Performance of fattening cattle and lactating beef cows on diets high in chemically treated wheat straw and poultry litter

Three experiments were carried out to study the effect of chemical treatment on the nutritive value of wheat straw (WS) and the effect of diets containing such treated straw and poultry litter (PL) on the performance of fattening cattle and lactating beef cows. The chemical treatment consisted of treating half of the wheat straw with 60 kg sodium hydroxide/t and the other with 60 kg sulphuric acid/t, and then mixing the two to give “Celephos”. The digestibility coefficient of organic matter was 68.0 and 41.7 for “Celephos” and untreated straw, respectively.For a long term feeding trial, two mixtures were formulated: (a) including 23% WS and 19% PL; (b) including 30% chemically treated WS and 16% PL. A conventional high grain fattening diet (c) served as control. The metabolizable energy concentrations in the above diets were 2.37, 2.38 and 2.78 Mcal/kg DM. Protein content of the diets was regulated by PL or soya bean meal. Liveweight gain was 1059, 1137 and 1180 g/day, metabolizable energy conversion ratio to liveweight was 22.8, 20.7 and 20.0 Mcal/kg, and carcass gain was 565, 606 and 656 g/day for treatment groups (a), (b) and (c), respectively.In a third trial, lactating beef cows were fed on long straw or Celephos, PL and 1.5 kg grain per head per day. Intake of Celephos was 28% higher than that of untreated straw and milk output was 3 kg/day higher. This was reflected in an increase of 67 g/day in gain of suckled calves.     

The use of DPPD (N,N'-diphenyl-P-phenylenediamine) as an anti-inflammatory agent

The anti-oxidant compound, DPPD, was found to be an effctive anti-inflammatory compound by inhibiting carrageenin rat paw edema, adjuvant athritis and serum sickness expression of vascular and renal injury. It is proposed these effects are due to the inhibition of prostaglandin synthesis or fatty acid peroxide formation.     

DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity

Retroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation. We have developed a new in vitro integration assay using physiologically-relevant, reconstituted genomic acceptor chromatin and high-throughput determination of nucleosome positions and integration sites, in parallel. A quantitative analysis of the resulting data reveals a chromatin-dependent redistribution of the integration sites and establishes a link between integration sites and nucleosome positions. The co-activator LEDGF/p75 enhanced integration but did not modify the integration sites under these conditions. We also conducted an in cellulo genome-wide comparative study of nucleosome positions and human immunodeficiency virus type-1 (HIV-1) integration sites identified experimentally in vivo. These studies confirm a preferential integration in nucleosome-covered regions. Using a DNA mechanical energy model, we show that the physical properties of DNA probed by IN binding are important in determining IN selectivity. These novel in vitro and in vivo approaches confirm that IN has a preference for integration into a nucleosome, and suggest the existence of two levels of IN selectivity. The first depends on the physical properties of the target DNA and notably, the energy required to fit DNA into the IN catalytic pocket. The second depends on the DNA deformation associated with DNA wrapping around a nucleosome. Taken together, these results indicate that HIV-1 IN is a shape-readout DNA binding protein.     

The Imidazoquinoline Toll-Like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes

Background

Newborns and young infants are at higher risk for infections than adults, and manifest suboptimal vaccine responses, motivating a search for novel immunomodulators and/or vaccine adjuvants effective in early life. In contrast to most TLR agonists (TLRA), TLR8 agonists such as imidazoquinolines (IMQs) induce adult-level Th1-polarizing cytokine production from human neonatal cord blood monocytes and are candidate early life adjuvants. We assessed whether TLR8-activating IMQ congeners may differ in potency and efficacy in inducing neonatal cytokine production in vitro, comparing the novel TLR7/8-activating IMQ analogues Hybrid-2, Meta-amine, and Para-amine to the benchmark IMQ resiquimod (R848).

Methods

TLRA-induced NF-κB activation was measured in TLR-transfected HEK cells. Cytokine production in human newborn cord and adult peripheral blood and in monocyte-derived dendritic cell cultures were measured by ELISA and multiplex assays. X-ray crystallography characterized the interaction of human TLR8 with Hybrid-2.

Results

Hybrid-2 selectively activated both TLR7 and 8 and was more potent than R848 in inducing adult-like levels of TNF-α, and IL-1β. Consistent with its relatively high in vitro activity, crystallographic studies suggest that absence in Hybrid-2 of an ether oxygen of the C2-ethoxymethyl substituent, which can engage in unfavorable electrostatic and/or dipolar interactions with the carbonyl oxygen of Gly572 in human TLR8, may confer greater efficacy and potency compared to R848.

Conclusions

Hybrid-2 is a selective and potent TLR7/8 agonist that is a candidate adjuvant for early life immunization.