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1.
Front Public Health ; 12: 1339267, 2024.
Article En | MEDLINE | ID: mdl-38855458

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants. Materials and methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility ( Δ ß ) between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants. Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated Δ ß between variants, revealing that: ( i ) Δ ß increased progressively from the Alpha to the Omicron variant; ( i i ) Δ ß showed a high degree of variability within Omicron variants; ( i i i ) a higher Δ ß was associated with a later emergence of the variant within a country; ( i v ) a higher degree of immunization of the population against previous variants was associated with a higher Δ ß for the Delta variant; ( v ) larger countries exhibited smaller Δ ß , suggesting regionally diverse outbreaks within the same country; and finally ( v i ) the model reliably captures the dynamics of competing variants, even in complex scenarios. Conclusion: The use of mathematical models allows for precise and reliable estimation of daily cases of each variant. By quantifying Δ ß , we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. Additionally, we have shown that the geographical characteristics of a country, as well as the timing of new variant entrances, can explain some of the observed differences in variant substitution dynamics across countries.


COVID-19 , Models, Theoretical , SARS-CoV-2 , Humans , COVID-19/transmission , COVID-19/epidemiology , Europe/epidemiology , SARS-CoV-2/genetics
2.
NAR Genom Bioinform ; 6(2): lqae061, 2024 Jun.
Article En | MEDLINE | ID: mdl-38846349

Population genomics has revolutionized our ability to study bacterial evolution by enabling data-driven discovery of the genetic architecture of trait variation. Genome-wide association studies (GWAS) have more recently become accompanied by genome-wide epistasis and co-selection (GWES) analysis, which offers a phenotype-free approach to generating hypotheses about selective processes that simultaneously impact multiple loci across the genome. However, existing GWES methods only consider associations between distant pairs of loci within the genome due to the strong impact of linkage-disequilibrium (LD) over short distances. Based on the general functional organisation of genomes it is nevertheless expected that majority of co-selection and epistasis will act within relatively short genomic proximity, on co-variation occurring within genes and their promoter regions, and within operons. Here, we introduce LDWeaver, which enables an exhaustive GWES across both short- and long-range LD, to disentangle likely neutral co-variation from selection. We demonstrate the ability of LDWeaver to efficiently generate hypotheses about co-selection using large genomic surveys of multiple major human bacterial pathogen species and validate several findings using functional annotation and phenotypic measurements. Our approach will facilitate the study of bacterial evolution in the light of rapidly expanding population genomic data.

3.
Angew Chem Int Ed Engl ; : e202402798, 2024 May 22.
Article En | MEDLINE | ID: mdl-38776235

The direct auration of arenes is a key step in numerous gold-catalyzed reactions. Although reported more than 100 years ago, understanding of its underlying mechanism has been hampered by the difficulties in the isolation of relevant intermediates given the propensity of gold(III) species to undergo reductive elimination. Here, we report the synthesis and isolation of a new family of intriguing zwitterionic [C(sp3)^C(sp2)]-auracyclopentanes, as well as of their alkyl-gold(III) precursors and demonstrate their value as mechanistic probes to study the Csp2-Au bond-forming event. Experimental investigations employing Kinetic Isotope Effects (KIE), Hammett plot, and Eyring analysis provided important insights into the formation of the auracycle. The data suggest a SEAr mechanism wherein the slowest step might be the p-coordination between the arene and the gold(III) center, en route to the Wheland intermediate. We also show that these auracyclopentanes can work as catalysts in several gold-promoted transformations.

4.
Front Neuroanat ; 18: 1348032, 2024.
Article En | MEDLINE | ID: mdl-38645671

The brain contains thousands of millions of synapses, exhibiting diverse structural, molecular, and functional characteristics. However, synapses can be classified into two primary morphological types: Gray's type I and type II, corresponding to Colonnier's asymmetric (AS) and symmetric (SS) synapses, respectively. AS and SS have a thick and thin postsynaptic density, respectively. In the cerebral cortex, since most AS are excitatory (glutamatergic), and SS are inhibitory (GABAergic), determining the distribution, size, density, and proportion of the two major cortical types of synapses is critical, not only to better understand synaptic organization in terms of connectivity, but also from a functional perspective. However, several technical challenges complicate the study of synapses. Potassium ferrocyanide has been utilized in recent volume electron microscope studies to enhance electron density in cellular membranes. However, identifying synaptic junctions, especially SS, becomes more challenging as the postsynaptic densities become thinner with increasing concentrations of potassium ferrocyanide. Here we describe a protocol employing Focused Ion Beam Milling and Scanning Electron Microscopy for studying brain tissue. The focus is on the unequivocal identification of AS and SS types. To validate SS observed using this protocol as GABAergic, experiments with immunocytochemistry for the vesicular GABA transporter were conducted on fixed mouse brain tissue sections. This material was processed with different concentrations of potassium ferrocyanide, aiming to determine its optimal concentration. We demonstrate that using a low concentration of potassium ferrocyanide (0.1%) improves membrane visualization while allowing unequivocal identification of synapses as AS or SS.

5.
J Wrist Surg ; 13(2): 176-180, 2024 Apr.
Article En | MEDLINE | ID: mdl-38505212

Introduction Continuing advances in wrist arthroscopy and better understanding of carpal conditions have created the need to design new wrist access portals that facilitate the implementation of new surgical techniques. The aim of this study was to define and verify the safety of the medial triquetrohamate (MTH) portal. Description of the technique The MTH portal is located about 5-10 mm ulnar and 2-3 mm distal to the midcarpal ulnar portal, ulnar to the extensor digitorum communis (EDC) tendon of the fourth and fifth fingers, and radial to the extensor digiti quinti (minimi) (EDQ) tendon. Methods An anatomical study was performed on 15 upper limb specimens from 15 human cadavers. Iatrogenic injuries to potentially at-risk neurovascular and tendinous structures were assessed, and the distance from the portal to these structures was measured. Results There were no iatrogenic injuries to the structures at risk. Mean distances from the MTH portal to the EDC tendon of the fourth and fifth fingers and to the EDQ tendon were 4.67 ± 0.35 mm and 7.27 ± 0.18 mm, respectively. No differences were observed between the left and right wrists. The distance from the MTH portal to the dorsal sensory branch of the ulnar nerve was 15.07 ± 0.44 mm. The structure with the highest risk of injury was the EDC tendon of the fourth and fifth fingers, with a distance of less than 5 mm. Conclusions The MTH portal is safe, reproducible and facilitates the implementation of various techniques related to midcarpal pathology.

6.
Plants (Basel) ; 13(3)2024 Jan 28.
Article En | MEDLINE | ID: mdl-38337921

Lettuce is a vegetable that contributes vitamins, minerals, fibre, phenolic compounds and antioxidants to the human diet. In the search for improving production conditions and crop health, the use of microorganisms with plant growth-promoting capabilities, such as soil yeasts (PGPY), in conjunction with nanotechnology could offer sustainable development of agroecosystems. This study evaluated the synthesis of health-promoting bioactive compounds in lettuce under the application of soil yeast and an iron nanoparticle (NP-Fe2O3) encapsulated in alginate beads. Two yeast strains, Candida guillermondii and Rhodotorula mucilaginosa, and a consortium of both yeasts were used in the presence and absence of Fe2O3-NPs. Phenolic compounds were identified and quantified via HPLC-ESI-Q-ToF and antioxidant activity. Ten phenolic compounds were identified, highlighting the chicoric acid isomer and two quercetin glycosides with high concentrations of up to 100 µg g-1 in treatments with C. guillermondii. Treatments with R. mucilaginosa and NPs-Fe2O3 presented an increase in antioxidant activity, mainly in TEAC, CUPRAC and DPPH activities in leaves, with significant differences between treatments. Therefore, the use of encapsulated soil yeasts is a viable alternative for application in vegetables to improve the biosynthesis and accumulation of phenolic compounds in lettuce and other crops.

7.
Microb Genom ; 10(2)2024 Feb.
Article En | MEDLINE | ID: mdl-38376388

Accurate reconstruction of Escherichia coli antibiotic resistance gene (ARG) plasmids from Illumina sequencing data has proven to be a challenge with current bioinformatic tools. In this work, we present an improved method to reconstruct E. coli plasmids using short reads. We developed plasmidEC, an ensemble classifier that identifies plasmid-derived contigs by combining the output of three different binary classification tools. We showed that plasmidEC is especially suited to classify contigs derived from ARG plasmids with a high recall of 0.941. Additionally, we optimized gplas, a graph-based tool that bins plasmid-predicted contigs into distinct plasmid predictions. Gplas2 is more effective at recovering plasmids with large sequencing coverage variations and can be combined with the output of any binary classifier. The combination of plasmidEC with gplas2 showed a high completeness (median=0.818) and F1-Score (median=0.812) when reconstructing ARG plasmids and exceeded the binning capacity of the reference-based method MOB-suite. In the absence of long-read data, our method offers an excellent alternative to reconstruct ARG plasmids in E. coli.


Escherichia coli , High-Throughput Nucleotide Sequencing , Escherichia coli/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Plasmids/genetics
8.
Foods ; 13(2)2024 Jan 18.
Article En | MEDLINE | ID: mdl-38254611

One of the problems that most seriously affects oenology today is enzymatic browning, especially when grapes are infected by grey rot. We studied the capacity of glutathione (GSH) and a specific inactivated dry yeast rich in glutathione (IDY-GSH) to protect white grape must from browning compared to that of sulphur dioxide (SO2). The results indicate that SO2 drastically reduces the oxygen consumption rate (by around 72%), protects hydroxycinnamic acids from oxidation and prevents grape must against browning even in the presence of laccase. Specifically, the presence of SO2 reduced the colour's blue-yellow component (b*) by around 91% in control conditions and around 76% in the presence of laccase. GSH, pure or in the form of IDY-GSH, also reduces the oxygen consumption rate (by 23% and 36%, respectively) but to a lesser extent than SO2. GSH also favours the formation of grape reaction product (GRP) from hydroxycinnamic acids and effectively protects grape must against browning in healthy grape conditions. Specifically, the presence of GSH reduced b* by around 81% in control conditions. Nevertheless, in the presence of laccase, it was not effective enough, reducing b* by around 39% in the case of pure GSH and 24% in the case of IDY-GSH. Therefore, both forms of GSH can be considered as interesting alternative tools to SO2 for preventing browning in white grape must, but only when the grapes are healthy.

9.
Brain Pathol ; 34(3): e13222, 2024 May.
Article En | MEDLINE | ID: mdl-38012061

Significant progress has been made with regard to understanding how the adult brain responds after a stroke. However, a large number of patients continue to suffer lifelong disabilities without adequate treatment. In the present study, we have analyzed possible microanatomical alterations in the contralesional hippocampus from the ischemic stroke mouse model tMCAo 12-14 weeks after transient middle cerebral artery occlusion. After individually injecting Lucifer yellow into pyramidal neurons from the CA1 field of the hippocampus, we performed a detailed three-dimensional analysis of the neuronal complexity, dendritic spine density, and morphology. We found that, in both apical (stratum radiatum) and basal (stratum oriens) arbors, CA1 pyramidal neurons in the contralesional hippocampus of tMCAo mice have a significantly higher neuronal complexity, as well as reduced spine density and alterations in spine volume and spine length. Our results show that when the ipsilateral hippocampus is dramatically damaged, the contralesional hippocampus exhibits several statistically significant selective alterations. However, these alterations are not as significant as expected, which may help to explain the recovery of hippocampal function after stroke. Further anatomical and physiological studies are necessary to better understand the modifications in the "intact" contralesional lesioned brain regions, which are probably fundamental to recover functions after stroke.


Hippocampus , Pyramidal Cells , Humans , Mice , Animals , CA1 Region, Hippocampal , Neurons , Infarction, Middle Cerebral Artery , Dendritic Spines , Dendrites
10.
Ther Adv Psychopharmacol ; 13: 20451253231220907, 2023.
Article En | MEDLINE | ID: mdl-38152569

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

11.
Microbiol Spectr ; 11(6): e0020123, 2023 Dec 12.
Article En | MEDLINE | ID: mdl-37811975

IMPORTANCE: Enterococcus faecalis causes life-threatening invasive hospital- and community-associated infections that are usually associated with multidrug resistance globally. Although E. faecalis infections cause opportunistic infections typically associated with antibiotic use, immunocompromised immune status, and other factors, they also possess an arsenal of virulence factors crucial for their pathogenicity. Despite this, the relative contribution of these virulence factors and other genetic changes to the pathogenicity of E. faecalis strains remain poorly understood. Here, we investigated whether specific genomic changes in the genome of E. faecalis isolates influence its pathogenicity-infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection and intestinal colonization. Our findings indicate that E. faecalis genetics partially influence the infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection, possibly due to gut-to-bloodstream translocation, highlighting the potential substantial role of host and environmental factors, including gut microbiota, on the opportunistic pathogenic lifestyle of this bacterium.


Enterococcus faecalis , Gram-Positive Bacterial Infections , Humans , Virulence Factors/genetics , Virulence/genetics , Anti-Bacterial Agents , Gram-Positive Bacterial Infections/microbiology
12.
Molecules ; 28(20)2023 Oct 10.
Article En | MEDLINE | ID: mdl-37894486

Dark chocolate dragée confectionary was made with BRS Clara raisins pre-treated with extra virgin olive oil (EVOO). The evaluation of the changes in the phenolic composition (flavonols, hydrocinnamic acid derivatives (HCADs), stilbenes and flavan-3-ol monomers, dimers, and proanthocyanidins (PAs)) resulting from the covering process showed that the chocolate coating was responsible for an increase in the concentrations of flavan-3-ols and PAs when compared to just the raisins. For the flavonols and HCADs, a reduction in the total concentration of compounds was observed when comparing the dragées to the raisins. Furthermore, there was a strong influence of chocolate in the qualitative profile with the emergence of new compounds (quercetin-3-pentoside, kampfterol-3-rutinoside, p-coumaric acid, and caffeoyl-aspartate). The combination of these ingredients (raisins and chocolate) resulted in a dark chocolate coated raisin (DC) with good sensory acceptance and a more complex phenolic composition that may positively contribute to its functional quality.


Cacao , Chocolate , Proanthocyanidins , Vitis , Phenols/analysis , Flavonols/analysis , Proanthocyanidins/analysis , Chromatography, High Pressure Liquid/methods
13.
J Am Chem Soc ; 145(40): 21745-21751, 2023 Oct 11.
Article En | MEDLINE | ID: mdl-37756523

Reactions capable of transposing the oxidation levels of adjacent carbon atoms enable rapid and fundamental alteration of a molecule's reactivity. Herein, we report the 1,2-transposition of the carbon atom oxidation level in cyclic and acyclic tertiary amides, resulting in the one-pot synthesis of 1,2- and 1,3-oxygenated tertiary amines. This oxidation level transfer was facilitated by the careful orchestration of an iridium-catalyzed reduction with the functionalization of transiently formed enamine intermediates. A novel 1,2-carbonyl transposition is described, and the breadth of this redox transposition strategy has been further explored by the development of aminoalcohol and enaminone syntheses. The diverse ß-functionalized amine products were shown to be multifaceted and valuable synthetic intermediates, accessing challenging biologically relevant motifs.

14.
Rev. esp. quimioter ; 36(4): 346-379, aug. 2023. tab
Article En | IBECS | ID: ibc-223555

A progressively increasing percentage of the elderly live during the last years of their lives in nursing homes. Although these institutions are intended to mimic life at home as much as possible, they have characteristics that make them quite similar to a “nosocomiun”, i.e. an establishment for the treatment of the sick. The very coexistence among the elderly, the fact of sharing caregivers and the very significant exposure to third parties, together with the frequent predisposing diseases to infection in this population, make infection frequent among residents and also easily transmissible. This leads us to ask what can be done to prevent infection in this environment and more specifically what is the state of the art of the matter in a Western European nation such as ours. The Board of Trustees of the Health Sciences Foundation has asked itself a series of questions on the subject of infection prevention in Nursing Homes, the structure of procedures, the legislation available, compliance with the measures indicated, the best indicators of the processes and therefore, the need to promote in Spain a document of recommendations to avoid infections in this poplation whose morbidity and mortality need not be highlighted. To this end, a multidisciplinary group of experts in different aspects of this problem has been convened and asked the proposed questions. The questions were discussed by the group as a whole and led to a series of conclusions agreed upon by the participants. The results of the meeting are reported below (AU)


Un porcentaje progresivamente creciente de las personas mayores viven durante los últimos años de su vida en residencias de ancianos. Dichas instituciones, aunque pretenden remedar lo más posible la vida en el hogar, tienen características que las hace bastante parecidas a un nosocomio, es decir a un establecimiento destinado al tratamiento de enfermos. La propia convivencia entre los ancianos, el hecho de compartir cuidadores y la exposición muy importante a terceras personas, junto con las frecuentes enfermedades predisponentes a la infección de esta población, hacen que la infección sea frecuente entre los residentes y que además sea fácilmente transmisible. Esto nos lleva a preguntarnos qué puede hacerse para prevenir la infección en este medio y más concretamente cuál es el estado del arte de la cuestión en una nación de Europa Occidental como la nuestra. El patronato de la Fundación de Ciencias de la Salud se ha formulado una serie de preguntas sobre el tema de la prevención de la infección en las Residencias de Mayores, la estructura de la misma, la legislación vigente, el cumplimiento de las medidas indicadas, los indicadores de los procesos y por ende, la necesidad de fomentar en España un documento de recomendaciones para evitar infecciones en esta población cuya morbilidad y mortalidad no necesitan ser resaltadas. Para ello, se ha convocado a un grupo multidisciplinar de expertos en distintos aspectos de este problema a los que se les han formulado las preguntas propuestas. Las preguntas han sido discutidas por el grupo en su conjunto y han conducido a una serie de conclusiones consensuadas entre los participantes. Pasamos, a continuación a relatar los resultados de la reunión (AU)


Humans , Infection Control/methods , Long-Term Care , Old Age Assistance , Homes for the Aged , Spain
15.
NAR Genom Bioinform ; 5(3): lqad066, 2023 Sep.
Article En | MEDLINE | ID: mdl-37435357

Extrachromosomal elements of bacterial cells such as plasmids are notorious for their importance in evolution and adaptation to changing ecology. However, high-resolution population-wide analysis of plasmids has only become accessible recently with the advent of scalable long-read sequencing technology. Current typing methods for the classification of plasmids remain limited in their scope which motivated us to develop a computationally efficient approach to simultaneously recognize novel types and classify plasmids into previously identified groups. Here, we introduce mge-cluster that can easily handle thousands of input sequences which are compressed using a unitig representation in a de Bruijn graph. Our approach offers a faster runtime than existing algorithms, with moderate memory usage, and enables an intuitive visualization, classification and clustering scheme that users can explore interactively within a single framework. Mge-cluster platform for plasmid analysis can be easily distributed and replicated, enabling a consistent labelling of plasmids across past, present, and future sequence collections. We underscore the advantages of our approach by analysing a population-wide plasmid data set obtained from the opportunistic pathogen Escherichia coli, studying the prevalence of the colistin resistance gene mcr-1.1 within the plasmid population, and describing an instance of resistance plasmid transmission within a hospital environment.

16.
Cereb Cortex ; 33(17): 9691-9708, 2023 08 23.
Article En | MEDLINE | ID: mdl-37455478

The human anterior cingulate and temporopolar cortices have been proposed as highly connected nodes involved in high-order cognitive functions, but their synaptic organization is still basically unknown due to the difficulties involved in studying the human brain. Using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to study the synaptic organization of the human brain obtained with a short post-mortem delay allows excellent results to be obtained. We have used this technology to analyze layer III of the anterior cingulate cortex (Brodmann area 24) and the temporopolar cortex, including the temporal pole (Brodmann area 38 ventral and dorsal) and anterior middle temporal gyrus (Brodmann area 21). Our results, based on 6695 synaptic junctions fully reconstructed in 3D, revealed that Brodmann areas 24, 21 and ventral area 38 showed similar synaptic density and synaptic size, whereas dorsal area 38 displayed the highest synaptic density and the smallest synaptic size. However, the proportion of the different types of synapses (excitatory and inhibitory), the postsynaptic targets, and the shapes of excitatory and inhibitory synapses were similar, regardless of the region examined. These observations indicate that certain aspects of the synaptic organization are rather homogeneous, whereas others show specific variations across cortical regions.


Gyrus Cinguli , Synapses , Humans , Temporal Lobe , Brain
17.
Foods ; 12(13)2023 Jul 05.
Article En | MEDLINE | ID: mdl-37444346

The BRS Carmem grape was developed as an alternative for processing juices and wines. This study aimed to determine the phenolic compounds (PC) in the edible parts of this grape from two harvests-one harvested at ideal maturation time and another when the grapes were still immature-using HPLC-DAD-ESI-MS/MS. Student's t-test was used (α = 0.05) to evaluate differences in the PC content between the edible parts and between the harvests. Both skins showed a predominance of flavonols, anthocyanins, hydroxycinnamic acids derivatives (HCAD) and stilbenes, with higher concentrations for harvest 1 than harvest 2. For both harvests (harvest 1 and harvest 2), the HCAD (mg of caftaric acid•kg fruit-1) was higher in whole grapes (383.98 and 67.09) than in their skins (173.95 and 21.74), with a predominance of trans-caffeic acid for all samples; the flavan-3-ols and proanthocyanidins (mg of (+)-catechin•kg fruit-1) presented higher concentrations in the seeds (flavan-3-ols: 203.20 and 182.71, proanthocyanidins: 453.57 and 299.86) than in the skins (flavan-3-ols: 1.90 and 4.56, proanthocyanidins: 37.58 and 98.92); the stilbenes concentration (µg 3-glc-resveratrol•kg fruit-1) was higher for the seeds from harvest 2 (896.25) than those from harvest 1 (48.67). BRS Carmem grapes contain a phenolic composition complex, and still have a relevant concentration of flavonols, anthocyanins and stilbenes, even when immature.

18.
Nat Commun ; 14(1): 3294, 2023 06 15.
Article En | MEDLINE | ID: mdl-37322051

Escherichia coli is a leading cause of invasive bacterial infections in humans. Capsule polysaccharide has an important role in bacterial pathogenesis, and the K1 capsule has been firmly established as one of the most potent capsule types in E. coli through its association with severe infections. However, little is known about its distribution, evolution and functions across the E. coli phylogeny, which is fundamental to elucidating its role in the expansion of successful lineages. Using systematic surveys of invasive E. coli isolates, we show that the K1-cps locus is present in a quarter of bloodstream infection isolates and has emerged in at least four different extraintestinal pathogenic E. coli (ExPEC) phylogroups independently in the last 500 years. Phenotypic assessment demonstrates that K1 capsule synthesis enhances E. coli survival in human serum independent of genetic background, and that therapeutic targeting of the K1 capsule re-sensitizes E. coli from distinct genetic backgrounds to human serum. Our study highlights that assessing the evolutionary and functional properties of bacterial virulence factors at population levels is important to better monitor and predict the emergence of virulent clones, and to also inform therapies and preventive medicine to effectively control bacterial infections whilst significantly lowering antibiotic usage.


Escherichia coli Infections , Escherichia coli Proteins , Humans , Escherichia coli , Escherichia coli Infections/microbiology , Virulence/genetics , Virulence Factors/genetics , Escherichia coli Proteins/genetics , Phylogeny
19.
Exp Appl Acarol ; 90(1-2): 83-98, 2023 Jun.
Article En | MEDLINE | ID: mdl-37285111

Ticks attaching to ear canals of humans and animals are the cause of otoacariasis, common in rural areas of Nepal. The plant Clerodendrum viscosum is used in multiple indigenous systems of medicine by ethnic communities in the Indo-Nepali-Malaysian region. Visiting the Chitwan National Park, we learned that in indigenous medicine, flower extract of C. viscosum is utilized to treat digestive disorders and extracts from leaves as tick repellent to prevent ticks from invading or to remove them from the ear canal. The objective of our study was to provide support to indigenous medicine by characterizing the in vivo effect of leave extracts on ticks under laboratory conditions and its phytochemical composition. We collected plant parts of C. viscosum (leaves and flowers) and mango (Mangifera indica) leaves at the Chitwan National Park, previously associated with repellent activity to characterize their effect on Ixodes ricinus ticks by in vivo bioassays. A Q-ToF high-resolution analysis (HPLC-ESI-QToF) was conducted to elucidate phenolic compounds with potential repellent activity. Clerodendrum viscosum and M. indica leaf extracts had the highest tick repellent efficacy (%E = 80-100%) with significant differences when compared to C. viscosum flowers extracts (%E = 20-60%) and phosphate-buffered saline. Phytochemicals with tick repellent function as caffeic acid, fumaric acid and p-coumaric acid glucoside were identified in C. viscosum leaf extracts by HPLC-ESI-QToF, but not in non-repellent flower extracts. These results support the Nepali indigenous medicine application of C. viscosum leaf extracts to repel ticks. Additional research is needed for the development of natural and green repellent formulations to reduce the risks associated with ticks resistant to acaricides.


Acaricides , Clerodendrum , Insect Repellents , Ixodes , Humans , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Clerodendrum/chemistry , Insect Repellents/pharmacology
20.
Phys Rev E ; 107(2-2): 025305, 2023 Feb.
Article En | MEDLINE | ID: mdl-36932491

We present a data-driven approach to learning surrogate models for amplitude equations and illustrate its application to interfacial dynamics of phase field systems. In particular, we demonstrate learning effective partial differential equations describing the evolution of phase field interfaces from full phase field data. We illustrate this on a model phase field system, where analytical approximate equations for the dynamics of the phase field interface (a higher-order eikonal equation and its approximation, the Kardar-Parisi-Zhang equation) are known. For this system, we discuss data-driven approaches for the identification of equations that accurately describe the front interface dynamics. When the analytical approximate models mentioned above become inaccurate, as we move beyond the region of validity of the underlying assumptions, the data-driven equations outperform them. In these regimes, going beyond black box identification, we explore different approaches to learning data-driven corrections to the analytically approximate models, leading to effective gray box partial differential equations.

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