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1.
Cell ; 182(6): 1474-1489.e23, 2020 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-32841603

RESUMEN

Widespread changes to DNA methylation and chromatin are well documented in cancer, but the fate of higher-order chromosomal structure remains obscure. Here we integrated topological maps for colon tumors and normal colons with epigenetic, transcriptional, and imaging data to characterize alterations to chromatin loops, topologically associated domains, and large-scale compartments. We found that spatial partitioning of the open and closed genome compartments is profoundly compromised in tumors. This reorganization is accompanied by compartment-specific hypomethylation and chromatin changes. Additionally, we identify a compartment at the interface between the canonical A and B compartments that is reorganized in tumors. Remarkably, similar shifts were evident in non-malignant cells that have accumulated excess divisions. Our analyses suggest that these topological changes repress stemness and invasion programs while inducing anti-tumor immunity genes and may therefore restrain malignant progression. Our findings call into question the conventional view that tumor-associated epigenomic alterations are primarily oncogenic.


Asunto(s)
Cromatina/metabolismo , Cromosomas/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Metilación de ADN , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica/genética , División Celular , Senescencia Celular/genética , Secuenciación de Inmunoprecipitación de Cromatina , Cromosomas/genética , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Biología Computacional , Metilación de ADN/genética , Epigenómica , Células HCT116 , Humanos , Hibridación Fluorescente in Situ , Microscopía Electrónica de Transmisión , Simulación de Dinámica Molecular , RNA-Seq , Análisis Espacial , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
2.
Cell ; 164(4): 668-80, 2016 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-26871632

RESUMEN

Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.


Asunto(s)
Células Madre Embrionarias/citología , Genes myc , Proteínas Proto-Oncogénicas c-myc/genética , Animales , Blastocisto/metabolismo , Proliferación Celular , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Células Madre Embrionarias/metabolismo , Femenino , Técnicas de Inactivación de Genes , Masculino , Ratones , Ratones Endogámicos C57BL
3.
Cell ; 159(2): 253-66, 2014 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-25284151

RESUMEN

To study how microbes establish themselves in a mammalian gut environment, we colonized germ-free mice with microbial communities from human, zebrafish, and termite guts, human skin and tongue, soil, and estuarine microbial mats. Bacteria from these foreign environments colonized and persisted in the mouse gut; their capacity to metabolize dietary and host carbohydrates and bile acids correlated with colonization success. Cohousing mice harboring these xenomicrobiota or a mouse cecal microbiota, along with germ-free "bystanders," revealed the success of particular bacterial taxa in invading guts with established communities and empty gut habitats. Unanticipated patterns of ecological succession were observed; for example, a soil-derived bacterium dominated even in the presence of bacteria from other gut communities (zebrafish and termite), and human-derived bacteria colonized germ-free bystander mice before mouse-derived organisms. This approach can be generalized to address a variety of mechanistic questions about succession, including succession in the context of microbiota-directed therapeutics.


Asunto(s)
Bacterias/clasificación , Bacterias/crecimiento & desarrollo , Tracto Gastrointestinal/microbiología , Ratones/microbiología , Animales , Bacterias/metabolismo , Ecosistema , Estuarios , Vida Libre de Gérmenes , Humanos , Isópteros/microbiología , Interacciones Microbianas , Piel/microbiología , Microbiología del Suelo , Simbiosis , Lengua/microbiología , Pez Cebra/microbiología
4.
Cell ; 152(3): 453-66, 2013 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-23374342

RESUMEN

There are ~650,000 Alu elements in transcribed regions of the human genome. These elements contain cryptic splice sites, so they are in constant danger of aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about the molecular mechanisms preventing their inclusion. Here, we present a mechanism for protecting the human transcriptome from the aberrant exonization of transposable elements. Quantitative iCLIP data show that the RNA-binding protein hnRNP C competes with the splicing factor U2AF65 at many genuine and cryptic splice sites. Loss of hnRNP C leads to formation of previously suppressed Alu exons, which severely disrupt transcript function. Minigene experiments explain disease-associated mutations in Alu elements that hamper hnRNP C binding. Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease.


Asunto(s)
Elementos Alu , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Proteínas Nucleares/metabolismo , Ribonucleoproteínas/metabolismo , Transcriptoma , Evolución Molecular , Exones , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HeLa , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoprecipitación , Sitios de Empalme de ARN , Análisis de Secuencia de ARN , Factor de Empalme U2AF
5.
Nat Immunol ; 16(9): 933-41, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26237553

RESUMEN

Expression of tissue-restricted self antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential for the induction of self-tolerance and prevents autoimmunity, with each TRA being expressed in only a few mTECs. How this process is regulated in single mTECs and is coordinated at the population level, such that the varied single-cell patterns add up to faithfully represent TRAs, is poorly understood. Here we used single-cell RNA sequencing and obtained evidence of numerous recurring TRA-co-expression patterns, each present in only a subset of mTECs. Co-expressed genes clustered in the genome and showed enhanced chromatin accessibility. Our findings characterize TRA expression in mTECs as a coordinated process that might involve local remodeling of chromatin and thus ensures a comprehensive representation of the immunological self.


Asunto(s)
Autoantígenos/genética , Células Epiteliales/inmunología , Regulación de la Expresión Génica/inmunología , ARN Mensajero/metabolismo , Autotolerancia/inmunología , Timo/inmunología , Animales , Autoinmunidad/inmunología , Ensamble y Desensamble de Cromatina , Células Epiteliales/metabolismo , Perfilación de la Expresión Génica , Humanos , Ratones , Autotolerancia/genética , Análisis de la Célula Individual , Timo/citología , Timo/metabolismo
6.
Curr Issues Mol Biol ; 46(4): 2819-2826, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38666906

RESUMEN

DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.

7.
Brief Bioinform ; 22(2): 642-663, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33147627

RESUMEN

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories. Contact:evbc@unj-jena.de.


Asunto(s)
COVID-19/prevención & control , Biología Computacional , SARS-CoV-2/aislamiento & purificación , Investigación Biomédica , COVID-19/epidemiología , COVID-19/virología , Genoma Viral , Humanos , Pandemias , SARS-CoV-2/genética
9.
Health Promot Pract ; : 15248399231177300, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37300243

RESUMEN

Padres Preparados, Jóvenes Saludables was a Latino family-based obesity prevention intervention implemented from 2017 to 2020 across eight programs in-person only, in a blended format (online/in-person), and online only. The intervention aimed to enhance father parenting skills to improve adolescent diet and activity behaviors. Mothers were encouraged to attend. Factors associated with participation were explored using a mixed-methods, qualitative (focus group/individual interviews by Zoom) and quantitative (process evaluation) design. Eleven focus group and 24 individual interviews were completed after participation with 24 fathers, 27 mothers, and 40 adolescents with responses not sorted by delivery method before analysis. Binomial logistic regression models examined associations between fathers' program completion and predictor variables of delivery characteristics, father demographic characteristics, and family attendance patterns. Parents were married (96% fathers, 76% mothers), had low income, a high school education or less (68% fathers, 81% mothers), and had lived in the United States a mean of 19 years. Parents were motivated to participate to improve health, and to be involved with and improve communication with their child. Common barriers to participation were work and life priorities and programmatic factors including scheduling conflicts and technological issues. Participation was greater for fathers attending sessions in-person compared with online only (OR = 11.6). Fathers were more likely to participate if they attended sessions with family members vs. not attending with family members (OR = 7.2). To maximize participation, findings suggest involving multiple parents/caregivers and adolescents, addressing contextual and programmatic barriers, and promoting benefits of better health and relations with family members.

10.
Int Nurs Rev ; 70(2): 185-193, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35768893

RESUMEN

BACKGROUND: Currently, there are no cut-off points for levels of empathy, making it difficult to assess the change experienced in its development or as a result of its intervention. It is an unsolved problem. INTRODUCTION: Empathy is a cognitive-affective attribute that enables nursing staff to maintain a professional relationship that entails various benefits for the patient. Its strengthening and development during university education is desirable. Empathy studies in Latin American nursing students are based on the direct scores obtained on an empathy test, based on which the variable is described and groups are compared. Statistical comparisons are not enough to discriminate substantive changes since two statistical values can show differences without implying that the post-intervention levels may correspond to a higher category in relation to those of pre-intervention or that two compared groups are qualitatively different. The above applies to empathic behaviour and is valid for students and professionals of health. This study aimed to establish cut-off points that allow defining ordinal categories in empathy. METHODS: In this multicenter and cross-sectional study, 3712 students from 11 Latin American nursing schools participated. The Jefferson Empathy Scale (JES) was applied; the psychometric properties were confirmed by Factor Analysis Confirmatory and Invariance. RESULTS: The JSE empathy scale is a measure with adequate reliability and construct validity. Examined cut-offs determined a structure of five empathy intervals that allowed them to be classified as empathy values in very high, high, medium, low and very low. DISCUSSION: The sequence of statistical tests carried out allowed us to determine ranges of categorical values in the empathy levels of groups of students. However, the determined categories may constitute a specific characteristic of them. It is not possible to extrapolate these results to regions other than those of Latin America. CONCLUSION: The estimated rankings allow comparing levels of empathy between groups of nursing students and the real effect of empathic interventions. IMPLICATIONS FOR NURSING: To contribute with strategies to evaluate changes in the empathic skills of nursing students, resulting in a well-valued skill in health services. IMPLICATIONS FOR NURSING POLICY: The cut-off points define evaluative categories (very low, low, medium, high and very high) that allow objective classification of levels of empathy achieved after (for example) an empathic intervention. This allows assessment of substantive changes experienced by nursing students (and professionals).


Asunto(s)
Estudiantes de Medicina , Estudiantes de Enfermería , Humanos , América Latina , Empatía , Psicometría , Estudiantes de Enfermería/psicología , Estudios Transversales , Reproducibilidad de los Resultados , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios
11.
Ann Hum Genet ; 86(5): 237-244, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35343586

RESUMEN

AIM: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic condition in which both lifestyle and genetic factors have a pathogenic role. The LEP gene encodes leptin, which regulates appetite, body weight, and several metabolic functions. Proopiomelanocortin (POMC), regulates food intake and energy balance. The aim of the study was to determine partial or complete deletions of genes associated with obesity in patients diagnosed with NAFLD. MATERIAL AND METHODS: Blood samples and DNA from 43 individuals diagnosed with NAFLD by ultrasonographic technique (Fibroscan) were obtained. The partial or complete deletions of genes were determined by MLPA (Multiplex Ligation-dependent Probe Amplification) using the SALSA probemix P220-B2 Obesity only on 43 individuals. Fifty blood samples from healthy individuals were included. RESULTS: Eleven out of 43 individuals analyzed by MLPA presented some deletion of the genes analyzed: six were female and five were male. The partial or complete deletion of the LEPR and POMC genes was observed in eight patients (18.6%), SIM1 in six patients (13.9%), GRIK2 and SH2B1 in two patients (4.7%), SEZGL2 in four patients (9.3%), and MCR4 in one patient (2.3%). CONCLUSION: Partial deletion was observed in LEPR, POMC, SIM1, GRIK2, SH2B1, SEZGL2, and MCR4 genes in 26% of the cases, and we suggest that these alterations probably has a potential relationship for the development of NAFLD.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Proteínas Adaptadoras Transductoras de Señales , Femenino , Humanos , Masculino , México , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/complicaciones , Obesidad/genética , Proopiomelanocortina/genética
12.
Curr Genet ; 68(3-4): 343-360, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35660944

RESUMEN

The GPN-loop GTPase Npa3 is encoded by an essential gene in the yeast Saccharomyces cerevisiae. Npa3 plays a critical role in the assembly and nuclear accumulation of RNA polymerase II (RNAPII), a function that may explain its essentiality. Genetic interactions describe the extent to which a mutation in a particular gene affects a specific phenotype when co-occurring with an alteration in a second gene. Discovering synthetic negative genetic interactions has long been used as a tool to delineate the functional relatedness between pairs of genes participating in common or compensatory biological pathways. Previously, our group showed that nuclear targeting and transcriptional activity of RNAPII were unaffected in cells expressing exclusively a C-terminal truncated mutant version of Npa3 (npa3∆C) lacking the last 106 residues naturally absent from the single GPN protein in Archaea, but universally conserved in all Npa3 orthologs of eukaryotes. To gain insight into novel cellular functions for Npa3, we performed here a genome-wide Synthetic Genetic Array (SGA) study coupled to bulk fluorescence monitoring to identify negative genetic interactions of NPA3 by crossing an npa3∆C strain with a 4,389 nonessential gene-deletion collection. This genetic screen revealed previously unknown synthetic negative interactions between NPA3 and 15 genes. Our results revealed that the Npa3 C-terminal tail extension regulates the participation of this essential GTPase in previously unknown biological processes related to mitochondrial homeostasis and ribosome biogenesis.


Asunto(s)
Proteínas de Unión al GTP Monoméricas , Proteínas de Saccharomyces cerevisiae , Núcleo Celular/metabolismo , GTP Fosfohidrolasas/genética , Proteínas de Unión al GTP Monoméricas/genética , Mutación , ARN Polimerasa II/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Fungal Genet Biol ; 159: 103656, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34974188

RESUMEN

C. glabrata is an opportunistic fungal pathogen and the second most common cause of opportunistic fungal infections in humans, that has evolved virulence factors to become a successful pathogen: strong resistance to oxidative stress, capable to adhere and form biofilms in human epithelial cells as well as to abiotic surfaces and high resistance to xenobiotics. Hst1 (a NAD+-dependent histone deacetylase), Sum1 (putative DNA binding protein) and Rfm1 (connector protein) form a complex (HRS-C) and control the resistance to oxidative stress, to xenobiotics (the antifungal fluconazole), and adherence to epithelial cells. Hst1 is functionally conserved within the Saccharomycetaceae family, Rfm1 shows a close phylogenetic relation within the Saccharomycetaceae family while Sum1 displays a distant phylogenetic relation with members of the family and is not conserved functionally. CDR1 encodes for an ABC transporter (resistance to fluconazole) negatively controlled by HRS-C, for which its binding site is located within 223 bp upstream from the ATG of CDR1. The absence of Hst1 and Sum1 renders the cells hyper-adherent, possibly due to the overexpression of AED1, EPA1, EPA22 and EPA6, all encoding for adhesins. Finally, in a neutrophil survival assay, HST1 and SUM1, are not required for survival. We propose that Sum1 in the HRS-C diverged functionally to control a set of genes implicated in virulence: adherence, resistance to xenobiotics and oxidative stress.


Asunto(s)
Candida glabrata , Fluconazol , Antifúngicos , Candida glabrata/genética , Fluconazol/farmacología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Humanos , Filogenia , Virulencia/genética , Xenobióticos
14.
Mol Cell ; 56(6): 808-18, 2014 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-25435138

RESUMEN

The structure of broken DNA ends is a critical determinant of the pathway used for DNA double-strand break (DSB) repair. Here, we develop an approach involving the hairpin capture of DNA end structures (HCoDES), which elucidates chromosomal DNA end structures at single-nucleotide resolution. HCoDES defines structures of physiologic DSBs generated by the RAG endonuclease, as well as those generated by nucleases widely used for genome editing. Analysis of G1 phase cells deficient in H2AX or 53BP1 reveals DNA ends that are frequently resected to form long single-stranded overhangs that can be repaired by mutagenic pathways. In addition to 3' overhangs, many of these DNA ends unexpectedly form long 5' single-stranded overhangs. The divergence in DNA end structures resolved by HCoDES suggests that H2AX and 53BP1 may have distinct activities in end protection. Thus, the high-resolution end structures obtained by HCoDES identify features of DNA end processing during DSB repair.


Asunto(s)
Cromosomas Humanos/genética , Análisis de Secuencia de ADN/métodos , Secuencia de Bases , Células Cultivadas , Roturas del ADN de Doble Cadena , Humanos
15.
Health Promot Int ; 37(4)2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36047639

RESUMEN

Adolescent obesity prevention programs focusing on Latino fathers may be useful to address Latino adolescent obesity. Adolescent obesity has become an urgent issue because of the coronavirus disease 2019 pandemic, with limited ability to deliver prevention programs in-person. This study aimed to assess the feasibility of a community-based, adolescent obesity prevention program for Latino father-adolescent dyads delivered remotely, adapted from the in-person Padres Preparados, Jóvenes Saludables program. A quasi-experimental design was used to assess the feasibility of the remotely delivered program based on criteria adapted from other feasibility studies of community-based health promotion programs for Latino families. Father-adolescent dyads were recruited at two sites in a Midwestern state during 2020; mothers were also encouraged to participate. Recruitment met the feasibility criteria (65 families expressed interest between August and October) with 26 families participating in this study. The retention ratio (percentage of participants who completed a post-session survey to those who completed the baseline survey) among fathers was acceptable (77%), while a lower percentage of adolescents were retained (68%). The session attendance ratio (number of sessions attended of the eight total sessions offered) was higher among adolescents (88%) and lower among fathers (68%) compared to the criteria. Satisfaction ratings (≥88%) and completeness of data collection at both baseline and post-session survey (≥76%) were acceptable. Favorable results were obtained for parent outcomes, while adolescent outcomes were not favorably changed. This remotely delivered adolescent obesity prevention program was feasible for Latino fathers; however, additional engagement with adolescents may be needed.


Adolescent obesity became a more urgent issue because of the coronavirus disease 2019 pandemic with less physical activity under lockdown, more food insecure families and limited in-person access to programs. Our study concluded that a remotely delivered version of a community-based, adolescent obesity prevention program for Latino father­adolescent dyads (the Padres Preparados, Jóvenes Saludables program) was feasible based on participation, satisfaction and parent outcomes. Additional engagement in activities to improve adolescent health behaviors may be needed to improve the overall effectiveness of the program.


Asunto(s)
COVID-19 , Obesidad Infantil , Adolescente , COVID-19/prevención & control , Estudios de Factibilidad , Hispánicos o Latinos , Humanos , Padres , Obesidad Infantil/prevención & control
16.
Bioinformatics ; 36(16): 4532-4534, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32573705

RESUMEN

SUMMARY: RegulonDB has collected, harmonized and centralized data from hundreds of experiments for nearly two decades and is considered a point of reference for transcriptional regulation in Escherichia coli K12. Here, we present the regutools R package to facilitate programmatic access to RegulonDB data in computational biology. regutools gives researchers the possibility of writing reproducible workflows with automated queries to RegulonDB. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages. We demonstrate the integration of regutools with Bioconductor by analyzing transcription factor DNA binding sites and transcriptional regulatory networks from RegulonDB. We anticipate that regutools will serve as a useful building block in our progress to further our understanding of gene regulatory networks. AVAILABILITY AND IMPLEMENTATION: regutools is an R package available through Bioconductor at bioconductor.org/packages/regutools.


Asunto(s)
Ecosistema , Escherichia coli K12 , Biología Computacional , Escherichia coli K12/genética , Redes Reguladoras de Genes , Programas Informáticos
17.
Appl Environ Microbiol ; 87(21): e0114921, 2021 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-34406827

RESUMEN

The cnm gene, coding for the glycosylated collagen- and laminin-binding surface adhesin Cnm, is found in the genomes of approximately 20% of Streptococcus mutans clinical isolates and is associated with systemic infections and increased caries risk. Other surface-associated collagen-binding proteins of S. mutans, such as P1 and WapA, have been demonstrated to form an amyloid quaternary structure with functional implications within biofilms. In silico analysis predicted that the ß-sheet-rich N-terminal collagen-binding domain (CBD) of Cnm has a propensity for amyloid aggregation, whereas the threonine-rich C-terminal domain was predicted to be disorganized. In this study, thioflavin-T fluorescence and electron microscopy were used to show that Cnm forms amyloids in either its native glycosylated or recombinant nonglycosylated form and that the CBD of Cnm is the main amyloidogenic unit of Cnm. We then performed a series of in vitro, ex vivo, and in vivo assays to characterize the amylogenic properties of Cnm. In addition, Congo red birefringence indicated that Cnm is a major amyloidogenic protein of S. mutans biofilms. Competitive binding assays using collagen-coated microtiter plates and dental roots, a substrate rich in collagen, revealed that Cnm monomers inhibit S. mutans binding to collagenous substrates, whereas Cnm amyloid aggregates lose this property. Thus, while Cnm contributes to recognition and initial binding of S. mutans to collagen-rich surfaces, amyloid formation by Cnm might act as a negative regulatory mechanism to modulate collagen-binding activity within S. mutans biofilms and warrants further investigation. IMPORTANCE Streptococcus mutans is a keystone pathogen that promotes caries by acidifying the dental biofilm milieu. The collagen- and laminin-binding glycoprotein Cnm is a virulence factor of S. mutans. Expression of Cnm by S. mutans is hypothesized to contribute to niche expansion, allowing colonization of multiple sites in the body, including collagen-rich surfaces such as dentin and heart valves. Here, we suggest that Cnm function might be modulated by its aggregation status. As a monomer, its primary function is to promote attachment to collagenous substrates via its collagen-binding domain (CBD). However, in later stages of biofilm maturation, the same CBD of Cnm could self-assemble into amyloid fibrils, losing the ability to bind to collagen and likely becoming a component of the biofilm matrix. Our findings shed light on the role of functional amyloids in S. mutans pathobiology and ecology.


Asunto(s)
Adhesinas Bacterianas/metabolismo , Amiloide , Proteínas Amiloidogénicas/metabolismo , Proteínas Portadoras/metabolismo , Colágeno/metabolismo , Streptococcus mutans , Amiloide/metabolismo , Streptococcus mutans/genética
18.
Arch Virol ; 166(11): 3239-3244, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34417873

RESUMEN

In this article, we - the Bacterial Viruses Subcommittee and the Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) - summarise the results of our activities for the period March 2020 - March 2021. We report the division of the former Bacterial and Archaeal Viruses Subcommittee in two separate Subcommittees, welcome new members, a new Subcommittee Chair and Vice Chair, and give an overview of the new taxa that were proposed in 2020, approved by the Executive Committee and ratified by vote in 2021. In particular, a new realm, three orders, 15 families, 31 subfamilies, 734 genera and 1845 species were newly created or redefined (moved/promoted).


Asunto(s)
Virus de Archaea/clasificación , Bacteriófagos/clasificación , Sociedades Científicas/organización & administración , Archaea/virología , Bacterias/virología
19.
BMC Public Health ; 21(1): 912, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33985468

RESUMEN

BACKGROUND: Food security status has been assessed as a representative score for households; however, different members in the same household may perceive and report food insecurity differently. A high prevalence of food insecurity has been reported among Latino households, therefore understanding differences in reporting food insecurity by Latino father-mother dyads may improve accuracy of assessment and plans to address food insecurity. This study aimed to 1) determine demographic characteristics and/or food-related factors associated with perceptions of food security status among Latino father-mother dyads, and 2) identify factors associated with discordance in perceptions of food insecurity between dyads. METHODS: Baseline data were used from a community-based, youth obesity prevention program among Latino families (n = 106 father-mother dyads). Food security was assessed with a 2-item food insecurity screen. Logistic regression models were used to evaluate associations between reporting food security status and predictor variables for fathers, mothers, and dyad-discordant responses. RESULTS: Food insecurity was reported by 39% of fathers and 55% of mothers. Adjusted odds of reporting food insecurity were significantly higher for fathers perceiving their neighborhood was unsafe vs. safe (OR: 3.7, p < 0.05) and reporting lower vs. higher household income (OR: 3.2, p < 0.05). Adjusted odds of reporting food insecurity were significantly higher for mothers perceiving their neighborhood was unsafe vs. safe (OR: 4.1, p < 0.01) and reporting lower vs. higher home availability of fruit and vegetable (OR: 5.5, p < 0.01). Dyad discordance in reporting food security status occurred in 24% of the dyads. Adjusted odds of dyad discordant reports of food insecurity status were significantly higher for dyads reporting discordant responses regarding previous nutrition education (OR: 3.4, p < 0.05) and higher home fruit and vegetable accessibility (OR: 3.1, p < 0.05) compared to dyads reporting concordant responses. Among the 28 dyads who reported discordant nutrition education participation, 21 reported that fathers had never participated but mothers had participated more than once. CONCLUSIONS: Differential factors were associated with reporting food security among Latino father-mother dyads. Nutrition education for fathers that improves awareness of home food supplies and a better understanding of how food accessibility influences maternal perceptions may improve dyad discordance in reporting household food security.


Asunto(s)
Padre , Madres , Adolescente , Estudios Transversales , Femenino , Inseguridad Alimentaria , Abastecimiento de Alimentos , Hispánicos o Latinos , Humanos , Masculino
20.
Eur J Dent Educ ; 25(4): 785-795, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33387384

RESUMEN

BACKGROUND: Empathy is an attribute that has an important role in the dentist-patient therapeutic relationship, clinical care and adherence to treatment, amongst other benefits. The aim of this research was to determine empathy in dentists in the process of specialisation. MATERIALS AND METHODS: Through an observational and cross-sectional study, all postgraduate students of Dentistry Faculty of Universidad Andrés Bello (Chile) were analysed (N = 195). The Jefferson Scale of Physician Empathy Scale was applied. RESULTS: The results show an adequate reliability of the empathy measure (α = 0.819, ω = 0.928). A three-factor structure is evidenced by confirmatory factor analysis (χ2 /df = 1.445, GFI = 0.952, RMSEA = 0.047) and adequate factor invariance between men and women. Women showed greater empathy on the global scale and in the perspective adoption dimension, with no gender differences found in the dimension Compassionate care and putting oneself in the other's shoes (POOS). The median empathy reaches 120 points. Below, are placed, the specialty of oral rehabilitation (Med = 114.5), surgery (Med = 117) and periodontics (Med. = 117.5). With superior scores, temporomandibular disorder (Med. = 121), endodontics (Med. = 121), Orthodontics and dentofacial orthopedics Med. = 122), Implantology (Med. = 125) and Pediatric dentistry (Med. = 127.5) are located. CONCLUSION: Women were more empathetic than men. In general, empathy levels are relatively high, but the common feature in which all students examined in different specialties have low levels in dimension POOS.


Asunto(s)
Empatía , Estudiantes de Medicina , Niño , Estudios Transversales , Educación en Odontología , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Especialidades Odontológicas
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