Characterisation of a newly identified family of lipid transfer proteins at membrane contact sites

Non-vesicular intracellular lipid traffic is mediated by lipid transfer proteins (LTPs), which contain domains with an internal cavity that can solubilise and transfer lipids. One of the most widespread LTP folds is the Steroidogenic Acute Regulatory Transfer (StART) domain, which forms a hydrophobic pocket, and appears in proteins with different localisations and lipid specificities. The aim of this study was to characterise a new StART-like domain family, which we identified by a bioinformatics approach. I studied aspects of the localisations, functions and structural properties of six StART-like proteins in S. cerevisiae. The yeast StART-like proteins were endoplasmic reticulum (ER)-integral membrane proteins with transmembrane domains, and they localised at membrane contact sites: Lam1p/Lam3p, and Lam2p/Lam4p at junctions between ER and plasma membrane (PM); Lam5p/Lam6p at junctions between the ER and the vacuolar membrane, at nucleus-vacuole junction (NVJ) and at ER-mitochondria contacts. To study their functions, I purified the second StART-like domain of Lam4p, and I identified sterol as its lipid ligand from in vitro binding assays and in a spectroscopy approach with fluorescent ergosterol. We named the whole family LAM for Lipid transfer proteins Anchored at Membrane contact sites. The sterol binding property of the domains was related to a phenotype shared by LAM1, LAM2 and LAM3 delete strains, which showed an increased sensitivity to the sterol-sequestering polyene antifungal drug Amphotericin B (AmB). The two most sensitive strains (lam1∆ and lam3∆), displayed low sphingolipid levels, which is as yet unexplained. All AmB phenotypes were rescued by StART-like domains from the human LAMa, Lam2/4p and Lam5/6p, suggesting that these domains bind sterol. Simultaneous deletion of LAM1, LAM2, and LAM3 significantly reduced the extent of cortical ER-PM contacts, implying that they create the structure of the particularly punctate contact site they target. Finally, I started structural analysis of Lam4S2 to study the mechanism of sterol binding and to confirm our structural model

DESIGN OF A STATED RANKING EXPERIMENT TO STUDY INTERACTIVE FREIGHT BEHAVIOUR: AN APPLICATION TO ROME'S LTZ

City logistics policies require an understanding of several issues (e.g. freight distribution context, preferences and relationship among agents) seldom accounted for in current research. Policies run the risk of producing unsatisfactory results because behavioural and contextual aspects are not considered. The acquisition of relevant data is crucial to test hypothesis and forecast agents' reactions to policy changes. Despite recent methodological advances in modelling interactive behaviour the development of apt survey instruments is still lacking to test innovative policies acceptability. This paper expands and innovate the methodological literature by describing a stated ranking experiment to study freight agent interactive behaviour and discusses the experimental design implemented to incorporate agent-specific priors when efficient design techniques are employed.urban freight distribution, group decision making, agent-specific interaction, stated preference, stated ranking experiments

Are differences in stage at presentation a credible explanation for reported differences in the survival of patients with colorectal cancer in Europe?

Popular reporting of a comparison of cancer survival rates across 17 European countries, based on data collected by national and regional cancer registries, has left an impression of inadequate treatment of patients in the UK. A subsequent study has suggested that the poor survival rates reported for the UK can, in large part, be explained by more advanced stage at presentation. We believe this conclusion to be unsound and use this study as an example to illustrate the methodological difficulties which may arise during such international comparisons. As the NHS cancer plan aspires to achieve for the UK parity with the best cancer care in Europe, careful thought needs to be given to identifying countries with which the UK can usefully compare itself and the most appropriate indicators for this comparison. http://www.bjcancer.com © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Growth response and body composition of sharpsnout sea bream (Diplodus puntazzo) fed a high energy diet with different protein levels.

A study was undertaken to determine the effect of a high energy diet with two different protein levels on growth, feed efficiency and whole body composition of sharpsnout sea bream (Diplodus puntazzo). Two isoenergetic diets (24.1-24.7 MJ Kg-1 dry weight) with two different protein levels (46.7 and 52.5 % dry weight) were fed to satiety to duplicate groups of 300 fish (initial body weight 27.7 \ub1 0.2 g) for 94 days. At the end of the experiment, the fish fed 52.5 % protein showed a statistically higher (P < 0.05) daily intake rate (DIR) of feed. Feed conversion rate (FCR) was similar among groups. Whole body composition was similar among treatments while the high enrgy level of the diets significantly modified lipid and moisture content in comparison with fish at the beginning of the experiment. Protein efficiency ratio (PER), gross protein efficiency (GPE) of fish fed 46.7 % protein diet were statistically higher than those for the other diet. It may be concluded that the diet with a lower protein level has given better protein utilization and a protein sparing effect but tended to result in reduced weight gain and feed intake, when compared with diet containing higher protein levels

Integrating radiomics into holomics for personalised oncology: from algorithms to bedside.

Radiomics, artificial intelligence, and deep learning figure amongst recent buzzwords in current medical imaging research and technological development. Analysis of medical big data in assessment and follow-up of personalised treatments has also become a major research topic in the area of precision medicine. In this review, current research trends in radiomics are analysed, from handcrafted radiomics feature extraction and statistical analysis to deep learning. Radiomics algorithms now include genomics and immunomics data to improve patient stratification and prediction of treatment response. Several applications have already shown conclusive results demonstrating the potential of including other "omics" data to existing imaging features. We also discuss further challenges of data harmonisation and management infrastructure to shed a light on the much-needed integration of radiomics and all other "omics" into clinical workflows. In particular, we point to the emerging paradigm shift in the implementation of big data infrastructures to facilitate databanks growth, data extraction and the development of expert software tools. Secured access, sharing, and integration of all health data, called "holomics", will accelerate the revolution of personalised medicine and oncology as well as expand the role of imaging specialists

Metallogeny of Serpentinite-Hosted Magnetite Deposits : Hydrothermal Overgrowth on Chromite or Metamorphic Transformation of Chromite?

Peculiar and rare occurrences of serpentinite-hosted magnetite deposits with mineable sizes are found in the Mesozoic ophiolites of Greece (Skyros), Iran (Nain and Sabzevar) and Oman (Aniba). These deposits have diverse thickness (from a few centimeters up to 50 m) and length (2 to &gt;500 m). Magnetite ores show variable textures, including massive, nodular and banded ores, veins, net and fine-grained disseminations in serpentinites. Intriguingly, the investigated magnetite deposits can be mistaken for chromitite pods. Serpentinite-hosted magnetite deposits show three modes of occurrences including: (i) boulders strewn across the serpentinites (i.e. Skyros Island) (ii) ore bodies along the nonconformity contacts between serpentinites and limestones (i.e. Aniba); (iii) irregular and discontinuous trails of massive and semi-massive ore bodies within highly sheared serpentinite masses (i.e. Nain; Sabzevar). In all of these magnetite ore bodies, relicts of chromian spinel grains are occasionally enclosed in magnetite crystals. The chemistry of Cr-spinel relics found in these magnetite bodies are comparable to those of accessory Cr-spinels in the surrounding serpentinized peridotites. BSE images and elemental mapping revealed that magnetite occurs as a nucleation on chromian spinels but not being involved in reaction either with chromite or ferritchromite. Low-grade metamorphic transformation of chromite into Fe-chromite is documented along the cracks and fractures of a few chromite grains. Generally, magnetite has typical hydrothermal compositions, characterized by low Cr, V and Ti and high Mg and Mn. It is crucial to note that a few magnetite grains with metamorphic origin are characterized by high Cr and low Ti and Ni. The potential source of iron is essentially the Fe-rich olivine, We believe that multi-episodic serpentinization of peridotite systems at high fluid-rock ratios is the main process responsible for precipitation of magnetite at ore levels whereas low-grade metamorphic transformation of chromite to magnetite has minor contribution. Cumulative factors in generation of these deposits are modal volume of mantle olivine, peridotite composition, fluid chemistry, fluid-rock ratio, mechanisms of transportation and precipitation, structural controls such as cracks and shear zones

Low-temperature behavior of natural kalsilite with P31c symmetry: An in situ single-crystal X-ray diffraction study

The low-temperature behavior of a natural kalsilite (ideal formula KAlSiO4) with P31c symmetry has been investigated by in situ single-crystal diffraction. A series of intensity data collections and structural refinements have been performed at 298, 250, 200, 150, and 100 K on decreasing temperature, and 175, 225, and 275 K on increasing T. The variations of the unit-cell parameters of kalsilite as a function of T are continuous, and show no evidence of any phase transitions or thermo-elastic anomalies in this temperature range. An expansion is observed along [0001] with decreasing temperature. The axial and volume thermal expansion coefficients ({alpha}j = lj-1{middle dot}{partial}lj/{partial}T, {alpha}V = V-1{middle dot}{partial}V/{partial}T) between 298 and 100 K, calculated by weighted linear regression through the data points, are {alpha}a = {alpha}b = 1.30(6){middle dot}10-5, {alpha}c = -1.5(1){middle dot}10-5, {alpha}V = 1.1(2){middle dot}10-5 K-1. The main structural change on decreasing temperature is a cooperative anti-rotation of tetrahedra forming the six-membered rings lying parallel to (0001). This tetrahedral rotation is coupled with a change in the distances between the extra-framework cations and the framework O atoms. A small decrease in the tetrahedral tilts perpendicular to [0001] is responsible for the negative thermal expansion along [0001]; the implications of these mechanisms for thermal expansion in nephelines and kalsilites are discussed

Alexithymia, impulsiveness, and psychopathology in Nonsuicidal self-injured adolescents

Introduction: Nonsuicidal self-injury (NSSI) is a multifaceted phenomenon and a major health issue among adolescents. A better understanding of self-injury comorbidities is crucial to improve our ability to assess, treat, and prevent NSSI. Purpose: This study aimed at analyzing some of the psychobehavioral correlates of NSSI: psychological problems, alexithymia, impulsiveness, and sociorelational aspects. Patients and methods: This was a case-control study. The clinical sample (n=33) included adolescents attending our unit for NSSI and other issues; the controls (n=79) were high-school students. Data were collected using six questionnaires: Youth Self-Report, Barratt\u2019s Impulsiveness Scale, Toronto Alexithymia Scale, Children\u2019s Depression Inventory, Symptom Checklist-90-R, and Child Behavior Checklist. Results: Cases scored significantly higher in all questionnaires. Habitual self-injurers scored higher on impulsiveness and alexithymia. The gesture\u2019s repetition seems relevant to the global clinical picture: habitual self-injurers appear more likely to seek help from the sociosanitary services. We found a difference between the self-injurers\u2019 and their parents\u2019 awareness of the disorder. Conclusion: Habitual self-injurers show signs of having difficulty with assessing the consequences of their actions (nonplanning impulsiveness) and the inability to manage their feelings. Given the significantly higher scores found for cases than for controls on all the psychopathological scales, NSSI can be seen as a cross-category psychiatric disorder, supporting the Diagnostic and Statistical Manual of Mental Disorders decision to include it as a pathological entity in its own right

A single-crystal neutron diffraction study of wardite, NaAl3(PO4)2(OH)4&#183;2H2O

The crystal structure and crystal chemistry of wardite, ideally NaAl3(PO4)2(OH)4\ub72H2O, was investigated by single-crystal neutron diffraction (data collected at 20 K) and electron microprobe analysis in wavelength-dispersive mode. The empirical formula of the sample used in this study is: (Na0.91Ca0.01)\u3a3 = 0.92(Al2.97Fe3+0.05Ti0.01)\u3a3 = 3.03(P2.10O8)(OH)4\ub71.74H2O. The neutron diffraction data confirm that the crystal structure of wardite can be described with a tetragonal symmetry (space group P41212, a = b = 7.0577(5) and c = 19.0559(5) \uc5 at 20 K) and consists of sheets made of edge-sharing Na-polyhedra and Al-octahedra along with vertex-sharing Al-octahedra, parallel to (001), connected by P-tetrahedra and H bonds to form a (001) layer-type structure, which well explains the pronounced {001} cleavage of the wardite crystals. The present data show that four crystallographically independent H sites occur in the structure of wardite, two belonging to a H2O molecule (i.e., H1\u2013O6\u2013H2) and two forming hydroxyl groups (i.e., O5\u2013H3 and O7\u2013H4). The location of the hydrogen atoms allows us to define the extensive network of H bonds: the H atoms belonging to the H2O molecule form strong H bonds, whereas both the H atoms belonging to the two independent hydroxyl groups form weak interactions with bifurcated bonding schemes. As shown by the root-mean-square components of the displacement ellipsoids, oxygen and hydrogen atoms have slightly larger anisotropic displacement parameters compared to the other sites (populated by P, Al and Na). The maximum ratio of the max and min root-mean-square components of the displacement ellipsoids is observed for the protons of the hydroxyl groups, which experience bifurcated H-bonding schemes. A comparative analysis of the crystal structure of wardite and fluorowardite is also provided