Toward Light-Controlled Supramolecular Peptide Dimerization

The selective photodeprotection of the NVoc-modified FGG tripeptide yields the transformation of its 1:1 receptor−ligand complex with cucurbit[8]uril into a homoternary FGG2@CB8 assembly. The resulting lightinduced dimerization of the model peptide provides a tool for the implementation of stimuli-responsive supramolecular chemistry in biologically relevant contexts.The work was supported by the Associate Laboratory for Green ChemistryLAQV (UIDB/50006/2020) and by the Applied Molecular Biosciences UnitUCIBIO (UIDB/ 04378/2020), both financed by FCT. FCT/MCTES is also acknowledged for supporting the National Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016, cofinanced by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC) and for the grants PTDC/QUICOL/32351/2017, PTDC/QUI-QFI/30951/2017, and CEECIND/00466/2017 (N.B.). U.P. thanks the Spanish Ministry of Science, Innovation, and Universities (CTQ2017-89832-P). We are grateful to Dr. J.P. Da Silva for the mass spectrometry data (equipment financed by CRESC Algarve 2020 and COMPETE 2020; project EMBRC.PT ALG-01-0145-FEDER022121). Funding for open access charge: Universidad de Huelva / CBU

Photomodulation of ultrastable host–guest complexes in water and their application in light-controlled steroid release

The cucurbit[8]uril (CB8) synthetic receptor is shown to form high-affinity host-guest complexes with dicationic dithienylethene (DTE) photoswitches in water. ITC experiments combined with computational studies suggest that the formation of the inclusion complexes is mainly driven by a combination of hydrophobic effects, ion-dipole, hydrogen- and chalcogen-bonding interactions. The binding affinities were observed to be much higher for the DTE closed isomers, reaching values in the picomolar range (up to 1011 M−1) while the open isomers display up to 10 000-fold lower affinities, setting ideal conditions for the development of robust photoswitchable host-guest complexes. The light-responsive affinity of these photoswitches toward CB8 was explored to control the encapsulation and release of nanomolar affinity steroids via competitive guest replacement.publishersversionpublishe

All-Photonic Multifunctional Molecular Logic Device

Photochromes are photoswitchable, bistable chromophores which, like transistors, can implement binary logic operations. When several photochromes are combined in one molecule, interactions between them such as energy and electron transfer allow design of simple Boolean logic gates and more complex logic devices with all-photonic inputs and outputs. Selective isomerization of individual photochromes can be achieved using light of different wavelengths, and logic outputs can employ absorption and emission properties at different wavelengths, thus allowing a single molecular species to perform several different functions, even simultaneously. Here, we report a molecule consisting of three linked photochromes that can be configured as AND, XOR, INH, half-adder, half-subtractor, multiplexer, demultiplexer, encoder, decoder, keypad lock, and logically reversible transfer gate logic devices, all with a common initial state. The system demonstrates the advantages of light-responsive molecules as multifunctional, reconfigurable nanoscale logic devices that represent an approach to true molecular information processing units

An All-Photonic Molecule-Based D Flip-Flop

The photochromic fluorescence switching of a fulgimide derivative was used to implement the first molecule-based D (delay) flip-flop device, which works based on the principles of sequential logic. The device operates exclusively with photonic signals and can be conveniently switched in repeated cycles. \ua9 2011 American Chemical Society

Photofunctional Scope of Fluorescent Dithienylethene Conjugates with Aza-Heteroaromatic Cations

A series of dithienylethene (DTE) photoswitches with aza-heteroaromatic cationic moieties is synthesized. The switches are characterized regarding their photochemical and photophysical properties in acetonitrile and in water. The efficiency of the switching and the photostationary state composition depend on the degree of π-conjugation of the heteroaromatic systems. Thus, DTEs with acridinium-derived moieties have very low quantum yields for the ring-closing process, which is in contrast to switches with pyridinium and quinolinium moieties. All switches emit fluorescence in their open forms. The involved electronic transitions are traced back to an integrative picture including the DTE core and the cationic arms. The emission can be fine-tuned by the π-conjugation of the heteroaromatic cations, reaching the red spectral region for DTEs with acridinium moieties. On ring-closing of the DTEs the fluorescence is not observable anymore. Theoretical calculations point to rather low-lying energy levels of the highly conjugated ring-closed DTEs, which would originate near-infrared emission (> 1200 nm). The latter is predicted to be very weak due to the concurrent non-radiative deactivation, according to the energy-gap law. In essence, an ON-OFF fluorescence switching as the result of the electrocyclic ring-closing reaction is observed.The authors acknowledge the financial support by the Spanish Ministerio de Ciencia e Innovación (grant PID2020-119992GB-I00 for U.P., PID2019-104293GB-I00 for F.N., PID2019-108292RA-I00, EUR2020-112189 for A.J.M.-M.), the Consejería de Universidad, Investigación e Innovación/Junta de Andalucía (grant P18-FR-4080 for U.P.), the European Research and Development Fund (ERDF), and the Junta de Andalucía / University of Huelva (grant UHU-202070 for U.P.). A.J.M.-M. thanks the AEI Research State Agency for a Ramón y Cajal research contract (RYC-2017-21783). The authors are indebted to the Supercomputing and Bioinformatics Centre (SCBI) of the University of Málaga for making available the computer resources that were employed for the theoretical calculations

OFF-ON-OFF Fluorescence Switch with T-Latch Function

A novel molecular system with characteristics of an OFF-ON-OFF fluorescence switch was designed to integrate the function of a T-latch. In detail, a receptor(1)-fluorophore-receptor(2) architecture was adopted to achieve fluorescence switching upon addition of protons

Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis

T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis. Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim here was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis. We demonstrated \u201cAutophagic memory\u201d as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD4+ T cells subsets from autoimmune arthritis patients. Using RNA-sequencing, transcription factor gene regulatory network and methylation analyses we identified MYC as a key regulator of autophagic memory. We validated MYC levels using qPCR and further demonstrated that inhibiting MYC increased autophagy. The present study proposes the novel concept of autophagic memory and suggests that autophagic memory confers metabolic advantage to pathogenic T cells from arthritis and supports its resilience and long term survival. Particularly, suppression of MYC imparted the heightened autophagy levels in pathogenic T cells. These studies have a direct translational valency as they identify autophagy and its metabolic controllers as a novel therapeutic target

Development process of a clinical guideline to manage type 2 diabetes in adults by Ayurvedic practitioners

Background: Type 2 diabetes mellitus (T2DM), a common chronic health condition, has major health and socioeconomic consequences. In the Indian subcontinent, it is a health condition for which individuals commonly consult Ayurvedic (traditional medical system) practitioners and use their medicines. However, to date, a good quality T2DM clinical guideline for Ayurvedic practitioners, grounded on the best available scientific evidence, is not available. Therefore, the study aimed to systematically develop a clinical guideline for Ayurvedic practitioners to manage T2DM in adults. Methods: The development work was guided by the UK’s National Institute for Health and Care Excellence (NICE) manual for developing guidelines, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. First, a comprehensive systematic review was conducted which evaluated Ayurvedic medicines’ effectiveness and safety in managing T2DM. In addition, the GRADE approach was used for assessing the certainty of the findings. Next, using the GRADE approach, the Evidence-to-Decision framework was developed, and we focused on glycemic control and adverse events. Subsequently, based on the Evidence-to-Decision framework, a Guideline Development Group of 17 international members made recommendations on Ayurvedic medicines’ effectiveness and safety in T2DM. These recommendations formed the basis of the clinical guideline, and additional generic content and recommendations were adapted from the T2DM Clinical Knowledge Summaries of the Clarity Informatics (UK). The feedback given by the Guideline Development Group on the draft version was used to amend and finalize the clinical guideline. Results: A clinical guideline for managing T2DM in adults by Ayurvedic practitioners was developed, which focuses on how practitioners can provide appropriate care, education, and support for people with T2DM (and their carers and family). The clinical guideline provides information on T2DM, such as its definition, risk factors, prevalence, prognosis, and complications; how it should be diagnosed and managed through lifestyle changes like diet and physical activity and Ayurvedic medicines; how the acute and chronic complications of T2DM should be detected and managed (including referral to specialists); and advice on topics like driving, work, and fasting including during religious/socio-cultural festivals. Conclusion: We systematically developed a clinical guideline for Ayurvedic practitioners to manage T2DM in adults

Abitare il pianeta. Futuro demografico, migrazioni e tensioni etniche. Volume secondo. USA, URSS e aree asiatiche e australe

Le ripercussioni e le conseguenze della pressione demografica esercitata dai Paesi in Via di Sviluppo non riguardano soltanto l'Europa; in altre zone del mondo i problemi dell'integrazione etnica e razziale, delle immigrazioni e dello squili-brio demografico sono altrettanto urgenti: in questo volume vengono ripercorse le linee evolutive ed analizzate le tendenze di alcune società extra europee, scelte per l'emblematicità dei casi che rappresentano.- Indice #7- Prima parte Immigrazioni e diversità etnico-razziali nell'evoluzione demografica degli Stati Uniti d'America #9- Il cambiamento demografico negli Stati Uniti: le tendenze recenti e le prospettive future, Thomas J. Espenshade #11- Immigrazione e diversità etnico-razziale: il caso degli Stati Uniti, S. Philip Morgan #47- Seconda parte Considerazioni sul mutamento etnico e demografico in Unione Sovietica #69- La popolazione complessiva e per repubbliche dell'Unione Sovietica, Guido Ortona #71- I gruppi etnici in Unione Sovietica, Marco Buttino #91- Terza parte L'evoluzione delle società multietniche nelle aree asiatica e australe #143- La popolazione indiana, 1951-2021, Enrica Collotti Pischel e Francesco Gallucci #145- Diversità etnica ed emigrazione: il caso delle migrazioni dal Sud-est asiatico all'Australia, Subbiah Gunasekaran e Gerard Sullivan #215- Il mutamento demografico e lo sviluppo di una società multiculturale in Australia, Stephen Castles #243- Stime e proiezioni sull'area asiatico-australe, Gian Carlo Blangiardo #289- Quarta parte Alcune considerazioni sui fenomeni complessivi #303- Le grandezze in campo: sulle conseguenze politiche degli scenari demografici mondiali, Piero Gastaldo #30