Recent Advances in the Preparation of Delivery Systems for the Controlled Release of Scents

©2023.the Authors. This manuscript version is made available under the CC-BY-4.0 license https://creativecommons.org/licenses/by/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in International Journal of Molecular Sciences. To access the final edited and published work see https://doi.org/10.3390/ijms24054685Scents are volatile compounds highly employed in a wide range of manufactured items, such as fine perfumery, household products, and functional foods. One of the main directions of the research in this area aims to enhance the longevity of scents by designing efficient delivery systems to control the release rate of these volatile molecules and also increase their stability. Several approaches to release scents in a controlled manner have been developed in recent years. Thus, different controlled release systems have been prepared, including polymers, metal–organic frameworks and mechanically interlocked systems, among others. This review is focused on the preparation of different scaffolds to accomplish a slow release of scents, by pointing out examples reported in the last five years. In addition to discuss selected examples, a critical perspective on the state of the art of this research field is provided, comparing the different types of scent delivery systems

Stereoselective synthesis of β-lactams: recent examples

©2023 The Authors; published by The Royal Society of Chemistry. This manuscript version is made available under the CC-BY-NC 3.0 license https://creativecommons.org/licenses/by-nc/3.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Organic & Biomolecular Chemistry. To access the final edited and published work see https://doi.org/10.1039/D3OB00309DThe synthesis of β-lactam derivatives is a research topic of great interest due to the biological activity of these molecules. Indeed, there are several antibiotics which include a β-lactam core in their structures, such as penicilins, monobactams, carbacephems and cephamycins. The development of stereoselective approaches to access these molecular architectures turns out to be necessary in order to take advantage of the distinct properties provided by the different stereoisomers. This review covers recent advances towards the stereoselective synthesis of β-lactams, including Staudinger syntheses, cascade reactions, metal-catalyzed syntheses and base-promoted cyclizations. Within these methods, some particularly novel synthetic approaches are highlighted, such as the induction of chirality through bimetallic synergistic catalysis or the transfer of chirality between components in mechanically interlocked molecules. Additionally, a critical opinion on the state of the art of this research field is offered, remarking key points on which the future research should be focused on

Functional and evolutionary analysis of DXL1, a non-essential gene encoding a 1-deoxy-D-xylulose 5-phosphate synthase like protein in Arabidopsis thaliana

The synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP), catalyzed by the enzyme DXP synthase (DXS), represents a key regulatory step of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis. In plants DXS is encoded by small multigene families that can be classified into, at least, three specialized subfamilies. Arabidopsis thaliana contains three genes encoding proteins with similarity to DXS, including the well-known DXS1/CLA1 gene, which clusters within subfamily I. The remaining proteins, initially named DXS2 and DXS3, have not yet been characterized. Here we report the expression and functional analysis of A. thaliana DXS2. Unexpectedly, the expression of DXS2 failed to rescue Escherichia coli and A. thaliana mutants defective in DXS activity. Coherently, we found that DXS activity was negligible in vitro, being renamed as DXL1 following recent nomenclature recommendation. DXL1 is targeted to plastids as DXS1, but shows a distinct expression pattern. The phenotypic analysis of a DXL1 defective mutant revealed that the function of the encoded protein is not essential for growth and development. Evolutionary analyses indicated that DXL1 emerged from DXS1 through a recent duplication apparently specific of the Brassicaceae lineage. Divergent selective constraints would have affected a significant fraction of sites after diversification of the paralogues. Furthermore, amino acids subjected to divergent selection and likely critical for functional divergence through the acquisition of a novel, although not yet known, biochemical function, were identified. Our results provide with the first evidences of functional specialization at both the regulatory and biochemical level within the plant DXS family

Semiología radiológica de aparato digestivo: transito esófago-gastro-duodenal y enema opaco

[SPA] Esta publicación, destacando la Semiología Radiológica Elemental de un sistema específico del organismo forma las bases de todos los procesos de entrenamiento del Radiodiagnóstico médico, tiene un formato electrónico, multimedia, interactivo y autoejecutable. Estas publicaciones resultan ser al mismo tiempo económicas y eficaces y ofrecen una excelente calidad de transmisión de los fundamentos de las especialidades médicas basadas en el Diagnóstico por Imagen.[ENG] This publication, outlining the Elementary Radiological Semeiology of a specific organic system which forms the basis of all Medical Radiodiagnostic procedure training, has an electronic, multimedia, interactive and self-executable format. These publications prove to be both economic and effective and offer an excellent quality of transmission of the fundamentals of those medical specialties based on Diagnostic Imaging.Campus Mare Nostrum, Universidad Politécnica de Cartagena, Universidad de Murcia, Región de Murci

Tele-enseñanza a través de internet: la protección radiológica en ciencias de la salud = E-learning through internet: radiological protection in health sciences

[SPA] La obtención de un proyecto interdepartamental subvencionado por el Ministerio de Educación y Ciencia español ha permitido crear materiales didácticos específicos de Protección Radiológica que se han publicado en varios manuales y cuadernos de actividades prácticas. Estas publicaciones han constituido la base del primer curso continuado sobre Protección Radiológica realizado a través de Internet en España (9 ediciones, durante los años 2000-2010). Durante el pregrado y el grado, la utilización de material didáctico digital apropiado determina el nivel de conocimientos que puede alcanzarse. La enseñanza multimedia y la tele-educación incrementan el interés de los alumnos en los temas más complicados y difíciles en Ciencias de la Salud. Posteriormente, cuando se abandona la Universidad y comienza la actividad profesional, la tele-enseñanza permite la formación continuada en las actualizaciones básicas sobre Protección Radiológica, permitiendo a todos los profesionales familiarizarse con medios y recursos que difícilmente podrán utilizar de forma personal y directa. Keywords: Radiología, tele-enseñanza, educación médica, protección radiológica, control de calidad. [ENG]The creation of an interdepartmental project subsidised by the Spanish Ministry of Education has made it possible to create teaching material for Radiological Protection, and led to the publication of several specific manuals and practical 758 notebook. This material constitutes the working basis for the first continuous e-learning training course in Spanish via Internet on this subject (9 editions during the years 2000-2010). The use of appropriate teaching materials during the training cycles determines the level of knowledge that can be reached. Interactive multimedia teaching and e-learning increase interest in subjects that were previously regarded their as boring and difficult health science students’. When the students have finished their university studies, e-learning systems can provide continued professional training that achieves the basic goals of Radiological Protection, allowing professionals to acquaint themselves with this type of content, which they would usually fond difficult to do themselves.[ENG] The creation of an interdepartmental project subsidised by the Spanish Ministry of Education has made it possible to create teaching material for Radiological Protection, and led to the publication of several specific manuals and practical 758 notebook. This material constitutes the working basis for the first continuous e-learning training course in Spanish via Internet on this subject (9 editions during the years 2000-2010). The use of appropriate teaching materials during the training cycles determines the level of knowledge that can be reached. Interactive multimedia teaching and e-learning increase interest in subjects that were previously regarded their as boring and difficult health science students’. When the students have finished their university studies, e-learning systems can provide continued professional training that achieves the basic goals of Radiological Protection, allowing professionals to acquaint themselves with this type of content, which they would usually fond difficult to do themselves.Campus Mare Nostrum, Universidad Politécnica de Cartagena, Universidad de Murcia, Región de Murci

SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

SUMOylation is a post¿translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)¿transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage¿specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream¿specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.The authors thank Dr. Alicia Barroso Del Jesus for excellent assistance and input with NSG methodology at the Genomic Unit and Dr. Laura Montosa at the Microscopy Unit (IPBLN-CSIC). This work was supported by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (RTI2018-098834-B-I00) and the Wellcome Trust (WTI 204697/Z/16/Z to MCF) and thegrant from the Argentinian National Agency for Promotion of Scientific and Technological Research to VEA (PICT/2016/0465)

Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia

Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and positive covariance with mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, and autism. Conversely, genetic variation with discordant effects only contributes to schizophrenia risk in males and is negatively correlated with those disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia than vice versa. These results illustrate the genetic footprint of LNL-ISO on schizophrenia

High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer

Breast cancer; Cancer models; Predictive markersCáncer de mama; Modelos de cáncer; Marcadores predictivosCàncer de pulmó; Models de càncer; Marcadors predictiusCDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies

DNA methylation, deamination, and translesion synthesis combine to generate footprint mutations in cancer driver genes in B-cell derived lymphomas and other cancers

Cancer genomes harbor numerous genomic alterations and many cancers accumulate thousands of nucleotide sequence variations. A prominent fraction of these mutations arises as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases followed by the replication/repair of edited sites by DNA polymerases (pol), as deduced from the analysis of the DNA sequence context of mutations in different tumor tissues. We have used the weight matrix (sequence profile) approach to analyze mutagenesis due to Activation Induced Deaminase (AID) and two error-prone DNA polymerases. Control experiments using shuffled weight matrices and somatic mutations in immunoglobulin genes confirmed the power of this method. Analysis of somatic mutations in various cancers suggested that AID and DNA polymerases η and θ contribute to mutagenesis in contexts that almost universally correlate with the context of mutations in A:T and G:C sites during the affinity maturation of immunoglobulin genes. Previously, we demonstrated that AID contributes to mutagenesis in (de)methylated genomic DNA in various cancers. Our current analysis of methylation data from malignant lymphomas suggests that driver genes are subject to different (de)methylation processes than non-driver genes and, in addition to AID, the activity of pols η and θ contributes to the establishment of methylation-dependent mutation profiles. This may reflect the functional importance of interplay between mutagenesis in cancer and (de)methylation processes in different groups of genes. The resulting changes in CpG methylation levels and chromatin modifications are likely to cause changes in the expression levels of driver genes that may affect cancer initiation and/or progression

Detección en urgencias de infección por VIH en pacientes que consultan por condiciones potencialmente relacionadas con infección oculta: resultados iniciales del programa "Urgències VIHgila"

Objective: To estimate the prevalence of unknown HIV infection in patients who consulted in hospital emergency services (ED) for conditions defined in the SEMES-GESIDA Consensus Document (DC), evaluate the efficiency of its im-plementation and investigate the efficiency of HIV serology determination in other conditions. Methods: Results were reviewed in 10 Catalan EDs for 12 months (July-21-June-22) after implementing CD recommendations: request HIV serology in case of suspected sexually transmitted infection, chemsex, post-exposure prophylaxis (PEP), mononucleosis syndrome, community pneumonia (18-65 y-o) or herpes zoster (18-65 y-o). Other reasons for request were included. Prevalence (%) of global seropositivity and for each circumstance was calculated, with a 95% confidence interval (95%CI). The efficient strategy was considered if the lower limit of the CI95%>0.1%. Results: A total of5,107 HIV serologies were performed: 2,847(56%) in situations specified in CD, and 2,266 (44%) in other 138 circumstances. Forty-eight unknown HIV infections were detected (prevalence=0.94%;95%CI=0.69-1.24). The prevalence was somewhat higher in DC requests (30 cas-es 1.12%) than the rest (18 cases 0.71%; p=0.16). The individualized prevalence of CD reasons ranged between 7.41% (95%CI=0.91-24.3) in chemsex and 0.42% 95%CI=0.14-0.98 in PPE, always efficient except herpes zoster (0.76%; CI95%=0.02-4.18). In other reasons, cases were detected in 12 circumstances, and in four the determination could be efficient: lymphopenia (10%;CI95%=0.25-44.5), fever with polyarthralgia-polyarthritis (7.41%;CI95% =0.91-24.3), behavioral alteration-confusion-encephalopathy (3.45%;95%CI=0.42-11.9) and fever of unknown origin (2.50%;95%CI=0.82-5.74). Conclusions: The determination of HIV serology in HES in the processes defined by DC SEMES-GESIDA is efficient. Some circumstances are identified that could be added to those previously contemplated to increase efficiency