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1.
bioRxiv ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38746185

RESUMO

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

2.
Res Sq ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38746130

RESUMO

Friedreich's Ataxia (FRDA) is a neuromuscular degenerative disorder caused by trinucleotide expansions in the first intron of the frataxin (FXN) gene, resulting in insufficient levels of functional FNX protein. Deficits in FXN involve mitochondrial disruptions including iron-sulfur cluster synthesis and impaired energetics. These studies were to identify unique protein-protein interactions with FXN to better understand its function and design therapeutics. Two complementary approaches were employed, BioID and Co-IP, to identify protein interactions with FXN at the direct binding, indirect binding, and non-proximal levels. Forty-one novel protein interactions were identified by BioID and IP techniques. The FXN protein landscape was further analyzed incorporating both interaction type and functional pathways using a maximum path of 6 proteins with a potential direct interaction between FXN and NFS1. Probing the intersection between FXN-protein landscape and biological pathways associated with FRDA, we identified 41 proteins of interest. Peroxiredoxin 3 (Prdx3) was chosen for further analysis because of its role in mitochondrial oxidative injury. Our data has demonstrated the strengths of employing complementary methods to identify a unique interactome for FXN. Our data provides new insights into FXN function and regulation, a potential direct interaction between FXN and NFS1, and pathway interactions between FXN and Prdx3.

3.
Sci Rep ; 13(1): 16181, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37758719

RESUMO

Sulfate-reducing bacteria (SRB) are terminal members of any anaerobic food chain. For example, they critically influence the biogeochemical cycling of carbon, nitrogen, sulfur, and metals (natural environment) as well as the corrosion of civil infrastructure (built environment). The United States alone spends nearly $4 billion to address the biocorrosion challenges of SRB. It is important to analyze the genetic mechanisms of these organisms under environmental stresses. The current study uses complementary methodologies, viz., transcriptome-wide marker gene panel mapping and gene clustering analysis to decipher the stress mechanisms in four SRB. Here, the accessible RNA-sequencing data from the public domains were mined to identify the key transcriptional signatures. Crucial transcriptional candidate genes of Desulfovibrio spp. were accomplished and validated the gene cluster prediction. In addition, the unique transcriptional signatures of Oleidesulfovibrio alaskensis (OA-G20) at graphene and copper interfaces were discussed using in-house RNA-sequencing data. Furthermore, the comparative genomic analysis revealed 12,821 genes with translation, among which 10,178 genes were in homolog families and 2643 genes were in singleton families were observed among the 4 genomes studied. The current study paves a path for developing predictive deep learning tools for interpretable and mechanistic learning analysis of the SRB gene regulation.


Assuntos
Desulfovibrio , Transcriptoma , Humanos , Perfilação da Expressão Gênica , Cadeia Alimentar , Sulfatos
4.
bioRxiv ; 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37461680

RESUMO

The ChemoReceptor-Effector Interaction Database (CREID) is a collection of bacterial chemoreceptor and effector protein and interaction data to understand the process that chemoreceptors and effectors play in various environments. Our website includes terms associated with chemosensory pathways to educate users and those involved in collaborative research to help them understand this complex biological network. It includes 2,440 proteins involved in chemoreceptor and effector systems from 7 different bacterial families with 1,996 chemoeffector interactions. It is available at https://reactcreid.bicbioeng.org.

5.
Front Microbiol ; 14: 1086021, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37125195

RESUMO

The growth and survival of an organism in a particular environment is highly depends on the certain indispensable genes, termed as essential genes. Sulfate-reducing bacteria (SRB) are obligate anaerobes which thrives on sulfate reduction for its energy requirements. The present study used Oleidesulfovibrio alaskensis G20 (OA G20) as a model SRB to categorize the essential genes based on their key metabolic pathways. Herein, we reported a feedback loop framework for gene of interest discovery, from bio-problem to gene set of interest, leveraging expert annotation with computational prediction. Defined bio-problem was applied to retrieve the genes of SRB from literature databases (PubMed, and PubMed Central) and annotated them to the genome of OA G20. Retrieved gene list was further used to enrich protein-protein interaction and was corroborated to the pangenome analysis, to categorize the enriched gene sets and the respective pathways under essential and non-essential. Interestingly, the sat gene (dde_2265) from the sulfur metabolism was the bridging gene between all the enriched pathways. Gene clusters involved in essential pathways were linked with the genes from seleno-compound metabolism, amino acid metabolism, secondary metabolite synthesis, and cofactor biosynthesis. Furthermore, pangenome analysis demonstrated the gene distribution, where 69.83% of the 116 enriched genes were mapped under "persistent," inferring the essentiality of these genes. Likewise, 21.55% of the enriched genes, which involves specially the formate dehydrogenases and metallic hydrogenases, appeared under "shell." Our methodology suggested that semi-automated text mining and network analysis may play a crucial role in deciphering the previously unexplored genes and key mechanisms which can help to generate a baseline prior to perform any experimental studies.

6.
bioRxiv ; 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37205598

RESUMO

Nanowires (NW) have been extensively studied for Shewanella spp. and Geobacter spp. and are mostly produced by Type IV pili or multiheme c-type cytochrome. Electron transfer via NW is the most studied mechanism in microbially induced corrosion, with recent interest in application in bioelectronics and biosensor. In this study, a machine learning (ML) based tool was developed to classify NW proteins. A manually curated 999 protein collection was developed as an NW protein dataset. Gene ontology analysis of the dataset revealed microbial NW is part of membranal proteins with metal ion binding motifs and plays a central role in electron transfer activity. Random Forest (RF), support vector machine (SVM), and extreme gradient boost (XGBoost) models were implemented in the prediction model and were observed to identify target proteins based on functional, structural, and physicochemical properties with 89.33%, 95.6%, and 99.99% accuracy. Dipetide amino acid composition, transition, and distribution protein features of NW are key important features aiding in the model's high performance.

7.
Microorganisms ; 11(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36677411

RESUMO

A significant amount of literature is available on biocorrosion, which makes manual extraction of crucial information such as genes and proteins a laborious task. Despite the fast growth of biology related corrosion studies, there is a limited number of gene collections relating to the corrosion process (biocorrosion). Text mining offers a potential solution by automatically extracting the essential information from unstructured text. We present a text mining workflow that extracts biocorrosion associated genes/proteins in sulfate-reducing bacteria (SRB) from literature databases (e.g., PubMed and PMC). This semi-automatic workflow is built with the Named Entity Recognition (NER) method and Convolutional Neural Network (CNN) model. With PubMed and PMCID as inputs, the workflow identified 227 genes belonging to several Desulfovibrio species. To validate their functions, Gene Ontology (GO) enrichment and biological network analysis was performed using UniprotKB and STRING-DB, respectively. The GO analysis showed that metal ion binding, sulfur binding, and electron transport were among the principal molecular functions. Furthermore, the biological network analysis generated three interlinked clusters containing genes involved in metal ion binding, cellular respiration, and electron transfer, which suggests the involvement of the extracted gene set in biocorrosion. Finally, the dataset was validated through manual curation, yielding a similar set of genes as our workflow; among these, hysB and hydA, and sat and dsrB were identified as the metal ion binding and sulfur metabolism genes, respectively. The identified genes were mapped with the pangenome of 63 SRB genomes that yielded the distribution of these genes across 63 SRB based on the amino acid sequence similarity and were further categorized as core and accessory gene families. SRB's role in biocorrosion involves the transfer of electrons from the metal surface via a hydrogen medium to the sulfate reduction pathway. Therefore, genes encoding hydrogenases and cytochromes might be participating in removing hydrogen from the metals through electron transfer. Moreover, the production of corrosive sulfide from the sulfur metabolism indirectly contributes to the localized pitting of the metals. After the corroboration of text mining results with SRB biocorrosion mechanisms, we suggest that the text mining framework could be utilized for genes/proteins extraction and significantly reduce the manual curation time.

8.
J Mol Biol ; 435(2): 167895, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36463932

RESUMO

Micrograph comparison remains useful in bioscience. This technology provides researchers with a quick snapshot of experimental conditions. But sometimes a two- condition comparison relies on researchers' eyes to draw conclusions. Our Bioimage Analysis, Statistic, and Comparison (BASIN) software provides an objective and reproducible comparison leveraging inferential statistics to bridge image data with other modalities. Users have access to machine learning-based object segmentation. BASIN provides several data points such as images' object counts, intensities, and areas. Hypothesis testing may also be performed. To improve BASIN's accessibility, we implemented it using R Shiny and provided both an online and offline version. We used BASIN to process 498 image pairs involving five bioscience topics. Our framework supported either direct claims or extrapolations 57% of the time. Analysis results were manually curated to determine BASIN's accuracy which was shown to be 78%. Additionally, each BASIN version's initial release shows an average 82% FAIR compliance score.


Assuntos
Biofilmes , Disciplinas das Ciências Biológicas , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Software , Processamento de Imagem Assistida por Computador/métodos , Fluxo de Trabalho , Conjuntos de Dados como Assunto , Disciplinas das Ciências Biológicas/métodos
9.
Front Microbiol ; 13: 1008536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386676

RESUMO

Sensing surface topography, an upsurge of signaling biomolecules, and upholding cellular homeostasis are the rate-limiting spatio-temporal events in microbial attachment and biofilm formation. Initially, a set of highly specialized proteins, viz. conditioning protein, directs the irreversible attachment of the microbes. Later signaling molecules, viz. autoinducer, take over the cellular communication phenomenon, resulting in a mature microbial biofilm. The mandatory release of conditioning proteins and autoinducers corroborated the existence of two independent mechanisms operating sequentially for biofilm development. However, both these mechanisms are significantly affected by the availability of the cofactor, e.g., Copper (Cu). Generally, the Cu concentration beyond threshold levels is detrimental to the anaerobes except for a few species of sulfate-reducing bacteria (SRB). Remarkably SRB has developed intricate ways to resist and thrive in the presence of Cu by activating numerous genes responsible for modifying the presence of more toxic Cu(I) to Cu(II) within the periplasm, followed by their export through the outer membrane. Therefore, the determinants of Cu toxicity, sequestration, and transportation are reconnoitered for their contribution towards microbial adaptations and biofilm formation. The mechanistic details revealing Cu as a quorum quencher (QQ) are provided in addition to the three pathways involved in the dissolution of cellular communications. This review articulates the Machine Learning based data curing and data processing for designing novel anti-biofilm peptides and for an in-depth understanding of QQ mechanisms. A pioneering data set has been mined and presented on the functional properties of the QQ homolog in Oleidesulfovibrio alaskensis G20 and residues regulating the multicopper oxidase properties in SRB.

11.
Data Brief ; 42: 108283, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35656124

RESUMO

Experimental studies exploring the effects of intranasal oxytocin are typically underpowered due to small samples. Open access to experimental data and procedures and the use of previously employed measures is critical to building more robust and replicable findings, especially in less studied areas of oxytocin research. In this paper, data is provided from a double-blind placebo-controlled crossover study exploring the effects of intranasal oxytocin (IN-OT: 24 IU) on social preference to romantic partners, parents, peers, and strangers. Young adults (N = 44; 91% female) in committed dating relationships completed three phases of data collection including a screening survey followed by two cmd kwdnextpage ?>laboratory visits. In addition to romantic partner-, and stranger attraction ratings, the data is the first to provide comparisons between attachment and social preference ratings to parents, close friends, and romantic partners under placebo and IN-OT conditions. The data also include differences by situational and life history factors known to moderate oxytocin effects. The detailed protocol, and dataflow can be accessed to verify the analysis and findings or to conduct a replication study. The standardized experimental design and common IN-OT protocol add to the capacity for a meta-analysis exploring oxytocin effects on partner preference and may also be directly ported to existing or future studies with related questions to increase sample size and power.

12.
Cancers (Basel) ; 14(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35406526

RESUMO

This study investigates the effects of a dual selective Class I histone deacetylase (HDAC)/lysine-specific histone demethylase 1A (LSD1) inhibitor known as 4SC-202 (Domatinostat) on tumor growth and metastasis in a highly metastatic murine model of Triple Negative Breast Cancer (TNBC). 4SC-202 is cytotoxic and cytostatic to the TNBC murine cell line 4T1 and the human TNBC cell line MDA-MB-231; the drug does not kill the normal breast epithelial cell line MCF10A. Furthermore, 4SC-202 reduces cancer cell migration. In vivo studies conducted in the syngeneic 4T1 model, which closely mimics human TNBC in terms of sites of metastasis, reveal reduced tumor burden and lung metastasis. The mechanism of action of 4SC-202 may involve effects on cancer stem cells (CSC) which can self-renew and form metastatic lesions. Approximately 5% of the total 4T1 cell population grown in three-dimensional scaffolds had a distinct CD44high/CD24low CSC profile which decreased after treatment. Bulk transcriptome (RNA) sequencing analyses of 4T1 tumors reveal changes in metastasis-related pathways in 4SC-202-treated tumors, including changes to expression levels of genes implicated in cell migration and cell motility. In summary, 4SC-202 treatment of tumors from a highly metastatic murine model of TNBC reduces metastasis and warrants further preclinical studies.

13.
Front Microbiol ; 13: 1059123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620046

RESUMO

Protective coatings based on two dimensional materials such as graphene have gained traction for diverse applications. Their impermeability, inertness, excellent bonding with metals, and amenability to functionalization renders them as promising coatings for both abiotic and microbiologically influenced corrosion (MIC). Owing to the success of graphene coatings, the whole family of 2D materials, including hexagonal boron nitride and molybdenum disulphide are being screened to obtain other promising coatings. AI-based data-driven models can accelerate virtual screening of 2D coatings with desirable physical and chemical properties. However, lack of large experimental datasets renders training of classifiers difficult and often results in over-fitting. Generate large datasets for MIC resistance of 2D coatings is both complex and laborious. Deep learning data augmentation methods can alleviate this issue by generating synthetic electrochemical data that resembles the training data classes. Here, we investigated two different deep generative models, namely variation autoencoder (VAE) and generative adversarial network (GAN) for generating synthetic data for expanding small experimental datasets. Our model experimental system included few layered graphene over copper surfaces. The synthetic data generated using GAN displayed a greater neural network system performance (83-85% accuracy) than VAE generated synthetic data (78-80% accuracy). However, VAE data performed better (90% accuracy) than GAN data (84%-85% accuracy) when using XGBoost. Finally, we show that synthetic data based on VAE and GAN models can drive machine learning models for developing MIC resistant 2D coatings.

14.
Front Microbiol ; 12: 754140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777309

RESUMO

Sulfate-reducing bacteria (SRB) have a unique ability to respire under anaerobic conditions using sulfate as a terminal electron acceptor, reducing it to hydrogen sulfide. SRB thrives in many natural environments (freshwater sediments and salty marshes), deep subsurface environments (oil wells and hydrothermal vents), and processing facilities in an industrial setting. Owing to their ability to alter the physicochemical properties of underlying metals, SRB can induce fouling, corrosion, and pipeline clogging challenges. Indigenous SRB causes oil souring and associated product loss and, subsequently, the abandonment of impacted oil wells. The sessile cells in biofilms are 1,000 times more resistant to biocides and induce 100-fold greater corrosion than their planktonic counterparts. To effectively combat the challenges posed by SRB, it is essential to understand their molecular mechanisms of biofilm formation and corrosion. Here, we examine the critical genes involved in biofilm formation and microbiologically influenced corrosion and categorize them into various functional categories. The current effort also discusses chemical and biological methods for controlling the SRB biofilms. Finally, we highlight the importance of surface engineering approaches for controlling biofilm formation on underlying metal surfaces.

15.
Psychoneuroendocrinology ; 134: 105415, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34607172

RESUMO

Animal studies confirm oxytocin's (OT) role in regulating monogamous sexual behavior in pair-bonding rodents; and human studies are beginning to translate how this highly conserved neuropeptide is implicated in romantic attachment formation. A number of studies have shown how OT promotes relationship exclusivity by diminishing interest in strangers and increasing reward response to partners. Less clear is whether these effects are modulated by romantic duration or life history factors, or if OT's social distancing effects generalize beyond strangers to close relationships. We report the results of a double-blind, placebo-controlled crossover study on the effects of a single dose of intranasal OT (24 IU) on forty-four young adults (91% female) in different stages of romantic attachment formation (M duration=21 months). Participants completed a screening survey and two lab visits separated by 4-weeks, including a diagrammatic measure of attachment to parents and peers, attitudes related to sexual conservatism and partner infidelity, ratings scales of closeness to romantic partners, and visual attractiveness ratings of strangers. Individual differences were examined by life history factors, including maternal love withdrawal and parental separation. Results indicated that OT administration decreased attachment to mothers, decreased attachment to subsidiary attachment figures, and decreased attraction to strangers. In all cases, emotional distancing was stronger among participants in newer romantic relationships. OT increased arousal to partner infidelity and increased sexual conservatism among participants with negative life history experiences (parental separation and high love withdrawal), whereas the reverse was true for participants reporting a more positive life history. Findings suggest that OT supports exclusivity through social distancing from strangers and close others within a sensitive period of attachment formation. In addition, findings indicate OT plays a different role in mate retention strategies by life history.

16.
Neuroscience ; 475: 185-196, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455014

RESUMO

Structural and functional abnormalities in the cerebellar region have been shown in patients with Parkinson's disease (PD). Since the cerebellar region has been associated with cognitive and lower-limb motor functions, it is imperative to study cerebellar oscillations in PD. Here, we evaluated cerebellar electroencephalography (EEG) during cognitive processing and lower-limb motor performances in PD. Cortical and cerebellar EEG were collected from 74 PD patients and 37 healthy control subjects during a 7-second interval timing task, 26 PD patients and 13 controls during a lower-limb pedaling task, and 23 PD patients during eyes-open/closed resting conditions. Analyses were focused on the mid-cerebellar Cbz electrode and further compared to the mid-occipital Oz and mid-frontal Cz electrodes. Increased alpha-band power was observed during the eyes-closed resting-state condition over Oz, but no change in alpha power was observed over Cbz. PD patients showed higher dispersion when performing the 7-second interval timing cognitive task and executed the pedaling motor task with reduced speed compared to controls. PD patients exhibited attenuated cue-triggered theta-band power over Cbz during both the interval timing and pedaling motor tasks. Connectivity measures between Cbz and Cz showed theta-band differences, but only during the pedaling motor task. Cbz oscillatory activity also differed from Oz across multiple frequency bands in both groups during both tasks. Our cerebellar EEG data along with previous magnetoencephalography and animal model studies clearly show alterations in cerebellar oscillations during cognitive and motor processing in PD.


Assuntos
Doença de Parkinson , Cerebelo , Cognição , Eletroencefalografia , Humanos , Magnetoencefalografia
17.
Parasitol Res ; 120(4): 1209-1217, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33559752

RESUMO

Common bed bugs (Cimex lectularius L.) are hematophagous pests present in urban environments across the globe. It is widely established that they have a strong host preference for humans. However, there are records of C. lectularius feeding upon a range of mammalian and avian hosts, including rodents, in the field. There is little information available about how frequently common bed bugs feed on alternative hosts in residential settings, but understanding this phenomenon has implications for both management of infestations and public health. Here, we examined cohorts of C. lectularius collected from 13 different dwellings in the state of New Jersey, USA, that were known to be simultaneously infested with house mice (Mus musculus domesticus). Host-specific quantitative polymerase chain reaction (qPCR) was used to determine if blood meals were taken from mice, while 16S rRNA gene amplicon sequencing was used to screen the bed bugs for the presence of zoonotic bacterial pathogens. We found no evidence that any of the bed bugs we collected fed on mice. Furthermore, the insects harbored depauperate bacterial communities that did not include known human pathogens. However, host-specific qPCR detected feline DNA in a pool of bed bugs from one dwelling, suggesting that interaction with domestic pets should be further investigated. Although sampling in this study was limited, the approach described herein will be useful for additional studies of the interactions between bed bugs and alternative blood meal hosts.


Assuntos
Bactérias/isolamento & purificação , Percevejos-de-Cama/microbiologia , Sangue/microbiologia , Animais , Bactérias/genética , Gatos , DNA/sangue , Feminino , Especificidade de Hospedeiro , Humanos , Masculino , Camundongos , RNA Bacteriano/genética , RNA Ribossômico 16S/genética
18.
Comput Struct Biotechnol J ; 18: 1704-1721, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670510

RESUMO

Infectious diseases, including vector-borne diseases transmitted by arthropods, are a leading cause of morbidity and mortality worldwide. In the era of big data, addressing broad-scale, fundamental questions regarding the complex dynamics of these diseases will increasingly require the integration of diverse datasets to produce new biological knowledge. This review provides a current snapshot of the systematic assessment of the relationships between microbial pathogens, arthropod vectors and mammalian hosts using data mining and machine learning. We employ PRISMA to identify 32 key papers relevant to this topic. Our analysis shows an increasing use of data mining and machine learning tasks and techniques, including prediction, classification, clustering, association rules mining, and deep learning, over the last decade. However, it also reveals a number of critical challenges in applying these to the study of vector-host-pathogen interactions at various systems biology levels. Here, relevant studies, current limitations and future directions are discussed. Furthermore, the quality of data in relevant papers was assessed using the FAIR (Findable, Accessible, Interoperable, Reusable) compliance criteria to evaluate and encourage reproducibility and shareability of research outcomes. Although shortcomings in their application remain, data mining and machine learning have significant potential to break new ground in understanding fundamental aspects of vector-host-pathogen relationships and their application in this field should be encouraged. In particular, while predictive modeling, feature engineering and supervised machine learning are already being used in the field, other data mining and machine learning methods such as deep learning and association rules analysis lag behind and should be implemented in combination with established methods to accelerate hypothesis and knowledge generation in the domain.

19.
Cancers (Basel) ; 12(3)2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32210076

RESUMO

Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC's) and lysine demethylase (LSD1). Here, we investigate the effect of a small molecule epigenetic modulator known as Domatinostat (4SC-202), which inhibits both class I HDAC's and Lysine Demethylase (LSD1), on ATRT cell survival and single cell heterogeneity. Our findings suggest that 4SC-202 is both cytotoxic and cytostatic to ATRT in 2D and 3D scaffold cell culture models and may target cancer stem cells. Single-cell RNA sequencing data from ATRT-06 spheroids treated with 4SC-202 have a reduced population of cells overexpressing stem cell-related genes, including SOX2. Flow cytometry and immunofluorescence on 3D ATRT-06 scaffold models support these results suggesting that 4SC-202 reduces expression of cancer stem cell markers SOX2, CD133, and FOXM1. Drug-induced changes to the systems biology landscape are also explored by multi-omics enrichment analyses. In summary, our data indicate that 4SC-202 has both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and is an important potential cancer therapeutic to be investigated in vivo.

20.
IDCases ; 19: e00696, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31988849

RESUMO

Body lice and bed bugs are hematophagous insects that parasitize humans. Body lice are established vectors of several bacterial pathogens (e.g. Bartonella quintana, Borrelia recurrentis). Bed bugs are biologically competent vectors of some of the same agents, but their vectorial capacity for these in nature is unclear. In particular, a lack of exposure to louse-borne pathogens in bed bugs in the field could be a factor that limits their contribution to transmission. Here, we describe a case of a patient seen in an urban emergency department who was suffering from infestation with both body lice and bed bugs. Insects were collected from the patient and tested for the presence of louse-borne bacterial pathogens using 16S rRNA gene amplicon sequencing. Although no Bartonella, Borrelia, or Rickettsia were detected, this case provides evidence of ecological overlap between body lice and bed bugs and highlights several potential risk factors for co-infestation. The ecological relationships between bed bugs, body lice, and louse-borne bacteria should be further investigated in the field to determine the frequency of co-infestations and identify possible instances of pathogen infection in bed bugs.

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