Structural basis of substrate selectivity in the glycerol-3-phosphate: phosphate antiporter GlpT.

Major facilitators represent the largest superfamily of secondary active transporter proteins and catalyze the transport of an enormous variety of small solute molecules across biological membranes. However, individual superfamily members, although they may be architecturally similar, exhibit strict specificity toward the substrates they transport. The structural basis of this specificity is poorly understood. A member of the major facilitator superfamily is the glycerol-3-phosphate (G3P) transporter (GlpT) from the Escherichia coli inner membrane. GlpT is an antiporter that transports G3P into the cell in exchange for inorganic phosphate (Pi). By combining large-scale molecular-dynamics simulations, mutagenesis, substrate-binding affinity, and transport activity assays on GlpT, we were able to identify key amino acid residues that confer substrate specificity upon this protein. Our studies suggest that only a few amino acid residues that line the transporter lumen act as specificity determinants. Whereas R45, K80, H165, and, to a lesser extent Y38, Y42, and Y76 contribute to recognition of both free Pi and the phosphate moiety of G3P, the residues N162, Y266, and Y393 function in recognition of only the glycerol moiety of G3P. It is the latter interactions that give the transporter a higher affinity to G3P over Pi.

Determinants of human rights attitudes and behavior: A comparison and integration of psychological perspectives

Following several political-psychological approaches, the present research analyzed whether orientations toward human rights are a function of right-wing authoritarianism (RWA), social dominance orientation (SDO), basic human values in the sense of Schwartz (1992), and political ideology. Three dimensions of human rights attitudes (endorsement, restriction, and enforcement) were differentiated from human rights knowledge and behavior. In a time-lagged Internet survey (N = 479), using structural equation modeling, RWA, universalism and power values, and political ideology (measured at Time 1) differentially predicted dimensions of human rights attitudes (measured at Time 2 five months later). RWA and universalism values also predicted self-reported human rights behavior, with the effects mediated through human rights endorsement. Human rights knowledge also predicted behavior. The psychological roots of positive and negative orientations toward human rights, consequences for human rights education, and the particular role of military enforcement of human rights are discussed.

The determinants of knowledge transfer within collaborative new product development projects

Purpose – This paper explores the factors which determine the degree of knowledge transfer in inter-firm new product development projects. We test a theoretical model exploring how inter-firm knowledge transfer is enabled or hindered by a buyer’s learning intent, the degree of supplier protectiveness, inter-firm knowledge ambiguity, and absorptive capacity. Design/methodology/approach – A sample of 153 R&D intensive manufacturing firms in the UK automotive, aerospace, pharmaceutical, electrical, chemical, and general manufacturing industries were used to test the framework. Two-step structural equation modeling in AMOS 7.0 was used to analyse the data. Findings – Our results indicate that a buyer’s learning intent increases inter-firm knowledge transfer, but also acts as an incentive for suppliers to protect their knowledge. Such defensive measures increase the degree of inter-firm knowledge ambiguity, encouraging buyer firms to invest in absorptive capacity as a means to interpret supplier knowledge, but also increase the degree of knowledge transfer. Practical implications – Our paper illustrates the effects of focusing on acquisition, rather than accessing, supplier technological knowledge. We show that an overt learning strategy can be detrimental to knowledge transfer between buyer-supplier, as supplier’s react by restricting the flow of information. Organisations are encouraged to consider this dynamic when engaging in multi-organisational new product development projects. Originality/value – This paper examines the dynamics of knowledge transfer within inter-firm NPD projects, showing how transfer is influenced by the buyer firm’s learning intention, supplier’s response, characteristics of the relationship and knowledge to be transferred.

Determinants of WTP for Prosecco wine: A latent class regression with attitudinal responses

Purpose – Under investigation is Prosecco wine, a sparkling white wine from North-East Italy.
Information collection on consumer perceptions is particularly relevant when developing market
strategies for wine, especially so when local production and certification of origin play an important
role in the wine market of a given district, as in the case at hand. Investigating and characterizing the
structure of preference heterogeneity become crucial steps in every successful marketing strategy. The
purpose of this paper is to investigate the sources of systematic differences in consumer preferences.
Design/methodology/approach – The paper explores the effect of inclusion of answers to
attitudinal questions in a latent class regression model of stated willingness to pay (WTP) for this
specialty wine. These additional variables were included in the membership equations to investigate
whether they could be of help in the identification of latent classes. The individual specific WTPs from
the sampled respondents were then derived from the best fitting model and examined for consistency.
Findings – The use of answers to attitudinal question in the latent class regression model is found to
improve model fit, thereby helping in the identification of latent classes. The best performing model
obtained makes use of both attitudinal scores and socio-economic covariates identifying five latent
classes. A reasonable pattern of differences in WTP for Prosecco between CDO and TGI types were
derived from this model.
Originality/value – The approach appears informative and promising: attitudes emerge as
important ancillary indicators of taste differences for specialty wines. This might be of interest per se
and of practical use in market segmentation. If future research shows that these variables can be of use
in other contexts, it is quite possible that more attitudinal questions will be routinely incorporated in
structural latent class hedonic models.

Psychological determinants of consumer acceptance of personalised nutrition in 9 European countries

OBJECTIVE: To develop a model of the psychological factors which predict people's intention to adopt personalised nutrition. Potential determinants of adoption included perceived risk and benefit, perceived self-efficacy, internal locus of control and health commitment.

METHODS: A questionnaire, developed from exploratory study data and the existing theoretical literature, and including validated psychological scales was administered to N=9381 participants from 9 European countries (Germany, Greece, Ireland, Poland, Portugal, Spain, the Netherlands, the UK, and Norway).

RESULTS: Structural equation modelling indicated that the greater participants' perceived benefits to be associated with personalised nutrition, the more positive their attitudes were towards personalised nutrition, and the greater their intention to adopt it. Higher levels of nutrition self-efficacy were related to more positive attitudes towards, and a greater expressed intention to adopt, personalised nutrition. Other constructs positively impacting attitudes towards personalised nutrition included more positive perceptions of the efficacy of regulatory control to protect consumers (e.g. in relation to personal data protection), higher self-reported internal health locus of control, and health commitment. Although higher perceived risk had a negative relationship with attitude and an inverse relationship with perceived benefit, its effects on attitude and intention to adopt personalised nutrition was less influential than perceived benefit. The model was stable across the different European countries, suggesting that psychological factors determining adoption of personalised nutrition have generic applicability across different European countries.

CONCLUSION: The results suggest that transparent provision of information about potential benefits, and protection of consumers' personal data is important for adoption, delivery of public health benefits, and commercialisation of personalised nutrition.

Novel Genetic Determinants of Diabetic Kidney Disease

Diabetic kidney disease (DKD) is a devastating diabetes complication, with known heritability not fully revealed by previous genetics studies. We performed the largest genome-wide association study of type 1 DKD to date, in a 13-cohort consortium of 15,590 individuals of European ancestry genotyped on the Illumina HumanCoreExome Beadchip, which allows exploration of coding variation in addition to genomic markers.

As prior work has shown that different characterizations of the DKD phenotype highlight distinct genetic associations, we investigated a spectrum of DKD definitions based on proteinuria and renal function criteria. Controls were DKD-free after a minimum of 15 years diabetes duration; cases had diabetes for at least 10 years prior to DKD diagnosis. We also performed a quantitative trait analysis of estimated glomerular filtration rate in all participants.

Our top finding was a missense mutation in COL4A3, rs55703767 (Asp326Tyr); the minor allele is common in Europeans (20%) and East Asians (13%) but not Africans (2%). This SNP had a genome-wide significant association with traditionally defined DKD (macroalbuminuria or end-stage renal disease [ESRD], (OR= 0.79, P=1.9×10-9), and a suggestive association with macroalbuminuria (OR= 0.79, P=1.6×10-6) and ESRD (OR= 0.79, P=4.5×10-5) individually. Though its PolyPhen score is 0.3 (benign), this SNP has been implicated as a splice site disruptor.

The COL4A3 gene encodes the alpha 3 subunit of Type IV collagen, the major structural component of basement membranes. Pathogenic mutations in COL4A3 have been identified in thin basement membrane nephropathy, familial focal segmental glomerulosclerosis, and Alport syndrome. A proxy (r2=0.6) for rs55703767 had no significant associations in the CKDGen consortium, suggesting its pathogenicity occurs solely in the setting of hyperglycemia.

By significantly increasing sample size we have discovered a novel locus underlying DKD risk, paving the way for better understanding of pathology, prevention, and treatment.