1,994 research outputs found
A CO2 sensing module modulates β-1,3-glucan exposure in Candida albicans.
This work was funded by a program grant to A.J.P.B., N.A.R.G., L.P.E., and M.G.N. from the UK Medical Research Council [www.mrc.ac.uk: MR/M026663/1, MR/M026663/2]. The work was also supported by the Medical Research Council Centre for Medical Mycology [MR/N006364/1, MR/N006364/2], by a grant to C.d.E. from the European Commission [FunHoMic: H2020-MSCA-ITN-2018–812969], and by the Wellcome Trust via Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards [www.wellcome.ac.uk: 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208, 217163, 224323]. Work in the d’Enfert laboratory was supported by grants from the Agence Nationale de Recherche (ANR-10-LABX-62-IBEID) and the Swiss National Science Foundation (Sinergia CRSII5_173863/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD
Using Image Translation To Synthesize Amyloid Beta From Structural MRI
Amyloid-beta and brain atrophy are known hallmarks of Alzheimer’s Disease (AD) and can be quantified with positron emission tomography (PET) and structural magnetic resonance imaging (MRI), respectively. PET uses radiotracers that bind to amyloid-beta, whereas MRI can measure brain morphology. PET scans have limitations including cost, invasiveness (involve injections and ionizing radiation exposure), and have limited accessibility, making PET not practical for screening early-onset AD. Conversely, MRI is a cheaper, less-invasive (free from ionizing radiation), and is more widely available, however, it cannot provide the necessary molecular information. There is a known relationship between amyloid-beta and brain atrophy. This thesis aims to synthesize amyloid-beta PET images from structural MRI using image translation, an advanced form of machine learning. The developed models have reported high-similarity metrics between the real and synthetic PET images and high-degree of accuracy in radiotracer quantification. The results are highly impactful as it enables amyloid-beta measurements form every MRI, for free
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UVSSA regulates transcription-coupled genome maintenance
DNA damage is a constant threat to our genomes which drives genome instability and contributes to cancer progression. DNA damage interferes with important DNA transactions such as transcription and replication. DNA lesions are removed by repair pathways that ensure genome stability during transcription and replication. Here, we identify and characterize distinct roles for the ultra violet stimulated scaffold protein A (UVSSA) in the maintenance of genome stability during transcription in human cells.
First, we unravel a novel function for UVSSA in transcription-coupled repair of DNA interstrand crosslinks (ICLs), genotoxic adducts that covalently bind opposing strands of the DNA and block transcription and replication. UVSSA knockout cells are sensitive to ICL inducing drugs, and UVSSA is specifically required for transcription-coupled repair of ICLs in a fluorescence-based reporter assay. Based on analysis of the UVSSA protein interactome in crosslinker treated cells we propose a model for transcription-coupled ICL repair (TC-ICR) that is initiated by stalling of transcribing RNA polymerase II (Pol II) at an ICL. Stalled Pol II is first bound by CSA and CSB, followed by UVSSA which recruits TFIIH to initiate downstream lesion removal steps.
Second, we establish that UVSSA counteracts MYC dependent transcription stress to promote genome stability in cells aberrantly expressing the cMYC oncogene. UVSSA knockdown sensitizes cells to MYC expression, resulting in synthetic sickness and increased doubling time. UVSSA knockdown impacts Pol II dynamics in MYC activated cells. We conclude that UVSSA is required for regulation of Pol II during MYC induced transcription to prevent transcription stress. Together, these studies expand our understanding of UVSSA’s role in genome stability during transcription and elucidates the poorly understood transcription-coupled ICL repair pathway
Selected Advances of Quantum Biophotonics – a Short Review
This article discusses four fields of study with the potential to revolutionize our understanding and interaction with biological systems: quantum biophotonics, molecular and supramolecular bioelectronics, quantum-based approaches in gaming, and nano-biophotonics. Quantum biophotonics uses photonics, biochemistry, biophysics, and quantum information technologies to study biological systems at the sub-nanoscale level. Molecular and supramolecular bioelectronics aim to develop biosensors for medical diagnosis, environmental monitoring, and food safety by designing materials and devices that interface with biological systems at the molecular level. Quantum-based approaches in gaming improve modeling of complex systems, while nanomedicine enhances disease diagnosis, treatment, and prevention using nanoscale devices and sensors developed with quantum biophotonics. Lastly, nano-biophotonics studies cellular structures and functions with unprecedented resolution
Investigating the early interaction between Mycobacterium avium ssp paratuberculosis and the host using a bovine enteroid system
Mycobacterium avium ssp paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic granulomatous enteritis of ruminant’s prevalent world-wide. Infection of calves occurs through the faecal oral route, typically in animals <6 months old. Animals are asymptomatic for 2-5 years before clinical signs begin to show, which typically present as emaciation and chronic diarrhoea. In the subclinical phase, animals will have decreased milk yield, increased susceptibility to other diseases and decreased feed conversion. This has a severe impact on the farming economy and animal welfare, as affected animals are often prematurely culled.
Infected subclinical animals are extremely difficult to identify but can still act as a source of transmission for the rest of the herd by shedding MAP in their faeces. There is no treatment for JD, and the current diagnostic tests are ineffective. By investigating the initial interaction between MAP and the host at the intestinal lining, a greater understanding of MAP pathogenesis can be gained and better diagnostic and therapeutic targets can be identified.
In this work, proteins expressed on the surface of MAP were assessed for their ability to aid attachment, invasion and intracellular survival in epithelial and phagocytic cells when expressed on the membrane of a non-invasive E. coli host strain. The proteins investigated were encoded by mammalian cell entry (mce) genes, mce1A, mce1D, mce3C and mce4A, which have been implicated in attachment and invasion of epithelial cells by other mycobacteria. Interestingly, E. coli expressing Mce1A had enhanced uptake by phagocytic cells and E. coli expressing Mce1D had enhanced attachment and invasion of epithelial cells, but neither protein conferred this phenotype in both eukaryotic cell types investigated.
To identify key intestinal cell types involved in MAP pathogenesis, bovine intestinal organoids (enteroids) were assessed for their ability to model a MAP infection in a physiologically representative system. Baso-out 3D enteroids, apical-out 3D enteroids and 2D monolayers were created, and the cell types present were compared to bovine intestinal tissue samples using RT-PCR and immunofluorescence microscopy. The models contained the mature epithelial cell types of the intestine including goblet cells, enteroendocrine cells, Paneth cells and enterocytes. 3D baso-out enteroids and 2D
monolayers also contained proliferative cells, but the 3D apical-out enteroids did not and so could not be maintained past 2 weeks of culture.
The models were infected with two strains of MAP over the course of 72 hours, the reference strain K10, and a recent clinical isolate C49. MAP C49 was shown to be present in all three intestinal models in consistently higher numbers than MAP K10, quantified using qPCR of the genomic DNA. This indicates that MAP C49 was better able to infect these models than K10, which may suggest a loss of virulence in MAP K10.
Overall, the data presented has increased our understanding of MAP pathogenesis by emphasising the need for multicellular models which accurately represent the pathogen target cell type/s in vivo and the confirmation of the role of two hypothetical MAP proteins in cellular interactions
MXene nanomaterials in biomedicine: A bibliometric perspective
Purpose: MXene is two-dimensional (2D) nanomaterials that comprise transition metal carbides, nitrides, and carbonitrides. Their unique nanostructure attributes it a special role in medical applications. However, bibliometric studies have not been conducted in this field. Therefore, the aim of the present study was to conduct a bibliometric analysis to evaluate the global scientific output of MXene in biomedical research, explore the current situation of this field in the past years and predicte its research hotpots.Methods: We utilized visual analysis softwares Citespace and Bibliometrix to analyze all relevant documents published in the period of 2011–2022. The bibliometric records were obtained from the Web of Science Core Collection.Results: A total of 1,489 publications were analyzed in this study. We observed that China is the country with the largest number of publications, with Sichuan University being the institution with the highest number of publications in this field. The most publications on MXene medicine research in the past year were found primarily in journals about Chemistry/Materials/Physics. Moreover, ACS Applied Materials and Interfaces was found to be the most productive journal in this field. Co-cited references and keyword cluster analysis revealed that #antibacterial# and #photothermal therapy# are the research focus keyword and burst detection suggested that driven wearable electronics were newly-emergent research hot spots.Conclusion: Our bibliometric analysis indicates that research on MXene medical application remains an active field of study. At present, the research focus is on the application of MXene in the field of antibacterial taking advantage of its photothermal properties. In the future, wearable electronics is the research direction of MXene medical application
Studies on dosimetry of positron emitting radiopharmaceuticals
Positron emission tomography (PET) is a non-invasive method for studying physiological phenomena in a living subject with radiopharmaceuticals. The physical decay of radioactive radiopharmaceuticals induce ionization in subjects, which results in an absorbed dose. Developing a new radiopharmaceutical always raises the question of how much of this substance can we inject into the patient? Administering radioactive substance to patients should always be justified and the potential benefit should outweigh the risk. Determining radiation doses for new positron emitting radiopharmaceuticals is an important part of the benefit-risk assessment of the use of radioactivity.
In this study, the evaluation of radiation doses was conducted using PET imaging technology. Prior to PET/CT scanners, studies were limited to dynamic imaging of just one part of the body (brain, thorax, abdomen or skeletal muscle). However, developments in the performance of PET scanners enabled producing series of whole body PET scans. With this whole body scanning method, more source organs were evaluated per participant and the number of measurements was increased per timepoint with the same number of participants. This produced more precise temporal time-activity-curves for source organs and more precise radiation dose calculations.
Radiation doses were calculated using computer programs that are commonly used in published dosimetry studies. There were updates in the programs during the course of the study as mathematical models of the human anatomy became more sophisticated and coefficients reflecting the harm caused by radiation to tissues became more accurate.
Dosimetry is only one part in development of a new radiopharmaceutical, and based on the results in this thesis these radiopharmaceuticals can be introduced for clinical use from a radiation safety point of view.---
Positroniemissiotomografia (PET) soveltuu hyvin erilaisten fysiologisten ilmiöiden kajoamattomaan kuvantamiseen elävässä kohteessa radiolääkkeiden avulla. Kun radiolääkkeen radioaktiivisuus hajoaa, syntyy ionisoivaa säteilyä, joka aiheuttaa kohteeseen säteilyrasitusta, absorboitunutta annosta. Uuden radiolääkkeen tuottamisen jälkeen herää kysymys, paljonko kyseistä radiolääkettä voi ihmiseen injektoida, jotta sen käyttö olisi oikeutettua ja radioaktiivisuuden käytöstä saatava hyöty olisi sen mahdollisesti aiheuttamaa haittaa suurempi. Säteilyannosten määrittäminen uusille positroneja emittoiville radiolääkkeille on tärkeä osa radioaktiivisuuden käytön hyöty-haitta arviointia.
Tässä tutkimuksessa säteilyannosten arviointiin käytettiin PET-kuvaustekniikkaa. Aluksi tutkimukset toteutettiin yhden kehon osan (aivot, rintakehä, vatsa tai reisilihakset) dynaamisella kuvaamisella, mutta PET-kameroiden suorituskyvyn kehityksen myötä otettiin käyttöön tutkittavan henkilön koko kehon PET kuvaussarja menetelmä. Tämän kehitysaskeleen johdosta voitiin mitata lukumääräisesti samasta koehenkilöiden joukosta useampia lähde-elimien mittausarvoja kussakin mittapisteessä ja laskettiin tarkempi arvio säteilyannoksesta.
Säteilyannokset laskettiin tietokoneohjelmilla, joita käytetään yleisesti tieteellisissä dosimetriajulkaisuissa. Ohjelmassa tapahtui kehitystä tutkimuksen aikana, koska ihmiskehon anatomian matemaattinen malli muuttui ja säteilyn kudoksille aiheuttamaa haittaa kuvastavat kertoimet tarkentuivat.
Säteilyannosten määrittäminen uudelle radiolääkkeelle on yksi osa radiolääkekehitystä. Tässä tutkimuksessa julkaistujen tulosten perusteella säteilyturvallisuuden näkökulmasta nämä radiolääkkeet voitiin ottaa kliiniseen käyttöön
Zinc oxide nanoparticles prepared through microbial mediated synthesis for therapeutic applications: a possible alternative for plants
Zinc oxide nanoparticles (ZnO-NPs) synthesized through biogenic methods have gained significant attention due to their unique properties and potential applications in various biological fields. Unlike chemical and physical approaches that may lead to environmental pollution, biogenic synthesis offers a greener alternative, minimizing hazardous environmental impacts. During biogenic synthesis, metabolites present in the biotic sources (like plants and microbes) serve as bio-reductants and bio-stabilizers. Among the biotic sources, microbes have emerged as a promising option for ZnO-NPs synthesis due to their numerous advantages, such as being environmentally friendly, non-toxic, biodegradable, and biocompatible. Various microbes like bacteria, actinomycetes, fungi, and yeast can be employed to synthesize ZnO-NPs. The synthesis can occur either intracellularly, within the microbial cells, or extracellularly, using proteins, enzymes, and other biomolecules secreted by the microbes. The main key advantage of biogenic synthesis is manipulating the reaction conditions to optimize the preferred shape and size of the ZnO-NPs. This control over the synthesis process allows tailoring the NPs for specific applications in various fields, including medicine, agriculture, environmental remediation, and more. Some potential applications include drug delivery systems, antibacterial agents, bioimaging, biosensors, and nano-fertilizers for improved crop growth. While the green synthesis of ZnO-NPs through microbes offers numerous benefits, it is essential to assess their toxicological effects, a critical aspect that requires thorough investigation to ensure their safe use in various applications. Overall, the presented review highlights the mechanism of biogenic synthesis of ZnO-NPs using microbes and their exploration of potential applications while emphasizing the importance of studying their toxicological effects to ensure a viable and environmentally friendly green strategy
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