Homoisoleucine: A Translationally Active Leucine Surrogate of Expanded Hydrophobic Surface Area

Hil of a strong peptide! Homoisoleucine (Hil) serves as an effective surrogate for leucine with respect to protein translation in bacterial cells. Replacement of Leu by Hil stabilizes coiled-coil peptides, as shown by the elevation of the thermal denaturation temperature. The increase in denaturation temperature is larger than that observed previously for replacement of Leu by trifluoroleucine

Delays by people living with HIV/AIDS in accessing antiretroviral therapy

Objective: To understand, by qualitative enquiry, the underlying reasons and narratives for patients that delay in accessing antiretroviral treatment.Design: A qualitative design was used, where patients were interviewed using the free attitude interview technique, after being selected based on a screening question: “How long did it take you to present at a clinic or hospital for treatment after receiving your human immunodeficiency virus-positive result?”Setting and subjects: Eight patients from the human immunodeficiency virus clinic at Potchefstroom were interviewed.Outcome measures: The interviews were transcribed verbatim and organised into themes.Results: The following themes were identified: stigma and discrimination, ignorance and lack of perceived risk of infection, denial and healthcare system constraints. These are discussed and quotations from the interviewed patients included.Conclusion: This qualitative study has contributed to an understanding of why patients delay in accessing highly active antiretroviral therapy. Some of the reasons supplied by patients have been documented globally. Others are poignantly coloured by personal stories. By understanding patients’ perspectives and feelings, emphasis can be placed on the reduction of stigma, denial, practical clinic constraints and appropriate types of health education.Keywords: qualitative research, delays, access, antiretroviral drugs, ARV

Hydration dynamics at fluorinated protein surfaces

Water-protein interactions dictate many processes crucial to protein function including folding, dynamics, interactions with other biomolecules, and enzymatic catalysis. Here we examine the effect of surface fluorination on water-protein interactions. Modification of designed coiled-coil proteins by incorporation of 5,5,5-trifluoroleucine or (4S)-2-amino-4-methylhexanoic acid enables systematic examination of the effects of side-chain volume and fluorination on solvation dynamics. Using ultrafast fluorescence spectroscopy, we find that fluorinated side chains exert electrostatic drag on neighboring water molecules, slowing water motion at the protein surface

Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans

In this double-blind, cross-over, placebo-controlled, randomized study, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in conjunction with placebo and once with granulocyte colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF was administered subcutaneously 24 hours before endotoxin challenge. In group 1, G-CSF significantly enhanced the release of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)-induced soluble TNF receptor release was further augmented, whereas LPS-induced IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and the release of elastase and lactoferrin. Both pretreatments also down-regulated neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary neutrophil accumulation during the first 2 hours after endotoxin challenge. These data indicate that two different pretreatments with G-CSF result in differential effects on LPS-induced cytokine release but similar effects on LPS-induced neutrophil activation and changes in expression of cell surface molecules. Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G-CSF blocks LPS-induced pulmonary granulocyte accumulatio

Delineating knowledge management through lexical analysis - a retrospective

PURPOSE - Academic authors tend to define terms that meet their own needs. Knowledge Management (KM) is a term that comes to mind and is examined in this study. Lexicographical research identified KM terms used by authors from 1996 to 2006 in academic outlets to define KM. Data were collected based on strict criteria which included that definitions should be unique instances. From 2006 onwards, these authors could not identify new unique instances of definitions with repetitive usage of such definition instances. Analysis revealed that KM is directly defined by People (Person and Organisation), Processes (Codify, Share, Leverage, and Process) and Contextualised Content (Information). The paper aims to discuss these issues. DESIGN / METHODOLOGY / APPOACH – The aim of this paper is to add to the body of knowledge in the KM discipline and supply KM practitioners and scholars with insight into what is commonly regarded to be KM so as to reignite the debate on what one could consider as KM. The lexicon used by KM scholars was evaluated though the application of lexicographical research methods as extended though Knowledge Discovery and Text Analysis methods. FINDINGS – By simplifying term relationships through the application of lexicographical research methods, as extended though Knowledge Discovery and Text Analysis methods, it was found that KM is directly defined by People (Person and Organisation), Processes (Codify, Share, Leverage, Process) and Contextualised Content (Information). One would therefore be able to indicate that KM, from an academic point of view, refers to people processing contextualised content. RESEARCH LIMITATIONS / IMPLICATIONS – In total, 42 definitions were identified spanning a period of 11 years. This represented the first use of KM through the estimated apex of terms used. From 2006 onwards definitions were used in repetition, and all definitions that were considered to repeat were therefore subsequently excluded as not being unique instances. All definitions listed are by no means complete and exhaustive. The definitions are viewed outside the scope and context in which they were originally formulated and then used to review the key concepts in the definitions themselves. SOCIAL IMPLICATIONS – When the authors refer to the aforementioned discussion of KM content as well as the presentation of the method followed in this paper, the authors may have a few implications for future research in KM. First the research validates ideas presented by the OECD in 2005 pertaining to KM. It also validates that through the evolution of KM, the authors ended with a description of KM that may be seen as a standardised description. If the authors as academics and practitioners, for example, refer to KM as the same construct and/or idea, it has the potential to speculatively, distinguish between what KM may or may not be. ORIGINALITY / VALUE – By simplifying the term used to define Knowledge Management, by focussing on the most common definitions, the paper assist in refocussing Knowledge Management by reconsidering the dimensions that is the most common in how it has been defined over time. This would hopefully assist in reigniting discussions about Knowledge Management and how it may be used to the benefit of an organisation.http://www.emeraldinsight.com/loi/ajimhb201

AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product for HD

Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California

Background: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. Methods: The present study included 15,744 cancer cases (aged 0–19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998–2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned “ever/never” and “high/low exposed/unexposed” exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. Results: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the “ever exposed” group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). Conclusions: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks

Genetic parameters of interspecific hybrids of Eucalyptus grandis and E.urophylla seedings and cuttings

The current E. grandis x E. urophylla hybrid breeding strategy of South Africa’s Forestry Industry is to maintain large breeding populations of both parental species in which parents are selected based on their general combining ability (GCA) estimates or predicted individual tree breeding values and are used for interspecific hybrid crosses. The hybrid material is first screened in seedling progeny trials after which superior individuals are selected and tested as clones. Although this strategy has delivered superior clones for commercial production in South Africa, it is a time consuming strategy to follow and more cost effective strategies are being investigated. In order to review the current hybrid breeding strategy, information on the genetic control of the traits of interest is needed for E. grandis x E. urophylla seedling and clonal populations. The main objectives of this study were therefore to firstly estimate genetic parameters for E. grandis x E. urophylla hybrid seedling and clonal populations; secondly to investigate the correlation between E. grandis and E. urophylla parental (GCA) or individual breeding values and their general hybridising ability (GHA); and lastly to determine the correlation between E. grandis x E. urophylla hybrid seedling ortets and their ramets. Results of our study indicated that non-additive genetic variation explained the majority of the total genetic variation in E. grandis x E. urophylla seedling and clonal populations. Due to the pre-eminence of non-additive variance, the pure-hybrid correlations were weak, especially for clonal populations. It would therefore seem that GCA or predicted individual breeding values are not good predictors of GHA for growth performance in the observed populations. Our study also indicated a weak coefficient of correlation between the growth performance of seedling ortets and their ramets. These results suggest that: firstly a hybrid breeding strategy to capture non-additive genetic variation should be adopted; and secondly that the first phase of screening E. grandis x E. urophylla hybrid material as seedlings should be revisited. Genetic Parameters of Interspecific Hybrids of Eucalyptus grandis and E. urophylla Seedlings and Cuttings.Mondi training departmenthttp://www.sauerlaender-verlag.com/zeitschriften/silvae-geneticaPlant Production and Soil Scienc

Кинетика восстановления железа при восстановительной плавке рудоугольных окатышей

Исследовано влияние интенсивности теплообмена на кинетику восстановления железа в процессе плавки рудоугольных окатышей. Показано, что с ростом интенсивности теплообмена повышается скорость восстановительных процессов. Вследствие роста коэффициента теплообмена увеличивается глубина восстановленного слоя окатыша, существенно изменяются его структура и химический состав образующейся металлической фазы.Досліджено вплив інтенсивності теплообміну на кінетику відновлення заліза в процесі плавки рудовугільних окатишів. Показано, що при зростанні інтенсивності теплообміну підвищується швидкість відновлювальних процесів. Внаслідок зростання коефіцієнту теплообміну збільшується глибина відновленого шару окатиша, суттєво змінюються його структура та хімічний склад металевої фази, що утворюється.Influence of intensity of heat exchange is investigational on kinetics reduction of iron in the process of melting ore-coal pellets. It is rotined that speed of reduction processes rises with growth of intensity of heat exchange. Because of growth of coefficient of heat exchange the depth of the recovered layer of pellet is increased, his structure and chemical composition of appearing metallic phase changes substantially

Estimates of genetic parameters and genetic gains for growth traits of two Eucalyptus urophylla populations in Zululand, South Africa

In South Africa, Eucalyptus urophylla is an important species due to its disease tolerance to fungal diseases like Crysoporthe austroafricana and the Coniothyrium sp. cankers. It is mainly planted as a parental species in a hybrid combination with E. grandis. Generally, the E. grandis x E. urophylla hybrid has better disease tolerance and higher wood density than pure E. grandis. The current strategy is to maintain large breeding populations of both parental species in order to provide improved elite selections for hybrid crosses on a regular basis. With this in mind, two E. urophylla populations, consisting of five provenance/progeny trials, were established in the subtropical region of Zululand. The aims of this study were firstly to determine the magnitude of genotype by environment interaction of E. urophylla in Zululand; secondly to estimate genetic parameter and correlations for DBH, height and volume; and lastly to identify selections to advance the current breeding population as well as to hybridise with E. grandis. Results indicated that genotype by environment interaction effects would be practically negligible for growth in Zululand and a single breeding population will therefore be appropriate. In general, all growth traits were under low to moderate genetic control, with narrow sense heritabilities ranging between 0.14 and 0.48 for volume. The genetic correlations between growth traits were high (0.98 and 0.99 for DBH-volume). This is an indication that DBH is a sufficient growth measure to use in E. urophylla breeding programmes. BLUP estimates indicated that a selection scenario of 200 individuals will generate genetic gains of 44.7% over the population mean. The estimated gains for the top 50 individuals that could potentially be used as hybrid parents to cross with E. grandis was 59.8% over the population mean.Funding was provided by Mondi training department.http://www.tandfonline.com/loi/tsfs202017-08-31hb2016Plant Production and Soil Scienc