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1.
Am J Hum Genet ; 110(2): 251-272, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36669495

RESUMO

For neurodevelopmental disorders (NDDs), a molecular diagnosis is key for management, predicting outcome, and counseling. Often, routine DNA-based tests fail to establish a genetic diagnosis in NDDs. Transcriptome analysis (RNA sequencing [RNA-seq]) promises to improve the diagnostic yield but has not been applied to NDDs in routine diagnostics. Here, we explored the diagnostic potential of RNA-seq in 96 individuals including 67 undiagnosed subjects with NDDs. We performed RNA-seq on single individuals' cultured skin fibroblasts, with and without cycloheximide treatment, and used modified OUTRIDER Z scores to detect gene expression outliers and mis-splicing by exonic and intronic outliers. Analysis was performed by a user-friendly web application, and candidate pathogenic transcriptional events were confirmed by secondary assays. We identified intragenic deletions, monoallelic expression, and pseudoexonic insertions but also synonymous and non-synonymous variants with deleterious effects on transcription, increasing the diagnostic yield for NDDs by 13%. We found that cycloheximide treatment and exonic/intronic Z score analysis increased detection and resolution of aberrant splicing. Importantly, in one individual mis-splicing was found in a candidate gene nearly matching the individual's specific phenotype. However, pathogenic splicing occurred in another neuronal-expressed gene and provided a molecular diagnosis, stressing the need to customize RNA-seq. Lastly, our web browser application allowed custom analysis settings that facilitate diagnostic application and ranked pathogenic transcripts as top candidates. Our results demonstrate that RNA-seq is a complementary method in the genomic diagnosis of NDDs and, by providing accessible analysis with improved sensitivity, our transcriptome analysis approach facilitates wider implementation of RNA-seq in routine genome diagnostics.


Assuntos
Perfilação da Expressão Gênica , Transtornos do Neurodesenvolvimento , Humanos , RNA-Seq , Cicloeximida , Análise de Sequência de RNA/métodos , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética
2.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37544661

RESUMO

With the development of chromosome conformation capture technology, the genome-wide investigation of higher-order chromatin structure by using high-throughput chromatin conformation capture (Hi-C) technology is emerging as an important component for understanding the mechanism of gene regulation. Considering genetic and epigenetic differences are typically used to explore the pathological reasons on the chromosome and gene level, visualizing multi-omics data and performing an intuitive analysis by using an interactive browser become a powerful and welcomed way. In this paper, we develop an effective sequence and chromatin interaction data display browser called HiBrowser for visualizing and analyzing Hi-C data and their associated genetic and epigenetic annotations. The advantages of HiBrowser are flexible multi-omics navigation, novel multidimensional synchronization comparisons and dynamic interaction system. In particular, HiBrowser first provides an out of the box web service and allows flexible and dynamic reconstruction of custom annotation tracks on demand during running. In order to conveniently and intuitively analyze the similarities and differences among multiple samples, such as visual comparisons of normal and tumor tissue samples, and pan genomes of multiple (consanguineous) species, HiBrowser develops a clone mode to synchronously display the genome coordinate positions or the same regions of multiple samples on the same page of visualization. HiBrowser also supports a pluralistic and precise search on correlation data of distal cis-regulatory elements and navigation to any region on Hi-C heatmap of interest according to the searching results. HiBrowser is a no-build tool, and could be easily deployed in local server. The source code is available at https://github.com/lyotvincent/HiBrowser.


Assuntos
Visualização de Dados , Software , Genoma , Cromossomos , Cromatina
3.
Proteomics ; 24(14): e2300431, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38468111

RESUMO

SWATH is a data acquisition strategy acclaimed for generating quantitatively accurate and consistent measurements of proteins across multiple samples. Its utility for proteomics studies in nonlaboratory animals, however, is currently compromised by the lack of sufficiently comprehensive and reliable public libraries, either experimental or predicted, and relevant platforms that support their sharing and utilization in an intuitive manner. Here we describe the development of the Veterinary Proteome Browser, VPBrowse (http://browser.proteo.cloud/), an on-line platform for genome-based representation of the Bos taurus proteome, which is equipped with an interactive database and tools for searching, visualization, and building quantitative mass spectrometry assays. In its current version (VPBrowse 1.0), it contains high-quality fragmentation spectra acquired on QToF instrument for over 36,000 proteotypic peptides, the experimental evidence for over 10,000 proteins. Data can be downloaded in different formats to enable analysis using popular software packages for SWATH data processing whilst normalization to iRT scale ensures compatibility with diverse chromatography systems. When applied to published blood plasma dataset from the biomarker discovery study, the resource supported label-free quantification of additional proteins not reported by the authors previously including PSMA4, a tissue leakage protein and a promising candidate biomarker of animal's response to dehorning-related injury.


Assuntos
Proteoma , Proteômica , Software , Espectrometria de Massas em Tandem , Bovinos , Animais , Espectrometria de Massas em Tandem/métodos , Proteômica/métodos , Proteoma/análise , Bases de Dados de Proteínas , Genoma/genética
4.
BMC Bioinformatics ; 25(1): 277, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192184

RESUMO

Over the past two decades, scientists have increasingly realized the importance of the three-dimensional (3D) genome organization in regulating cellular activity. Hi-C and related experiments yield 2D contact matrices that can be used to infer 3D models of chromosome structure. Visualizing and analyzing genomes in 3D space remains challenging. Here, we present ARGV, an augmented reality 3D Genome Viewer. ARGV contains more than 350 pre-computed and annotated genome structures inferred from Hi-C and imaging data. It offers interactive and collaborative visualization of genomes in 3D space, using standard mobile phones or tablets. A user study comparing ARGV to existing tools demonstrates its benefits.


Assuntos
Realidade Aumentada , Genoma , Imageamento Tridimensional/métodos , Software , Humanos , Genômica/métodos
5.
BMC Genomics ; 25(1): 405, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658835

RESUMO

Graph-based pangenome is gaining more popularity than linear pangenome because it stores more comprehensive information of variations. However, traditional linear genome browser has its own advantages, especially the tremendous resources accumulated historically. With the fast-growing number of individual genomes and their annotations available, the demand for a genome browser to visualize genome annotation for many individuals together with a graph-based pangenome is getting higher and higher. Here we report a new pangenome browser PPanG, a precise pangenome browser enabling nucleotide-level comparison of individual genome annotations together with a graph-based pangenome. Nine rice genomes with annotations were provided by default as potential references, and any individual genome can be selected as the reference. Our pangenome browser provides unprecedented insights on genome variations at different levels from base to gene, and reveals how the structures of a gene could differ for individuals. PPanG can be applied to any species with multiple individual genomes available and it is available at https://cgm.sjtu.edu.cn/PPanG .


Assuntos
Genômica , Genômica/métodos , Oryza/genética , Anotação de Sequência Molecular , Genoma de Planta , Variação Genética , Software , Navegador , Bases de Dados Genéticas , Nucleotídeos/genética , Genoma
6.
Sensors (Basel) ; 24(20)2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39460240

RESUMO

This study introduces an integrated computational environment that leverages Brain-Computer Interface (BCI) technology to enhance information access for individuals with severe disabilities. Traditional assistive technologies often rely on physical interactions, which can be challenging for this demographic. Our innovation focuses on creating new assistive technologies that use novel Human-Computer interfaces to provide a more intuitive and accessible experience. The proposed system offers four key applications to users controlled by four thoughts: an email client, a web browser, an e-learning tool, and both command-line and graphical user interfaces for managing computer resources. The BCI framework translates ElectroEncephaloGraphy (EEG) signals into commands or events using advanced signal processing and machine learning techniques. These identified commands are then processed by an integrative strategy that triggers the appropriate actions and provides real-time feedback on the screen. Our study shows that our framework achieved an 82% average classification accuracy using four distinct thoughts of 62 subjects and a 95% recognition rate for P300 signals from two users, highlighting its effectiveness in translating brain signals into actionable commands. Unlike most existing prototypes that rely on visual stimulation, our system is controlled by thought, inducing brain activity to manage the system's Application Programming Interfaces (APIs). It switches to P300 mode for a virtual keyboard and text input. The proposed BCI system significantly improves the ability of individuals with severe disabilities to interact with various applications and manage computer resources. Our approach demonstrates superior performance in terms of classification accuracy and signal recognition compared to existing methods.


Assuntos
Interfaces Cérebro-Computador , Pessoas com Deficiência , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Pessoas com Deficiência/reabilitação , Processamento de Sinais Assistido por Computador , Aprendizado de Máquina , Interface Usuário-Computador , Masculino , Adulto , Feminino , Potenciais Evocados P300/fisiologia , Tecnologia Assistiva
7.
Behav Res Methods ; 56(2): 690-708, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36800108

RESUMO

A lack of self-control has long been theorized to predict an individual's likelihood to engage in antisocial behaviors. However, existing definitions of self-control encompass multiple psychological constructs and lab-based measures of aggression have not allowed for the examination of aggression upon provocation where self-control is needed most. We introduce two versions of a novel paradigm, the Retaliate or Carry-on: Reactive AGgression Experiment (RC-RAGE) to fill this methodological gap. Using large online samples of US adults (N = 354 and N = 366), we evaluate to what extent dispositional impulsivity, self-control, aggression, and state anger contribute to aggression upon provocation when there is a financial cost involved. Results showed that costly retaliation on this task was related to trait aggression and being in an angry emotional state, but not related to social desirability. Importantly, we show that the tendency to act impulsively is a better predictor of costly retaliation than other forms of self-control, such as the ability to delay gratification, resist temptation, or plan ahead. As a browser-based task, the RC-RAGE provides a tool for the future investigation of reactive aggression in a variety of experimental settings.


Assuntos
Agressão , Ira , Adulto , Humanos , Agressão/psicologia , Emoções , Comportamento Impulsivo
8.
BMC Bioinformatics ; 24(1): 174, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37106333

RESUMO

We describe POInTbrowse, a web portal that gives access to the orthology inferences made for polyploid genomes with POInT, the Polyploidy Orthology Inference Tool. Ancient, or paleo-, polyploidy events are widely distributed across the eukaryotic phylogeny, and the combination of duplicated and lost duplicated genes that these polyploidies produce can confound the identification of orthologous genes between genomes. POInT uses conserved synteny and phylogenetic models to infer orthologous genes between genomes with a shared polyploidy. It also gives confidence estimates for those orthology inferences. POInTbrowse gives both graphical and query-based access to these inferences from 12 different polyploidy events, allowing users to visualize genomic regions produced by polyploidies and perform batch queries for each polyploidy event, downloading genes trees and coding sequences for orthologous genes meeting user-specified criteria. POInTbrowse and the associated data are online at https://wgd.statgen.ncsu.edu .


Assuntos
Genoma , Genômica , Humanos , Sintenia , Filogenia , Poliploidia , Evolução Molecular
9.
Int J Med Microbiol ; 313(6): 151591, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38043216

RESUMO

Listeria monocytogenes is a Gram positive foodborne pathogen that regularly causes outbreaks of systemic infectious diseases. The bacterium maintains a facultative intracellular lifestyle; it thrives under a variety of environmental conditions and is able to infect human host cells. L. monocytogenes is genetically tractable and therefore has become an attractive model system to study the mechanisms employed by facultative intracellular bacteria to invade eukaryotic cells and to replicate in their cytoplasm. Besides its importance for basic research, L. monocytogenes also serves as a paradigmatic pathogen in genomic epidemiology, where the relative stability of its genome facilitates successful outbreak detection and elucidation of transmission chains in genomic pathogen surveillance systems. In both terms, it is necessary to keep the annotation of the L. monocytogenes genome up to date. Therefore, we have created the database ListiWiki (http://listiwiki.uni-goettingen.de/) which stores comprehensive information on the widely used L. monocytogenes reference strain EDG-e. ListiWiki is designed to collect information on genes, proteins and RNAs and their relevant functional characteristics, but also further information such as mutant phenotypes, available biological material, and publications. In its present form, ListiWiki combines the most recent annotation of the EDG-e genome with published data on gene essentiality, gene expression and subcellular protein localization. ListiWiki also predicts protein-protein interactions networks based on protein homology to Bacillus subtilis proteins, for which detailed interaction maps have been compiled in the sibling database SubtiWiki. Furthermore, crystallographic information of proteins is made accessible through integration of Protein Structure Database codes and AlphaFold structure predictions. ListiWiki is an easy-to-use web interface that has been developed with a focus on an intuitive access to all information. Use of ListiWiki is free of charge and its content can be edited by all members of the scientific community after registration. In our labs, ListiWiki has already become an important and easy to use tool to quickly access genome annotation details that we can keep updated with advancing knowledge. It also might be useful to promote the comprehensive understanding of the physiology and virulence of an important human pathogen.


Assuntos
Listeria monocytogenes , Listeriose , Humanos , Listeria monocytogenes/genética , Genes Bacterianos , Mapas de Interação de Proteínas , Genômica , Listeriose/epidemiologia , Proteínas de Bactérias/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-37595882

RESUMO

Ruminants differ in the pattern how small particles and liquids pass through their gastrointestinal tract, and in particular their reticulorumen (RR). Based on that they may be classified into 'moose-type' and 'cattle-type' species (smaller and larger differences between particle and liquid passage, respectively). The ratio between the retention of particles and fluids is called the 'selectivity factor' (SF) and is a species-specific characteristic, studied in tragulids, giraffids and bovids, but not in many cervid species. Recently, it has been suggested that a high SF might also serve to wash digesta clean of external abrasives prior to regurgitation for rumination. In this study, we measured SF and passage kinetics (using a liquid marker and markers of different particle size, fed with the diet) in a capreoline deer, the southern pudu (Pudu puda, n = 5, 10.3 ± 2.9 kg, kept at two zoos) and a cervine deer, the Reeves's muntjac (Muntiacus reevesi, n = 6, 11.0 ± 1.7 kg, kept at a research facility). The relative daily dry matter intake (38 ± 3 g/kg0.75 for pudu and 76 ± 5 g/kg0.75 for muntjac) was higher, and the mean retention times (MRT) correspondingly shorter (e.g., MRT small particles in the total digestive tract 39 ± 8 h for pudu and 15 ± 2 h for muntjac), in the muntjac. The SF for small particles/liquid in the reticulorumen were, however, similar for both species, at 1.47 ± 0.21 for pudu and 1.66 ± 0.20 for muntjac, indicating a 'moose-type' physiology for both, irrespective of their different phylogenetic origin. To date, SF recorded in bovids attain distinctively higher values than the few reported for cervids. This situation reflects the degree of hypsodonty (tooth crown height) attained by these taxa, which is higher in bovids than in cervids. Together, constraints in hypsodonty as well as SF might limit cervids to more mesic habitats without distinct loads of external abrasives (such as dust or grit) on their food. In both species, some animals showed the typical ruminant pattern of a longer MRT for large than for small particle markers, but in some animals, this difference was not evident. This may be due to variable degrees of marker chewing during ingestion.


Assuntos
Cervos , Cervo Muntjac , Bovinos , Animais , Filogenia , Especificidade da Espécie , Alimentos
11.
Sensors (Basel) ; 23(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36991796

RESUMO

The urgent need to protect user privacy and security has emerged as the World Wide Web has become an increasingly necessary part of daily life. Browser fingerprinting is a very interesting topic in the industry of technology security. New technology will always raise new security issues and browser fingerprinting will undoubtedly follow the same process. It has become one of the most popular topics in online privacy because, to date, there is still no exact solution as to how to stop it entirely. The majority of solutions just aim to reduce the likelihood of obtaining a browser fingerprint. Research on browser fingerprinting is unquestionably required since it is essential to educate users, developers, policymakers, and law enforcement about it so that they can make strategic choices based on knowledge. Browser fingerprinting must be recognised in order to defend against privacy problems. A browser fingerprint is described as data gathered by the receiving server to identify a distant device, and it is different from cookies. Websites frequently utilize browser fingerprinting to obtain information about the type and version of the browser, as well as the operating system, and other current settings. It has been known that even when cookies are disabled, fingerprints can be used to fully or partially identify users or devices. In this communication paper, a new insight into the challenge of browser fingerprint is encouraged as a new venture. Thus, the initial way to truly understand the browser fingerprint is the need to collect browser fingerprints. In this work, the process of data collection for browser fingerprinting through scripting, to offer a complete all-in-one fingerprinting test suite, has been thoughtfully divided into appropriate sections and grouped with key information to be carried out. The objective is to gather fingerprint data with no personal identification information and make it an open source of raw datasets in the industry for any future research purposes. To our best knowledge, there are no open datasets made available for browser fingerprints in the research field. The dataset will be widely accessible by anyone interested in obtaining those data. The dataset collected will be very raw and will be in the form of a text file. Thus, the main contribution of this work is to share an open dataset of browser fingerprints along with its collection methodology.

12.
Behav Res Methods ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620744

RESUMO

The COVID-19 pandemic massively changed the context and feasibility of developmental research. This new reality, as well as considerations about sample diversity and naturalistic settings for developmental research, highlights the need for solutions for online studies. In this article, we present e-Babylab, an open-source browser-based tool for unmoderated online studies targeted for young children and babies. e-Babylab offers an intuitive graphical user interface for study creation and management of studies, users, participant data, and stimulus material, with no programming skills required. Various kinds of audiovisual media can be presented as stimuli, and possible measures include webcam recordings, audio recordings, key presses, mouse-click/touch coordinates, and reaction times. An additional feature of e-Babylab is the possibility to administer short adaptive versions of MacArthur-Bates Communicative Development Inventories (Chai et al. Journal of Speech, Language, and Hearing Research, 63, 3488-3500, 2020). Information pages, consent forms, and participant forms are customizable. e-Babylab has been used with a variety of measures and paradigms in over 12 studies with children aged 12 months to 8 years (n = 1516). We briefly summarize some results of these studies to demonstrate that data quality, participant engagement, and overall results are comparable between laboratory and online settings. Finally, we discuss helpful tips for using e-Babylab and present plans for upgrades.

13.
Appl Intell (Dordr) ; 53(12): 15923-15945, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36466774

RESUMO

Machine learning and deep learning models are commonly developed using programming languages such as Python, C++, or R and deployed as web apps delivered from a back-end server or as mobile apps installed from an app store. However, recently front-end technologies and JavaScript libraries, such as TensorFlow.js, have been introduced to make machine learning more accessible to researchers and end-users. Using JavaScript, TensorFlow.js can define, train, and run new or existing, pre-trained machine learning models entirely in the browser from the client-side, which improves the user experience through interaction while preserving privacy. Deep learning models deployed on front-end browsers must be small, have fast inference, and ideally be interactive in real-time. Therefore, the emphasis on development and deployment is different. This paper aims to review the development and deployment of these deep-learning web apps to raise awareness of the recent advancements and encourage more researchers to take advantage of this technology for their own work. First, the rationale behind the deployment stack (front-end, JavaScript, and TensorFlow.js) is discussed. Then, the development approach for obtaining deep learning models that are optimized and suitable for front-end deployment is then described. The article also provides current web applications divided into seven categories to show deep learning potential on the front end. These include web apps for deep learning playground, pose detection and gesture tracking, music and art creation, expression detection and facial recognition, video segmentation, image and signal analysis, healthcare diagnosis, recognition, and identification.

14.
Hum Mutat ; 43(8): 998-1011, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35088925

RESUMO

The UCSC Genome Browser has been an important tool for genomics and clinical genetics since the sequence of the human genome was first released in 2000. As it has grown in scope to display more types of data it has also grown more complicated. The data, which are dispersed at many locations worldwide, are collected into one view on the Browser, where the graphical interface presents the data in one location. This supports the expertise of the researcher to interpret variants in the genome. Because the analysis of single nucleotide variants and copy number variants require interpretation of data at very different genomic scales, different data resources are required. We present here several Recommended Track Sets designed to facilitate the interpretation of variants in the clinic, offering quick access to datasets relevant to the appropriate scale.


Assuntos
Bases de Dados Genéticas , Software , Variações do Número de Cópias de DNA , Genoma Humano/genética , Genômica , Humanos , Internet
15.
BMC Genomics ; 23(1): 855, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575383

RESUMO

BACKGROUND: As the amount of genomic data continues to grow, there is an increasing need for systematic ways to organize, explore, compare, analyze and share this data. Despite this, there is a lack of suitable platforms to meet this need. RESULTS: OpenGenomeBrowser is a self-hostable, open-source platform to manage access to genomic data and drastically simplifying comparative genomics analyses. It enables users to interactively generate phylogenetic trees, compare gene loci, browse biochemical pathways, perform gene trait matching, create dot plots, execute BLAST searches, and access the data. It features a flexible user management system, and its modular folder structure enables the organization of genomic data and metadata, and to automate analyses. We tested OpenGenomeBrowser with bacterial, archaeal and yeast genomes. We provide a docker container to make installation and hosting simple. The source code, documentation, tutorials for OpenGenomeBrowser are available at opengenomebrowser.github.io and a demo server is freely accessible at opengenomebrowser.bioinformatics.unibe.ch . CONCLUSIONS: To our knowledge, OpenGenomeBrowser is the first self-hostable, database-independent comparative genome browser. It drastically simplifies commonly used bioinformatics workflows and enables convenient as well as fast data exploration.


Assuntos
Gerenciamento de Dados , Genômica , Filogenia , Genoma , Biologia Computacional , Software
16.
Mol Ecol ; 31(6): 1615-1626, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35043486

RESUMO

Dietary DNA metabarcoding enables researchers to identify and characterize trophic interactions with a high degree of taxonomic precision. It is also sensitive to sources of bias and contamination in the field and laboratory. One of the earliest and most common strategies for dealing with such sensitivities has been to remove all low-abundance sequences and conduct ecological analyses based on the presence or absence of food taxa. Although this step is now often perceived to be necessary, evidence of its sufficiency is lacking and more attention to the risk of introducing other errors is needed. Using computer simulations, we demonstrate that common strategies to remove low-abundance sequences can erroneously eliminate true dietary sequences in ways that impact downstream inferences. Using real data from well-studied wildlife populations in Yellowstone National Park, we further show how these strategies can markedly alter the composition of dietary profiles in ways that scale-up to obscure ecological interpretations about dietary generalism, specialism, and composition. Although the practice of removing low-abundance sequences may continue to be a useful strategy to address research questions that focus on a subset of relatively abundant foods, its continued widespread use risks generating misleading perceptions about the structure of trophic networks. Researchers working with dietary DNA metabarcoding data-or similar data such as environmental DNA, microbiomes, or pathobiomes-should be aware of drawbacks and consider alternative bioinformatic, experimental, and statistical solutions.


Assuntos
Código de Barras de DNA Taxonômico , DNA Ambiental , Animais , Animais Selvagens , DNA , Dieta
17.
BMC Pulm Med ; 22(1): 480, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36528564

RESUMO

BACKGROUND: Acute lung injury and the acute respiratory distress syndrome are characterized by pulmonary inflammation, reduced endothelial barrier integrity and filling of the alveolar space with protein rich edema fluid and infiltrating leukocytes. Animal models are critical to uncovering the pathologic mechanisms of this devastating syndrome. Intravital imaging of the intact lung via two-photon intravital microscopy has proven a valuable method to investigate lung injury in small rodent models through characterization of inflammatory cells and vascular changes in real time. However, respiratory motion complicates the analysis of these time series images and requires selective data extraction to stabilize the image. Consequently, analysis of individual alveoli may not provide a complete picture of the integrated mechanical, vascular and inflammatory processes occurring simultaneously in the intact lung. To address these challenges, we developed a web browser-based visualization application named Alveolus Analysis to process, analyze and graphically display intravital lung microscopy data. RESULTS: The designed tool takes raw temporal image data as input, performs image preprocessing and feature extraction offline, and visualizes the extracted information in a web browser-based interface. The interface allows users to explore multiple experiments in three panels corresponding to different levels of detail: summary statistics of alveolar/neutrophil behavior, characterization of alveolar dynamics including lung edema and inflammatory cells at specific time points, and cross-experiment analysis. We performed a case study on the utility of the visualization with two members or our research team and they found the tool useful because of its ability to preprocess data consistently and visualize information in a digestible and informative format. CONCLUSIONS: Application of our software tool, Alveolus Analysis, to intravital lung microscopy data has the potential to enhance the information gained from these experiments and provide new insights into the pathologic mechanisms of inflammatory lung injury.


Assuntos
Lesão Pulmonar , Animais , Navegador , Lesão Pulmonar/patologia , Alvéolos Pulmonares/patologia , Pulmão/patologia , Microscopia Intravital
18.
Molecules ; 27(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35889494

RESUMO

We here outline the importance of open-source, accessible tools for computer-aided drug discovery (CADD). We begin with a discussion of drug discovery in general to provide context for a subsequent discussion of structure-based CADD applied to small-molecule ligand discovery. Next, we identify usability challenges common to many open-source CADD tools. To address these challenges, we propose a browser-based approach to CADD tool deployment in which CADD calculations run in modern web browsers on users' local computers. The browser app approach eliminates the need for user-initiated download and installation, ensures broad operating system compatibility, enables easy updates, and provides a user-friendly graphical user interface. Unlike server apps-which run calculations "in the cloud" rather than on users' local computers-browser apps do not require users to upload proprietary information to a third-party (remote) server. They also eliminate the need for the difficult-to-maintain computer infrastructure required to run user-initiated calculations remotely. We conclude by describing some CADD browser apps developed in our lab, which illustrate the utility of this approach. Aside from introducing readers to these specific tools, we are hopeful that this review highlights the need for additional browser-compatible, user-friendly CADD software.


Assuntos
Computadores , Software , Descoberta de Drogas , Internet , Ligantes , Interface Usuário-Computador , Navegador
19.
J Anim Physiol Anim Nutr (Berl) ; 106(4): 922-938, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35587535

RESUMO

The aim of this study was to determine the effect of an increased mono- and disaccharide (MD) intake on selected functions and structure of the gastrointestinal tract (GIT), and selected blood parameters in Reeves's muntjac (Muntiacus reevesi), a small browsing ruminant. Eighteen male muntjacs were fed diets consisting of lucerne (ad libitum), a high fibre pellet (100 g/day) and wheat bran (30 g/day) without (MD0) or with addition of 10 or 20 g of glucose, fructose and sucrose mixture/day (MD10 and MD20, respectively) for 14 days. MD dosages were set to increase intake of these saccharides by 25% and 50% relative to MD0, which resulted in a range of water-soluble carbohydrate content in the consumed dry matter from 7% to 12%. Compared to MD0 animals, MD20 animals had a lower dry matter intake, a higher MD concentrations in the reticulorumen (RR), abomasal and small intestinal digesta, higher ruminal butyrate concentration, higher SGLT1 expression in the epithelium of proximal jejunum, higher plasma glucose, lower RR tissue weight but greater caecal tissue weight (p ≤ 0.05), and had or tended to have shorter papillae and lower mucosa surface area in the Atrium ruminis (by 44%; p = 0.02 and p = 0.10, respectively); MD10 animals tended to have higher MD concentrations in the abomasal and small intestinal digesta (p ≤ 0.10), and a higher amylolytic activity (p = 0.02) as well as a tendency to lower xylanolytic activity in the RR digesta (p = 0.06). MD supplementation did not affect ruminal pH. In conclusion, low to moderate increase of MD intake increased MD concentrations in the RR, abomasal and intestinal digesta, and SGLT1 expression in intestinal epithelium, suggesting incomplete fermentation of those saccharides in the RR. MD supplementation dose-dependently affects structure of GIT in Reeves's muntjac.


Assuntos
Ração Animal , Cervo Muntjac , Ração Animal/análise , Animais , Dieta/veterinária , Fibras na Dieta/farmacologia , Dissacarídeos/metabolismo , Dissacarídeos/farmacologia , Fermentação , Trato Gastrointestinal , Masculino , Rúmen/metabolismo
20.
J Anim Physiol Anim Nutr (Berl) ; 106(6): 1208-1215, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34791696

RESUMO

In investigations of differences between ruminant species feeding on browse or grass, it is often unclear whether observed differences are animal- or forage-specific. Ruminant species have been classified as 'moose-type', with little rumen content stratification, or 'cattle-type' with a distinct rumen contents stratification, including a gas layer. To which extent putative differences in forestomach motility are involved in these patterns is unknown. Using sonography, we investigated the frequency of reticular contractions and the stratification of rumen contents in goats fed exclusively on grass hay (n = 6) or dried browse (n = 5) directly after feeding, and after another 6 and 12 h with no access to feed. The frequency of reticular contractions decreased from immediately after feeding (1.8 ± 0.3 min-1 ) to 6 h afterwards (1.2 ± 0.2 min-1 ) and then remained constant, with no difference between diets. A gas dome became more visible over time, but neither its incidence nor its extent differed between diets. The results are in accord with classifying goats as 'cattle-type' in terms of their digestive physiology, and they add to a growing body of evidence that differences in digestive physiology between ruminant species are more due to species characteristics than different kinds of ingested forages.


Assuntos
Cervos , Cabras , Bovinos , Animais , Cabras/fisiologia , Rúmen/fisiologia , Ração Animal/análise , Dieta/veterinária , Ruminantes/fisiologia , Cervos/fisiologia
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