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1.
Cell ; 186(24): 5269-5289.e22, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37995656

RESUMEN

A generic level of chromatin organization generated by the interplay between cohesin and CTCF suffices to limit promiscuous interactions between regulatory elements, but a lineage-specific chromatin assembly that supersedes these constraints is required to configure the genome to guide gene expression changes that drive faithful lineage progression. Loss-of-function approaches in B cell precursors show that IKAROS assembles interactions across megabase distances in preparation for lymphoid development. Interactions emanating from IKAROS-bound enhancers override CTCF-imposed boundaries to assemble lineage-specific regulatory units built on a backbone of smaller invariant topological domains. Gain of function in epithelial cells confirms IKAROS' ability to reconfigure chromatin architecture at multiple scales. Although the compaction of the Igκ locus required for genome editing represents a function of IKAROS unique to lymphocytes, the more general function to preconfigure the genome to support lineage-specific gene expression and suppress activation of extra-lineage genes provides a paradigm for lineage restriction.


Asunto(s)
Cromatina , Genoma , Linfocitos B/metabolismo , Factor de Unión a CCCTC/metabolismo , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina , Humanos , Animales , Ratones
2.
Nat Immunol ; 23(11): 1628-1643, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36316479

RESUMEN

T cell differentiation requires Notch1 signaling. In the present study, we show that an enhancer upstream of Notch1 active in double-negative (DN) mouse thymocytes is responsible for raising Notch1 signaling intrathymically. This enhancer is required to expand multipotent progenitors intrathymically while delaying early differentiation until lineage restrictions have been established. Early thymic progenitors lacking the enhancer show accelerated differentiation through the DN stages and increased frequency of B, innate lymphoid (IL) and natural killer (NK) cell differentiation. Transcription regulators for T cell lineage restriction and commitment are expressed normally, but IL and NK cell gene expression persists after T cell lineage commitment and T cell receptor ß VDJ recombination, Cd3 expression and ß-selection have been impaired. This Notch1 enhancer is inactive in double-positive (DP) thymocytes. Its aberrant reactivation at this stage in Ikaros mutants is required for leukemogenesis. Thus, the DN-specific Notch1 enhancer harnesses the regulatory architecture of DN and DP thymocytes to achieve carefully orchestrated changes in Notch1 signaling required for early lineage restrictions and normal T cell differentiation.


Asunto(s)
Inmunidad Innata , Timocitos , Ratones , Animales , Timocitos/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Linfocitos/metabolismo , Timo , Diferenciación Celular/genética , Linaje de la Célula/genética
3.
J Autoimmun ; 144: 103177, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38368767

RESUMEN

Psoriasis (PS) and atopic dermatitis (AD) are common skin inflammatory diseases characterized by hyper-responsive keratinocytes. Although, some cytokines have been suggested to be specific for each disease, other cytokines might be central to both diseases. Here, we show that Tumor necrosis factor superfamily member 14 (TNFSF14), known as LIGHT, is required for experimental PS, similar to its requirement in experimental AD. Mice devoid of LIGHT, or deletion of either of its receptors, lymphotoxin ß receptor (LTßR) and herpesvirus entry mediator (HVEM), in keratinocytes, were protected from developing imiquimod-induced psoriatic features, including epidermal thickening and hyperplasia, and expression of PS-related genes. Correspondingly, in single cell RNA-seq analysis of PS patient biopsies, LTßR transcripts were found strongly expressed with HVEM in keratinocytes, and LIGHT was upregulated in T cells. Similar transcript expression profiles were also seen in AD biopsies, and LTßR deletion in keratinocytes also protected mice from allergen-induced AD features. Moreover, in vitro, LIGHT upregulated a broad spectrum of genes in human keratinocytes that are clinical features of both PS and AD skin lesions. Our data suggest that agents blocking LIGHT activity might be useful for therapeutic intervention in PS as well as in AD.


Asunto(s)
Dermatitis Atópica , Psoriasis , Humanos , Ratones , Animales , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Miembro 14 de Receptores del Factor de Necrosis Tumoral/metabolismo , Dermatitis Atópica/genética , Dermatitis Atópica/metabolismo , Receptor beta de Linfotoxina/genética , Receptor beta de Linfotoxina/metabolismo , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Queratinocitos/metabolismo , Citocinas/metabolismo , Psoriasis/genética , Psoriasis/metabolismo , Inflamación/metabolismo
4.
Environ Microbiol ; 23(8): 4200-4213, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33998121

RESUMEN

Climate change is projected to cause increased inflow of terrestrial dissolved organic matter to coastal areas in northerly regions. Estuarine bacterial community will thereby receive larger loads of organic matter and inorganic nutrients available for microbial metabolism. The composition of the bacterial community and its ecological functions may thus be affected. We studied the responses of bacterial community to inflow of terrestrial dissolved organic matter in a subarctic estuary in the northern Baltic Sea, using a 16S rRNA gene metabarcoding approach. Betaproteobacteria dominated during the spring river flush, constituting ~ 60% of the bacterial community. Bacterial diversity increased as the runoff decreased during summer, when Verrucomicrobia, Betaproteobacteria, Bacteroidetes, Gammaproteobacteria and Planctomycetes dominated the community. Network analysis revealed that a larger number of associations between bacterial populations occurred during the summer than in spring. Betaproteobacteria and Bacteroidetes populations appeared to display similar correlations to environmental factors. In spring, freshly discharged organic matter favoured specialists, while in summer a mix of autochthonous and terrestrial organic matter promoted the development of generalists. Our study indicates that increased inflows of terrestrial organic matter-loaded freshwater to coastal areas would promote specialist bacteria, which in turn might enhance the transformation of terrestrial organic matter in estuarine environments.


Asunto(s)
Estuarios , Bacterias/genética , ARN Ribosómico 16S/genética
5.
J Anim Ecol ; 90(8): 1961-1972, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33942301

RESUMEN

Our understanding of the plastic and evolutionary potential of ectothermic organisms and their populational impacts in the face of rapid global change remains limited. Studies attempting on the relationship between the magnitude of thermal variability across latitude and the degree of phenotypic plasticity exhibited by marine ectotherms are inconclusive. We state that the latter arises from the narrow range of thermal variability captured by the limited span of the latitudinal gradients studied to date. Using a mechanistic ecophysiological approach and a satellite-based assessment of the relevant environmental variables (i.e. temperature and food availability), we studied individuals of the intertidal barnacle Jehlius cirratus from seven local populations widely spread along the Humboldt current system that spanning two biogeographic regions. At the same time, we synthesized published information on the local abundance of our study species across a total of 76 sites representing 20° of latitude, and spanning from 18 to 42°S. We examined the effects of latitude and environmental variability on metabolic rate plasticity, thermal tolerance (thermal breadth and thermal safety margins) and their impacts on the abundance of this widespread marine invertebrate. We demonstrate that the phenotypic plasticity of metabolic rate in J. cirratus populations is not related to latitude. In turn, thermal breadth is explained by the temperature variability each population experiences. Furthermore, we found clinal variation with a poleward decrease of the critical thermal minimum, suggesting that episodic extreme low temperatures represent a ubiquitous selective force on the lower thermal limit for ectotherms. Across our study gradient, plasticity patterns indicate that populations at the equatorial extreme are more vulnerable to a warming climate, while populations located in the biogeographic transitional zone (i.e. high environmental heterogeneity), on the centre of the gradient, display higher levels of phenotypic plasticity and may represent a genetic buffer for the effects of ocean warming. Together, our results suggest the existence of a fitness trade-off involving the metabolic cost of plasticity and population density that is evident only across the vast latitudinal gradient examined.


Nuestro conocimiento del potencial plástico y evolutivo de organismos ectotérmicos y de los posibles impactos poblacionales a la luz del rápido cambio global sigue siendo limitado. Los estudios que relacionan la magnitud de la variabilidad térmica y el grado de plasticidad fenotípica a través de la latitud realizados en organismos ectotérmicos marinos no son concluyentes. Lo anterior creemos que es consecuencia del estrecho rango latitudinal y por consecuencia el menor rango de variabilidad térmica abarcado por los estudios previos. Utilizando un enfoque ecofisiológico mecanicista e información satelital de las variables ambientales relevantes (i.e., temperatura y disponibilidad de alimento), estudiamos individuos del cirripedio intermareal Jehlius cirratus a lo largo de siete poblaciones locales que se distribuyen ampliamente a lo largo del Sistema de la corriente de Humboldt abarcando dos regiones biogeográficas. Al mismo tiempo, sintetizamos la información publicada sobre la abundancia local de nuestro modelo de estudio en un total de 76 sitios que representan 20 grados de latitud y abarcan desde los 18° a los 42°S. Examinamos los efectos de la latitud y la variabilidad ambiental en la plasticidad de la tasa metabólica, la tolerancia térmica (i.e. amplitud térmica y márgenes de seguridad térmica) y los impactos en la abundancia de este invertebrado marino con amplia distribución geográfica. Demostramos que la plasticidad fenotípica de la tasa metabólica en poblaciones de J. cirratus no está relacionada con la latitud. A su vez, la amplitud térmica se explica por la variabilidad térmica que cada población experimenta. Además, encontramos un patrón de variación clinal con una disminución hacia los polos del crítico térmico mínimo, lo que sugiere que las temperaturas episódicas extremadamente bajas representan una fuerza selectiva ubicua en el límite térmico inferior para los ectotermos. A lo largo de nuestro gradiente estudiado, los patrones de plasticidad indican que las poblaciones en el extremo ecuatorial son más vulnerables al calentamiento, mientras que las poblaciones ubicadas en la zona de transición biogeográfica (i.e., alta heterogeneidad ambiental), en el centro del gradiente, muestran mayores niveles de plasticidad fenotípica, lo que puede representar un reservorio genético para los efectos del calentamiento de los océanos. Nuestros resultados sugieren la existencia de un compromiso en la adecuación biológica que involucra el costo metabólico de la plasticidad y la densidad de población que es sólo evidente dado el vasto gradiente latitudinal examinado.


Asunto(s)
Thoracica , Adaptación Fisiológica , Animales , Calor , Temperatura
6.
Mem Inst Oswaldo Cruz ; 113(1): 24-29, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29211105

RESUMEN

BACKGROUND: Vector transmission of Trypanosoma cruzi appears to be interrupted in Chile; however, data show increasing incidence of Chagas' disease, raising concerns that there may be a reemerging problem. OBJECTIVE: To estimate the actual risk in a changing world it is necessary to consider the historical vector distribution and correlate this distribution with the presence of cases and climate change. METHODS: Potential distribution models of Triatoma infestans and Chagas disease were performed using Maxent, a machine-learning method. FINDINGS: Climate change appears to play a major role in the reemergence of Chagas' disease and T. infestans in Chile. The distribution of both T. infestans and Chagas' disease correlated with maximum temperature, and the precipitation during the driest month. The overlap of Chagas' disease and T. infestans distribution areas was high. The distribution of T. infestans, under two global change scenarios, showed a minimal reduction tendency in suitable areas. MAIN CONCLUSION: The impact of temperature and precipitation on the distribution of T. infestans, as shown by the models, indicates the need for aggressive control efforts; the current control measures, including T. infestans control campaigns, should be maintained with the same intensity as they have at present, avoiding sylvatic foci, intrusions, and recolonisation of human dwellings.


Asunto(s)
Cambio Climático , Insectos Vectores/parasitología , Triatoma/parasitología , Trypanosoma cruzi/aislamiento & purificación , Animales , Enfermedad de Chagas/transmisión , Chile , Humanos , Modelos Biológicos , Factores de Riesgo
7.
bioRxiv ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38746164

RESUMEN

HiChIP enables cost-effective and high-resolution profiling of regulatory and structural loops. To leverage the increasing number of publicly available HiChIP datasets from diverse cell lines and primary cells, we developed the Loop Catalog (https://loopcatalog.lji.org), a web-based database featuring HiChIP loop calls for 1319 samples across 133 studies and 44 high-resolution Hi-C loop calls. We demonstrate its utility in interpreting fine-mapped GWAS variants (SNP-to-gene linking), in identifying enriched sequence motifs and motif pairs at loop anchors, and in network-level analysis of loops connecting regulatory elements (community detection). Our comprehensive catalog, spanning over 4M unique 5kb loops, along with the accompanying analysis modalities constitutes an important resource for studies in gene regulation and genome organization.

8.
Cureus ; 16(7): e63772, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39100034

RESUMEN

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide. Surgical treatments, including mastectomy and subsequent breast reconstruction, are critical components of breast cancer management. This systematic review compares the outcomes of flap versus implant reconstruction post-mastectomy, focusing on aesthetic differences, pain, recovery, and psychological adaptation. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we conducted a comprehensive literature search across PubMed, Cochrane, and ScienceDirect databases. Inclusion criteria targeted studies comparing aesthetic outcomes, pain, recovery costs, duration, and psychological adaptation between flap and implant breast reconstructions. We excluded non-English and non-Spanish studies, case reports, and those without full-text availability. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). From an initial pool of 25,881 articles, 16 high-quality studies involving 14,196 participants were selected for synthesis. Flap reconstruction was associated with higher patient satisfaction regarding aesthetic outcomes and psychological well-being but also had higher complication rates, including infections and wound dehiscence. Implant reconstruction showed fewer complications but did not achieve the same level of patient satisfaction. Flap reconstruction, despite its higher complication rates, tends to provide superior aesthetic and psychological outcomes compared to implant reconstruction. These findings highlight the importance of personalized treatment plans considering individual patient needs and preferences. Future research should focus on long-term randomized controlled trials (RCTs) and standardized outcome measures to further delineate the comparative effectiveness of these reconstruction techniques. Personalized care and ongoing research are essential to improving the quality of life for breast cancer survivors undergoing reconstruction.

9.
Mar Pollut Bull ; 194(Pt B): 115380, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37562239

RESUMEN

Human settlements within the Antarctic continent have caused significant coastal pollution by littering plastic. The present study assessed the potential presence of microplastics in the gastrointestinal tract of the Antarctic fish Harpagifer antarcticus, endemic to the polar region, and in the sub-Antarctic fish Harpagifer bispinis. H. antarcticus. A total of 358 microfibers of multiple colors were found in 89 % of H. antarcticus and 73 % of H. bispinis gastrointestinal track. A Micro-FTIR analysis characterized a sub-group (n = 42) of microfibers. It revealed that most of the fibers were cellulose (69 %). Manmade fibers such as microplastics polyethylene terephtalate, acrylics, and semisynthetic/natural cellulosic fibers were present in the fish samples. All the microfibers extracted were textile fibers of blue, black, red, green, and violet color. Our results suggest that laundry greywater discharges of human settlements near coastal waters in Antarctica are a major source of these pollutants in the Antarctic fish.


Asunto(s)
Perciformes , Contaminantes Químicos del Agua , Animales , Humanos , Microplásticos , Plásticos/análisis , Regiones Antárticas , Textiles , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/métodos
10.
Sci Rep ; 13(1): 5420, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37012431

RESUMEN

Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (< 2 Mb) interactions, chromatin looping, formation of TAD, chromatin state switching into a more active state, and amplification of ATP-binding cassette transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Carboplatino/farmacología , Carboplatino/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Xenoinjertos , Genoma , Cromatina
11.
Rev Chilena Infectol ; 29(4): 388-94, 2012 Aug.
Artículo en Español | MEDLINE | ID: mdl-23096537

RESUMEN

Dengue is considered an emerging disease with an increasing prevalence especially in South America. In 2002, an epidemic of classic Dengue (DENV-1) occurred unexpectedly on Easter Island, where it had never been detected before. It reappeared in 2006-2007 and 2008, 2009 and 2011. The aim of this study was to estimate the most relevant parameters of the epidemiological dynamics of transmission of Dengue on Easter Island and to model the dynamics since 2002, comparing the predictions with the actual situation observed. Of the total cases, 52.27% were females and 47.73% men. The average age of infection was 31.38 ± 18.37 years, similar in men and women. We estimated the reproductive number R0 = 3.005 with an IC0,95 = [1.92, 4.61]. The inter-epidemic period reached an estimated T = 5.20 to 6.8 years. The case simulation showed recurrent epidemics with decreasing magnitude (damped oscillations), which is a known phenomenon in models of dengue and malaria. There was good qualitative fit to the epidemiological dynamics from 2002 onwards. It accurately predicted the rise in cases between 2006 and 2011. The predicted number of cases during the 2002 epidemic is greater than the confirmed cases and the predicted epidemic was faster than notified cases. Interepidemic period in the simulation was 6.72 years between 2002 and 2008 and 4.68 years between 2008 and 2013. From the theoretical perspective, the first epidemic had affected 94% of the population (approximately 3500 cases), but 639 were reported suggesting underreporting and a lot of sub-clinical cases occurred. Future epidemic of decreasing size are expected, although the main danger are epidemics of hemorrhagic dengue fever resulting from the introduction of different dengue virus serotypes.


Asunto(s)
Virus del Dengue , Dengue/transmisión , Epidemias/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Dengue/epidemiología , Notificación de Enfermedades/estadística & datos numéricos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Polinesia/epidemiología , Recurrencia , Dengue Grave/epidemiología , Distribución por Sexo , Adulto Joven
12.
Data Brief ; 44: 108543, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36091475

RESUMEN

In this research, we build two food systems datasets in Mexico; The first one describes the structure of agricultural production units and the second one describes food security aspects of the rural population in these agricultural production units. We also build a third dataset, consisting of path diagrams and path coefficients (derived from Structural Equation Modeling) that relate the first dataset to the second dataset in the four most populated ecoregions of Mexico. The description of the path models and the insights they bring to the current state of food security in Mexican rural households are detailed in an associated article entitled "Is food security primarily associated with smallholder agriculture or with commercial agriculture?: An approach to the case of Mexico using structural equation modeling" (https://doi.org/10.1016/j.agsy.2021.103091). The agricultural variables (in the first dataset) include farm size, destination of the farmer's production, cultivation practice / water management, predominant source of income of the household, land tenure type, crop diversity, agricultural surface expansion, and the presence of forest cover. They are based on the primary data of the full, latest available agricultural census in Mexico and corresponding official land use / land cover data. The second dataset consists of four food security indicators designed and built for the first food security model in Mexico that incorporates food availability, food accessibility and food utilization aspects. They include the Food Self-sufficiency Index (the balance between food production and food consumption), the Food Access Index (inversely related to marginalization), the Entitlement to Public Health Care index, and the Undernutrition Infrequency index (related to hospital sickness records). We provide the path tables and diagrams that describe the links between the agricultural structure and food security. These diagrams provide the first nationwide statistical evidence for the prominent role of smallholder agriculture in rural food security at the national level and at ecoregion scale for a country of the global South. In order to further investigate the structure of the agricultural production units and their relationships with socio-economic, territorial and landscape data, artificial intelligence (i.e. data mining and machine learning) techniques could be performed on this compendium of datasets. The food security data may stir the development of more food security models in Mexico in relation to other drivers such as consumption habits and non-agricultural activities of rural households.

13.
Geospat Health ; 17(1)2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35579246

RESUMEN

Malnutrition is one of the main risk factors related to chronic non-communicable diseases and child undernourishment on a planetary scale. Mexico is one of the countries with the highest levels of malnutrition, but there is also an accelerated increase in overweight or obesity. This study explored the spatiotemporal behaviour of mortality associated with chronic non-communicable diseases such as type II diabetes mellitus, hypertension, ischemic heart disease and cerebrovascular disease. The analysis was carried out at the municipality level for the 2000-2020 period targeting two age groups: ≥60-year olds and 20-59-year olds. In addition, 0-4-year olds were investigated with respect to undernourishment. National databases were gathered and standardized for each disease and SaTScan spatiotemporal cluster analyses were performed. We found that mortality associated with most of the diseases evaluated has increased since 2016 except for mortality caused by child undernourishment, which showed a downward trend during the study period. To focus on active conglomerates of diseases is important as they currently represent a threat to public health. Our results contribute to the potential spatial prioritization of the allocation of resources and campaigns for prevention and treatment of chronic non-communicable diseases and child undernourishment. Generally, geographical studies are fundamental for the discovery of disease aetiology and they provide valuable and timely information to multiple stakeholders.


Asunto(s)
Trastornos de la Nutrición del Niño , Diabetes Mellitus Tipo 2 , Desnutrición , Enfermedades no Transmisibles , Niño , Salud Global , Humanos , Desnutrición/epidemiología , México/epidemiología
14.
J Cell Biol ; 221(4)2022 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-35171230

RESUMEN

The molecular circuitry that causes stem cells to exit from pluripotency remains largely uncharacterized. Using chromatin RNA in situ reverse transcription sequencing, we identified Peln1 as a novel chromatin RNA component in the promoter complex of Oct4, a stem cell master transcription factor gene. Peln1 was negatively associated with pluripotent status during somatic reprogramming. Peln1 overexpression caused E14 cells to exit from pluripotency, while Peln1 downregulation induced robust reprogramming. Mechanistically, we discovered that Peln1 interacted with the Oct4 promoter and recruited the DNA methyltransferase DNMT3A. By de novo altering the epigenotype in the Oct4 promoter, Peln1 dismantled the intrachromosomal loop that is required for the maintenance of pluripotency. Using RNA reverse transcription-associated trap sequencing, we showed that Peln1 targets multiple pathway genes that are associated with stem cell self-renewal. These findings demonstrate that Peln1 can act as a new epigenetic player and use a trans mechanism to induce an exit from the pluripotent state in stem cells.


Asunto(s)
Cromosomas de los Mamíferos/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Línea Celular , Reprogramación Celular/genética , Metilación de ADN/genética , ADN Metiltransferasa 3A/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Factor 3 de Transcripción de Unión a Octámeros , Unión Proteica , ARN Largo no Codificante/genética
15.
Front Public Health ; 9: 654410, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34869133

RESUMEN

This is the first pilot study on alternative conceptions and obstacles pertaining to pneumonia in adolescents of different school vulnerability indexes. Countries with low socioeconomic levels are disproportionately affected, with Latin America and the Caribbean (LAC) being the second-most affected area in the world, after sub-Saharan Africa. In spite of this fact, pneumonia is not included as an important component within the contents of the microbiology curriculum unit in the natural science school program. Therefore, we wanted to study how students knew about this topic by putting One Health into action by building and validating qualitative and quantitative questionnaires, put together by different experts in pedagogy, didactics, microbiology, and veterinary to find out what students knew about pneumonia and their misconceptions about it. A total of 148 students (in 8th and 9th grade) participated in this survey. The results reveal that no statistically significant differences between the different scholar grades (p = 0.3360 Pearson chi∧2) or genders (p = 0.8000 Fisher's exact test) presented higher or lower School Vulnerability Index (SVI). Regardless of the social stratum or the level of vulnerability of the students, they have heard about this disease primarily through their family/relatives, maintaining a superficial notion of the disease, learning wrong ideas about microorganisms and treatments that can contribute to the risk to public health.


Asunto(s)
Curriculum , Salud Única , Adolescente , Femenino , Humanos , Masculino , Proyectos Piloto , Instituciones Académicas , Estudiantes
16.
Sci Immunol ; 6(65): eabi8823, 2021 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-34797693

RESUMEN

TNF and IL-17 are two cytokines that drive dysregulated keratinocyte activity, and their targeting is highly efficacious in patients with psoriasis, but whether these molecules act with other inflammatory factors is not clear. Here, we show that mice having a keratinocyte-specific deletion of Fn14 (Tnfrsf12a), the receptor for the TNF superfamily cytokine TWEAK (Tnfsf12), displayed reduced imiquimod-induced skin inflammation, including diminished epidermal hyperplasia and less expression of psoriasis signature genes. This corresponded with Fn14 being expressed in keratinocytes in human psoriasis lesions and TWEAK being found in several subsets of skin cells. Transcriptomic studies in human keratinocytes revealed that TWEAK strongly overlaps with IL-17A and TNF in up-regulating the expression of CXC chemokines, along with cytokines such as IL-23 and inflammation-associated proteins like S100A8/9 and SERPINB1/B9, all previously found to be highly expressed in the lesional skin of patients with psoriasis. TWEAK displayed strong synergism with TNF or IL-17A in up-regulating messenger RNA for many psoriasis-associated genes in human keratinocytes, including IL23A, IL36G, and multiple chemokines, implying that TWEAK acts with TNF and IL-17 to enhance feedback inflammatory activity. Correspondingly, therapeutic treatment of mice with anti-TWEAK was equally as effective as antibodies to IL-17A or TNF in reducing clinical and immunological features of psoriasis-like skin inflammation and combination targeting of TWEAK with either cytokine had no greater inhibitory effect, reinforcing the conclusion that all three cytokines function together. Thus, blocking TWEAK could be comparable to targeting TNF or IL-17 and might be considered as an alternate therapeutic treatment for psoriasis.


Asunto(s)
Citocina TWEAK/inmunología , Interleucina-17/inmunología , Queratinocitos/inmunología , Psoriasis/inmunología , Factores de Necrosis Tumoral/inmunología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Psoriasis/terapia
17.
Front Public Health ; 9: 637901, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33718324

RESUMEN

Introduction: Biodiversity is inextricably linked to human health. As an important area of research of the Convention on Biological Diversity and a key avenue for the dissemination of biodiversity and health knowledge, we investigated how well-embedded biodiversity and health interlinkages are in institutional higher education offerings. Methods: Using One Health education programs as a starting point, we collected a global list of institutions potentially carrying out education in the links between biodiversity and health through previously published research, academic partners of global conglomerates, and our own networks. We then analyzed the offerings from these institutions to determine the degree of integration of biodiversity and health interlinkages. Results: We found 105 educational offerings in biodiversity and health interlinkages from 89 institutions in 30 countries. These were primarily found in faculties of public health, veterinary sciences, and medicine, with varying degrees of coverage of the interlinkages. Conclusion: Education incorporating the links between biodiversity and health exists globally, but should be more widely integrated, particularly through inter-faculty and inter-institutional collaboration.


Asunto(s)
Biodiversidad , Docentes , Humanos
18.
Front Public Health ; 9: 687110, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34631640

RESUMEN

Professionals throughout the world have been working to assess the interdisciplinary interaction and interdependence between health and wellbeing in a constantly changing environment. The One Health concept was developed to encourage sustainable collaborative partnerships and to promote optimal health for people, animals, plants, the environment, and the whole planet. The dissemination of scientific discoveries and policies, by working directly with diverse communities, has been one of the main goals for Global One Health. The One Health concept has also been referred or related to as "One Medicine, One Medicine-One Health, One World-One Health, EcoHealth," and Planetary Health," depending on each fundamental view and approach. In Latin America, despite the concept still being discussed among health professionals and educators, several One Health initiatives have been used daily for more than decades. One Health action has been applied especially in rural and underserved urban areas where low socioeconomic status, lack of health professionals, and scarcity of medical resources may require professionals to work together. Local communities from diverse social and economic statuses, including indigenous populations have been working with institutions and social organizations for many years, accomplishing results through grassroots movements. These "bottom-up" socio-community approaches have also been tools for the prevention and control of diseases, such practice has preceded the One Health concepts in Latin American countries. It is strongly believed that collaborative, multidisciplinary, political, and economic initiatives with prosocial focus may become investments toward obtaining significant results in the face of global, economic and health challenges; working for a healthier world with inclusivity, equity, and equality. In this study, it is briefly presented how the One Health approach has been initiated and developed in Latin America, highlighting the events and actions taken in Brazil, Chile, and Colombia.


Asunto(s)
Salud Única , Brasil/epidemiología , Chile , Colombia , Humanos , América Latina/epidemiología
19.
Genome Biol ; 22(1): 233, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34412677

RESUMEN

BACKGROUND: A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter. RESULTS: We identify Platr10 as an Oct4 - Sox2 binding lncRNA that is activated in somatic cell reprogramming. Platr10 is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressed Platr10 functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show that Platr10 interacts with multiple pluripotency-associated genes, including Oct4, Sox2, Klf4, and c-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate that Platr10 helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show that Platr10 contains an Oct4 binding element that interacts with the Oct4 promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishes Platr10 activity. CONCLUSION: These data suggest that Platr10 functions as a novel chromatin RNA molecule to control pluripotency in trans by modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.


Asunto(s)
Reprogramación Celular , Cromatina/metabolismo , Células Madre Pluripotentes/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Metilación de ADN , Fibroblastos/metabolismo , Ratones , Factor 3 de Transcripción de Unión a Octámeros/genética , Regiones Promotoras Genéticas , ARN Largo no Codificante/genética , Secuencias Reguladoras de Ácidos Nucleicos , Factores de Transcripción SOXB1/metabolismo , Análisis de Secuencia de ARN
20.
Biol Res ; 43(1): 75-81, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21157634

RESUMEN

In this report, we explore the matching of structures to functional needs by comparing previously reported data of maximal oxygen consumption and the development of the lung in the leaf-eared mouse Phyllotis darwini in warm and cold environments. We discuss whether the state of structural design is commensurate with functional needs from regulated morphogenesis as predicted by the hypothesis of symmorphosis. We found a close match between respiratory structures and functional needs during postnatal development, expressed as safety factors close to unity. However, in the adult stage the safety factors were greater than two, which suggests that adult animals acquired a structure greater than that required considering their maximum capacities. A high safety factor in the respiratory system of adult mice may be a consequence of the symmorphosis that operates during ontogeny and does not necessarily support a rejection of this hypothesis.


Asunto(s)
Pulmón/crecimiento & desarrollo , Consumo de Oxígeno/fisiología , Sigmodontinae/fisiología , Adaptación Fisiológica , Animales , Metabolismo Basal/fisiología , Constitución Corporal , Frío , Femenino , Calor , Pulmón/fisiología , Masculino , Ratones , Sigmodontinae/clasificación
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