Structural mobility and transformations in globular proteins

Although globular proteins are endowed with well defined three-dimensional structures, they exhibit substantial mobility within the framework of the given threedimensional structure. The different types of mobility found in proteins by and large correspond to the different levels of organisational hierarchy in protein architecture. They are of considerable structural and functional significance, and can be broadly classified into(a) thermal and conformational fluctuations, (b) segmental mobility, (c) interdomain mobility and (d) intersubunit mobility. Protein crystallographic studies has provided a wealth of information on all of them. The temperature factors derived from X-ray diffraction studies provide a measure of atomic displacements caused by thermal and conformational fluctuations. The variation of displacement along the polypeptide chain have provided functionally significant information on the flexibility of different regions of the molecule in proteins such as myoglobin, lysozyme and prealbumin. Segmental mobility often involves the movement of a region or a segment of a molecule with respect to the rest, as in the transition between the apo and the holo structures of lactate dehydrogenase. It may also involve rigidification of a disordered region of the molecule as in the activation of the zymogens of serine proteases. Transitions between the apo and the holo structures of alcohol dehydrogenase,and between the free and the sugar bound forms of hexokinase, are good examples of interdomain mobility caused by hinge-bending. The capability of different domains to move semi-independently contributes greatly to the versatility of immunoglobulin molecules. Interdomain mobility in citrate synthase appears to be more complex and its study has led to an alternative description of domain closure. The classical and the most thoroughly studied case of intersubunit mobility is that in haemoglobin. The stereochemical mechanism of the action of this allosteric protein clearly brings out the functional subtilities that could be achieved through intersubunit movements. In addition to ligand binding and activation,environmental changes also often cause structural transformations. The reversible transformation between 2 Zn insulin and 4 Zn insulin is caused by changes in the ionic strength of the medium. Adenylate Kinase provides a good example for functionally significant reversible conformational transitions induced by variation in pH. Available evidences indicate that reversible structural transformations in proteins could also be caused by changes in the aqueous environment, including those in the amount of water surrounding protein molecules.

Intra-cluster correlation structure in longitudinal data analysis: Selection criteria and misspecification tests

Selection criteria and misspecification tests for the intra-cluster correlation structure (ICS) in longitudinal data analysis are considered. In particular, the asymptotical distribution of the correlation information criterion (CIC) is derived and a new method for selecting a working ICS is proposed by standardizing the selection criterion as the p-value. The CIC test is found to be powerful in detecting misspecification of the working ICS structures, while with respect to the working ICS selection, the standardized CIC test is also shown to have satisfactory performance. Some simulation studies and applications to two real longitudinal datasets are made to illustrate how these criteria and tests might be useful.

Cluster model of the glass transition

A cluster model of the glass transition has been developed, treating the relative size of the cluster as an order parameter. The model accounts for some of the features of the glass transition.

Cluster analysis of rainfall stations of the Indian peninsula

Principal component analysis is applied to derive patterns of temporal variation of the rainfall at fifty-three stations in peninsular India. The location of the stations in the coordinate space determined by the amplitudes of the two leading eigenvectors is used to delineate them into eight clusters. The clusters obtained seem to be stable with respect to variations in the grid of stations used. Stations within any cluster occur in geographically contiguous areas.

Association of microRNA 17–92 cluster host gene (MIR17HG) polymorphisms with breast cancer

Breast cancer incidence and mortality rates are increasing despite our current knowledge on the disease. Ninety-five percent of breast cancer cases correspond to sporadic forms of the disease and are believed to involve an interaction between environmental and genetic determinants. The microRNA 17–92 cluster host gene (MIR17HG) has been shown to regulate expression of genes involved in breast cancer development and progression. Study of single-nucleotide polymorphisms (SNPs) located in this cluster gene could help provide a further understanding of its role in breast cancer. Therefore, this study investigated six SNPs in the MIR17HG using two independent Australian Caucasian case–control populations (GRC-BC and GU-CCQ BB populations) to determine association to breast cancer susceptibility. Genotyping was undertaken using chip-based matrix assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry (MS). We found significant association between rs4824505 and breast cancer at the allelic level in both study cohorts (GRC-BC p = 0.01 and GU-CCQ BB p = 0.03). Furthermore, haplotypic analysis of results from our combined population determined a significant association between rs4824505/rs7336610 and breast cancer susceptibility (p = 5 × 10−4). Our study is the first to show that the A allele of rs4824505 and the AC haplotype of rs4824505/rs7336610 are associated with risk of breast cancer development. However, definitive validation of this finding requires larger cohorts or populations in different ethnical backgrounds. Finally, functional studies of these SNPs could provide a deeper understanding of the role that MIR17HG plays in the pathophysiology of breast cancer.

Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: A cluster-randomised controlled trial protocol

Introduction: Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care. Methods and analysis: A cluster-randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush- Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants’ demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data. Ethics and dissemination: The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer-reviewed journals.

Estimating crop area using seasonal time series of enhanced vegetation index from MODIS satellite imagery

Cereal grain is one of the main export commodities of Australian agriculture. Over the past decade, crop yield forecasts for wheat and sorghum have shown appreciable utility for industry planning at shire, state, and national scales. There is now an increasing drive from industry for more accurate and cost-effective crop production forecasts. In order to generate production estimates, accurate crop area estimates are needed by the end of the cropping season. Multivariate methods for analysing remotely sensed Enhanced Vegetation Index (EVI) from 16-day Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery within the cropping period (i.e. April-November) were investigated to estimate crop area for wheat, barley, chickpea, and total winter cropped area for a case study region in NE Australia. Each pixel classification method was trained on ground truth data collected from the study region. Three approaches to pixel classification were examined: (i) cluster analysis of trajectories of EVI values from consecutive multi-date imagery during the crop growth period; (ii) harmonic analysis of the time series (HANTS) of the EVI values; and (iii) principal component analysis (PCA) of the time series of EVI values. Images classified using these three approaches were compared with each other, and with a classification based on the single MODIS image taken at peak EVI. Imagery for the 2003 and 2004 seasons was used to assess the ability of the methods to determine wheat, barley, chickpea, and total cropped area estimates. The accuracy at pixel scale was determined by the percent correct classification metric by contrasting all pixel scale samples with independent pixel observations. At a shire level, aggregated total crop area estimates were compared with surveyed estimates. All multi-temporal methods showed significant overall capability to estimate total winter crop area. There was high accuracy at pixel scale (>98% correct classification) for identifying overall winter cropping. However, discrimination among crops was less accurate. Although the use of single-date EVI data produced high accuracy for estimates of wheat area at shire scale, the result contradicted the poor pixel-scale accuracy associated with this approach, due to fortuitous compensating errors. Further studies are needed to extrapolate the multi-temporal approaches to other geographical areas and to improve the lead time for deriving cropped-area estimates before harvest.

Reversals of polypeptide chain in globular proteins.

A simple algorithm has been developed to detect β-bends and 'loops'-chain reversals containing five amino acid residues, using only coordinates of Cα-atoms from crystal structure data of globular proteins using the above algorithm. Analysis of bends have showed that the total number of bends in each protein (TB) is linearly related to total number of non-hydrophobic residues in that protein which in turn is related linearly to total number of amino acid residues. Secondly, we found that a large number of consecutive bends occur in each protein which give rise to on an average only three independent residues per turn. Positional preference of amino acid residues in chain reversals is stressed. Consideration of pairs of amino acid residues in positions (i + 1) and (i + 2) of bends seems to provide a more reliable basis for predicting chain reversals in proteins.

Poor adoption of ley-pastures in south-west Queensland: biophysical, economic and social constraints.

The present review identifies various constraints relating to poor adoption of ley-pastures in south-west Queensland, and suggests changes in research, development and extension efforts for improved adoption. The constraints include biophysical, economic and social constraints. In terms of biophysical constraints, first, shallower soil profiles with subsoil constraints (salt and sodicity), unpredictable rainfall, drier conditions with higher soil temperature and evaporative demand in summer, and frost and subzero temperature in winter, frequently result in a failure of established, or establishing, pastures. Second, there are limited options for legumes in a ley-pasture, with the legumes currently being mostly winter-active legumes such as lucerne and medics. Winter-active legumes are ineffective in improving soil conditions in a region with summer-dominant rainfall. Third, most grain growers are reluctant to include grasses in their ley-pasture mix, which can be uneconomical for various reasons, including nitrogen immobilisation, carryover of cereal diseases and depressed yields of the following cereal crops. Fourth, a severe depletion of soil water following perennial ley-pastures (grass + legumes or lucerne) can reduce the yields of subsequent crops for several seasons, and the practice of longer fallows to increase soil water storage may be uneconomical and damaging to the environment. Economic assessments of integrating medium- to long-term ley-pastures into cropping regions are generally less attractive because of reduced capital flow, increased capital investment, economic loss associated with establishment and termination phases of ley-pastures, and lost opportunities for cropping in a favourable season. Income from livestock on ley-pastures and soil productivity gains to subsequent crops in rotation may not be comparable to cropping when grain prices are high. However, the economic benefits of ley-pastures may be underestimated, because of unaccounted environmental benefits such as enhanced water use, and reduced soil erosion from summer-dominant rainfall, and therefore, this requires further investigation. In terms of social constraints, the risk of poor and unreliable establishment and persistence, uncertainties in economic and environmental benefits, the complicated process of changing from crop to ley-pastures and vice versa, and the additional labour and management requirements of livestock, present growers socially unattractive and complex decision-making processes for considering adoption of an existing medium- to long-term ley-pasture technology. It is essential that research, development and extension efforts should consider that new ley-pasture options, such as incorporation of a short-term summer forage legume, need to be less risky in establishment, productive in a region with prevailing biophysical constraints, economically viable, less complex and highly flexible in the change-over processes, and socially attractive to growers for adoption in south-west Queensland.

High pressure transport behaviour of AgI-Ag2O-MoO3 glasses and the cluster model

The effect of pressure on the conductivity of fast ion conducting AgI-Ag2O-MoO3 glasses has been investigated down to 150 K. The observed variation of conductivities appears to support the application of cluster model to the ionic glasses.

Ongoing poor management of medicines in the older-aged living independently in a rental retirement village

Background In a low socioeconomic status, small, rental retirement village, we have shown the older-aged managed their medicines poorly [1]. Objective As the number of participants was only 25, and the population in the rental retirement village turns over regularly; our objective was to determine whether the findings were consistent and ongoing. Methods We returned to the rental retirement villages after one and two years, and reassessed the management of medicines, using the same semi-structured interview method. Main outcome measure The main outcome measure was the perception of present and ongoing adherence. Results Although similar numbers (23-25) participated in the studies in 2011-2013, the actual participants changed with only 3 being interviewed on 3 occasions. Nevertheless, the findings over the 3 years were similar: less than 50% of the participants were adherent at the time of the study and unlikely to have problems in the next 6-12 months; only 50% had a good knowledge of their illnesses. Conclusions The management of medicines by the older-aged living in a low socioeconomic, rental retirement village is poor, and this finding is ongoing and consistent. This supports the need for extra assistance and resources for the older-aged, living in rental retirement villages, to manage their medicines.

Identification and analysis of extended strands and beta-sheets in globular proteins

A method to identify β-sheets in globular proteins from extended strands, using only α-carbon positions, has been developed. The strands that form β-sheets are picked up by means of simple distance criteria. The method has been tested by applying it to three proteins with accurately known secondary structures. It has also been applied to ten other proteins wherein only α-carbon coordinates are available, and the list of β-sheets obtained. The following points are worth noting: (i) The sheets identified by the algorithm are found to agree satisfactorily with the reported ones based on backbone hydrogen bonding, wherever this information is available. (ii) β-Strands that do not form parts of any sheet are a common feature of protein structures. (iii) Such isolated β-strands tend to be short. (iv) The conformation corresponding to the preferred right-handed twist of the sheet is overwhelmingly observed in both the sheet-forming and isolated β-strands.

Musculoskeletal disorders and psychosocial factors at work : Effects of a participatory ergonomics intervention in a cluster randomized controlled trial

This study examined the efficacy of a participatory ergonomics intervention in preventing musculoskeletal disorders (MSDs) and changing unsatisfactory psychosocial working conditions among municipal kitchen workers. The occurrence of multiple-site musculoskeletal pain (MSP) and associations between MSP and psychosocial factors at work over time were studied secondarily. A cluster randomized controlled trial was conducted during 2002-2005 in 119 municipal kitchens with 504 workers. The kitchens were randomized to an intervention (n = 59) and control (n = 60) group. The intervention lasted 11 to 14 months. The workers identified strenuous work tasks and sought solutions for decreasing physical and mental workload. The main outcomes were the occurrence of and trouble caused by musculoskeletal pain in seven anatomical sites, local musculoskeletal fatigue after work, and musculoskeletal sick leaves. Psychosocial factors at work (job control, skill discretion, co-worker relationships, supervisor support, mental strenuousness of work, hurry, job satisfaction) and mental stress were studied as intermediate outcomes of the intervention. Questionnaire data were collected at three months intervals during the intervention and the one-year post-intervention follow-up. Response rates varied between 92 % and 99 %. In total, 402 ergonomic changes were implemented. In the control group, 80 changes were spontaneously implemented within normal activity. The intervention did not reduce perceived physical workload and no systematic differences in any health outcomes were found between the intervention and control groups during the intervention or during the one-year follow-up. The results suggest that the intervention as studied in the present trial was not more effective in reducing perceived physical workload or preventing MSDs compared with no such intervention. Little previous evidence of the effectiveness of ergonomics interventions in preventing MSDs exists. The effects on psychosocial factors at work were adverse, especially in the two of the participating cities where re-organization of foodservices timed simultaneously with the intervention. If organizational reforms at workplace are expected to occur, the execution of other workplace interventions at the same time should be avoided. The co-occurrence of musculoskeletal pain at several sites is observed to be more common than pain at single anatomical sites. However, the risk factors of MSP are largely unknown. This study showed that at baseline, 73 % of the women reported pain in at least two, 36 % in four or more, and 10 % in six to seven sites. The seven pain symptoms occurred in over 80 different combinations. When co-occurrence of pain was studied in three larger anatomical areas (neck/low back, upper limbs, lower limbs), concurrent pain in all three areas was the most common combination (36 %). The 3-month prevalence of MSP (≥ 3 of seven sites) varied between 50 % and 61 % during the two-year follow-up period. Psychosocial factors at work and mental stress were strong predictors for MSP over time and, vice versa, MSP predicted psychosocial factors at work and mental stress. The reciprocality of the relationships implies either two mutually dependent processes in time, or some shared common underlying factor(s).

Glass transition. A new approach based on cluster model of glasses

The structure of real glasses has been considered to be microheterogeneous, composed of clusters and connective tissue. Particles in the cluster are assumed to be highly correlated in positions. The tissue is considered to have a truly amorphous structure with its particles vibrating in highly anharmonic potentials. Glass transition is recognized as corresponding to the melting of clusters. A simple mathematical model has been developed which accounts for various known features associated with glass transition, such as range of glass transition temperature,T g, variation ofT g with pressure, etc. Expressions for configurational thermodynamic properties and transport properties of glass forming systems are derived from the model. The relevence and limitations of the model are also discussed.