Grazing Periods and Forage Production on the National Forests

Stockmen in the West have always had confidence in the adequacy of the native forage crop to provide pasturage for their livestock. Indeed, under normal climatic conditions this enormous natural resource has not failed the grazier, except where it has been called upon to meet unreasonable demands. The productivity of the range has declined sharply, however, wherever the requirements of plant growth have been disregarded for many years in succession. Where there has been too early or too frequent and to heavy grazing, undue trampling, or some other unsatisfactory feature of range use, the results have been uniformly bad. Many conspicuous examples show that abundant nutritious forage can not be expected in the absence of rational grazing and livestock management

On the Finite Dimensional Laws of Threshold GARCH Processes

In this chapter we establish bounds for the finite dimensional laws of a threshold GARCH process, X, with generating process Z. In this class of models the conditional standard deviation has different reactions according to the sign of past values of the process. So, we firstly find lower and upper bounds for the law of \left ({X}_{1}^{+},-{X}_{1}^{+},\ldots,{X}_{n}^{+},-{X}_{n}^{+}\right), in certain regions of R^{2n}, and use them to find bounds of the law of \left ({X}_{1},\ldots,{X}_{n}\right). Some of these bounds only depend on the parameters of the model and on the distribution function of the independent generating process, Z. An application of these bounds to control charts for time series is presented

Antimicrobial Activity of Human Prion Protein Is Mediated by Its N-Terminal Region

BACKGROUND: Cellular prion-related protein (PrP(c)) is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c), and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c) could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking) liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense

Long-Term Safety of Intraperitoneal Radio Transmitter Implants in Brown Bears (Ursus arctos)

Intraperitoneal radio transmitters have been widely used in free-ranging wild mammals, but there are no long-term studies on their biocompatibility or technical stability within the abdominal cavity of animals. Possible negative health effects may bias results from ecological studies on instrumented animals and raise concerns over animal welfare issues. The aim of this study was to evaluate the long-term technical stability and pathological effects of Telonics intraperitoneal very high frequency (VHF) radio transmitters in brown bears (Ursus arctos). We instrumented 305 individual bears with intraperitoneal VHF radio transmitters during a 19-year period. We surgically removed devices that had been in bears for 1–9 years and collected transmitters from animals that died 1–13 years after implantation. We took biopsies for histopathology from tissue encapsulating implants in live bears. Retrieved transmitters underwent a technical inspection. Of the 125 transmitters removed from live bears, 66 were free-floating in the peritoneal cavity [a mean (SD) of 3.8 (1.5) years after implantation], whereas 59 were encapsulated in the greater omentum [4.0 (1.8) years after implantation]. Histopathology of biopsies of the 1–15 mm thick capsules in 33 individuals showed that it consisted of organized layers of connective tissue. In one third of the bears, the inner part of the capsule was characterized by a foreign body reaction. We inspected 68 implants that had been in bears for 3.9 (2.4) years. The batteries had short-circuited four (5.9%) of these devices. This resulted in the death of two animals 10 and 13 years after implantation. In two other bears that underwent surgery, we found the short-circuited devices to be fully encapsulated within the peritoneal cavity 5 and 6 years after implantation. A significant proportion of the other 64 inspected implants showed serious technical problems, such as corrosion of metal parts or the batteries (50%), detachment of the end cap (11.8%), and erosion (7.4%) or melting (5.9%) of the wax coating. We conclude that the wax coating of the transmitters was not biocompatible, that the technical quality of the devices was poor, and that these implants should not be used in brown bears

End-Tagging of Ultra-Short Antimicrobial Peptides by W/F Stretches to Facilitate Bacterial Killing

BACKGROUND: Due to increasing resistance development among bacteria, antimicrobial peptides (AMPs), are receiving increased attention. Ideally, AMP should display high bactericidal potency, but low toxicity against (human) eukaryotic cells. Additionally, short and proteolytically stable AMPs are desired to maximize bioavailability and therapeutic versatility. METHODOLOGY AND PRINCIPAL FINDINGS: A facile approach is demonstrated for reaching high potency of ultra-short antimicrobal peptides through end-tagging with W and F stretches. Focusing on a peptide derived from kininogen, KNKGKKNGKH (KNK10) and truncations thereof, end-tagging resulted in enhanced bactericidal effect against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Through end-tagging, potency and salt resistance could be maintained down to 4-7 amino acids in the hydrophilic template peptide. Although tagging resulted in increased eukaryotic cell permeabilization at low ionic strength, the latter was insignificant at physiological ionic strength and in the presence of serum. Quantitatively, the most potent peptides investigated displayed bactericidal effects comparable to, or in excess of, that of the benchmark antimicrobial peptide LL-37. The higher bactericidal potency of the tagged peptides correlated to a higher degree of binding to bacteria, and resulting bacterial wall rupture. Analogously, tagging enhanced peptide-induced rupture of liposomes, particularly anionic ones. Additionally, end-tagging facilitated binding to bacterial lipopolysaccharide, both effects probably contributing to the selectivity displayed by these peptides between bacteria and eukaryotic cells. Importantly, W-tagging resulted in peptides with maintained stability against proteolytic degradation by human leukocyte elastase, as well as staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo for pig skin infected by S. aureus and E. coli. CONCLUSIONS/SIGNIFICANCE: End-tagging by hydrophobic amino acid stretches may be employed to enhance bactericidal potency also of ultra-short AMPs at maintained limited toxicity. The approach is of general applicability, and facilitates straightforward synthesis of hydrophobically modified AMPs without the need for post-peptide synthesis modifications

Lipoprotein ability to exchange and remove lipids from model membranes as a function of fatty acid saturation and presence of cholesterol

Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as 'good' and 'bad' cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understanding the onset and development of cardiovascular disease. In order to elucidate the impact of phospholipid tail saturation and the presence of cholesterol in cell membranes on these processes, neutron reflection was employed in the present investigation to follow lipid exchange with both HDL and LDL against model membranes. Mirroring clinical risk factors for the development of atherosclerosis, lower exchange was observed in the presence of cholesterol, as well as for an unsaturated phospholipid, compared to faster exchange when using a fully saturated phospholipid. These results highlight the importance of membrane composition on the interaction with lipoproteins, chiefly the saturation level of the lipids and presence of cholesterol, and provide novel insight into factors of importance for build-up and reversibility of atherosclerotic plaque. In addition, the correlation between the results and well-established clinical risk factors suggests that the approach taken can be employed also for understanding a broader set of risk factors including, e.g., effects of triglycerides and oxidative stress, as well as local effects of drugs on atherosclerotic plaque formation

Non-Equilibrium in Adsorbed Polymer Layers

High molecular weight polymer solutions have a powerful tendency to deposit adsorbed layers when exposed to even mildly attractive surfaces. The equilibrium properties of these dense interfacial layers have been extensively studied theoretically. A large body of experimental evidence, however, indicates that non-equilibrium effects are dominant whenever monomer-surface sticking energies are somewhat larger than kT, a common case. Polymer relaxation kinetics within the layer are then severely retarded, leading to non-equilibrium layers whose structure and dynamics depend on adsorption kinetics and layer ageing. Here we review experimental and theoretical work exploring these non-equilibrium effects, with emphasis on recent developments. The discussion addresses the structure and dynamics in non-equilibrium polymer layers adsorbed from dilute polymer solutions and from polymer melts and more concentrated solutions. Two distinct classes of behaviour arise, depending on whether physisorption or chemisorption is involved. A given adsorbed chain belonging to the layer has a certain fraction of its monomers bound to the surface, f, and the remainder belonging to loops making bulk excursions. A natural classification scheme for layers adsorbed from solution is the distribution of single chain f values, P(f), which may hold the key to quantifying the degree of irreversibility in adsorbed polymer layers. Here we calculate P(f) for equilibrium layers; we find its form is very different to the theoretical P(f) for non-equilibrium layers which are predicted to have infinitely many statistical classes of chain. Experimental measurements of P(f) are compared to these theoretical predictions.Comment: 29 pages, Submitted to J. Phys.: Condens. Matte

Highly Selective End-Tagged Antimicrobial Peptides Derived from PRELP

Background: Antimicrobial peptides (AMPs) are receiving increasing attention due to resistance development against conventional antibiotics. Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in an array of infections such as ocular infections, cystic fibrosis, wound and post-surgery infections, and sepsis. The goal of the study was to design novel AMPs against these pathogens. Methodology and Principal Findings: Antibacterial activity was determined by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was evaluated by hemolysis and effects on human epithelial cells. Liposome and fluorescence studies provided mechanistic information. Protease sensitivity was evaluated after subjection to human leukocyte elastase, staphylococcal aureolysin and V8 proteinase, as well as P. aeruginosa elastase. Highly active peptides were evaluated in ex vivo skin infection models. C-terminal end-tagging by W and F amino acid residues increased antimicrobial potency of the peptide sequences GRRPRPRPRP and RRPRPRPRP, derived from proline arginine-rich and leucine-rich repeat protein (PRELP). The optimized peptides were antimicrobial against a range of Gram-positive S. aureus and Gram-negative P. aeruginosa clinical isolates, also in the presence of human plasma and blood. Simultaneously, they showed low toxicity against mammalian cells. Particularly W-tagged peptides displayed stability against P. aeruginosa elastase, and S. aureus V8 proteinase and aureolysin, and the peptide RRPRPRPRPWWWW-NH2 was effective against various "superbugs'' including vancomycin-resistant enterococci, multi-drug resistant P. aeruginosa, and methicillin-resistant S. aureus, as well as demonstrated efficiency in an ex vivo skin wound model of S. aureus and P. aeruginosa infection. Conclusions/Significance: Hydrophobic C-terminal end-tagging of the cationic sequence RRPRPRPRP generates highly selective AMPs with potent activity against multiresistant bacteria and efficiency in ex vivo wound infection models. A precise "tuning'' of toxicity and proteolytic stability may be achieved by changing tag-length and adding W-or F-amino acid tags