Role of Pr160gag-pol in mediating the selective incorporation of tRNA(Lys) into human immunodeficiency virus type 1 particles

COS-7 cells transfected with human immunodeficiency virus type 1 (HIV-1) proviral DNA produce virus in which three tRNA species are most abundant in the viral tRNA population. These tRNAs have been identified through RNA sequencing techniques as tRNA(3Lys) the primer tRNA in HIV-1, and members of the tRNA(1,2Lys) isoacceptor family. These RNAs represent 60% of the low-molecular-weight RNA isolated from virus particles, while they represent only 6% of the low-molecular-weight RNA isolated from the COS cell cytoplasm. Thus, tRNA(Lys) is selectively incorporated into HIV-1 particles. We have measured the ratio of tRNA(3Lys) molecules to copies of genomic RNA in viral RNA samples and have calculated that HIV-1 contains approximately eight molecules of tRNA(3Lys) per two copies of genomic RNA. We have also obtained evidence that the Pr160gag-pol precursor is involved in primer tRNA(3Lys) incorporation into virus. First, selective tRNA(Lys) incorporation and wild-type amounts of tRNA(3Lys) were maintained in a protease-negative virus unable to process Pr55gag and Pr160gag-pol precursors, indicating that precursor processing was not required for primer tRNA incorporation. Second, viral particles containing only unprocessed Pr55gag protein did not selectively incorporate tRNA(Lys), while virions containing both unprocessed Pr55gag and Pr160gag-pol proteins demonstrated select tRNA(3Lys) packaging. Third, studies with a proviral mutant containing a deletion of most of the reverse transcriptase sequences and approximately one-third of the integrase sequence in the Pr160gag-pol precursor resulted in the loss of selective tRNA incorporation and an eightfold decrease in the amount of tRNA(3Lys) per two copies of genomic RNA. We have also confirmed herein finding of a previous study which indicated that the primer binding site is not required for the selective incorporation of tRNA(Lys).

π-Selective stationary phases: (II) Adsorption behaviour of substituted aromatic compounds on n-alkyl-phenyl stationary phases

The frontal analysis method was used to measure the adsorption isotherms of phenol, 4-chlorophenol, p-cresol, 4-methoxyphenol and caffeine on a series of columns packed with home-made alkyl-phenyl bonded silica particles. These ligands consist of a phenyl ring tethered to the silica support via a carbon chain of length ranging from 0 to 4 atoms. The adsorption isotherm models that fit best to the data account for solute–solute interactions that are likely caused by π–π interactions occurring between aromatic compounds and the phenyl group of the ligand. These interactions are the dominant factor responsible for the separation of low molecular weight aromatic compounds on these phenyl-type stationary phases. The saturation capacities depend on whether the spacer of the ligands have an even or an odd number of carbon atoms, with the even alkyl chain lengths having a greater saturation capacity than the odd alkyl chain lengths. The trends in the adsorption equilibrium constant are also significantly different for the even and the odd chain length ligands.

Performance of columns packed with the new shell particles, Kinetex-C18

The performance of the new Kinetex-C₁₈ column was investigated. Packed with a new brand of porous shell particles, this column has an outstanding efficiency. Once corrected for the contribution of the instrument extra column volume, the minimum values of the reduced plate heights for a number of low molecular weight compounds (e.g., anthracene and naphtho[2,3-a]pyrene) were between 1.0 and 1.3, breaking the legendary record set 3 years ago by Halo-C₁₈ packed columns. The liquid-solid mass transfer of proteins (e.g., insulin and lyzozyme) is exceptionally fast on Kinetex-C₁₈ much faster than on the Halo-C₁₈ column. The different contributions of dispersion and mass transfer resistances to the column efficiency were determined and discussed. The possible reasons for this extremely high column efficiency are discussed.

Effect of pregnancy for females born small on later life metabolic disease risk

There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. 

Control of crystallization in supramolecular soft materials engineering

As one class of the most important supramolecular functional materials, gels formed by low molecular weight gelators (LMWGs) have many important applications. The key important parameters affecting the in-use performance of a gel are determined by the hierarchical fiber network structures. Fiber networks consisting of weakly interacting multiple domains are commonly observed in gels formed by LMWGs. The rheological properties, particularly the elasticity, of a gel with such a fiber network are weak due to the weak interactions between the individual domains. As achieving desirable rheological properties of such a gel is practically relevant, in this work, we demonstrate the engineering of gels with such a type of fiber network by controlling crystallization of the gelator. Two example gels formed by a glutamic acid derivative in a non-ionic surfactant Tween 80 and in propylene glycol were engineered by controlling the thermodynamic driving force for crystallization. For a fixed gelator concentration, the thermodynamic driving force was manipulated by controlling the temperature for fiber crystallization. It was observed that there exists an optimal temperature at which a gel with maximal elasticity can be fabricated. This will hopefully provide guidelines for producing high performance soft materials by engineering their fiber network structures.

The relationship of the incidence of medullated fibres to the dimensional properties of mohair over the lifetime of Angora goats

In a range of animals, increasing mean fibre diameter (MFD) of fibre is associated with an increasing incidence of medullated fibres (Med). It would thus be expected that Med in mohair fleeces, from animals in a flock, would be related to the MFD of those fleeces. MFD of mohair is not the only dimensional attribute of fibres. Med in mohair is phenotypically and genetically related to the size of animals. This study examined how Med is related to dimensional properties of mohair over the lifetime of Angora goats and how the relationship varies with other lifetime factors. The relationship found is then examined to determine the extent that the relationship can be explained by variations in animal size of the goats. Measurements were made over 11 shearing periods on a population of Angora goats representing the current range and diversity of genetic origins in Australia, including South African, Texan and interbred admixtures of these and Australian sources. Records of breed, sire, dam, date of birth, dam age, birth weight, birth parity, weaning weight, live weight, fleece growth and fleece attributes were taken for castrated males (wethers). Animals’ fleece-free live weight (FFLwt, kg) were determined for each goat at shearing time by subtracting the greasy fleece weight from the live weight recorded immediately prior to shearing. The average of the FFLwt at the start of the period and the FFLwt at the end of the period was calculated. Two restricted maximum likelihood (REML) models were developed to relate Med to MFD, staple length (SL) and other lifetime factors. One model allowed FFLwt in the model and the other excluded FFLwt. With the exception of the 1.5 years shearing, Med strongly increased with increasing MFD whether or not adjustments were made for FFLwt measurements. In particular Med increased by 2.0% for each 1 μm increase in MFD, with no adjustment for FFLwt measurements, and increased by 1.5% for each 1 μm increase in MFD, with adjustment for FFLwt measurements. Within each shearing interval increasing average FFLwt was associated with increasing incidence of Med in a similar way to that which has been previously reported without including MFD in the model. There was no evidence that SL needed to be included in the models for Med. Mohair grown by the goats of Mixed genetic background grew mohair which had a higher incidence of Med at ages 2 and 2.5 years and the trend was apparent in other shearing periods. We can conclude that there is both a large response of Med to live weight and a large response to MFD, and that these responses are largely functionally separate. While the response to MFD is in accord with earlier work, there is an unrelated and unreported physiological mechanism that favours the production of Med in larger Angora goats. Clearly, larger Angora goats are biologically different compared with smaller animals from the same flock, in ways that are not purely related to the allometrics of size.

Ion conduction and phase morphology in sulfonate copolymer ionomers based on ionic liquid–sodium cation mixtures

A series of sulfonate based copolymer ionomers based on a combination of ionic liquid and sodium cations have been prepared in different ratios. This system was designed to improve the ionic conductivity of ionomers by partially replacing sodium cations with bulky cations that are less associated with anion centres on the polymer backbone. This provides more conduction sites for sodium to ‘hop’ to in the ionomers. Characterization showed the glass transition and 15N chemical shift of the ionomers did not vary significantly as the amount of Na+ varied, while the ionic conductivity increased with decreasing Na+ content, indicating conductivity is increasingly decoupled from Tg. Optical microscope images showed phase separation in all compositions, which indicated the samples were inhomogeneous. The introduction of low molecular weight plasticizer (PEG) reduced the Tg and increased the ionic conductivity significantly. The inclusion of PEG also led to a more homogeneous material.

The value of visual fleece assessment in addition to objective measurements in identifying Angora goats of greater clean mohair production

Visual assessment of the fleece of Merino sheep is an accepted method to aid genetic improvement but there is little evidence to support the use of visual assessment for improving mohair production. This paper examines the extent that visual traits, including staple length, character (staple crimp), staple definition, tippiness, style and staple entanglement, are related to clean fleece weight in animals of similar live weight and mean fibre diameter (MFD) from the same flock. Measurements were made over 9 shearing periods on a population of castrated Angora males (wethers) goats representing the current range and diversity of genetic origins in Australia, including South African, Texan and interbred admixtures of these and Australian sources (these different genetic origins are defined as Breed in this work). Data on genetic origin, sire, dam, lifetime characteristics (date of birth, dam age, birth weight, birth parity (single or twin), weaning weight), live weight, fleece growth and visual fleece attributes were recorded. A restricted maximum likelihood (REML) model was developed to relate clean fleece weight with age, MFD, average fleece-free live weight, lifetime characteristics and visual fleece attributes. There were separate linear responses of clean fleece weight to MFD and staple length for each age group, a quadratic response to the square root of average fleece-free live weight, an effect of sire breed and linear responses to dam age, staple definition score and character. Depending on age at shearing, the increase in clean fleece weight was between about 50 and 80. g for each increase of 1. μm in MFD. At similar MFD, clean fleece weight was generally greater at summer shearings compared with winter shearings. There was a strong increase in clean fleece weight with average fleece-free live weight up to around 50. kg but little response in clean fleece weight for animals larger than 50. kg. There was some evidence of a smaller increase in clean fleece weight as the age of dam increased. There was an effect of Breed in the model but this effect disappeared when a random sire effect was included in the model. There was a positive response to staple length at some age groups but the response did not differ from zero in other age groups. This response varied from negligible to about 70. g per 1. cm increase in staple length. Clean fleece weight increased about 40. g per unit increase in staple definition score and increased about 30. g for every 4 units increase in the number of staple crimps. There was no evidence that clean fleece weight was affected by staple style, staple tip score or staple entanglement score or lifetime factors such as birth weight, date of birth, birth parity, or weaning weight. The results show that using a combination of measuring MFD and visually assessing the fleece for staple length, staple definition and crimps can help identify the most profitable Angora goats. In this process, the objective measurement of MFD appears essential. Visual assessment will provide some extra benefit in identifying these animals above that provided by measuring MFD alone. Animal size should be considered by mohair producers when identifying more productive mohair producing animals. © 2014 Elsevier B.V.

Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients

Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin.

Organogelators based on the norbornane scaffold

Using the rigid norbornane scaffold, a series of low-molecular-weight organogelators has been synthesised and evaluated. Three separate compounds (16, 19 and 20) were identified as organogelators in three aromatic organic solvents (PhMe, anisole and o-xylene). The formation of fibrillar assemblies at nanometre level was confirmed using atomic force microscopy and transmission electron microscopy.

Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.