Alun Jones

Bio: Alun Jones is an academic researcher from University of Queensland. The author has contributed to research in topics: Peptide & Venom. The author has an hindex of 55, co-authored 235 publications receiving 10527 citations. Previous affiliations of Alun Jones include Cooperative Research Centre & University of Manchester.

In situ neutralization in Boc-chemistry solid phase peptide synthesis. Rapid, high yield assembly of difficult sequences.

Abstract: Simple, effective protocols have been developed for manual and machine-assisted Boc-chemistry solid phase peptide synthesis on polystyrene resins. These use in situ neutralization [i.e. neutralization simultaneous with coupling], high concentrations (> 0.2 M) of Boc-amino acid-OBt esters plus base for rapid coupling, 100% TFA for rapid Boc group removal, and a single short (30 s) DMF flow wash between deprotection/coupling and between coupling/deprotection. Single 10 min coupling times were used throughout. Overall cycle times were 15 min for manual and 19 min for machine-assisted synthesis (75 residues per day). No racemization was detected in the base-catalyzed coupling step. Several side reactions were studied, and eliminated. These included: pyrrolidonecarboxylic acid formation from Gln in hot TFA-DMF; chain-termination by reaction with excess HBTU; and, chain termination by acetylation (from HOAc in commercial Boc-amino acids). The in situ neutralization protocols gave a significant increase in the efficiency of chain assembly, especially for “difficult” sequences arising from sequence-dependent peptide chain aggregation in standard (neutralization prior to coupling) Boc-chemistry SPPS protocols or in Fmoc-chemistry SPPS. Reported syntheses include HIV-1 protease(1–50,Cys.amide), HIV-1 protease(53–99), and the full length HIV-1 protease(1–99).

Enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin microcystin LR.

Abstract: An isolated bacterium, identified as a new Sphingomonas species, was demonstrated to contain a novel enzymatic pathway which acted on microcystin LR, the most common cyanobacterial cyclic peptide toxin. Degradation of microcystin LR was mediated by at least three intracellular hydrolytic enzymes. The use of classic protease inhibitors allowed (i) the classification of these enzymes into general protease families and (ii) the in vitro accumulation of otherwise transient microcystin LR degradation products. The initial site of hydrolytic cleavage of the parent cyclic peptide by an enzyme that we designate microcystinase is at the 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda)-Arg peptide bond. Two intermediates of microcystin LR enzymatic degradation have been identified; one is linearized (acyclo-) microcystin LR, NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-Leu-beta-methylas partate-Arg-OH, and the other is the tetrapeptide NH2-Adda-Glu(iso)-methyldehydroalanine-Ala-OH. The intermediate degradation products were less active than the parent cyclic peptide; the observed 50% inhibitory concentrations for crude chicken brain protein phosphatase were 0.6 nM for microcystin LR, 95 nM for linear LR, and 12 nM for the tetrapeptide. These linear peptides were nontoxic to mice at doses up to 250 micrograms/kg. Ring opening of the potent hepatotoxin microcystin LR by bacterial microcystinase effectively renders the compound nontoxic by dramatically reducing the interaction with the target protein phosphatase.

A climate model study of indirect radiative forcing by anthropogenic sulphate aerosols

Abstract: ANTHROPOGENIC sulphate aerosols are believed to affect the radiation budget of the Earth in two ways. Through the direct effect they scatter solar radiation back to space, producing a radiative forcing whose global annual mean has been estimated to lie in the range −0.3 to −0.9 W m−2 (refs 1–3). This is significant compared to the longwave forcing due to increases in anthropogenic trace gases since the beginning of the industrial era, estimated at +2 to +2.5 W m−2 (ref. 4). Aerosols also have an indirect effect, altering the distribution and concentration of cloud condensation nuclei (CCN) and hence the number density and size distribution of cloud droplets, thus affecting the solar radiative characteristics of clouds5,6. This is harder to quantify than the direct effect, because it depends on complex and poorly understood interactions between aerosols, CCN and cloud properties. Here we use sulphate aerosol data derived from a three-dimensional chemical transport model7 to estimate the indirect radiative forcing by low-level water clouds using a general circulation model. We estimate that the indirect aerosol effect at the top of the atmosphere is approximately −1.3 W m−2 in the global annual mean. Although this value is subject to a high level of uncertainty, even if the effect is only half as large it would still exceed many estimates of the direct effect, demonstrating its potential importance in climate change.

Psychological problems following ICU treatment

Abstract: Treatment in an intensive care unit can be stressful and may leave patients with persisting psychological symptoms that impair quality of life This postal questionnaire study of patients who had previously been treated in a general adult intensive care unit showed that 38 (47%) of 80 patients who returned fully completed questionnaires reported clinically significant anxiety and depression as measured by the Hospital Anxiety and Depression Scale Thirty (38%) reported significant symptoms of post-traumatic stress disorder, of whom 12 (15%) reached levels consistent with a diagnosis of full post-traumatic stress disorder as measured by the Trauma Symptom Checklist 33 and the Impact of Events Scale We describe a new measure of psychological distress specifically related to the experience of intensive care management, the Experience after Treatment in Intensive Care 7 Item Scale, and compare it to the other scales The Experience after Treatment in Intensive Care 7 Item Scale shows that at least a proportion of the post-traumatic stress reported was directly attributable to the experience of treatment in the intensive care unit

Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

Abstract: Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.

Modern Applied Statistics With S

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Biological properties of extracellular vesicles and their physiological functions

Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Synthesis of proteins by native chemical ligation

Abstract: Proteins of moderate size having native peptide backbones are produced by a method of native chemical ligation. Native chemical ligation employs a chemoselective reaction of two unprotected peptide segments to produce a transient thioester-linked intermediate. The transient thioester-linked intermediate then spontaneously undergoes a rearrangement to provide the full length ligation product having a native peptide bond at the ligation site. Full length ligation products are chemically identical to proteins produced by cell free synthesis. Full length ligation products may be refolded and/or oxidized, as allowed, to form native disulfide-containing protein molecules. The technique of native chemical ligation is employable for chemically synthesizing full length proteins.