Novel U-Shaped D-A-D π-conjugated Systems with Mechanochromic Properties: An Experimental and Theoretical Vibrational Spectroscopic Investigation

Π-conjugated compounds have been widely studied in the last few decades due to their huge field of application in organic electronics. Specifically, stimuli-responsive Π-conjugated materials which are sensitive to external stimulus (i.e., temperature, pressure, etc) have several uses like sensors, probes and security inks, for example.1 In this work, we study two U-shape Donor-Acceptor-Donor (D-A-D) systems that are found to exhibit interesting thermal- and pressure-dependent properties. 2 They consist on two different conformers of phenothiazine-dibenzo[a,j]phenazine-phenothiazine which differs from the position of the phenothiazine respect to the dibenzophenzaine central core. Compound 1R is the equatorial-equatorial conformer and 1Y is the axial-axial conformer (Figure 1). The dibenzophenzaine group acts as an electron-acceptor whereas the phenothiazine unit acts as an electron-donor. It has been reported that this U-shape D-A-D compound shows a multi-active color changing in 3 steps and their luminescence changes with temperature, pressure and acid exposition.2 In this work, we aim to elucidate how the external stimuli (i.e. temperature, pressure, acid ambient) affects the molecular structure at both intra- and intermolecular level. To this end, we use UV-Vis absorption, Raman (Figure 1) and Infrared spectroscopy experiments in combination with DFT calculations.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Piezochromic properties of a D-A-D platform: A joint experimental and theoretical perspective

Organic π-conjugated molecules with mechanochromic luminescence properties have attracted great interest in the last two decades due to their numerous applications in the optoelectronic field, such as sensors, probes and security inks. Materials that modify their colour under pressure are known as piezochromic materials. Usually, this variation is provoked by changes in the molecular structure, for example, crystal-to-amorphous phase transitions, modifications in dihedral angles or bond distances, and intermolecular interactions. The molecule proposed in this study is a TADF (Thermally activated delayed fluorescence) U-shaped molecule composed by two donors and one acceptor (D-A-D) units with a π-conjugated skeleton [1]. It was synthetized as a powder which under different crystallization methods gives rise to different conformers varying the dihedral angle of the bond that links the D and A units. The donors are two phenothiazine units and the acceptor is a dibenzo[a,j]phenazine unit located in the central core. Two different conformers have been analysed: the quasi equatorial - quasi equatorial (denoted as 1R) and the quasi axial - quasi axial (denoted as 1Y). In this project, we study the configurational changes triggering the piezochromic effects combining density functional theory (DFT) calculations with Raman spectroscopy experiments of the 1R and 1Y conformers during heating or in compression via a sapphire anvil cell [2]. Both show pressure and temperature dependence properties. Besides, these changes are reversible meaning that when the stimuli stop they revert to its original conformation. When these molecules are exposed to different ambient (like pressure or temperature variations) they evolved to a third conformer with an intermediate dihedral angle that results in different Raman, emission and absorption behaviour.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sentinel-3 MWR Microwave Radiometer – Our contribution to the success of the Copernicus programme

Revista oficial de la Asociación Española de Teledetección[EN] The MWR builds, together with the SRAL altimeter, the S3 topography mission. The MWR, developed by EADS CASA Espacio as prime contractor, provides information for tropospheric path correction of SRAL measurements. MWR data can also be used for determining surface emissivity and soil moisture over land, surface energy budget investigations and ice characterization. The MWR instrument is a Noise Injection Radiometer (NIR), working at two frequencies (23.8/36.5 GHz), embarking a dual frequency horn antenna pointing to the cold sky for embedded autonomous calibration.[ES] El radiómetro MWR, desarrollado por EADS CASA Espacio, constituye la misión topográfica de Sentinel-3 (S3) junto al radar altímetro SRAL. Su función es la entrega de información auxiliar para la corrección troposférica de las medidas del SRAL. Sus datos también pueden servir para caracterizar magnitudes físicas del suelo y la criosfera, así como para la evaluación de balances energéticos. El MWR es un radiómetro de inyección de ruido (NIR) que funciona a dos frecuencias (23,8 y 36,5 GHz) e incorpora una bocina para la obtención de la temperatura de brillo del cielo como medio de calibración autónoma.Los autores querrían agradecer el apoyo y la contribución por parte de los clientes del MWR (ESA y TAS-F), así como de los principales subcontratistas, TAS-E, CRISA, TAS-I, CDE, RYMSA, COBHAM, HVS, ABSL, APCO, IABG e ITD.Palacios, M.; Bergadà, M.; González, R.; Gamonal, A.; García-Fernández, J.; Camacho, Y. (2014). El radiómetro de microondas MWR de Sentinel-3: Nuestra contribución al éxito de Copernicus. Revista de Teledetección. (41):79-88. doi:10.4995/raet.2014.2294.SWORD798841Aguirre, M., Berruti, B., Bezy, J.L., Drinkwater, M., Heliere, F., Klein, U., Mavrocordatos, C., Silvestrin, P., Greco, B., Benveniste, J., 2007. Sentinel-3. The Ocean and Medium-Resolution Land Mission for GMES Operational Services. ESA bulletin, 131, 24-29.Guijarro, J., Auriol, A., Costes, M., Jayles, C., Vincent, P., 2000. MWR & DORIS-Supporting Envisat Radar Altimetry Mission, ESA bulletin, 104, 41-46.L'Abbate, M., Bombaci, O., Alberti, G., Femenias, P., 2003. ENVISAT-1 MWR, in flight functional and performance verification. En: Proceedings of Envisat Validation Workshop, Frascati (Italy).Xie, Y., Chen, J., Liu, D., Lv, C., Liu, K., & Miao, J. (2013). DEVELOPMENT AND CALIBRATION OF A K-BAND GROUND-BASED HYPERSPECTRAL MICROWAVE RADIOMETER FOR WATER VAPOR MEASUREMENTS. Progress In Electromagnetics Research, 140, 415-438. doi:10.2528/pier1305070

Stretch-induced activation of pannexin 1 channels can be prevented by pka-dependent phosphorylation

Indexación ScopusPannexin 1 channels located in the cell membrane are permeable to ions, metabolites, and signaling molecules. While the activity of these channels is known to be modulated by phosphorylation on T198, T308, and S206, the possible involvement of other putative phosphorylation sites remains unknown. Here, we describe that the activity of Panx1 channels induced by mechanical stretch is reduced by adenosine via a PKA-dependent pathway. The mechanical stretch-induced activity—measured by changes in DAPI uptake—of Panx1 channels expressed in HeLa cell transfectants was inhibited by adenosine or cAMP analogs that permeate the cell membrane. Moreover, inhibition of PKA but not PKC, p38 MAPK, Akt, or PKG prevented the effects of cAMP analogs, suggesting the involvement of Panx1 phosphorylation by PKA. Accordingly, alanine substitution of T302 or S328, two putative PKA phosphorylation sites, prevented the inhibitory effect of cAMP analogs. Moreover, phosphomimetic mutation of either T302 or S328 to aspartate prevented the mechanical stretch-induced activation of Panx1 channels. A molecular dynamics simulation revealed that T302 and S328 are located in the water–lipid interphase near the lateral tunnel of the intracellular region, suggesting that their phosphorylation could promote conformational changes in lateral tunnels. Thus, Panx1 phosphorylation via PKA could be modulated by G protein-coupled receptors associated with the Gs subunit. © 2020, MDPI AG. All rights reserved.https://www.mdpi.com/1422-0067/21/23/918

The impact of muscle relaxation techniques on the quality of life of cancer patients, as measured by the FACT-G questionnaire

Introduction Patients with cancer frequently suffer from emotional distress, characterized by psychological symptoms such as anxiety or depression. The presence of psychological symptoms combined with the complex nature of oncology processes can negatively impact patients' quality of life. We aimed to determine the impact of a relaxation protocol on improving quality of life in a sample of oncological patients treated in the Spanish National Public Health System. Materials and methods We conducted a multicenter interventional study without a control group. In total, 272 patients with different oncologic pathologies and showing symptoms of anxiety were recruited from 10 Spanish public hospitals. The intervention comprised abbreviated progressive muscle relaxation training, according to Bernstein and Borkovec. This was followed by weekly telephone calls to each patient over a 1-month period. We collected sociodemographic variables related to the disease process, including information about mental health and the intervention. Patients' quality of life was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. Bivariate and univariate analyses were performed, along with an analysis of multiple correspondences to identify subgroups of patients with similar variations on the FACT-G. Results Patients showed statistically significant improvements on the FACT-G overall score (W = 16806; p<0.001), with an initial mean score of 55.33±10.42 and a final mean score of 64.49±7.70. We also found significant improvements for all subscales: emotional wellbeing (W = 13118; p<0.001), functional wellbeing (W = 16155.5; p<0.001), physical wellbeing (W = 8885.5; p<0.001), and social and family context (W = ?1840; p = 0.037). Conclusions Patients with cancer who learned and practiced abbreviated progressive muscle relaxation experienced improvement in their perceived quality of life as measured by the FACT-G. Our findings support a previous assumption that complementary techniques (including relaxation techniques) are effective in improving the quality of life of patients with cancer

Study of Leading Hadrons in Gluon and Quark Fragmentation

The study of quark jets in e+e- reactions at LEP has demonstrated that the hadronisation process is reproduced well by the Lund string model. However, our understanding of gluon fragmentation is less complete. In this study enriched quark and gluon jet samples of different purities are selected in three-jet events from hadronic decays of the Z collected by the DELPHI experiment in the LEP runs during 1994 and 1995. The leading systems of the two kinds of jets are defined by requiring a rapidity gap and their sum of charges is studied. An excess of leading systems with total charge zero is found for gluon jets in all cases, when compared to Monte Carlo Simulations with JETSET (with and without Bose-Einstein correlations included) and ARIADNE. The corresponding leading systems of quark jets do not exhibit such an excess. The influence of the gap size and of the gluon purity on the effect is studied and a concentration of the excess of neutral leading systems at low invariant masses (<~ 2 GeV/c^2) is observed, indicating that gluon jets might have an additional hitherto undetected fragmentation mode via a two-gluon system. This could be an indication of a possible production of gluonic states as predicted by QCD.Comment: 19 pages, 6 figures, Accepted by Phys. Lett.

Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: data from the iNTD registry

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport or degradation of neurotransmitters or co-factors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter (DAT) deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders, and b) previously underreported behavioral traits

Gene expression profiling integrated into network modelling reveals heterogeneity in the mechanisms of BRCA1 tumorigenesis

Background: gene expression profiling has distinguished sporadic breast tumour classes with genetic and clinical differences. Less is known about the molecular classification of familial breast tumours, which are generally considered to be less heterogeneous. Here, we describe molecular signatures that define BRCA1 subclasses depending on the expression of the gene encoding for oestrogen receptor, ESR1. Methods: for this purpose, we have used the Oncochip v2, a cancer-related cDNA microarray to analyze 14 BRCA1-associated breast tumours. Results: signatures were found to be molecularly associated with different biological processes and transcriptional regulatory programs. The signature of ESR1-positive tumours was mainly linked to cell proliferation and regulated by ER, whereas the signature of ESR1-negative tumours was mainly linked to the immune response and possibly regulated by transcription factors of the REL/NFκB family. These signatures were then verified in an independent series of familial and sporadic breast tumours, which revealed a possible prognostic value for each subclass. Over-expression of immune response genes seems to be a common feature of ER-negative sporadic and familial breast cancer and may be associated with good prognosis. Interestingly, the ESR1-negative tumours were substratified into two groups presenting slight differences in the magnitude of the expression of immune response transcripts and REL/NFκB transcription factors, which could be dependent on the type of BRCA1 germline mutation. Conclusion: this study reveals the molecular complexity of BRCA1 breast tumours, which are found to display similarities to sporadic tumours, and suggests possible prognostic implications

Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers

Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. Methods A case–control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares–class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. Results Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. Conclusions These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials.projects RD12/0017/0031, RD16/0025/ 0013, and SAF2015-66193-R as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008– 2011 and 2013–2016) and cofinanced by the Institute of Health Carlos III (ISCIII), Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund. NR is a Miguel Servet investigator from the ISCIII (CP14/00198), Madrid, Spain. C Restrepo was funded by project RD12/0017/ 0031 and is currently funded by project RD16/0025/0013. M García is a predoctoral student co-funded by grant CP14/00198 and an Intramural Research Scholarship from Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD)