980 research outputs found
Effect of Pre-and Post-weaning Nutrition and Management on Performance of Weaned Pigs to circa 35 kg.
End of Project ReportThe objective of this project was to examine the factors
affecting performance (growth rate, appetite, feed conversion efficiency)
of pigs in the stage from weaning to 35 kg liveweight.
The study involved three stages, creep feeding during the suckling
period, management during the first weaner stage (c. 4 weeks
from weaning or 6 kg to 15 kg liveweight) and management during
the second weaner stage (c. 15 kg to 35 kg liveweight.
Creep feed intake before weaning was low c. 2.5 to 3.0 kg
per litter but where it was consumed the response in terms of feed
conversion efficiency was good with litter weight increasing in
weight by about 1.1 kg for each 1 kg creep consumed. Milk
replacer in liquid form was very readily consumed but its preparation
and feeding is very laborious. Weaning weight was poorly
related to post weaning performance and weaning age seemed to
be more critical which is probably a reflection of the greater
maturity of older animals.
In the first weaner stage, feeding of cooked cereal containing
diets was found to have little benefit in pig performance.
Acidification of feeds is likely to have only a minor influence on
pig performance. An experiment on choice feeding of starter and
link feeds did not confirm that smaller pigs require a higher quality
diet and, in a choice situation will eat a greater proportion of the
more nutrient dense diet.
In the second weaner stage, comparison of three commercial
weaner feeds with a cereal based control diet showed good performance
on all four diets. Pigs fed a high lysine weaner diet grew
better in the weaner stage but by slaughter those pigs fed the low
lysine weaner diet, after all pigs were fed a common finisher diet,
had overtaken them. The high lysine group did, however, have
leaner carcasses.
Residual effects of early nutrition need to be investigated in
more detail including the effect of pregnancy feeding on prenatal
development and the relationship between prenatal growth and
postnatal growth, in particular development of muscle.European Union Structural Funds (EAGGF
Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels
The cloning of the cDNA for the α1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these α1 subunits and the skeletal muscle α2/δ, β and γ subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the α1-, β- and γ-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The α1, β and γ mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle α2/δ subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the α1, β and γ subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner
Pressure Induced Hydration Dynamics of Membranes
Pressure-jump initiated time-resolved x-ray diffraction studies of dynamics
of the hydration of the hexagonal phase in biological membranes show that (i)
the relaxation of the unit cell spacing is non-exponential in time; (ii) the
Bragg peaks shift smoothly to their final positions without significant
broadening or loss in crystalline order. This suggests that the hydration is
not diffusion limited but occurs via a rather homogeneous swelling of the whole
lattice, described by power law kinetics with an exponent .Comment: REVTEX 3, 10 pages,3 figures(available on request),#
A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion
Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al
Monoolein Lipid Phases as Incorporation and Enrichment Materials for Membrane Protein Crystallization
The crystallization of membrane proteins in amphiphile-rich materials such as lipidic cubic phases is an established methodology in many structural biology laboratories. The standard procedure employed with this methodology requires the generation of a highly viscous lipidic material by mixing lipid, for instance monoolein, with a solution of the detergent solubilized membrane protein. This preparation is often carried out with specialized mixing tools that allow handling of the highly viscous materials while minimizing dead volume to save precious membrane protein sample. The processes that occur during the initial mixing of the lipid with the membrane protein are not well understood. Here we show that the formation of the lipidic phases and the incorporation of the membrane protein into such materials can be separated experimentally. Specifically, we have investigated the effect of different initial monoolein-based lipid phase states on the crystallization behavior of the colored photosynthetic reaction center from Rhodobacter sphaeroides. We find that the detergent solubilized photosynthetic reaction center spontaneously inserts into and concentrates in the lipid matrix without any mixing, and that the initial lipid material phase state is irrelevant for productive crystallization. A substantial in-situ enrichment of the membrane protein to concentration levels that are otherwise unobtainable occurs in a thin layer on the surface of the lipidic material. These results have important practical applications and hence we suggest a simplified protocol for membrane protein crystallization within amphiphile rich materials, eliminating any specialized mixing tools to prepare crystallization experiments within lipidic cubic phases. Furthermore, by virtue of sampling a membrane protein concentration gradient within a single crystallization experiment, this crystallization technique is more robust and increases the efficiency of identifying productive crystallization parameters. Finally, we provide a model that explains the incorporation of the membrane protein from solution into the lipid phase via a portal lamellar phase
Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening
The flatworm disease schistosomiasis infects over 200 million people with just one drug (praziquantel) available—a concern should drug resistance develop. Present drug discovery approaches for schistosomiasis are slow and not conducive to automation in a high-throughput format. Therefore, we designed a three-component screen workflow that positions the larval (schistosomulum) stage of S. mansoni at its apex followed by screens of adults in culture and, finally, efficacy tests in infected mice. Schistosomula are small enough and available in sufficient numbers to interface with automated liquid handling systems and prosecute thousands of compounds in short time frames. We inaugurated the workflow with a 2,160 compound library that includes known drugs in order to cost effectively ‘re-position’ drugs as new therapies for schistosomiasis and/or identify compounds that could be modified to that end. We identify a variety of ‘hit’ compounds (antibiotics, psychoactives, antiparasitics, etc.) that produce behavioral responses (phenotypes) in schistosomula and adults. Tests in infected mice of the most promising hits identified a number of ‘leads,’ one of which compares reasonably well with praziquantel in killing worms, decreasing egg production by the parasite, and ameliorating disease pathology. Efforts continue to more fully automate the workflow. All screen data are posted online as a drug discovery resource
Clinicians' caseload management behaviours as explanatory factors in patients' length of time on caseloads : a predictive multilevel study in paediatric community occupational therapy
Peer reviewedPublisher PD
Study of 2 beta-decay of Mo-100 and Se-82 using the NEMO3 detector
After analysis of 5797 h of data from the detector NEMO3, new limits on neutrinoless double beta decay of Mo-100 (T-1/2 > 3.1 x 10(23) y, 90% CL) and Se-82 (T-1/2 > 1.4 x 10(23) y, 90% CL) have been obtained. The corresponding limits on the effective majorana neutrino mass are: 1.4 x 10(22) y (90% CL) for Mo-100 and T-1/2 > 1.2 x 10(22) y (90% CL) for Se-82. Corresponding bounds on the Majoron-neutrino coupling constant are < (0.5-0.9) x 10(- 4) and <(0.7-1.6) x 10(- 4). Two-neutrino 2beta-decay half-lives have been measured with a high accuracy, (T1/2Mo)-Mo-100 = [7.68 +/- 0.02(stat) +/- 0.54(syst)] x 10(18) y and (T1/2Se)-Se-82 = [10.3 +/- 0.3(stat) +/- 0.7(syst)] x 10(19) y. (C) 2004 MAIK "Nauka/Interperiodica"
Surfactant protein D modulates HIV infection of both T-cells and dendritic cells
Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo
Positive Selection Drives Preferred Segment Combinations during Influenza Virus Reassortment
Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 and the remaining six segments from H3N2. By deep sequencing the entire viral genome, we monitored the evolution of reassortment, quantifying the relative abundance of all IAV genome segments from the two parent strains over time and measuring the selection coefficients of the reassorting segments. Additionally, we observed several mutations coemerging with reassortment that were not found during passaging of pure parental IAV strains. Our results demonstrate how reassortment of the segmented genome can accelerate viral evolution in IAV, potentially enabled by the emergence of a small number of individual mutation
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