Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 735
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 176(4): 816-830.e18, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30595451

RESUMO

The temporal order of DNA replication (replication timing [RT]) is highly coupled with genome architecture, but cis-elements regulating either remain elusive. We created a series of CRISPR-mediated deletions and inversions of a pluripotency-associated topologically associating domain (TAD) in mouse ESCs. CTCF-associated domain boundaries were dispensable for RT. CTCF protein depletion weakened most TAD boundaries but had no effect on RT or A/B compartmentalization genome-wide. By contrast, deletion of three intra-TAD CTCF-independent 3D contact sites caused a domain-wide early-to-late RT shift, an A-to-B compartment switch, weakening of TAD architecture, and loss of transcription. The dispensability of TAD boundaries and the necessity of these "early replication control elements" (ERCEs) was validated by deletions and inversions at additional domains. Our results demonstrate that discrete cis-regulatory elements orchestrate domain-wide RT, A/B compartmentalization, TAD architecture, and transcription, revealing fundamental principles linking genome structure and function.


Assuntos
Período de Replicação do DNA/fisiologia , Replicação do DNA/genética , Replicação do DNA/fisiologia , Animais , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Cromatina , DNA/genética , Período de Replicação do DNA/genética , Células-Tronco Embrionárias , Elementos Facilitadores Genéticos/genética , Mamíferos/genética , Mamíferos/metabolismo , Camundongos , Proteínas Repressoras/metabolismo , Análise Espaço-Temporal
2.
J Neurosci ; 44(9)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38123981

RESUMO

Excessive oscillatory activity across basal ganglia (BG) nuclei in the ß frequencies (12-30 Hz) is a hallmark of Parkinson's disease (PD). While the link between oscillations and symptoms remains debated, exaggerated ß oscillations constitute an important biomarker for therapeutic effectiveness in PD. The neuronal mechanisms of ß-oscillation generation however remain unknown. Many existing models rely on a central role of the subthalamic nucleus (STN) or cortical inputs to BG. Contrarily, neural recordings and optogenetic manipulations in normal and parkinsonian rats recently highlighted the central role of the external pallidum (GPe) in abnormal ß oscillations, while showing that the integrity of STN or motor cortex is not required. Here, we evaluate the mechanisms for the generation of abnormal ß oscillations in a BG network model where neuronal and synaptic time constants, connectivity, and firing rate distributions are strongly constrained by experimental data. Guided by a mean-field approach, we show in a spiking neural network that several BG sub-circuits can drive oscillations. Strong recurrent STN-GPe connections or collateral intra-GPe connections drive γ oscillations (>40 Hz), whereas strong pallidostriatal loops drive low-ß (10-15 Hz) oscillations. We show that pathophysiological strengthening of striatal and pallidal synapses following dopamine depletion leads to the emergence of synchronized oscillatory activity in the mid-ß range with spike-phase relationships between BG neuronal populations in-line with experiments. Furthermore, inhibition of GPe, contrary to STN, abolishes oscillations. Our modeling study uncovers the neural mechanisms underlying PD ß oscillations and may thereby guide the future development of therapeutic strategies.


Assuntos
Doença de Parkinson , Núcleo Subtalâmico , Ratos , Animais , Gânglios da Base/fisiologia , Globo Pálido/fisiologia , Neurônios/fisiologia , Ritmo beta/fisiologia
3.
PLoS Pathog ; 19(12): e1011899, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38150475

RESUMO

Centrins are small calcium-binding proteins that have a variety of roles and are universally associated with eukaryotic centrosomes. Rapid proliferation of the malaria-causing parasite Plasmodium falciparum in the human blood depends on a particularly divergent and acentriolar centrosome, which incorporates several essential centrins. Their precise mode of action, however, remains unclear. In this study calcium-inducible liquid-liquid phase separation is revealed as an evolutionarily conserved principle of assembly for multiple centrins from P. falciparum and other species. Furthermore, the disordered N-terminus and calcium-binding motifs are defined as essential features for reversible biomolecular condensation, and we demonstrate that certain centrins can form co-condensates. In vivo analysis using live cell STED microscopy shows liquid-like dynamics of centrosomal centrin. Additionally, implementation of an inducible protein overexpression system reveals concentration-dependent formation of extra-centrosomal centrin assemblies with condensate-like properties. The timing of foci formation and dissolution suggests that centrin assembly is regulated. This study thereby provides a new model for centrin accumulation at eukaryotic centrosomes.


Assuntos
Cálcio , Parasitos , Animais , Humanos , Cálcio/metabolismo , Parasitos/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Centrossomo/metabolismo
4.
PLoS Pathog ; 19(12): e1011807, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38051755

RESUMO

Malaria is caused by the rapid proliferation of Plasmodium parasites in patients and disease severity correlates with the number of infected red blood cells in circulation. Parasite multiplication within red blood cells is called schizogony and occurs through an atypical multinucleated cell division mode. The mechanisms regulating the number of daughter cells produced by a single progenitor are poorly understood. We investigated underlying regulatory principles by quantifying nuclear multiplication dynamics in Plasmodium falciparum and knowlesi using super-resolution time-lapse microscopy. This confirmed that the number of daughter cells was consistent with a model in which a counter mechanism regulates multiplication yet incompatible with a timer mechanism. P. falciparum cell volume at the start of nuclear division correlated with the final number of daughter cells. As schizogony progressed, the nucleocytoplasmic volume ratio, which has been found to be constant in all eukaryotes characterized so far, increased significantly, possibly to accommodate the exponentially multiplying nuclei. Depleting nutrients by dilution of culture medium caused parasites to produce fewer merozoites and reduced proliferation but did not affect cell volume or total nuclear volume at the end of schizogony. Our findings suggest that the counter mechanism implicated in malaria parasite proliferation integrates extracellular resource status to modify progeny number during blood stage infection.


Assuntos
Malária Falciparum , Malária , Parasitos , Animais , Humanos , Parasitos/fisiologia , Malária Falciparum/parasitologia , Malária/parasitologia , Plasmodium falciparum/fisiologia , Merozoítos/fisiologia , Eritrócitos/parasitologia
5.
J Neurosci ; 43(1): 56-67, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36400530

RESUMO

In rodents, cortical information is transferred to the substantia nigra pars reticulata (SNr) through motor and medial prefrontal (mPF) basal ganglia (BG) circuits implicated in motor and cognitive/motivational behaviors, respectively. The serotonergic 5-HT2A receptors are located in both of these neuronal networks, displaying topographical differences with a high expression in the associative/limbic territories, and a very low expression in the subthalamic nucleus. This study investigated whether the stimulation of 5-HT2A receptors could have a specific signature on the dynamic regulation of BG circuits, preferentially modulating the mPF information processing through trans-striatal pathways. We performed in vivo single-unit extracellular recordings to assess the effect of the 5-HT2A agonist TCB-2 on the spontaneous and cortically evoked activity of lateral and medial SNr neurons in male rats (involved in motor and mPF circuits, respectively). TCB-2 (50-200 µg/kg, i.v.) increased the basal firing rate and enhanced the cortically evoked inhibitory response of medial SNr neurons (transmission through the direct striato-nigral pathway). A prior administration of the preferential 5-HT2A receptor antagonist MDL11939 (200 µg/kg, i.v.) did not modify any electrophysiological parameter, but occluded TCB-2-induced effects. In animals treated with the 5-HT synthesis inhibitor pCPA (4-chloro-dl-phenylalanine methyl ester hydrochloride), TCB-2 failed to induce the above-mentioned effects, thus suggesting the contribution of endogenous 5-HT. However, the mobilization of 5-HT induced by the acute administration of fluoxetine (10 mg/kg, i.p.) did not mimic the effects triggered by TCB-2. Overall, these data suggest that 5-HT2A receptors have a preferential modulatory action on the dynamic regulation of BG circuitry.SIGNIFICANCE STATEMENT Motor and medial prefrontal (mPF) basal ganglia (BG) circuits play an important role in integrative brain functions like movement control or cognitive/motivational behavior, respectively. Although these neuronal networks express 5-HT2A receptors, the expression is higher in associative/limbic structures than in the motor ones. We show a topographical-dependent dissociation in the effects triggered by the 5HT2A agonist TCB-2, which specifically increases the medial substantia nigra pars reticulata neuron activity and has a preferential action on mPF information processing through the striato-nigral direct pathway. These are very likely to be 5-HT2A receptor-mediated effects that require mobilization of the endogenous 5-HT system. These findings provide evidence about the specific signature of 5-HT2A receptors on the dynamic regulation of BG circuits.


Assuntos
Receptor 5-HT2A de Serotonina , Serotonina , Ratos , Masculino , Animais , Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Ratos Sprague-Dawley , Gânglios da Base/fisiologia , Corpo Estriado/fisiologia , Substância Negra/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-39320093

RESUMO

COVID-19 commonly presents as pneumonia, with those most severely affected progressing to respiratory failure. Patient responses to SARS-CoV-2 infection are varied, with comorbidities acting as contributors to varied outcomes. Focusing on one such major comorbidity, we assessed whether pharmacological induction of Type I Diabetes Mellitus (T1DM) would increase the severity of lung injury in a murine model of COVID-19 pneumonia utilizing wild type mice infected with mouse-adapted SARS-CoV-2. Hyperglycemic mice exhibited increased weight loss and reduced blood oxygen saturation in comparison to their euglycemic counterparts, suggesting that these animals indeed experienced more severe lung injury. Transcriptomic analysis revealed a significant impairment of the adaptive immune response in the lungs of diabetic mice compared to those of control. In order to expand the options available for tissue analysis due to biosafety restrictions, we employed a new technique to digest highly fixed tissue into a single cell suspension, originally designed for scRNA-Seq, which we then adapted for flow cytometric analysis. Flow immunophenotyping and scRNA-Seq confirmed impaired recruitment of T cells into the lungs of T1DM animals. Additionally, scRNA-Seq revealed a distinct, highly inflammatory macrophage profile in the diabetic cohort that correlates with the more severe infection these mice experienced clinically, allowing insight into a possible mechanism for this phenomenon. Recognizing the near certainty that respiratory viruses will continue to present significant public health concerns for the foreseeable future, our study provides key insights into how T1DM results in a much more severe infection and identifies possible targets to ameliorate comorbidity-associated severe disease.

7.
Phys Rev Lett ; 132(9): 094002, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489623

RESUMO

We study the statistics of velocity circulation in two-dimensional classical and quantum turbulence. We perform numerical simulations of the incompressible Navier-Stokes and the Gross-Pitaevskii (GP) equations for the direct and inverse cascades. Our GP simulations display clear energy spectra compatible with the double cascade theory of two-dimensional classical turbulence. In the inverse cascade, we found that circulation intermittency in quantum turbulence is the same as in classical turbulence. We compare GP data to Navier-Stokes simulations and experimental data from Zhu et al. [Phys. Rev. Lett. 130, 214001 (2023)PRLTAO0031-900710.1103/PhysRevLett.130.214001]. In the direct cascade, for nearly incompressible GP flows, classical and quantum turbulence circulation displays the same self-similar scaling. When compressibility becomes important, quasishocks generate quantum vortices and the equivalence of quantum and classical turbulence only holds for low-order moments. Our results establish the boundaries of the equivalence between two-dimensional classical and quantum turbulence.

8.
Phys Rev Lett ; 132(9): 093801, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489636

RESUMO

We report the first experimental demonstration of the replica symmetry breaking (RSB) phenomenon in a fiber laser system supporting standard mode-locking (SML) regime. Though theoretically predicted, this photonic glassy phase remained experimentally undisclosed so far. We employ an ytterbium-based mode-locked fiber laser with a very rich phase diagram. Two phase transitions are observed separating three different regimes: cw, quasi-mode-locking (QML), and SML. The regimes are intrinsically related to the distinct dynamics of intensity fluctuations in the laser spectra. We set the connection between the RSB glassy phase with frustrated modes and onset of L-shaped intensity distributions in the QML regime, which impact directly the replica overlap measure.

9.
FASEB J ; 37(8): e23037, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37392372

RESUMO

The striatum is a brain structure involved in the control of voluntary movement. Striatum contains high amounts of retinoic acid, the active metabolite of vitamin A, as well as retinoid receptors, RARß and RXRγ. Previous studies revealed that disruption of retinoid signaling initiated during development is deleterious for striatal physiology and related motor functions. However, the alteration of retinoid signaling, and the importance of vitamin A supply during adulthood on striatal physiology and function has never been established. In the present study, we investigated the impact of vitamin A supply on striatal function. Adult Sprague-Dawley rats were fed with three specific diets, either sub-deficient, sufficient, or enriched in vitamin A (0.4, 5, and 20 international units [IU] of retinol per g of diet, respectively) for 6 months. We first validated that vitamin A sub-deficient diet in adult rats constitutes a physiological model of retinoid signaling reduction in the striatum. We then revealed subtle alterations of fine motor skills in sub-deficient rats using a new behavioral apparatus specifically designed to test forepaw reach-and-grasp skills relying on striatal function. Finally, we showed using qPCR analysis and immunofluorescence that the striatal dopaminergic system per se was not affected by vitamin A sub-deficiency at adult age. Rather, cholinergic synthesis in the striatum and µ-opioid receptor expression in striosomes sub-territories were the most affected by vitamin A sub-deficiency starting at adulthood. Taken together these results revealed that retinoid signaling alteration at adulthood is associated with motor learning deficits together with discrete neurobiological alterations in the striatum.


Assuntos
Corpo Estriado , Vitamina A , Ratos , Animais , Ratos Sprague-Dawley , Retinoides , Dieta
10.
Inorg Chem ; 63(18): 8131-8141, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38639743

RESUMO

Mixed metal oxyhalides are an exciting class of photocatalysts, capable of the sustainable generation of fuels and remediation of pollutants with solar energy. Bismuth oxyhalides of the types Bi4MO8X (M = Nb and Ta; X = Cl and Br) and Bi2AO4X (A = most lanthanides; X = Cl, Br, and I) have an electronic structure that imparts photostability, as their valence band maxima (VBM) are composed of O 2p orbitals rather than X np orbitals that typify many other bismuth oxyhalides. Here, flux-based synthesis of intergrowth Bi4NbO8Cl-Bi2GdO4Cl is reported, testing the hypothesis that both intergrowth stoichiometry and M identity serve as levers toward tunable optoelectronic properties. X-ray scattering and atomically resolved electron microscopy verify intergrowth formation. Facile manipulation of the Bi4NbO8Cl-to-Bi2GdO4Cl ratio is achieved with the specific ratio influencing both the crystal and electronic structures of the intergrowths. This compositional flexibility and crystal structure engineering can be leveraged for photocatalytic applications, with comparisons to the previously reported Bi4TaO8Cl-Bi2GdO4Cl intergrowth revealing how subtle structural and compositional features can impact photocatalytic materials.

11.
Sensors (Basel) ; 24(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38474913

RESUMO

The field of learning-based navigation for mobile robots is experiencing a surge of interest from research and industry sectors. The application of this technology for visual aircraft inspection tasks within a maintenance, repair, and overhaul (MRO) hangar necessitates efficient perception and obstacle avoidance capabilities to ensure a reliable navigation experience. The present reliance on manual labour, static processes, and outdated technologies limits operation efficiency in the inherently dynamic and increasingly complex nature of the real-world hangar environment. The challenging environment limits the practical application of conventional methods and real-time adaptability to changes. In response to these challenges, recent years research efforts have witnessed advancement with machine learning integration aimed at enhancing navigational capability in both static and dynamic scenarios. However, most of these studies have not been specific to the MRO hangar environment, but related challenges have been addressed, and applicable solutions have been developed. This paper provides a comprehensive review of learning-based strategies with an emphasis on advancements in deep learning, object detection, and the integration of multiple approaches to create hybrid systems. The review delineates the application of learning-based methodologies to real-time navigational tasks, encompassing environment perception, obstacle detection, avoidance, and path planning through the use of vision-based sensors. The concluding section addresses the prevailing challenges and prospective development directions in this domain.

12.
Sensors (Basel) ; 24(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38610473

RESUMO

The integration of machine learning and robotics brings promising potential to tackle the application challenges of mobile robot navigation in industries. The real-world environment is highly dynamic and unpredictable, with increasing necessities for efficiency and safety. This demands a multi-faceted approach that combines advanced sensing, robust obstacle detection, and avoidance mechanisms for an effective robot navigation experience. While hybrid methods with default robot operating system (ROS) navigation stack have demonstrated significant results, their performance in real time and highly dynamic environments remains a challenge. These environments are characterized by continuously changing conditions, which can impact the precision of obstacle detection systems and efficient avoidance control decision-making processes. In response to these challenges, this paper presents a novel solution that combines a rapidly exploring random tree (RRT)-integrated ROS navigation stack and a pre-trained YOLOv7 object detection model to enhance the capability of the developed work on the NAV-YOLO system. The proposed approach leveraged the high accuracy of YOLOv7 obstacle detection and the efficient path-planning capabilities of RRT and dynamic windows approach (DWA) to improve the navigation performance of mobile robots in real-world complex and dynamically changing settings. Extensive simulation and real-world robot platform experiments were conducted to evaluate the efficiency of the proposed solution. The result demonstrated a high-level obstacle avoidance capability, ensuring the safety and efficiency of mobile robot navigation operations in aviation environments.

13.
J Oral Rehabil ; 51(7): 1109-1112, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38475861

RESUMO

OBJECTIVE: The objective of this commentary is to advocate for a holistic, ontology-based definition of bruxism. The intention is to synthesise the best aspects of current definitions into a structured ontological model, thereby refining and enhancing a comprehensive understanding of the full spectrum of bruxism. MATERIALS AND METHODS: The commentary elaborates on the process of integrating these insights into a hierarchical ontology that aligns with ontological principles. SETTINGS AND SAMPLE POPULATION: Not directly applicable as this is a commentary. RESULTS/CONCLUSION: The proposed ontology-based definition of bruxism aims to clarify communication within the medical community and advance research by enabling a comprehensive ontology-based classification of bruxism. By aligning with ontological principles, this approach aspires to act as a catalyst for further research, discussion and consensus in the field.


Assuntos
Bruxismo , Semântica , Terminologia como Assunto , Humanos , Ontologias Biológicas , Saúde Holística
14.
Can Vet J ; 65(9): 886-893, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39219609

RESUMO

A 15-month-old spayed female greater Swiss mountain dog was brought to our clinic because of relapsing episodes of urinary tract infection, present since her adoption at 2 mo of age. A diagnosis of chronic bacterial cystitis associated with an invasive, biofilm-forming uropathogenic Escherichia coli was made with bladder-wall histology and fluorescent in situ hybridization analysis. Local treatment with EDTA-tromethamine (EDTA-Tris) infusions along with parenteral cefquinome and prophylactic measures (Type-A proanthocyanidins and probiotics) coincided with clinical and bacterial remission. The dog has been free of clinical signs of urinary tract infection for >4 y. Biofilm-forming uropathogenic E. coli can cause chronic, recurrent cystitis due to low antibiotic efficacy and should be considered in cases of recurrent cystitis in dogs, especially in the absence of identified predisposing factors. This case report describes the diagnostic and therapeutic options that were used to manage a case of this type. Key clinical message: Fluorescent in situ hybridization analysis may be considered in the diagnosis of chronic bacterial cystitis in dogs, and intravesical instillations of EDTA-Tris may be helpful in managing such cases.


Traitement adjuvant intravésical avec de l'EDTA-trométhamine chez un chien présentant une cystite récurrente à Escherichia coli formant des biofilmsUne chienne grand bouvier suisse stérilisée de 15 mois nous a été présentée pour des épisodes d'infection du tractus urinaire récidivants depuis son adoption à l'âge de 2 mois. Une cystite bactérienne chronique associée à un Escherichia coli uropathogène formant des biofilms a été identifiée par l'examen histologique de la paroi vésicale et par hybridation in situ fluorescente. Des instillations intravésicales d'EDTA et trométhamine (EDTA-Tris) en complément d'une antibiothérapie parentérale de courte durée (cefquinome) et de mesures prophylactiques (proanthocyanidines de type A et probiotiques) ont permis une guérison clinique et bactériologique de la cystite pendant plus de 4 ans. Les infections par Escherichia coli formant des biofilms peuvent causer des cystites chroniques récurrentes dues à une faible efficacité des antibiotiques et doivent être incluses dans le diagnostic différentiel des cystites récurrentes chez le chien, particulièrement en l'absence d'autre facteur prédisposant. Ce rapport propose des stratégies diagnostiques et thérapeutiques ayant permis la prise en charge d'un de ces cas.Message clinique clé :L'analyse par hybridation in situ fluorescente peut être envisagé dans le diagnostic de cystite bactérienne chronique chez les chiens, et l'instillation intravésicale d'EDTA-Tris peut être utile dans la gestion de tels cas.(Traduit par les auteurs).


Assuntos
Antibacterianos , Biofilmes , Cistite , Doenças do Cão , Ácido Edético , Infecções por Escherichia coli , Cães , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/microbiologia , Feminino , Cistite/veterinária , Cistite/tratamento farmacológico , Cistite/microbiologia , Ácido Edético/uso terapêutico , Ácido Edético/administração & dosagem , Biofilmes/efeitos dos fármacos , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Administração Intravesical , Escherichia coli/efeitos dos fármacos , Recidiva
15.
Microcirculation ; 30(5-6): e12820, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392132

RESUMO

OBJECTIVE: Recent advances in tissue clearing and high-throughput imaging have enabled the acquisition of extended-volume microvasculature images at a submicron resolution. The objective of this study was to extract information from this type of images by integrating a sequence of 3D image processing steps on Terabyte scale datasets. METHODS: We acquired coronary microvasculature images throughout an entire short-axis slice of a 3-month-old Wistar-Kyoto rat heart. This dataset covered 13 × 10 × 0.6 mm at a resolution of 0.933 × 0.933 × 1.866 µm and occupied 700 Gigabytes of disk space. We used chunk-based image segmentation, combined with an efficient graph generation technique, to quantify the microvasculature in the large-scale images. Specifically, we focused on the microvasculature with a vessel diameter up to 15 µm. RESULTS: Morphological data for the complete short-axis ring were extracted within 16 h using this pipeline. From the analyses, we identified that microvessel lengths in the rat coronary microvasculature varied from 6 to 300 µm. However, their distribution was heavily skewed toward shorter lengths, with a mode of 16.5 µm. In contrast, vessel diameters ranged from 3 to 15 µm and had an approximately normal distribution of 6.5 ± 2 µm. CONCLUSION: The tools and techniques from this study will serve other investigations into the microcirculation, and the wealth of data from this study will enable the analysis of biophysical mechanisms using computer models.

16.
Bioinformatics ; 38(11): 3099-3105, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35438129

RESUMO

MOTIVATION: High parameter histological techniques have allowed for the identification of a variety of distinct cell types within an image, providing a comprehensive overview of the tissue environment. This allows the complex cellular architecture and environment of diseased tissue to be explored. While spatial analysis techniques have revealed how cell-cell interactions are important within the disease pathology, there remains a gap in exploring changes in these interactions within the disease process. Specifically, there are currently few established methods for performing inference on cell-type co-localization changes across images, hindering an understanding of how cellular environments change with a disease pathology. RESULTS: We have developed the spicyR R package to perform inference on changes in the spatial co-localization of types across groups of images. Application to simulated data demonstrates a high sensitivity and specificity. We the utility of spicyR by applying it to a type 1 diabetes imaging mass cytometry dataset, revealing changes in cellular associations that were relevant to the disease progression. Ultimately, spicyR allows changes in cellular environments to be explored under different pathologies or disease states. AVAILABILITY AND IMPLEMENTATION: R package is freely available at http://bioconductor.org/packages/release/bioc/html/spicyR.html and shiny app implementation at http://shiny.maths.usyd.edu.au/spicyR/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Software , Análise Espacial
17.
Cytometry A ; 103(7): 593-599, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36879360

RESUMO

Highly multiplexed in situ imaging cytometry assays have made it possible to study the spatial organization of numerous cell types simultaneously. We have addressed the challenge of quantifying complex multi-cellular relationships by proposing a statistical method which clusters local indicators of spatial association. Our approach successfully identifies distinct tissue architectures in datasets generated from three state-of-the-art high-parameter assays demonstrating its value in summarizing the information-rich data generated from these technologies.


Assuntos
Citometria por Imagem , Análise Espacial
18.
Phys Rev Lett ; 130(19): 190401, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37243652

RESUMO

We propose a novel spatially inhomogeneous setup for revealing quench-induced fractionalized excitations in entanglement dynamics. In this quench-probe setting, the region undergoing a quantum quench is tunnel coupled to a static region, the probe. Subsequently, the time-dependent entanglement signatures of a tunable subset of excitations propagating to the probe are monitored by energy selectivity. We exemplify the power of this generic approach by identifying a unique dynamical signature associated with the presence of an isolated Majorana zero mode in the postquench Hamiltonian. In this case excitations emitted from the topological part of the system give rise to a fractionalized jump of log(2)/2 in the entanglement entropy of the probe. This dynamical effect is highly sensitive to the localized nature of the Majorana zero mode, but does not require the preparation of a topological initial state.

19.
Inorg Chem ; 62(32): 13021-13029, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37537143

RESUMO

Manganese dioxide is a good candidate for effective energy storage and conversion as it possesses rich electrochemistry. The compound also shows a wide polymorphism. The γ-variety, an intergrowth of ß- and R-MnO2, has been extensively studied in several types of batteries (e.g., Zn/MnO2, Li-ion) and is a common electrode material for commercial batteries. It is well known that the insertion of protons thermodynamically stabilizes γ-MnO2 with respect to ß-MnO2. Protons can enter the structure either by forming groups of 4 hydroxyls around a Mn4+ vacancy, called a Ruetschi defect, or by forming a hydroxyl group near a Mn3+ ion, called a Coleman defect. These defects differently affect the electrochemistry of manganese oxide, and tailoring their amount in the structure can be used to tune the material properties. Previous studies have addressed the proton insertion process, but the role of the synthesis pathway on the amount of defects created is not well understood. We here investigate how the parameters in a hydrothermal synthesis of γ-MnO2 nanoparticles influence the amount and type of H-related defects. Structural investigations are carried out using Pair Distribution Function analysis, X-ray absorption spectroscopy, thermogravimetric analysis, and inelastic neutron scattering. We demonstrate the possibility to control the amount and type of defects introduced during the synthesis. While the amount of Ruetschi defects increases with synthesis temperature, it decreases with extended synthesis time, along with the amount of Coleman defects. Moreover, we discuss the arrangement of the defects in the γ-MnO2 nanoparticles.

20.
Environ Sci Technol ; 57(20): 7818-7827, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37172312

RESUMO

Contamination of the environment by pesticide residues is a growing concern given their widespread presence in the environment and their effects on ecosystems. Only a few studies have addressed the occurrence of pesticides in soils, and their results highlighted the need for further research on the persistence and risks induced by those substances. We monitored 111 pesticide residues (48 fungicides, 36 herbicides, 25 insecticides and/or acaricides, and two safeners) in 47 soils sampled across France under various land uses (arable lands, vineyards, orchards, forests, grasslands, and brownfields). Pesticides were found in 98% of the sites (46 of the 47 sampled), including untreated areas such as organic fields, forests, grasslands, and brownfields, with up to 33 different substances detected in one sample, mostly fungicides and herbicides. The concentrations of herbicides were the highest in soils with glyphosate, and its transformation product, AMPA, contributed 70% of the cumulative herbicides. Risk assessment underlined a moderate to high risk for earthworms in arable soils mostly attributed to insecticides and/or acaricides. Finally, the comparison with pesticide application by farmers underlines the presence of some residues long after their supposed 90% degradation and at concentrations higher than predicted environmental concentrations, leading to questions their real persistence in soils.


Assuntos
Acaricidas , Fungicidas Industriais , Herbicidas , Inseticidas , Resíduos de Praguicidas , Praguicidas , Poluentes do Solo , Resíduos de Praguicidas/análise , Solo/química , Agricultura , Fungicidas Industriais/análise , Ecossistema , Monitoramento Ambiental , Praguicidas/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA