28 research outputs found

    Dynamics and energetics of the mammalian phosphatidylinositol transfer protein phospholipid exchange cycle

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    Phosphatidylinositol-transfer proteins (PITPs) regulate phosphoinositide signaling in eukaryotic cells. The defining feature of PITPs is their ability to exchange phosphatidylinositol (PtdIns) molecules between membranes, and this property is central to PITP-mediated regulation of lipid signaling. However, the details of the PITP-mediated lipid exchange cycle remain entirely obscure. Here, all-atom molecular dynamics simulations of the mammalian StART-like PtdIns/phosphatidylcholine (PtdCho) transfer protein PITP alpha, both on membrane bilayers and in solvated systems, informed downstream biochemical analyses that tested key aspects of the hypotheses generated by the molecular dynamics simulations. These studies provided five key insights into the PITP alpha lipid exchange cycle: (i) interaction of PITP alpha with the membrane is spontaneous and mediated by four specific protein substructures; (ii) the ability of PITP alpha to initiate closure around the PtdCho ligand is accompanied by loss of flexibility of two helix/loop regions, as well as of the C-terminal helix; (iii) the energy barrier of phospholipid extraction from the membrane is lowered by a network of hydrogen bonds between the lipid molecule and PITP alpha; (iv) the trajectory of PtdIns or PtdCho into and through the lipidbinding pocket is chaperoned by sets of PITP alpha residues conserved throughout the StART-like PITP family; and (v) conformational transitions in the C-terminal helix have specific functional involvements in PtdIns transfer activity. Taken together, these findings provide the first mechanistic description of key aspects of the PITP alpha PtdIns/PtdCho exchange cycle and offer a rationale for the high conservation of particular sets of residues across evolutionarily distant members of the metazoan StART-like PITP family.Peer reviewe

    Hens vary their vocal repertoire and structure when anticipating different types of reward

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    The vocalizations of nonhuman animals are considered potential indicators of motivational or internal state. In many species, different call types, and structural variation within call types, encode information about physical characteristics such as age or sex, or about variable traits such as motivation. Domestic chickens, Gallus gallus, have an elaborate vocal repertoire, enabling investigation into whether reward-related arousal is encoded within their call type and structure. Twelve hens were given a Pavlovian conditioning paradigm using sound cues to signal the availability of two food rewards (mealworms, normal food), one nonfood reward (a container of substrate suitable for dustbathing), and a sound-neutral event (sound cue, no reward). A muted-neutral treatment (no sound cue, no reward) provided a baseline for vocal behaviour. Sound cues preceded a 15 s anticipation period during which vocalizations were recorded. Hens produced a ‘Food call’ (previously defined in other studies) in anticipation of all rewards, including the nonfood reward. ‘Food calls’ and ‘Fast clucks’ were more prevalent in anticipation of rewards, and most prevalent following the cue signalling the dustbathing substrate, suggesting that this reward induced the most arousal in hens. The peak frequency of ‘Food calls’ made in anticipation of the dustbathing substrate was significantly lower than those made in anticipation of food rewards, potentially reflecting differences in arousal. Vocalizations that reliably indicate hens' motivational state could be used as measures of welfare in on-farm assessment situations. Our study is the first to reveal variation in the frequency-related parameters of the ‘Food call’ in different contexts, and to show the prevalence of different call types in reward and nonreward contexts, which may have implications for welfare assessments

    Assessment and re-design of learning activities from young social work students’ perceptions and experiences: an empirical study on the subject “social work with groups” of the University of Alicante (Spain)

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    Background. This article aims to incorporate students’ visions in the design of learning activities based on an analysis of their perceptions and evaluations of their experience working in small groups carried out in the subject ”Social Work with Groups” of a Social Work Program (University of Alicante, Spain). Method. We followed a quantitative approach, using a survey to collect data. Participants were social work students (n = 69). Univariate and bivariate data analysis was carried out, and we used parametric and non-parametric tests, depending on the group sample size. Results. Students believe that the activity contributes to achievement of learning objectives and skill and content acquisition and consolidation. Global satisfaction with the evaluation system and the activity was adequate. We found some differences by group in terms of associations between perception and satisfaction and some sociodemographic and academic variables. Conclusion. The experience was evaluated positively by the students. The activity design puts students at the center of the teaching and learning process

    Metabolic Regulation by Multifunctional Glucose-6-phosphatase

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