of SRV. Four terminal SAIDS cases and one late-stage clinical SAIDS case were virus-positive when the number of macrophages in the cultures ranged from less than 50 to about 500. Terminal SAIDS monocyte-derived macrophages in culture as long as 17 days produced SRV. These data show that in monkeys with SAIDS the major effector functions of monocytes and macrophages involved in host defense are intact (even up until death). Additionally, some of the monocytes are productively infected, and these infected monocytes are viable and adherent in culture.     

Humoral immune response to immediate-early protein of pseudorabies virus in swine with induced or naturally acquired infection

Pseudorabies virus (PRV) immediate-early (IE) protein is a nonglycosylated polypeptide localized in the nuclei of infected cells. The IE protein is a regulatory protein that is only synthesized during viral replication and is presented to the immune system of PRV-infected swine. Antibodies to the IE protein were demonstrated in swine with induced or naturally acquired infection. However, antiserum raised against purified IE protein could not neutralize PRV in vitro.     

The apparent in vivo neuromuscular effects of the δ-endotoxin of Bacillus thuringiensis var. israelensis in mice and insects of four orders

Alkaline-dissolved crystal δ-endotoxin from Bacillus thuringiensis var. israelensis (serovar H 14) was injected into mice and seven species of insects representing the orders Lepidoptera, Orthoptera, Coleoptera, Hemiptera, and Diptera. High in vivo toxicity, at 1 to 5 ppm (μg toxin/g body wet wt), was observed with mice and some insects, including some that are not sensitive to the toxin when administered orally. Neuromuscular effects were observed when the toxin was injected directly into the body cavity of the test animals. Biochemical studies suggested that different protein fragments within the crystal δ-endotoxin may be responsible for the majority of the mosquito larvacidal activity and the neurotoxic symptoms observed in larvae of Trichoplusia ni.     

Dietary fibers from mushroom sclerotia: 1. Preparation and physicochemical and functional properties

Preparation of three novel dietary fibers (DFs) from mushroom sclerotia, namely, Pleurotus tuberregium, Polyporous rhinocerus, and Wolfiporia cocos, by a scale-up modified AOAC procedure using industrial enzymes was investigated. A remarkably high level of total dietary fiber (TDF) ranging from 81.7 to 96.3% sample dry matter (DM), in which a content of nonstarch polysaccharide (NSP) ranging from 86.6 to 94.3% sclerotial TDF DM, was obtained from the three sclerotia. All sclerotial DFs were rich in beta-glucan (the glucose residue ranged from 89.7 to 94.5% NSP DM) with a very low level of resistant glycogen (ranged from 3.77 to 3.94% sclerotial TDF DM). All three novel sclerotial DFs also exhibited similar, if not better, physicochemical and functional properties (pH, color, water binding capacity, oil holding capacity, and emulsifying properties) as those of barely DF control and commercial DF-rich ingredients. The potential use of the three mushroom sclerotial DFs as a new beta-glucan type DF-rich ingredient in the food industry was discussed.     

Transform high seas management to build climate resilience in marine seafood supply

Climate change is projected to redistribute fisheries resources, resulting in tropical regions suffering decreases in seafood production. While sustainably managing marine ecosystems contributes to building climate resilience, these solutions require transformation of ocean governance. Recent studies and international initiatives suggest that conserving high seas biodiversity and fish stocks will have ecological and economic benefits; however, implications for seafood security under climate change have not been examined. Here, we apply global‐scale mechanistic species distribution models to 30 major straddling fish stocks to show that transforming high seas fisheries governance could increase resilience to climate change impacts. By closing the high seas to fishing or cooperatively managing its fisheries, we project that catches in exclusive economic zones (EEZs) would likely increase by around 10% by 2050 relative to 2000 under climate change (representative concentration pathway 4.5 and 8.5), compensating for the expected losses (around ?6%) from ‘business‐as‐usual’. Specifically, high seas closure increases the resilience of fish stocks, as indicated by a mean species abundance index, by 30% in EEZs. We suggest that improving high seas fisheries governance would increase the resilience of coastal countries to climate change.     

Nitrogen and Phosphorus Leaching from Fertilizer Applied on Golf Course: Lysimeter Study

Fertilizers applied to turfgrass may pose a threat to surface and groundwater quality, and hence, a study was carried out to evaluate the fate of fertilizer applied to turfgrass of the Clearwater Bay Golf and Country Club in Hong Kong. Lysimeters with reconstituted soils collected from fairways and greens with Bermudagrass (Cynodon dactylon) growing in the surface were used to evaluate the leaching loss of nitrate (NO₃ ^-), ammonium (NH₄ ⁺), and phosphate (PO₄ ^3-) for 22 weeks under greenhouse condition. Both soils received a slow release fertilizer at an application rate of 25 (low) or 50 (high) kg N ha^-1, and an application frequency of monthly and fortnightly for fairways and greens, respectively, simulating the fertilizer application strategy of the golf course. Both low and high fertilizer application rate supported the same amount of biomass production for each soil type. Breakthrough of NO₃ ^- occurred only in greens after 11 weeks of leaching, but the total amount of NO₃ ^- leached did not differ significantly for the two different fertilizer application rates. The continued addition of fertilizer to greens resulted in a final leachate NO₃ ^- concentration exceeding 45 mg L^-1, while fairways maintained a concentration below 5 mg L^-1. Also PO₄ ^3- concentration in leachate of greens exceeded the surface water standard of 0.3 mg L^-1. The results of the lysimeter study showed that the current application rate on greens would create adverse environmental impacts on the surface water and groundwater due to leaching loss of PO₄ ^{3 -} and NO₃ ^-.