A Machine-Learning Model for Lung Age Forecasting by Analyzing Exhalations

Spirometers are important devices for following up patients with respiratory diseases. These are mainly located only at hospitals, with all the disadvantages that this can entail. This limits their use and consequently, the supervision of patients. Research efforts focus on providing digital alternatives to spirometers. Although less accurate, the authors claim they are cheaper and usable by many more people worldwide at any given time and place. In order to further popularize the use of spirometers even more, we are interested in also providing user-friendly lung-capacity metrics instead of the traditional-spirometry ones. The main objective, which is also the main contribution of this research, is to obtain a person’s lung age by analyzing the properties of their exhalation by means of a machine-learning method. To perform this study, 188 samples of blowing sounds were used. These were taken from 91 males (48.4%) and 97 females (51.6%) aged between 17 and 67. A total of 42 spirometer and frequency-like features, including gender, were used. Traditional machine-learning algorithms used in voice recognition applied to the most significant features were used. We found that the best classification algorithm was the Quadratic Linear Discriminant algorithm when no distinction was made between gender. By splitting the corpus into age groups of 5 consecutive years, accuracy, sensitivity and specificity of, respectively, 94.69%, 94.45% and 99.45% were found. Features in the audio of users’ expiration that allowed them to be classified by their corresponding lung age group of 5 years were successfully detected. Our methodology can become a reliable tool for use with mobile devices to detect lung abnormalities or diseases.This research was funded by the Spanish Ministerio de Ciencia e Innovación under contract PID2020-113614RB-C22

Enzymatic synthesis of N-acetyllactosamine from lactose enabled by recombinant β1,4-galactosyltransferases

Utilising a fast and sensitive screening method based on imidazolium-tagged probes, we report unprecedented reversible activity of bacterial β1,4-galactosyltransferases to catalyse the transgalactosylation from lactose to N-acetylglucosamine to form N-acetyllactosamine in the presence of UDP. The process is demonstrated by the preparative scale synthesis of pNP-β-LacNAc from lactose using β1,4-galactosyltransferase NmLgtB-B as the only biocatalyst

Biocatalytic Transfer of Pseudaminic Acid (Pse5Ac7Ac) Using Promiscuous Sialyltransferases in a Chemoenzymatic Approach to Pse5Ac7Ac-Containing Glycosides

Pseudaminic acid (Pse5Ac7Ac) is a nonmammalian sugar present on the cell surface of a number of bacteria including Pseudomonas aeruginosa, Campylobacter jejuni, and Acinetobacter baumannii. However, the role Pse5Ac7Ac plays in host–pathogen interactions remains underexplored, particularly compared to its ubiquitous sialic acid analogue Neu5Ac. This is primarily due to a lack of access to difficult to prepare Pse5Ac7Ac glycosides. Herein, we describe the in vitro biocatalytic transfer of an activated Pse5Ac7Ac donor onto glycosyl acceptors, enabling the enzymatic synthesis of Pse5Ac7Ac-containing glycosides. In a chemoenzymatic approach, chemical synthesis initially afforded access to a late-stage Pse5Ac7Ac biosynthetic intermediate, which was subsequently converted to the desired CMP-glycosyl donor in a one-pot two-enzyme process using biosynthetic enzymes. Finally, screening a library of 13 sialyltransferases (SiaT) with the unnatural substrate enabled the identification of a promiscuous inverting SiaT capable of turnover to afford β-Pse5Ac7Ac-terminated glycosides.</p

Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair

Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. We sequenced FAN1 in 176 additional families with histories of colorectal cancer and performed in vitro functional analyses of the mutant forms of FAN1 identified. We detected FAN1 mutations in approximately 3% of families who met the Amsterdam criteria and had mismatch repair-proficient cancers with no previously associated mutations. These findings link colorectal cancer predisposition to the Fanconi anemia DNA repair pathway, supporting the connection between genome integrity and cancer risk

Evaluating Person-Centred Integrated Care to People with Complex Chronic Conditions: Early Implementation Results of the ProPCC Programme

Introduction: The evaluation of integrated care programmes for high-need high-cost older people is a challenge. We aim to share the early implementation results of the ProPCC programme in the North-Barcelona metropolitan area, in Catalonia, Spain. Methods: We analysed the intervention with retrospective data from May 2018 to December 2021 by describing the cohort complexity and by showing its 6-months pre-post impact on time spent at home and resources used: primary care visits, emergency department visits, hospital admissions and hospital stay. Findings: 264 cases were included (91% at home; 9% in nursing homes). 6-month pre vs. 6-months post results were (mean, p-value): primary care visits 8.2 vs. 11.5 (p < 0.05); emergency department visits 1.4 vs. 0.9 (p < 0.05); hospital admissions 0.7 vs. 0.5 (p < 0.05); hospital stay 12.8 vs. 7.9 days (p < 0.05). Time spent at home was 169.2 vs.174.2 days (p < 0.05). Conclusion: Early implementation of the ProPCC programme results in an increase in time spent at home (up to 3%) and significant reductions in emergency department attendance (–37.2%) and hospital stays (–38.3%). The increased use of primary care resources is compensated by the hospital resources savings, with a result in the average total cost of –46.3%

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.

Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis

Síntesi i aplicació de phi-dipèptids amb estructura de 3 aminopiperidona. Síntesi de phi-melanotans

[cat] Els melanotans son pèptids derivats de la hormona melanotropínica (alfa-MSH). Aquesta forma part del sistema melanocortínic, juntament amb altres hormones com la ACTH, la beta-MSH o la gamma-MSH entre d’altres. Els pèptids melanocortínics presenten una mateixa seqüència central basada en els residus de His3-Phe4-Arg5-Trp6 que és la seqüència activa dels pèptids. Aquests, realitzen les seves funcions per interacció amb 5 receptors melonocortínics que es troben ampliament distribuïts per l’organisme. Amb anterioritat a aquest treball, s’havien sintetitzat una gran quantitat de pèptids derivats de la hormona alfa-MSH. Concretament la substitució de la Met de la posició 4 per Nle i la recemització de la Phe de la posició 7 en D-Phe van conduir a la síntesi del Melanotan-1 (MT1) un tridecapèptid linear el qual mostrava una millor estabilitat metabòlica i una activitat més potent quan es comparava amb la hormona model però que era poc selectiu per cap dels receptors de melanocortina humans. Per tal de restringir la conformació de l’MT1 i fer-lo més selectiu, el grup del Prof. Hruby de la Universitat d’Arizona va sintetitzar l’heptapèptid cíclic Melanotan-2 (MT2) el qual era molt més potent que MT1 però que com aquest va resultar ser poc selectiu. Degut a aquesta manca de selectivitat, és d’una importancia capital trobar lligands per a cadascun d’aquests receptors per tal de poder determinar el paper fisiològic que té cadascun d’ells. Així, la present tesi doctoral té per objectiu el disseny i la síntesi de pseudomelanotans a partir del pèptid model MT2 per tal de millorar-ne la selectivitat per a un determinat receptor. L’MT2 és un cicloheptapèptid que presenta un gir beta centrat en els residus d’His3-D-Phe4 i una ciclació per la cadena lateral dels residus d’Asp2 i Lys7. Treball previs d’altres autors s’han centrat sobretot en modificar la part activa de la molècula, mentre que en el present treball ens volem centrar en la part flexible per tal de no alterar-ne la seva activitat. En primer lloc, per tal de rigidificar la zona flexible de l’MT2 es va dur a terme la síntesis de diferents estructures pseudopeptídiques rígides: el lactam 13, la oxazolopiperidona 15 i els diazanorbornans 101b, 108 i 114 i el diazanorborné 115. Posteriorment, es descriu la incorporació d’aquestes estructures rígides en els pseudomelanotans derivats d’MT2 per síntesi peptídica en fase sòlida. Els pseudomelanotans obtinguts es poden classificar en 3 grups: a) Els compostos 13 i 108 es fan servir per substituir el Trp, donat que aquest es troba just al costat del gir beta. D’aquesta manera se sintetitzen els pèptids 120 i 121a i 121b. b) L’oxazolopiperidona 15 al ser un mimètic de gir beta es fa servir per substituir els redidus centrals del gir beta (His3-D-Phe4) per tal d’obtenir el pseudomelanotan 122. c) Pseudomelanotans en que la part flexible de la molècula ha estat modificada. D’aquesta manera s’obtenen els pseudopèptids 123, 124, 125 i 126 al modificar la Lys7 per l’oxazolopiperidona 15, els diazanorbornans 101b i 114 o pel diazanorbornè 115. Finalment, un cop sintetitzats els derivats d’MT2 van ser sotmesos a estudis de RMN. Aquesta tècnica és particularment útil ja que permet determinar la formació d’enllaços d’hidrogen, les distàncies interprotòniques i els angles diedres. A més a més, les dades ens serveixen com a restriccions per a càlculs de modelització molecular. Destaquen els resultats obtinguts pel compost 121a el qual manté el gir beta present en el compost model i a més a més mostra un gir complementari. En el cas dels pèptids 122 i 123 que inclouen l’oxazolopiperidona 15 en la seva estructura i de l’azapèptid 120 també s’observa un restricció conformacional respecte al model.[eng] Alpha-melanocyte stimulating hormone (alpha-MSH) is a linear tridecapeptide which plays a role in a wide range of biological responses like feeding behaviour, pain modulation, sexual function, energy homeostasis and thermoregulation. The principal pharmacophore groups of alpha-MSH were found to be the side chains of the central tetrapeptide His-Phe-Arg-Trp. Since the discovery of alpha-MSH, numerous linear analogues of native alpha-MSH have been synthesized to enhance melanotropic potency. Hence, substitution of the Nle for Met at the 4-position and racemization to D-phenylalanine at the 7-position led to Melanotan-1 (MT1) which showed enhanced metabolic stability and improved potency compared with alpha-MSH. In order to constrain MT1, the group of Prof. Hruby synthesized the cyclic heptapeptide MT2 which was a very potent but non-selective agonist for the human melanocortin receptor subtypes MC1R, MC3R, MC4R and MC5R. Because of the lack in selectivity, finding selective ligands for each of the receptors is crucial for the determination of their individual physiological roles. The aim of the present work is the design and synthesis of a collection of phimelanotans to improve their biological properties with respect to MT2. First of all, we have prepared several constrained pseudodipeptides (lactam 13, diazanorbornanes 101b and 108) or -turn mimics (oxazolopiperidone 15, diazanorbornane 114 and diazanorbornene 115) to replace native residues of MT2. Then, we describe the synthesis of the phi-melanotans incorporating our constrained scaffolds by SPPS. Three types of phi-melanotans are obtained: a) Compounds 120, 121a and 121b with modification of the active part of the molecule. b) Pseudopeptide 122 is obtained by substitution of oxazolopiperidone 15 for the central residues of the beta-turn (His3-D-Phe4). c) Pseudomelanotans 123, 124, 125 and 126 are prepared by modification of the flexible part of the model peptide. Finally, we have demonstrated by NMR studies that incorporation of our constrained scaffolds led to the formation of conformational constrained pseudopeptides

Identification of living Legionella pneumophila using species-specific metabolic lipopolysaccharide labeling.

International audienceLegionella pneumophila is a pathogenic bacterium involved in regular outbreaks characterized by a relatively high fatality rate and an important societal impact. Frequent monitoring of the presence of this bacterium in environmental water samples is necessary to prevent these epidemic events, but the traditional culture-based detection and identification method requires up to 10 days. Reported herein is a method allowing identification of Legionella pneumophila by metabolic lipopolysaccharide labeling which targets, for the first time, a precursor to monosaccharides that are specifically present within the O-antigen of the bacterium. This new approach allows easy detection of living Legionella pneumophila, while other Legionella species are not labeled

Rapid and Specific Enrichment of Culturable Gram Negative Bacteria Using Non-Lethal Copper-Free Click Chemistry Coupled with Magnetic Beads Separation.

Currently, identification of pathogenic bacteria present at very low concentration requires a preliminary culture-based enrichment step. Many research efforts focus on the possibility to shorten this pre-enrichment step which is needed to reach the minimal number of cells that allows efficient identification. Rapid microbiological controls are a real public health issue and are required in food processing, water quality assessment or clinical pathology. Thus, the development of new methods for faster detection and isolation of pathogenic culturable bacteria is necessary. Here we describe a specific enrichment technique for culturable Gram negative bacteria, based on non-lethal click chemistry and the use of magnetic beads that allows fast detection and isolation. The assimilation and incorporation of an analog of Kdo, an essential component of lipopolysaccharides, possessing a bio-orthogonal azido function (Kdo-N3), allow functionalization of almost all Gram negative bacteria at the membrane level. Detection can be realized through strain-promoted azide-cyclooctyne cycloaddition, an example of click chemistry, which interestingly does not affect bacterial growth. Using E. coli as an example of Gram negative bacterium, we demonstrate the excellent specificity of the technique to detect culturable E. coli among bacterial mixtures also containing either dead E. coli, or live B. subtilis (as a model of microorganism not containing Kdo). Finally, in order to specifically isolate and concentrate culturable E. coli cells, we performed separation using magnetic beads in combination with click chemistry. This work highlights the efficiency of our technique to rapidly enrich and concentrate culturable Gram negative bacteria among other microorganisms that do not possess Kdo within their cell envelope