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Different amounts of carbon nanotubes (CNT) have been incorporated in materials based on poly(vinylidene fluoride) (PVDF) by solvent blending followed by their further precipitation. Final processing was performed by compression molding. The morphological aspects and crystalline characteristics have been examined, additionally exploring in these nanocomposites the common routes described in the pristine PVDF to induce the β polymorph. This polar β phase has been found to be promoted by the simple inclusion of CNT. Therefore, coexistence of the α and β lattices occurs for the analyzed materials. The real-time variable-temperature X-ray diffraction measurements with synchrotron radiation at a wide angle have undoubtedly allowed us to observe the presence of the two polymorphs and determine the melting temperature of both crystalline modifications. Furthermore, the CNT plays a nucleating role in the PVDF crystallization, and also acts as reinforcement, increasing the stiffness of the nanocomposites. Moreover, the mobility within the amorphous and crystalline PVDF regions is found to change with the CNT content. Finally, the presence of CNT leads to a very remarkable increase in the conductivity parameter, in such a way that the transition from insulator to electrical conductor is reached in these nanocomposites at a percolation threshold ranging from 1 to 2 wt.%, leading to the excellent value of conductivity of 0.05 S/cm in the material with the highest content in CNT (8 wt.%).

Different materials, based on an L-rich polylactide (PLA) as matrix, acetyl tri-n-butyl citrate (ATBC) as plasticizer, and mesoporous Mobile Crystalline Material.41 (MCM-41) particles as nucleating agent, were attained by melt extrusion. These materials are constituted by (a) binary blends of PLA and ATBC with different contents of the latest; (b) a dual compound of PLA and a given amount of MCM-41 silica (5 wt.%); and (c) ternary composites that include PLA, ATBC at several compositions and mesoporous MCM-41 at 5 wt.%. Influence of the incorporation of the plasticizer and nucleating particles has been comprehensively analyzed on the different phase transitions: glass transition, cold crystallization, melt crystallization and melting processes. Presence of both additives moves down the temperature at which PLA phase transitions take place, while allowing the PLA crystallization from the melt at 10 °C/min in the composites. This tridimensional ordering is not noticeable in the pristine PLA matrix and, accordingly, PLA crystallization rate is considerably increased under dynamic conditions and also after isothermal crystallization from either the melt or the glassy state. An important synergistic effect of dual action of ATBC and MCM-41 has been, therefore, found., This research was funded by MCIN/AEI/10.13039/501100011033, grant number PID2020-114930GB-I00. Grant BES-2017-082284 was also funded by MCIN/AEI/10.13039/501100011033 and, thus, TMDR is also thankful for this pre-doctoral funding

Different composites based on an L-rich poly(lactic acid) (PLLA) and mesoporous SBA-15 functionalized with silver (SBA-15@Ag) are prepared by a solvent casting protocol, and subsequently processed as films by compression molding. Characterization of hybrid SBA-15@Ag particles shows that Ag is mainly incorporated as nanowires within the nanometric silica channels, and is able to provide its antimicrobial character to these hybrid particles. PLLA crystallinity, crystallization ability and the polymorphs able to be developed are strongly dependent on cooling rate and in less extent on silica content. These hybrid particles exert an important nucleating and reinforcing effect in the resultant composites. They also show very interesting and remarkable antimicrobial features, which are transferred to the PLLA composites. The most important antimicrobial activity is found against P. aeruginosa, E. coli and C. parapsilosis, Gram negative bacteria and yeast, respectively., Grants PID2020-114930 GB-I00 and PID2019-104600RB-I00 were funded by MCIN/AEI/10.13039/501100011033. Authors acknowledge this support together with that received from ALBA Synchrotron Light Facility. Grant BES-2017-082284 was also funded by MCIN/AEI/ 10.13039/501100011033 and, thus, TMDR is also thankful for her predoctoral funding. The synchrotron experiments were carried out in the beamline BL11-NCD-SWEET at ALBA Synchrotron Light Facility with the collaboration of ALBA staff.

A study of different nanocomposites based on poly(ε-caprolactone) (PCL) and mesoporous SBA-15 silica that were prepared by melt extrusion was carried out by analyzing the possible effect of this filler on the crystalline details of PCL, on its mechanical behavior, and on the eventual observation of the confinement of the polymeric chains within the hollow nanometric silica channels. Thus, simultaneous Small-Angle and Wide-Angle X-ray Scattering (SAXS/WAXS) synchrotron experiments at variable temperature were performed on these PCL nanocomposites with different mesoporous silica contents. The importance of the morphological and structural features was assessed by the changes that were observed during the mechanical response of the final materials, which determined that the presence of mesoporous particles leads to a noticeable reinforcing effect., his work was supported by the Agencia Estatal de Investigación (AEI, Spain) together with the European Regional Development Fund (FEDER, UE) (grant numbers MAT2016-79869-C2-1-P and PID2020-114930GB-I00) by CSIC (grant number 2020AEP129) and ALBA Synchrotron Light Facility. TMDR is also grateful for her pre-doctoral funding (contract number BES-2017-08228

Composites based on an L-rich poly(lactic acid) (PLLA) and MCM-41, either neat or modified with a silver (MCM-41@Ag), are achieved by solvent casting, being next processed by compression molding. Ag is mainly embedded as nanowires within the hybrid MCM-41@Ag particles, enabling its antimicrobial character. In these composites, the PLLA thermal stability, nucleation efficiency, and mechanical response are dependent on the MCM-41 nature and, to a lesser extent, on its content. Thus, differences in transitions of the PLLA matrix are noticed during cooling at 10 °C/min and in the subsequent heating when composites with neat or modified MCM-41 are compared. A very remarkable nucleation effect is played by pristine MCM-41, being inferior when MCM-41@Ag is incorporated into the PLLA. Wide angle X-ray scattering (WAXS) measurements using synchrotron radiation and performed under variable-temperature conditions in the composites containing MCM-41@Ag indicate that during cold crystallization, the disordered α′ polymorph is initially formed, but it rapidly transforms into ordered α crystals. A long spacing peak, clearly seen in pure PLLA, appears as a small shoulder in PLLAMCM@Ag4 and is undetectable in PLLAMCM@Ag9 and PLLAMCM@Ag20. Furthermore, an increase in MH with the silica content is found in the two sets of composites, the higher MH values being observed in the family of PLLA and MCM-41@Ag. Finally, remarkable antimicrobial features are noticeable in the composites with MCM-41@Ag since this modified silica transfers its biocidal characteristics into the PLLA composites.

Background: Glucagon-like peptide-2 (GLP-2) is an intestinal trophic factor that induces astrocyte proliferation through its own receptor (GLP-2R), but the control of its expression is not well known. Objective: To study the effects of glucose and of different mitogenic agents on the control of GLP-2R expression in cultured rat astrocytes. Methods: GLP-2R mRNA content was measured by quantitative RT-PCR. Results: GLP-2R expression was higher in proliferating than in resting cells. The expression was dependent of glucose concentration both in the absence and in the presence of GLP-2. In the presence of a high glucose concentration, GLP-2, PDGF, and PDGF plus GLP-2 presented opposite effects depending on the incubation time. However, insulin, IGF-1, and EGF alone, and plus GLP-2 had no effect. IGF-2, but not IGF-2 plus GLP-2, increased the expression. On the contrary, NGF decreased the GLP-2R expression, but NGF plus GLP-2 increased it even until values similar to those obtained with GLP-2 alone. Interestingly, in the presence of a low glucose concentration, leptin and NPY produced a significant reduction of GLP-2R expression. Conclusion: Astrocytes are distributed throughout the brain, where GLP-2 appears to have important functions. Since these cells express the GLP-2R, the results of this study could be considered of interest to advance the knowledge of the role of GLP-2 signaling in the CNS, which should lead a better understanding of the events that occur under normal and pathophysiological conditions.

Recycling of plastics is absolutely essential in a circular economy, especially in the case of commodity polymers from fossil resources, like isotactic polypropylene (iPP). Therefore, evaluation of the factors that are decisive for an optimum performance of the recycled based materials becomes mandatory for the obtainment of new products with optimal properties. One of the most important aspects is the protection of the plastics materials not only against the external degradation agents, but also from the radicals generated during their previous service life. Accordingly, several materials have been prepared by extrusion based on virgin iPP with different amounts of the same polypropylene severely degraded, which has been used as model component to be recycled. Previous to the extrusion, a mixture of antioxidants was added to all the samples, and special attention has been paid to consumption of those additives during the extrusion. The results show an increasing reduction of antioxidants with rising content of the degraded material. But, importantly, a rather analogous mechanical response has been found for all the recycled materials in relation to the virgin iPP, pointing out a satisfactory dilution effect of the existing degradation points within the virgin polymeric chains, and indicating the very relevant action of the antioxidants used., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Agencia Estatal de Investigación (AEI, Spain) (PID2020-114930 GB-I00 project) and ALBA Synchrotron Light Facility. Authors thank the funding. TMDR is also thankful for her pre-doctoral funding (contract number BES-2017-082284).

Two

Two L-rich polylactides (PLLA) with distinct contents in D isomer and their composites with an intermediate amount of mesoporous Santa Barbara Amorphous-15 (SBA-15) (about 9 wt.%) particles were attained by melt extrusion for the evaluation of the effect of content in D isomer and incorporation of mesoporous silica on the structural PLLA features and on their ultimate mechanical performance. For that, samples have been crystallized under dynamic and isothermal tests (from the melt and from the glassy states). The results from DSC and X-ray diffraction show obtainment of the pure α’ and α modifications at different intervals of crystallization temperature depending on the D steroisomer amount of the PLLA used. Furthermore, several phase transitions are observed depending on the crystallinity reached and the polymorphs developed during the isothermal crystallization from the glass: an additional cold crystallization, the α’/α transformation and the subsequent melting process, appearing all of them at temperatures clearly dependent on the D content. Rigidity, measured through microhardness in amorphous samples, is also affected by the D isomer and the presence of SBA-15 particles. Reinforcement effect of mesoporous silica is relatively more important in the matrix with the highest D content., This work was supported by the Agencia Estatal de Investigación (AEI, Spain) (PID2020-114930GB-I00 project) and ALBA Synchrotron Light Facility. Authors thank the funding. TMDR is also thankful for her pre-doctoral funding (contract number BES-2017-082284).

Several nanocomposites were prepared by extrusion from a commercial metallocene-type isotactic polypropylene (iPP) and different amounts of two types of graphene (G) nanofibers: ones with a high specific surface, named GHS, and the others with a low specific surface, labeled as GLS. The number of graphene layers was found to be around eight for GLS and about five in the GHS. Scanning electron microscopy (SEM) images of the resultant iPP nanocomposites showed a better homogeneity in the dispersion of the GLS nanofibers within the polymeric matrix compared with the distribution observed for the GHS ones. Crystallinity in the nanocomposites turned out to be dependent upon graphene content and upon thermal treatment applied during film preparation, the effect of the nature of the nanofiber being negligible. Graphene exerted a noticeable nucleating effect in the iPP crystallization. Furthermore, thermal stability was enlarged, shifting to higher temperatures, with increasing nanofiber amount. The mechanical response changed significantly with nanofiber type, along with its content, together with the thermal treatment applied to the nanocomposites. Features of nanofiber surface played a key role in the ultimate properties related to superficial and bulk stiffness., This work was supported by the Agencia Estatal de Investigación (AEI, Spain) (grant number PID2020-114930GB-I00).

Composites based on an L-rich poly(lactic acid), PLA, and different contents in mesoporous SBA-15 silica have been prepared by extrusion in order to evaluate the influence of incorporation of mesoporous particles on the structural PLA features and on their ultimate mechanical performance. For that, the samples have been isothermally cold crystallized for relatively long times at different temperatures, ranging from 65 to 120 °C. The results from DSC, X-ray diffraction and Raman spectroscopy show that the pure α′ modification is obtained at the lower annealing temperatures, while the α form is in majority above 85 °C. The temperature range at which α′ and α polymorphs were developed is somewhat atypical, being associated with the particular D stereoisomer content of the PLA used. Furthermore, several phase transitions are observed depending on the crystallinity reached and the polymorphs developed during the isothermal crystallization from the glass: an additional cold crystallization, the α′/α transformation and the subsequent melting processes. These transitions have been evaluated thoroughly by DSC measurements and real-time variable temperature experiments with synchrotron radiation. It was also found that rigidity of these materials is influenced by both the presence of SBA-15 particles and by the amount and perfection of crystallites. Thus, the relative reinforcement effect of SBA-15 particles is importantly reduced by differences in long spacing PLA values for the materials crystallized between 85 and 120 °C, mainly in the composites with the lowest SBA-15 content. Those are the temperatures where the α polymorph is the major existing crystalline structure., This research was funded by AEI, Spain/FEDER, EU (grant numbers MAT2016-79869-C2-1-P and PID2020-114930GB-I00), by CSIC, Spain (grant number 2020AEP129) and by ALBA Synchrotron Light Facility, Spain. TMDR is also grateful for her pre-doctoral funding (contract number BES-2017-082284). The FESEM, Raman and TGA measure- ments were carried out in the Characterization Service at ICTP-CSIC and authors are grateful for the help and advices received. The synchrotron experiments were performed in the beamline BL11-NCD-SWEET at ALBA Synchrotron Light Facility and authors would like to thank the collaboration and help of ALBA staf

Effect of electron beam (EB) irradiation is analyzed in low and high density polyethylenes (LDPE and HDPE, respectively) at different doses. Parameters as important as degree of crystallinity, melting or crystallization temperatures are dependent on the initial PE molecular architecture, which also controls the gel content developed by action of EB irradiation and the EB dose applied. Thus, this gel amount, ascribed to formation of chain crosslinkings, is raised as irradiation dose increases, being larger in the HDPE than in the LDPE. In both, a plateau value is reached at the highest doses. The molecular changes that take place in both PEs during EB irradiation lead to a hindrance in their crystallization capacity, once macrochains are molten, and, accordingly, to a reduction in crystallinity and to formation of thinner crystallites. Variation with temperature of rigid and soft fractions together with their respective relaxation times is followed in the irradiated LDPE and HDPE specimens by pulse mixed magic-sandwich echo nuclear magnetic resonance (MSE-NMR) measurements. The network structure promoted in these PEs is evaluated by using the multiple-quantum nuclear magnetic resonance (MQ-NMR) approach, showing important differences caused by EB irradiation due to their intrinsic molecular characteristics., Funding received from the 2017 Industrial Doctorate Program of the University of Cantabria, Spain, is gratefully acknowledged. Grants PID2020-119047RB-I00 and PID2020-114930GB-I00 were funded by MCIN/AEI/10.13039/501100011033.

Time-resolved variable-temperature synchrotron techniques have been employed for learning about semicrystalline structure and morphology of an L-rich (4.2 mol% in D-isomer) poly(lactic acid), PLLA. An amorphous specimen has been isothermally crystallized from the glassy state at different temperatures, aiming to gain knowledge about development of the two polymorphs, α′ and α. Subsequent melting of these cold crystallized samples has been analyzed by DSC and synchrotron techniques. Besides studying Lorentz-corrected SAXS profiles, one-dimensional correlation functions have been determined for two crystallization temperatures, selected for yielding neat α′ and α polymorphs respectively. Long spacing, crystal thickness and local crystallinity have been determined. Results show a clear discontinuity with temperature of some of these parameters when transition from disordered α′ to more ordered α modification occurs. Additionally, a SAXS-determined glass transition has been obtained and compared with that derived from the corresponding DSC results., Grant PID2020-114930GB-I00 was funded by MCIN/AEI/10.13039/ 501100011033. Authors acknowledge this support together with that received from ALBA Synchrotron Light Facility. Grant BES-2017-082284 was also funded by MCIN/AEI/10.13039/501100011033 and, thus, TMDR is also thankful for her pre-doctoral funding. The synchrotron experiments were carried out in the beamline BL11-NCD-SWEET at ALBA Synchrotron Light Facility with the collaboration of ALBA staff

Several composites based on an L-rich poly(lactic acid) (PLA) and mesoporous Santa Barbara Amorphous-15 (SBA-15) are prepared by their addition through two methods: solution-mixed (solvent casting) or melt-mixed (extrusion). Subsequently, films of all the materials are processed by compression molding. The nucleating capacity of silica on PLA crystallization is found to be strongly dependent on protocol used for SBA-15 incorporation. Thus, mesoporous particles induce some PLA ordering in composites when extrusion is used but nucleating ability is much more remarkable when PLA-SBA composites are prepared by SBA-15 addition through casting, PLA crystallization being observed on cooling even at 40 °C min. Crystallinity, crystallization temperature, and polymorphs developed are also dependent on preparation method and cooling rate. Mechanical properties are tested on the just compressed-molded films. At a given SBA-15 content, the melt-mixed composite is less stiff than the solution-mixed material despite both are completely amorphous. Accordingly, microhardness shows a smaller value in the former. For the solution-mixed approach, a partial coating (either external or internal) of the silica particles by PLA chains is suggested to occur during the first preparation stage, enabling a better transfer of reinforcement exerted by SBA-15 silica into the PLA matrix., This research was funded by AEI (grant number PID2020-114930GB-I00), and by ALBA Synchrotron Light Facility. T.M.D.-R. is also grateful for her pre-doctoral funding (contract number BES-2017-082284). Authors are grateful to the Characterization Service at ICTP-CSIC for the SEM facility. The synchrotron experiments were performed at beamline BL11-NCDSWEET at ALBA Synchrotron Light Facility and authors would like to thank the collaboration and help of ALBA staff.

Pipes of polypropylene random (PP-R) copolymers are the best choice for hot-and cold-water networks. Validation of a severe test, accomplishing the ISO 1167 standard, is mandatory to assess their service lifetime expectancy. This work evaluates the behavior shown by three commercial pipes, either the original ones (new pipes) or after being subjected to a hydrostatic pressure test at elevated temperature (aged pipes). Several features with relevance for the final performance have been examined: crystalline characteristics, phase transitions in crystalline regions, effect of high temperature and pressure on these transitions, and oxidation induction time. Moreover, the presence of inorganic fillers, and the content of different antioxidants together with their depletion, have also been analyzed. Films from the new pipes were also prepared for replication of the different environments in order to achieve a better and complete understanding of the phase transitions in the crystalline regions and of the consumption of antioxidants. Distinct environments surrounded the inner and outer parts of the pipes exposed to the failure aging test at 110C: hot water and warm dry air, respectively. These features play a key role in the loss of additives and in the subsequent initiation of degradation. Even if the crystalline characteristics are appropriate in the polymeric matrix, the success of a pipe lies in the homogeneous dispersion of components for avoiding damage at interfacial properties, and in a correct package of antioxidants used in its formulation., This research was funded by AEI/FEDER, UE (grant number MAT2016-79869-C2-1-P), by CSIC (grant number 2020AEP129) and ALBA Synchrotron Light Facility

Several composites were prepared based on a polypropylene random copolymer (PPR) and different amounts of date stone flour (DSF). This cellulosic fiber was silanized beforehand in order to reduce its hydrophilicity and improve the interfacial adhesion with the polymer. Other composites were also obtained, including a sorbitol derivative as an effective nucleant. Films made from these composites were prepared using two different thermal treatments, involving slow crystallization and rapid cooling from the melt. Scanning electron microscopy was used to evaluate the morphological features and the DSF particle dispersion within the PPR matrix. X‐ray diffraction experiments and differential scanning calorimetry tests were employed to assess the crystalline characteristics and for the phase transitions, paying especial attention to the effects of the DSF and nucleating agent on PPR crystallization. An important nucleation ability was found for DSF, and evidently for the sorbitol derivative. The peak crystallization temperature upon cooling was considerably increased by the incorporation of either the nucleant or DSF. Additionally, a much higher proportion of orthorhombic crystals developed in relation to the monoclinic ones. Moreover, the mechanical responses were estimated from the microhardness experiments and significant improvements were found with increasing DSF contents. All of these findings indicate that the use of silanized DSF is a fairly good approach for the preparation of polymeric eco‐composites, taking advantage of the widespread availability of this lignocellulosic material, which is otherwise wasted., This research was funded by AEI/FEDER, UE (grant number MAT2016-79869-C2-1-P), and CSIC (grant number 2020AEP129)

8 pags, 4 figs. -- The online version contains supplementary material available at https://doi.org/10.1038/s41467-021-26184-0, Development of sustainable processes for hydrocarbons synthesis is a fundamental challenge in chemistry since these are of unquestionable importance for the production of many essential synthetic chemicals, materials and carbon-based fuels. Current industrial processes rely on non-abundant metal catalysts, temperatures of hundreds of Celsius and pressures of tens of bars. We propose an alternative gas phase process under mild reaction conditions using only atomic carbon, molecular hydrogen and an inert carrier gas. We demonstrate that the presence of CH2 and H radicals leads to efficient C-C chain growth, producing micron-length fibres of unbranched alkanes with an average length distribution between C23-C33. Ab-initio calculations uncover a thermodynamically favourable methylene coupling process on the surface of carbonaceous nanoparticles, which is kinematically facilitated by a trap-and-release mechanism of the reactants and nanoparticles that is confirmed by a steady incompressible flow simulation. This work could lead to future alternative sustainable synthetic routes to critical alkane-based chemicals or fuels., We thank Jose Criado for the artwork schematics of the system, in figures 4 and S1; Funding: We thank the European Research Council for funding support under Synergy grant ERC-2013-SyG, G.A. 610256 (NANOCOSMOS). Also, we acknowledge partial support from the Spanish MINECO through grants PID2020-113142RB-C21, PID2019106315RB-I00, and PID2019-106315RB-I00, EU ERC CoG HyMAP 648319, and from the regional government through project S2018-NMT-4367 (FotoArt-CM). AM acknowledges to the Spanish Ministry of Science (RYC2018-024561-I), to the Regional Government of Aragon (DGA E13_20R), to the National Natural Science Foundation of China (NFSC-21850410448, NSFC-21835002), and to the The Centre for Highresolution Electron Microscopy (ChEM), supported by SPST of ShanghaiTech University under contract No. EM02161943. S.K. and G.H. acknowledge funding from the Turbulent Superstructures Program of the German National Science Foundation (DFG)

Functionalization of polyolefins has been proven to be a promising way to fine-tune their properties, among which, improved thermal stability is crucial for high performance in end-use applications. However, it still re mains in academia, as some important issues still need to be resolved for this methodology to move towards industrial scale-up, the most important of them being the development of one-step processes. This work focuses specifically on the development of a single-step functionalization route for the synthesis of high thermal and thermo-oxidative stability polypropylenes. The synthesis of Polypropylene (PP) bearing N-alkyl groups by copolymerization via metallocene catalysis is studied. The copolymers are found to exhibit high thermo oxidative stability, whose origin appears to be based, not only on the radical scavenging activity of N-alkyl moieties, but also on the associated crosslinking that takes place under processing conditions. Some exploratory results from a solid-state 13CNMR analysis provide support to a radical mechanism, involving coupling between benzyl-like pyrrolyl species., Consejo Superior de Investigaciones Científicas (CSIC: Project PIE202060E215)

Structuring at very high rates has become one of the current and important topics of interest in polymer science, because this is a common protocol in the processing of films or fibers with industrial applicability. This work presents the study by fast scanning calorimetry, FSC, of poly(vinylidene fluoride), paying special attention to the conditions for obtaining the &beta, phase of this polymer, because it is the one technologically more interesting. The results indicate that this &beta, phase of poly(vinylidene fluoride) is obtained when the sample is isothermally crystallized at temperatures below 60 &deg, C. Under non-isothermal conditions, the &beta, polymorph begins to be observed at rates above 400 &deg, C/s, although a coexistence with the &alpha, modification is observed, so that exclusively the &beta, phase is obtained only at rates higher than 3000 &deg, C/s.

A detailed study of the phase behavior of n-paraffin C23H48 has been performed by means of real-time variable-temperature experiments with synchrotron radiation. Two detectors were employed for simultaneous analysis of the small-angle (SAXS) and wide-angle X-ray-scattering (WAXS) regions. This paraffin presents a very interesting phase behavior, involving two crystal polymorphs, three rotator phases and the liquid state. The Ostwald rule of stages is invoked to find similarities of the rotator phases with the eventual transient mesomorphic structure in the multistage model of polymer crystallization. That study is complemented by variable-temperature Raman experiments covering frequencies down to 150 cm−1. It was found that the low-frequency region is the most informative regarding the phase transitions, and specifically the intensity of the first overtone. From these analyses, several parameters are evaluated as function of temperature., This research was funded by the Agencia Estatal de Investigación (AEI, Spain) and by the European Regional Development Fund (FEDER, UE) through the project with grant number MAT2016-79869-C2-1-P. R.B.-G. pre-doctoral contract (BES-2014-070972) was funded by MINECO through the project with grant number MAT2013-47972-C2-1-P. Synchrotron experiments were funded by ALBA Synchrotron Light Facility.

Additives are absolutely essential in the development of commercial polymeric materials. Accordingly, an exhaustive control of composition and evolution in these additives over time is necessary to validate their performance and safety during their shelf life and, consequently, their ultimate applications. Gas chromatography coupled with mass spectrometry, GC-MS, is described in the present work to identify and analyze the content of a wide variety of additives, commonly used in industrial polymeric materials. First, the identification under the present experimental protocol of additives with a relatively high molecular weight (Irganox 1330 and Irganox 1010) has been successfully attained. Second, the evolution under solar exposure over time has been analyzed by GC-MS for 11 additives and derived substances, which have been identified in a commercial polypropylene sample, estimating the corresponding depletion times. In addition, the resultant increase of carbonyl groups in the polymeric macrochains along the photo-oxidation has been also determined by infrared spectroscopy. Therefore, GC-MS is found to be a reliable tool for the analysis of the evolution of commonly used polymer additives under specific degradation conditions, which can be very useful in the formulation of improved future additivations. ©, This work was funded by project MAT2016-79869-C2-1-P(AEI/FEDER, UE)

Several copolymers based on propylene with 1-nonene as comonomer have been synthesized within a wide range of compositions using a metallocene catalyst and different temperatures. The effect of the two main variables, comonomer content and polymerization temperature, on the final microstructure obtained (polymerization activity, stereochemistry and molar mass, among other details) as well as on the capability of crystallization, formation of distinct polymorphs and phase transitions, is examined. Different ordered entities are developed in these isotactic poly(propylene-co-1-nonene) copolymers depending on 1-nonene molar content: monoclinic, orthorhombic, and mesomorphic ones. A detailed analysis of the phase transitions involved is performed using real-time variable-temperature wide-angle diffraction experiments with synchrotron radiation on the sample with the highest comonomer amount. Different crystallization conditions were tested in order to attain information of the whole phase behavior. From these results, it was found that the mesophase of isotactic poly(propylene) is competing with the crystalline structures, although it recrystallizes on melting into the monoclinic phase at common differential scanning calorimetry rates., AEI/FEDER, UE, Grant/Award Number: MAT2016-79869-C2-1-P

Several composites based on an L-rich poly(lactic acid) (PLA) with different contents of mesoporous Santa Barbara Amorphous (SBA-15) silica were prepared in order to evaluate the effect of the mesoporous silica on the resultant PLA materials by examining morphological aspects, changes in PLA phases and their transitions, and, primarily, the influence on some final properties. Melt extrusion was chosen for the obtainment of the composites, followed by quenching from the melt to prepare films. Completely amorphous samples were then attained, as deduced from X-ray diffraction and differential scanning calorimetry (DSC) analyses. Thermogravimetric analysis (TGA) results demonstrated that the presence of SBA-15 particles in the PLA matrix did not exert any significant influence on the thermal decomposition of these composites. An important nucleation effect of the silica was found in PLA, especially under isothermal crystallization either from the melt or from its glassy state. As expected, isothermal crystallization from the glass was considerably faster than from the molten state, and these high differences were also responsible for a more considerable nucleating role of SBA-15 when crystallizing from the melt. It is remarkable that the PLA under analysis showed very close temperatures for cold crystallization and its subsequent melting. Moreover, the type of developed polymorphs did not accomplish the common rules previously described in the literature. Thus, all the isothermal experiments led to exclusive formation of the &alpha, modification, and the observation of the &alpha, &rsquo, crystals required the annealing for long times at temperatures below 80 &deg, C, as ascertained by both DSC and X-ray diffraction experiments. Finally, microhardness (MH) measurements indicated a competition between the PLA physical aging and the silica reinforcement effect in the as-processed amorphous films. Physical aging in the neat PLA was much more important than in the PLA matrix that constituted the composites. Accordingly, the MH trend with SBA-15 content was strongly dependent on aging times.

The prevalence of overweight and obesity in the population, along with their associated complications, is a major factor contributing to increased morbidity and mortality in developed countries. The liver is a vital organ for maintaining metabolic homeostasis, especially in the adjustment periods in fasting and feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy metabolism in response to nutritional status. PASK-deficient mice with a high-fat diet (HFD) resist the development of obesity and hepatic steatosis, with improved insulin sensitivity. We have investigated the regulation of the PASK expression in an HFD, as well as its role in adapting to fasting and feeding conditions. PASK-deficient mice with an HFD record improved parameters for the following: body weight, glucose tolerance, insulin resistance and serum lipid parameters. An HFD alters the down-regulation of Pask expression produced by fasting, as normally happens in a standard-fat diet. PASK deficiency blocks or diminishes the expression of many genes overexpressed in HFD-fed mice, such as the following: transcription factors involved in the regulation of gluconeogenic enzymes, the transport of fatty acid into mitochondria, beta-oxidation and de novo lipogenesis. PASK also regulates gene expression posttranscriptionally through the short noncoding RNAs involved in lipid metabolism and glucose homeostasis. The expression of miR-33a and miR-143 changes in PASK-deficient mice with an HFD. Thus, PASK-deficient mice improved their adaptation to feeding/fasting through a highly regulated molecular mechanism that controls the expression and function of the transcription factors, enzymes and miRNAs involved in glucose and insulin signaling.

In this study, nanocomposites based on polycaprolactone (PCL) and two types of mesoporous silicas, MCM-41 and SBA-15, were attained by melt extrusion. The effect of the silica incorporated within the PCL matrix was observed, firstly, in the morphological characteristics and degradation behavior of the resultant composites. DSC experiments provided information on the existence of confinement in the PCL¿SBA-15 materials through the appearance of an additional small endotherm, located at about 25¿50¿C, and attributed to the melting of constrained crystallites. Displacement to a slightly lower temperature of this endothermic event was observed in the first heating run of PCL¿MCM-41 composites, attributed to the inferior pore size in the MCM-41 particles. Thus, this indicates variations in the inclusion of PCL chains within these two mesostructures with different pore sizes. Real-time variable-temperature small-angle X-ray scattering (SAXS) experiments with synchrotron radiation were crucial to confirm the presence of PCL within MCM-41 and SBA-15 pores. Accurate information was also deduced from these measurements regarding the influence of these two mesoporous MCM-41 and SBA-15 silicas on PCL long spacing. The differences found in these morphological and structural features were responsible for the ultimate mechanical response exhibited by the two sets of PCL nanocomposites, with a considerably higher increase of mechanical parameters in the SBA-15 family., This work was supported by the Agencia Estatal de Investigación (AEI, Spain) together with the European Regional Development Fund (FEDER, UE) (grant numbers MAT2016-79869-C2-1-P and PID2020-114930GB-I00), by CSIC (grant number 2020AEP129) and ALBA Synchrotron Light Facility. TMDR is also grateful for her pre-doctoral funding (contract number BES-2017-082284).

Incorporation of a low content of several plasticizers into a metallocene isotactic polypropylene (iPP) has been performed in order to learn about their stability and performance by the action of a thermo-oxidative degradation treatment at 95 °C for different times. Comparison with the behavior exhibited by the material with di(2-ethylhexyl) phthalate (DEHP) is established for a feasible replacement of its use for contributing to environmental and human health preservation. Dependence of these aggressive degrading conditions on plasticizer loss is analyzed as well as elucidation of degradation influence on the iPP crystalline characteristics. The results show that chemical changes associated with this degradation process hinder formation of the orthorhombic γ crystalline lattice and postpone the overall crystallization capability. Accordingly, the final features in the film surface and the mechanical response are significantly affected by degradation time. The TOTM plasticizer can be considered an excellent candidate for DEHP substitution., The financial support from project MAT2016-79869-C2-1-P (AEI/ FEDER, UE) is greatly acknowledged. The synchrotron experiments were performed at beamline BL11-NCD at ALBA Synchrotron Light Facility with the collaboration of ALBA staff. Authors are grateful for the funding received to perform these measurements. Authors would like to thank to Dr. N. García her help in the measurements with the optical profilometer.

The liver controls metabolic homeostasis in response to fasting and refeeding periods. Glucokinase (GCK) adjusts hepatic glucose phosphorylation to blood glucose levels, acting as a glucose sensor. Our objective was to determine whether PAS kinase (PASK), a nutrient sensor, could be affecting the expression or activity of liver GCK and the response to fasting and refeeding states of key hepatic metabolic pathways. PASK-deficient mice have impaired insulin signaling (AKT overactivation). Furthermore, PASK deficiency modified the expression of several transcription factors involved in the adjustment to fasting and refeeding. Foxo1 decreased under fasting conditions, while Ppara and Pparg were overexpressed in PASK-deficient mice. However, PEPCK protein levels were similar or higher, while the expression of Cpt1a decreased in PASK-deficient mice. By contrast, Lxra and Chrebp were overexpressed after refeeding, while the expression of Acc and Fas decreased in PASK-deficient mice. Likewise, with a decreased expression of Gck and increased nuclear location of the complex GCK-GCKR, GCK activity decreased in PASK-deficient mice. Therefore, PASK regulated some of the genes and proteins responsible for glucose sensing, such as glucokinase, and for insulin signalling, affecting glucose and lipid metabolism and consequently certain critical hepatic functions.

Metabolic dysfunction in the liver is the cause of numerous pathologies, which are associated with an altered redox state. PASK (PAS Domain Kinase) is a nutrient and bioenergetic sensor. We contend that PASK could act as an oxidative stress sensor in liver and/or control the metabolic balance, playing a role in the mitochondrial homeostasis. Using PASK-deficient mice, we observed that PASK deficiency promotes antioxidant response mechanisms: a lower production of ROS/RNS under non-fasting conditions, overexpression of genes coding to ROS-detoxifying enzymes and mitochondrial fusion proteins (MnSod Gpx, Mfn1 and Opa1), coactivator Ppargc1a, transcription factors (Pparg and FoxO3a) and deacetylase Sirt1. Also, under fasting conditions, PASK deficiency induced the overexpression of Ppargc1a, Ppara, Pparg, FoxO3a and Nrf2 leading to the overexpression of genes coding to antioxidant enzymes such as MnSOD, Cu/ZnSOD, GPx, HO1 and GCLm. Additionally, inducing PINK1 involved in cell survival and mitophagy. These changes kept ROS steady levels and improved the regenerative state. We suggest a new role for PASK as a controller of oxidative stress and mitochondrial dynamics in the liver. In fact, antioxidant response is PASK dependent. PASK-targeting could therefore be a good way of reducing the oxidative stress in order to prevent or treat liver diseases.

This article dives into the design of the next generation Mobile Transport Networks to simultaneously support the needs of various vertical industries with diverse range of networking and computing requirements. Network Slicing has emerged as the most promising approach to address this challenge by enabling per-slice management of virtualized resources. We aim to bring the Network Slicing paradigm into mobile transport networks by provisioning and managing slices tailored to the needs of different vertical industries, specifically: automotive, eHealth and media. Our technical approach is twofold: (i) enabling Vertical Industries to meet their service requirements within customized slices; and (ii) aggregating and federating transport networking and computing fabric, from the edge up to the core and cloud, to create and manage slices throughout a federated virtualized infrastructure. The main focus of the article is on major technical highlights of verticaloriented slicing mechanisms for 5G mobile networks. This work has been partially supported by the EU H2020 5GPPP 5G-TRANSFORMER project (Grant 761536)

Nanocomposites based on isotactic polypropylene (iPP) and different content of Al nanoparticles have been prepared in order to gain knowledge of their electromagnetic interference (EMI) shielding capability. This potential has been analyzed from attenuation upon reflection measurements at microwave frequency range. Moreover, shielding characteristics have been checked by Attenuated Total Reflectance (ATR) and correlated to the ones achieved by X-ray diffraction with synchrotron radiation. Very promising results have been obtained, with an excellent balance between shielding efficiency and sample weight. Hence, these materials are potentially good alternatives to replace metals for this application, avoiding electromagnetic environmental pollution. The effect of incorporation of Al nanoparticles on the iPP processing properties has been additionally evaluated by a rheological study at a very broad frequency range., The financial support of AEI , Spain /FEDER, UE (project MAT2016- 79869-C2-1-P) is acknowledged. The synchrotron work leading to these results received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 312284.

Several Ziegler-Natta copolymers of iPP with ethylene or 1-butene, and terpolymers with both counits have been characterized, devoting special attention to the effect of composition and processing conditions on the crystal structure and final properties. DSC and X-ray diffraction were used to study the polymorphism of copolymers and terpolymers. Comonomer insertion interrupts the isotactic sequences, acting as a structural defect, and the formation of g form is enhanced. Moreover, crystallinity decreases and crystal structure is modified. Comonomer type and concentration determine the extent of these modifications, resulting in important changes in macroscopic properties. In particular, the excellent optical properties of the analyzed terpolymers make them very attractive for applications such as transparent film or packaging, The financial support of MINECO (projects CYTED 311RT0417 and MAT2016-79869-C2-1-P (AEI/FEDER, UE)), is gratefully acknowledged

Blends of poly(ε-caprolactone) (PCL) and high-density polyethylene (HDPE) have been prepared at different compositions in order to assess the effect of HDPE on gas transport and mechanical behaviors of PCL. Previous to this evaluation, a complete morphological, structural, and thermal characterization were performed using techniques, including SEM, contact angle, FTIR, differential scanning calorimetry, and X-ray diffraction with synchrotron radiation at small and wide angles. Low HDPE incorporations allow interactions to be established at interfaces in the amorphous regions and the enhancement of the mechanical performance. Consequently, the addition of a small amount of HDPE (ranging from 5 to 10 wt%) appears to be appropriate in certain bio-applications where a higher mechanical behavior is required., This research was funded by the Agencia Estatal de Investigación (AEI, Spain) and by the European Regional Development Fund (FEDER, UE) through the project with grant number MAT2016-79869-C2-1-P. It was also funded by the Seventh Framework Programme (FP7/2007–2013) of the European Community for the synchrotron experiments (grant agreement n° 312284).

PAS kinase (PASK) is a nutrient sensor that is highly conserved throughout evolution. PASK-deficient mice reveal a metabolic phenotype similar to that described in S6 kinase-1 S6K1-deficient mice that are protected against obesity. Hypothalamic metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR), play an important role in feeding behavior, the homeostasis of body weight, and energy balance. These sensors respond to changes in nutrient levels in the hypothalamic areas involved in feeding behavior and in neuroblastoma N2A cells, and we have recently reported that those effects are modulated by the anorexigenic peptide glucagon-like peptide-1 (GLP-1). Here, we identified PASK in both N2A cells and rat VMH and LH areas and found that its expression is regulated by glucose and GLP-1. High levels of glucose decreased Pask gene expression. Furthermore, PASK-silenced N2A cells record an impaired response by the AMPK and mTOR/S6K1 pathways to changes in glucose levels. Likewise, GLP-1 effect on the activity of AMPK, S6K1, and other intermediaries of both pathways and the regulatory role at the level of gene expression were also blocked in PASK-silenced cells. The absence of response to low glucose concentrations in PASK-silenced cells correlates with increased ATP content, low expression of mRNA coding for AMPK upstream kinase LKB1, and enhanced activation of S6K1. Our findings indicate that, at least in N2A cells, PASK is a key kinase in GLP-1 actions and exerts a coordinated response with the other metabolic sensors, suggesting that PASK might play an important role in feeding behavior.

The competition between α, β, and γ polymorphs has been studied in several random copolymers and terpolymers of propylene, by performing X-ray diffraction and differential scanning calorimetry experiments. Formation of β-crystals, achieved by the addition of a β-nucleating agent, was found to be highly dependent on comonomer type and crystallization conditions. Additionally, the mechanical properties have been evaluated from stress-strain, microhardness and dynamic-mechanical thermal analyses. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers

In humans, glucagon-like peptide (GLP-1) functions during adult life as an incretin hormone with anorexigenic and antidiabetogenic properties. Also, the therapeutic potential of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and in bolstering the maintenance of human mesenchymal stem cell (hMSC) stores by promoting the proliferation and cytoprotection of hMSC seems to be relevant. Since these observations suggest a role for GLP-1 during developmental processes, the aim of the present work was to characterize GLP-1 in early development as well as its gene targets in mouse embryonic stem (mES) cells. Mouse embryos E6, E8, and E10.5 and pluripotent mES were used for the inmunodetection of GLP-1 and GLP-1 receptor. Quantitative real-time PCR was used to determine the expression levels of GLP-1R in several tissues from E12.5 mouse embryos. Additionally, GLP-1 gene targets were studied in mES by multiple gene expression analyses. GLP-1 and its receptors were identified in mES and during embryonic development. In pluripotent mES, GLP-1 modified the expression of endodermal, ectodermal, and mesodermal gene markers as well as sonic hedgehog , noggin , members of the fibroblast and hepatic growth factor families, and others involved in pancreatic development. Additionally, GLP-1 promoted the expression of the antiapoptotic gene bcl2 and at the same time reduced proapoptotic caspase genes. Our results indicate that apart from the effects and therapeutic benefits of GLP-1 in adulthood, it may have additional gene targets in mES cells during embryonic life. Furthermore, the pathophysiological implications of GLP-1 imbalance in adulthood may have a counterpart during development.

Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. However, the role of GLP-1 in human bone marrow-derived mesenchymal stem cells (hMSCs), if any, remains unknown. The effects of GLP-1 on hMSCs were tested with regard to cell proliferation, cytoprotection, and cell differentiation into adipocytes. The signaling pathways involved in these processes were also analyzed. Cells were characterized with biochemical and morphological approaches before and after being induced to differentiate into adipocytes. PCNA protein levels were used as a proliferation index, whereas cell apoptosis was studied by deprivation of fetal bovine serum. Isolated hMSCs expressed stem cell markers as well as mRNA and GLP-1 receptor protein. GLP-1 increased the proliferation of hMSCs, which decreased when they were induced to differentiate into adipocytes. This process produced biochemical and morphological changes in cells expressing PPARγ, C/EBPβ, AP2, and LPL in a time-dependent pattern. Notably, GLP-1 significantly reduced the expression of PPARγ, C/EBPβ, and LPL. These effects were exerted at least through the MEK and PKC signaling pathways. In addition, GLP-1 significantly reduced cell apoptosis. Our data indicate that, in hMSCs, GLP-1 promotes cellular proliferation and cytoprotection and prevents cell differentiation into adipocytes. These latter findings underscore the potential therapeutic role of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and, additionally, could bolster the maintenance of hMSC stores by promoting the proliferation and cytoprotection of undifferentiated hMSC.

Our previous description of functional glucokinase (GK) isoforms and their interactions with glucokinase regulatory protein (GKRP) in adult rat and human brains suggested that both participate in glucose sensing in the central nervous system. To determine whether both proteins are coexpressed and active before birth or during early post-natal life, we characterised these molecules in the brains of foetal and post-natal pup rats. We found GK and GKRP mRNAs that were similar to those previously reported in the adult rat brain. Likewise, GK and GKRP gene expression gave rise to proteins of 52 and 69 kDa, respectively. Immunohistochemistry experiments showed the colocalisation of both GK and GKRP proteins in the same brain cells of 21-day-old rat foetuses. Furthermore, coprecipitation of GK and GKRP in the presence of fructose 6-phosphate suggests interactions between both proteins. The presence of GK phosphorylating activity was detected in different brain areas of 21-day-old foetuses with a contribution to the total glucose-phosphorylating activity of between 17.2 +/- 1.7% and 12.4 +/- 3.7%, with the hypothalamus being the region of maximum activity. The hypothalamic GK activity in 21-day-old foetuses has a high apparent K(m) for glucose and no product inhibition by glucose 6-phosphate. Our findings indicate that both proteins may be functionally active before birth and that they can act within a glucose sensor system involved in controlling food intake.

In an attempt to gain better insight into the central effects of glucagon-like peptide (GLP-1), we studied the action of glucose and of regulatory peptides on the expression of its receptor (GLP-1R) in hypothalamic GT1-7 cells and in ventromedial (VMH) and lateral (LH) rat hypothalamus slices. The promoter activity of GLP-1R in transfected GT1-7 cells increased with leptin, whereas neuropeptide Y (NPY) did not modify it. Interestingly, when cells were incubated with both NPY and leptin, NPY blocked the stimulating effect of leptin. The effects of leptin and NPY were also confirmed at messenger RNA levels. In hypothalamic slices, GLP-1R messenger RNA levels increased at higher glucose concentrations in the VMH. In addition, leptin exerted a stimulating effect; and NPY did not modify receptor expression. By contrast, in the LH, the opposite effects were found for those parameters, except at 20 mmol/L glucose. These findings suggest that the stimulating effect of leptin on GLP-1R expression, with no changes in NPY-induced activity, could enhance the anorexic actions generated through this receptor. In addition, the different responses of the VMH and LH may be related to specific functions of these structures, as already known in vivo, highlighting the interest of hypothalamic slices for this kind of study.

In an attempt to study the role of glucokinase (GK) and the effects of glucose and peptides on GK gene expression and on the activity of this enzyme in the hypothalamus, we used two kinds of biological models: hypothalamic GT1-7 cells and rat hypothalamic slices. The expression of the GK gene in GT1-7 cells was reduced by insulin (INS) and was not modified by different glucose concentrations, while GK enzyme activities were significantly reduced by the different peptides. Interestingly, a distinctive pattern of GK activities between the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) were found, with higher enzyme activities in the VMH as the glucose concentrations rose, while LH enzyme activities decreased at 2.8 and 20 mM glucose, the latter effect being prevented by incubation with INS. These effects were produced only by d-glucose and the modifications found were due to GK, but not to other hexokinases. In addition, GK activities in the VMH and the LH were reduced by glucagon-like peptide 1, leptin, orexin B, INS, and neuropeptide Y (NPY), but this effect was only statistically significant for NPY in LH. Our results indicate that the effects of both glucose and peptides occur on GK enzyme activities rather than on GK gene transcription. Moreover, the effects of glucose and INS on GK activity suggest that in the brain GK behaves in a manner opposite to that in the liver, which might facilitate its role in glucose sensing. Finally, hypothalamic slices seem to offer a good physiological model to discriminate the effects between different areas.

[Aims/hypothesis]: Glucokinase (GCK) acts as a glucose sensor in the pancreatic beta cell and regulates insulin secretion. In the gene encoding GCK the heterozygous mutations that result in enzyme inactivation cause MODY2. Functional studies of naturally occurring GCK mutations associated with hyperglycaemia provide further insight into the biochemical basis of glucose sensor regulation. [Materials and methods]: Identification of GCK mutations in selected MODY patients was performed by single-strand conformation polymorphism and direct sequencing. The kinetic parameters and thermal stability of recombinant mutant human GCK were determined, and in pull-down assays the effect of these mutations on the association of GCK with glucokinase (hexokinase 4) regulator (GCKR, also known as glucokinase regulatory protein [GKRP]) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1, also known as PFK2) was tested. [Results]: We identified three novel GCK mutations: the insertion of an asparagine residue at position 161 (inserN161) and two missense mutations (M235V and R308W). We also identified a fourth mutation (R397L) reported in a previous work. Functional characterisation of these mutations revealed that insertion of asparagine residue N161 fully inactivates GCK, whereas the M235V and R308W mutations only partially impair enzymatic activity. In contrast, GCK kinetics was almost unaffected by the R397L mutation. Although none of these mutations affected the interaction of GCK with PFKFB1, we found that the R308W mutation caused protein instability and increased the strength of interaction with GCKR. [Conclusions/interpretation]: Our results show that different MODY2 mutations impair GCK function through different mechanisms such as enzymatic activity, protein stability and increased interaction with GCKR, helping further elucidate the regulation of GCK activity., This work was supported by the Instituto de Salud Carlos III grant PI030203 to M. A. Navas. M. Galán was supported by a predoctoral FPU fellowship from the Comunidad Autónoma de Madrid. M. A. Navas is a Ramón y Cajal researcher of the Spanish Ministry of Education and Science.

In order to gain better insight into the molecular events involved in the signal transduction generated through glucagon-like peptide-1 (GLP-1) receptors, we tested the effect of deletions and point mutations within the cytoplasmic tail of this receptor with a view to establishing relationships between signal transduction desensitisation and receptor internalisation. Wild-type and truncated (deletion of the last 27 amino acids (GLPR 435R) and deletion of 44 amino acids (GLPR 418R)) GLP-1 receptors bound the agonist with similar affinity. Deletion of the last 27 amino acids decreased the internalisation rate by 78%, while deletion of 44 amino acids containing all the phosphorylation sites hitherto described in this receptor decreased the internalisation rate by only 47%. Binding of the ligand to both receptors stimulated adenylyl cyclase. In contrast, deletion of the region containing amino acids 419 to 435 (GLPR 419Δ435) increased the internalisation rate by 268%, and the replacement of EVQ408–410 by alanine (GLPR A408–410) increased this process to 296%. In both receptors, the efficacy in stimulating adenylate cyclase was decreased. All the receptors studied were internalised by coated pits, except for the receptor with a deletion of the last 44 amino acids, which also had a faster resensitisation rate. Our findings indicate that the neighbouring trans-membrane domain of the carboxyl-terminal tail of the GLP-1 receptor contains sequence elements that regulate agonist-dependent internalisation and transmembrane signalling.