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1.
Front Res Metr Anal ; 9: 1355393, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903656

RESUMEN

The relevance of science diplomacy and open science in today's world is undeniable. Science diplomacy enables countries to jointly address pressing global challenges, such as climate change, pandemics, and food security. Open science, promoting accessible and transparent research, plays a pivotal role in this context. Nevertheless, the degree of openness is subject to specific circumstances, contingent upon varying factors, including local knowledge and resources. Latin America has not only been at the forefront of pioneering open access strategies, making it an interesting case to study, but it has also shown a tangible interest in using science diplomacy. Our research employs a mixed-methods approach, incorporating a quantitative survey involving 50 organizations and initiatives dedicated to promoting open science in Latin America, along with two qualitative focus group studies. Our primary objective is to assess if and how these entities use science diplomacy to achieve their objectives. Non-policy entities were prioritized due to their institutional stability in the region. We highlight successful strategies and delve into the existing barriers hindering the full implementation of open science principles. Our research aims to enhance collaboration between these organizations and policy and decision-makers by providing a set of recommendations in that direction. By shedding light on the current landscape and dynamics of open science in Latin America, we aspire to focus on science diplomacy, facilitate informed decision-making, and formulate policies that further propel the region along the path of openness, collaboration, and innovation in scientific research.

2.
Blood Cancer Discov ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856693

RESUMEN

Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences of SF3B1 mutations in human HSCs remain unclear. Here, we identify the mis-splicing program in human HSCs as a targetable vulnerability by precise gene editing of SF3B1 K700E mutations in primary CD34+ cells. Mutant SF3B1 induced pervasive mis-splicing and reduced expression of genes regulating mitosis and genome maintenance leading to altered differentiation, delayed G2/M progression, and profound sensitivity to CHK1 inhibition (CHK1i). Mis-splicing or reduced expression of mitotic regulators BUBR1 and CDC27 delayed G2/M transit and promoted CHK1i sensitivity. Clinical CHK1i prexasertib selectively targeted SF3B1-mutant HSCs and abrogated engraftment in vivo. These findings identify mis-splicing of mitotic regulators in SF3B1-mutant HSCs as a targetable vulnerability engaged by pharmacological CHK1 inhibition.

3.
Mol Cell ; 84(10): 1886-1903.e10, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38688280

RESUMEN

Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing, yet there is currently no therapeutic means to correct this mis-splicing. Here, we utilize synthetic introns uniquely responsive to mutant SF3B1 to identify trans factors required for aberrant mutant SF3B1 splicing activity. This revealed the G-patch domain-containing protein GPATCH8 as required for mutant SF3B1-induced splicing alterations and impaired hematopoiesis. GPATCH8 is involved in quality control of branchpoint selection, interacts with the RNA helicase DHX15, and functionally opposes SURP and G-patch domain containing 1 (SUGP1), a G-patch protein recently implicated in SF3B1-mutant diseases. Silencing of GPATCH8 corrected one-third of mutant SF3B1-dependent splicing defects and was sufficient to improve dysfunctional hematopoiesis in SF3B1-mutant mice and primary human progenitors. These data identify GPATCH8 as a novel splicing factor required for mis-splicing by mutant SF3B1 and highlight the therapeutic impact of correcting aberrant splicing in SF3B1-mutant cancers.


Asunto(s)
Neoplasias Hematológicas , Mutación , Fosfoproteínas , Factores de Empalme de ARN , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Humanos , Animales , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/metabolismo , Ratones , Empalme del ARN , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Hematopoyesis/genética , Células HEK293 , Intrones , ARN Helicasas/genética , ARN Helicasas/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
4.
Nucleic Acids Res ; 52(6): e34, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38375914

RESUMEN

Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway. Here, we present a system of reporters for comparative studies of EJC-independent and EJC-enhanced NMD. This system also enables the study of NMD-associated outcomes such as premature termination codon (PTC) readthrough and truncated protein degradation. These reporters are compatible with fluorescence or luminescence-based readouts via transient transfection or stable integration. Using this reporter system, we show that EJC-enhanced NMD RNA levels are reduced by 2- or 9-fold and protein levels are reduced by 7- or 12-fold compared to EJC-independent NMD, depending on the reporter gene used. Additionally, the extent of readthrough induced by G418 and an NMD inhibitor (SMG1i), alone and in combination, varies across NMD substrates. When combined, G418 and SMG1i increase readthrough product levels in an additive manner for EJC-independent reporters, while EJC-enhanced reporters show a synergistic effect. We present these reporters as a valuable toolkit to deepen our understanding of NMD and its associated mechanisms.


Asunto(s)
Exones , Genes Reporteros , Técnicas Genéticas , Degradación de ARNm Mediada por Codón sin Sentido , Exones/genética , Degradación de ARNm Mediada por Codón sin Sentido/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Humanos , Células HEK293 , Genes Reporteros/genética
5.
Hepatología ; 5(1): 25-33, ene 2, 2024. fig, tab
Artículo en Español | LILACS | ID: biblio-1525306

RESUMEN

Las enfermedades hepáticas presentan múltiples manifestaciones sistémicas, entre las cuales se destacan los hallazgos en piel, siendo los más comunes el prurito y la ictericia; así mismo, se pueden encontrar angiomas en araña, eritema palmar, xantomas, vasculitis y cambios en anexos. Este artículo tiene como objetivo describir los principales signos y síntomas cutáneos en las enfermedades hepáticas para brindar herramientas semiológicas al clínico en su práctica diaria


Liver disease present multiple systemic manifestations, among which skin findings stand out, being the most common pruritus and jaundice. Other findings can also be manifested like spider angiomas, palmar erythema, xanthomas, vasculitis and changes in skin appendages. The objective of this article is to describe the main skin signs and symptoms of liver diseases to provide semiological tools to the physician in his daily practice.


Asunto(s)
Humanos
6.
bioRxiv ; 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38014198

RESUMEN

Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway. Here, we present a system of reporters for comparative studies of EJC-independent and EJC-enhanced NMD. This system also enables the study of NMD-associated outcomes such as premature termination codon (PTC) readthrough and truncated protein degradation. These reporters are compatible with fluorescence or luminescence-based readouts via transient transfection or stable integration. Using this reporter system, we show that EJC-enhanced NMD RNA levels are reduced by 2- or 9-fold and protein levels are reduced by 7- or 12-fold compared to EJC-independent NMD, depending on the reporter gene used. Additionally, the extent of readthrough induced by G418 and SMG1i, alone and in combination, varies across NMD substrates. When combined, G418 and SMG1i increase readthrough product levels in an additive manner for EJC-independent reporters, while EJC-enhanced reporters show a synergistic effect. We present these reporters as a valuable toolkit to deepen our understanding of NMD and its associated mechanisms.

7.
RNA ; 29(7): 865-884, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37024263

RESUMEN

The gene expression pathway from DNA sequence to functional protein is not as straightforward as simple depictions of the central dogma might suggest. Each step is highly regulated, with complex and only partially understood molecular mechanisms at play. Translation is one step where the "one gene-one protein" paradigm breaks down, as often a single mature eukaryotic mRNA leads to more than one protein product. One way this occurs is through translation reinitiation, in which a ribosome starts making protein from one initiation site, translates until it terminates at a stop codon, but then escapes normal recycling steps and subsequently reinitiates at a different downstream site. This process is now recognized as both important and widespread, but we are only beginning to understand the interplay of factors involved in termination, recycling, and initiation that cause reinitiation events. There appear to be several ways to subvert recycling to achieve productive reinitiation, different types of stresses or signals that trigger this process, and the mechanism may depend in part on where the event occurs in the body of an mRNA. This perspective reviews the unique characteristics and mechanisms of reinitiation events, highlights the similarities and differences between three major scenarios of reinitiation, and raises outstanding questions that are promising avenues for future research.


Asunto(s)
Proteínas , Ribosomas , Ribosomas/genética , Ribosomas/metabolismo , Codón de Terminación/genética , Secuencia de Bases , Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sistemas de Lectura Abierta , Biosíntesis de Proteínas
8.
Rev. colomb. cardiol ; 29(6): 663-675, dic. 2022. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1423797

RESUMEN

Resumen: La hiperlipidemia es altamente prevalente y contribuye de forma sustancial a la enfermedad cardiovascular aterosclerótica, que es una de las principales causas de morbilidad y mortalidad en Colombia. La reducción del colesterol LDL (c-LDL) produce una disminución del riesgo de enfermedad cardiovascular aterosclerótica y de eventos cardiovasculares adversos. La terapia dirigida a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9; su sigla en inglés) ha surgido como una herramienta novedosa para el tratamiento de la hiperlipidemia. Inclisiran es un ARN pequeño de doble hebra, que actúa inhibiendo la transcripción de PCSK-9 en los hepatocitos, lo que conduce a una reducción marcada y sostenida del c-LDL. En contraste con otras terapias hipolipemiantes, como estatinas, ezetimibe y anticuerpos monoclonales (MAbs; su sigla en inglés) e inhibidores de PCSK9, inclisiran propone un régimen de dosificación infrecuente de dos o tres veces al año. Su efecto prolongado representa una ventaja frente al incumplimiento del tratamiento, que es una de las principales causas por las que no se alcanzan los objetivos de c-LDL con la terapia estándar. Esta revisión tiene como objetivo presentar y discutir los datos científicos actuales con relación a la eficacia, tolerabilidad y seguridad del inclisiran en el tratamiento de la hipercolesterolemia.


Abstract: Hyperlipidemia is a highly prevalent condition and contributes substantially to atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Colombia. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies (MAbs) PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice or three times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia.

9.
Pediatr Emerg Care ; 38(9): e1496-e1502, 2022 Sep 01.
Artículo en Español, Inglés | MEDLINE | ID: mdl-35802481

RESUMEN

OBJECTIVE: Sepsis is one of the most urgent health care issues worldwide. Guidelines for early identification and treatment are essential to decrease sepsis-related mortality. Our aim was to collect data on the epidemiology of pediatric septic shock (PSS) from the emergency department (PED) and to assess adherence to recommendations for its management in the first hour. METHODS: A multicenter, prospective, cross-sectional study was conducted evaluating children with PSS seen at the PED of 10 tertiary-care centers in Latin America. Adherence to guidelines was evaluated. RESULTS: We included 219 patients (median age, 3.7 years); 43% had comorbidities, 31% risk factors for developing sepsis, 74% clinical signs of "cold shock," and 13% of "warm shock," 22% had hypotension on admission. Consciousness was impaired in 55%. A peripheral line was used as initial access in 78% (median placement time, 10 minutes). Fluid and antibiotics infusion was achieved within a median time of 30 minutes (interquartile range [IQR], 20-60 minutes) and 40 minutes (IQR, 20-60 minutes), respectively; 40% responded inadequately to fluids requiring vasoactive drugs (median time at initiation, 60 minutes; IQR, 30-135 minutes). Delay to vasoactive drug infusion was significantly longer when a central line was placed compared to a peripheral line (median time, 133 minutes [59-278 minutes] vs 42 minutes [30-70 minutes], respectively [ P < 0.001]). Adherence to all treatment goals was achieved in 13%. Mortality was 10%. An association between mortality and hypotension on admission was found (26.1% with hypotension vs 4.9% without; P < 0.001). CONCLUSIONS: We found poor adherence to the international recommendations for the treatment of PSS in the first hour at the PED in third-level hospitals in Latin America.


OBJECTIVE: Sepsis is one of the most urgent health care issues worldwide. Guidelines for early identification and treatment are essential to decrease sepsis-related mortality. Our aim was to collect data on the epidemiology of pediatric septic shock (PSS) from the emergency department (PED) and to assess adherence to recommendations for its management in the first hour. METHODS: A multicenter, prospective, cross-sectional study was conducted evaluating children with PSS seen at the PED of 10 tertiary-care centers in Latin America. Adherence to guidelines was evaluated. RESULTS: We included 219 patients (median age, 3.7 years); 43% had comorbidities, 31% risk factors for developing sepsis, 74% clinical signs of "cold shock," and 13% of "warm shock," 22% had hypotension on admission. Consciousness was impaired in 55%. A peripheral line was used as initial access in 78% (median placement time, 10 minutes). Fluid and antibiotics infusion was achieved within a median time of 30 minutes (interquartile range [IQR], 20­60 minutes) and 40 minutes (IQR, 20­60 minutes), respectively; 40% responded inadequately to fluids requiring vasoactive drugs (median time at initiation, 60 minutes; IQR, 30­135 minutes). Delay to vasoactive drug infusion was significantly longer when a central line was placed compared to a peripheral line (median time, 133 minutes [59­278 minutes] vs 42 minutes [30­70 minutes], respectively [ P < 0.001]). Adherence to all treatment goals was achieved in 13%. Mortality was 10%. An association between mortality and hypotension on admission was found (26.1% with hypotension vs 4.9% without; P < 0.001). CONCLUSIONS: We found poor adherence to the international recommendations for the treatment of PSS in the first hour at the PED in third-level hospitals in Latin America.


Asunto(s)
Hipotensión , Sepsis , Choque Séptico , Niño , Preescolar , Estudios Transversales , Servicio de Urgencia en Hospital , Humanos , América Latina/epidemiología , Estudios Prospectivos , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Sepsis/epidemiología , Choque Séptico/diagnóstico , Choque Séptico/epidemiología , Choque Séptico/terapia
10.
Front Res Metr Anal ; 7: 893593, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35663098

RESUMEN

The current knowledge society has driven an unprecedented mobility of people, especially scientists, from emerging economies to developed countries. This mobility can allow the development of human talent and the access to first class infrastructure and resources, but it can also mean a loss for emerging economies due to the phenomenon of brain drain. To counteract this situation, some countries in Latin America and the Caribbean have developed models for the articulation of their scientific diaspora in projects and programs, with the aim of exchanging knowledge and capitalizing on human and technical resources to advance science, technology and innovation systems. Likewise, science diplomacy has become a tool for interlinking the work of various actors in order to advance the solution of national, transnational or global problems through scientific advice. Scientific diasporas are vital in new structures of cooperation, enabling them to innovate and solve problems jointly, advising their countries of origin and articulating policies and programs. This research seeks to analyze the interactions and initiatives identified between the organized scientific diaspora from Latin America and the Caribbean and their countries of origin in relation to science diplomacy processes, providing recommendations and proposals for public policy to improve the interaction between the diaspora and the governments of their countries of origin. Results show that diaspora organizations from Latin America and the Caribbean engage with governmental and non-state actors and are active science diplomacy stakeholders promoting the scientific developments of their country or their researchers, as well as enabling access to research resources creating alliances for scientific, institutional and academic collaborations. In the cases studied, these efforts are planned and executed by the diaspora without responding to any science diplomacy strategy of the country. Policies and programs are needed to effectively link the scientific diaspora organizations to the interests of the countries.

11.
Rev. Fac. Med. Hum ; 22(2): 232-243, Abril.- Jun. 2022.
Artículo en Inglés, Español | LILACS-Express | LILACS | ID: biblio-1371488

RESUMEN

Introducción. Para mejorar la calidad de atención en los Servicios de Emergencias Pediátricas (SEP), es indispensable realizar mediciones y relevamientos. Objetivo. Describir los recursos y funcionamiento de los SEP de hospitales públicos de Latinoamérica. Métodos. Estudio descriptivo, cuantitativo y retrospectivo. Encuesta realizada en SEP de hospitales latinoamericanos con financiación pública y con Unidad de Cuidados Intensivos Pediátricos (UCIP) (2019). Datos procesados mediante programas REDcap e InfoStat. Se presentan variables continuas como medianas y rangos; variables categóricas, como porcentajes; relaciones de productividad/recursos como razón. Se realizó análisis univariado. Resultados.De 371 servicios en 17 países, 107 (28,8%) contestaron la encuesta. Ciento dos servicios (95,3%) tienen sector de observación y 42(39,3%), salas de aislamiento. La mediana de consultas anuales/cama de observación fue 4830,6; la mediana de consultas diarias/consultorio 24,4. 6,1% de las consultas requirieron internación y 2,0% fueron asistidas en el Sector de Reanimación. Treinta y siete SEP (34,6%) disponen de > 80% de 27 ítems considerados imprescindibles por la Federación Internacional de Emergencias; 43 SEP (40,2%) carecen de equipo completo de vía aérea.En 74 servicios (69,2%) se realiza triaje. La mediana de consultas diarias es de 38,4/médico y 35,3/enfermero.En 83(77,6%) centros se manejan datos informatizados. En 68 SEP (64,1%) se utilizan cinco protocolos de situaciones críticas. En 10(9,4%) el personal médico cuenta con horario de docencia/investigación. Existe plan de mejora de calidad en 43 (41%) servicios. Conclusión. La información obtenida sobre los recursos y funcionamiento de los SEP públicos en Latinoamérica revela brechas importantes.


Introduction: To improve the quality of care in Pediatric Emergency Services (SEP) it is essential to carry out measurements and surveys. Purpose: Describe the resources and operation of the SEPs of public hospitals in Latin America. Methods: Descriptive, quantitative and retrospective study. Survey conducted in SEP of Latin American hospitals with public funding and with PICU (2019). Data processed by REDcap and InfoStat programs. Continuous variables are presented as medians and ranges; categorical variables as percentages; productivity / resource ratios as a ratio. Univariate analysis was performed. Results: Of 371 services in 17 countries, 107 (28.8%) answered the survey; 102 (95.3%) have an observation area and 42 (39.3%) have isolation rooms. The medians of annual visits / observation bed and daily visits / clinic were 4830.6 and 24.4, respectively. The number of beds increased by 74.1% in the seasonal peak, 6.1% of the consultations required hospitalization and 2.0% were assisted in the Resuscitation Sector. 37 (34.6%) SEP have> 80% of 27 items considered essential by the International Emergency Federation, 43 (40.2%) lack complete airway equipment and 74 (69.2%) perform triage. The median number of daily consultations is 38.4 / doctor and 35.3 / nurse. In 72 (67.9%) SEP there is a doctor and a nurse coordinator per shift, in 83 (77.6%) computerized data are handled, in 25 (23.4%) they do not perform diagnostic coding and in 16 (15% ) discharge summary is not prepared. 68 (64.1%) SEP use 5 protocols for critical situations, in 10 (9.4%) the medical personnel have teaching / research hours and in 43 (41%) there is a quality improvement plan. Conclusions:The information obtained regarding resources and operation of public PEDs in Latin America reveals important gaps.

12.
Development ; 148(13)2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34121118

RESUMEN

Development of a branching tree in the embryonic lung is crucial for the formation of a fully mature functional lung at birth. Sox9+ cells present at the tip of the primary embryonic lung endoderm are multipotent cells responsible for branch formation and elongation. We performed a genetic screen in murine primary cells and identified aurora kinase b (Aurkb) as an essential regulator of Sox9+ cells ex vivo. In vivo conditional knockout studies confirmed that Aurkb was required for lung development but was not necessary for postnatal growth and the repair of the adult lung after injury. Deletion of Aurkb in embryonic Sox9+ cells led to the formation of a stunted lung that retained the expression of Sox2 in the proximal airways, as well as Sox9 in the distal tips. Although we found no change in cell polarity, we showed that loss of Aurkb or chemical inhibition of Aurkb caused Sox9+ cells to arrest at G2/M, likely responsible for the lack of branch bifurcation. This work demonstrates the power of genetic screens in identifying novel regulators of Sox9+ progenitor cells and lung branching morphogenesis.


Asunto(s)
Aurora Quinasa B/genética , Aurora Quinasa B/metabolismo , Células Madre Embrionarias/metabolismo , Endodermo/metabolismo , Pulmón/embriología , Factor de Transcripción SOX9/metabolismo , Animales , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Noqueados , Organogénesis , Factor de Transcripción SOX9/genética
13.
Nature ; 591(7849): 281-287, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33568815

RESUMEN

Skeletal muscle regenerates through the activation of resident stem cells. Termed satellite cells, these normally quiescent cells are induced to proliferate by wound-derived signals1. Identifying the source and nature of these cues has been hampered by an inability to visualize the complex cell interactions that occur within the wound. Here we use muscle injury models in zebrafish to systematically capture the interactions between satellite cells and the innate immune system after injury, in real time, throughout the repair process. This analysis revealed that a specific subset of macrophages 'dwell' within the injury, establishing a transient but obligate niche for stem cell proliferation. Single-cell profiling identified proliferative signals that are secreted by dwelling macrophages, which include the cytokine nicotinamide phosphoribosyltransferase (Nampt, which is also known as visfatin or PBEF in humans). Nampt secretion from the macrophage niche is required for muscle regeneration, acting through the C-C motif chemokine receptor type 5 (Ccr5), which is expressed on muscle stem cells. This analysis shows that in addition to their ability to modulate the immune response, specific macrophage populations also provide a transient stem-cell-activating niche, directly supplying proliferation-inducing cues that govern the repair process that is mediated by muscle stem cells. This study demonstrates that macrophage-derived niche signals for muscle stem cells, such as NAMPT, can be applied as new therapeutic modalities for skeletal muscle injury and disease.


Asunto(s)
Macrófagos/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/lesiones , Mioblastos/citología , Nicotinamida Fosforribosiltransferasa/metabolismo , Nicho de Células Madre , Pez Cebra/metabolismo , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Humanos , Macrófagos/citología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mioblastos/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Factor de Transcripción PAX7/metabolismo , RNA-Seq , Receptores CCR5/genética , Receptores CCR5/metabolismo , Regeneración/fisiología , Análisis de la Célula Individual , Pez Cebra/inmunología
14.
Opt Express ; 28(6): 8528-8540, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32225476

RESUMEN

A coupled deep learning approach for coded aperture design and single-pixel measurements classification is proposed. A whole neural network is trained to simultaneously optimize the binary sensing matrix of a single-pixel camera (SPC) and the parameters of a classification network, considering the constraints imposed by the compressive architecture. Then, new single-pixel measurements can be acquired and classified with the learned parameters. This method avoids the reconstruction process while maintaining classification reliability. In particular, two network architectures were proposed, one learns re-projected measurements to the image size, and the other extracts small features directly from the compressive measurements. They were simulated using two image data sets and a test-bed implementation. The first network beats in around 10% the accuracy reached by the state-of-the-art methods. A 2x increase in computing time is achieved with the second proposed net.

15.
Appl Opt ; 58(7): B28-B38, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30874201

RESUMEN

Compressive spectral imaging (CSI) systems sense 3D spatio-spectral data cubes with just a few two-dimensional (2D) projections by using a coded aperture, a dispersive element, and a focal plane array (FPA). The coded apertures in these systems, whose main function is the modulation of the data cube, are often implemented through photomasks attached to piezoelectric devices. A remarkable improvement on this configuration has been recently proposed, the replacement of the block-unblock coded apertures by patterned optical filter arrays, referred to as "colored" coded apertures, which allow spatial and spectral modulation. When using these colored coded apertures, its real implementation in terms of cost and complexity directly depends on the number of filters to be used, as well as the number of shots to be captured. A shifting colored coded aperture optimization featuring these observations is proposed, with the aim to improve the imaging quality reconstruction and to generate an achievable optical implementation with a limited number of filters requiring only one mask to acquire any number of shots. The mathematical model of the computational imaging strategy to overcome the practical limitations of actual CSI systems is presented along with a testbed implementation. Simulations, as well as experimental results, will prove the accuracy and performance of the proposed shifting colored coded aperture design over the current literature designs.

16.
Pediatr. (Asunción) ; 44(3)dic. 2017.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1506956

RESUMEN

Este documento pretende poner al alcance de todo profesional de salud una guía actualizada en el diagnóstico y manejo de la gastroenteritis aguda en pediatría, ya que esta enfermedad es una de las principales causas de consultas y hospitalizaciones. Se realizó una revisión exhaustiva de la literatura proponiendo una herramienta útil con el objetivo de reducir el impacto de la enfermedad en términos de incidencia, morbilidad y mortalidad. El tratamiento de la gastroenteritis debe ir dirigido a la prevención de la deshidratación y el desequilibrio electrolítico que produce, con líquidos adecuados, sales de rehidratación oral y el mantenimiento de la alimentación oral. La causa de esta enfermedad es principalmente viral y los criterios para el uso de antibióticos es controversial. Los coadyuvantes para disminuir el tiempo de enfermedad así como la frecuencia de la diarrea, en muchos de los casos están en estudio; por lo tanto el manejo guiado, estructurado y sistematizado garantizará en muchos casos el éxito del tratamiento de la gastroenteritis en los niños.


This document aims to provide an updated guideline for the diagnosis and management of acute gastroenteritis in pediatrics, as this disease is one of the main causes of consultations and hospitalizations. By performing an exhaustive review of the literature to produce a useful tool, this proposal aims to reduce the impact of the disease incidence, morbidity and mortality. The goal of gastroenteritis treatment is to prevent dehydration and electrolyte imbalance that it can produce, with adequate liquids, oral rehydration salts and maintenance of oral feeding. The causes of this disease are mostly viral and the criteria for antibiotic use is controversial. Treatment modalities to reduce the time of illness as well as the frequency of diarrhea are, in many cases, currently under study; therefore, guided, structured and systematized management will ensure the successful treatment of gastroenteritis in most children.

17.
Appl Opt ; 56(22): 6332-6340, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29047832

RESUMEN

Coded aperture compressive spectral imagers (CSI) sense a three-dimensional data cube by using two-dimensional projections of the coded and spectrally dispersed input image. Recently, it has been shown that by combining spectral images acquired from a CSI sensor and a complementary sensor leads to substantial improvement in the quality of the fused image. To maximally exploit the benefits of the complementary information, the spatial structure of the coded apertures must be optimized inasmuch as these structures determine the sensing matrix properties and, accordingly, the quality of the reconstructed images. This paper proposes a method to use side information from a red-green-blue sensor to design the coded aperture patterns of a CSI imager, such that more detailed spatial images and wavelength profiles can be reconstructed. The side information is used as the input of an edge detection algorithm to approximate a version of the edges of the spectral images. The coded apertures are designed to follow the spatial structure determined by the estimated spectral edges, such that the high frequencies are promoted, leading to more detailed reconstructed spectral images. Simulations and experimental results indicate that when compared with random coded aperture structures, the designed coded apertures based on side information obtain up to 3 dB improvement in the quality of the reconstructed images.

18.
Genom Data ; 5: 346-51, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26484284

RESUMEN

The adaptation of the lungs to air breathing at birth requires the fine orchestration of different processes to control lung morphogenesis and progenitor cell differentiation. However, there is little understanding of the role that epigenetic modifiers play in the control of lung development. We found that the histone methyl transferase Ezh2 plays a critical role in lung lineage specification and survival at birth. We performed a genome-wide transcriptome study combined with a genome-wide analysis of the distribution of H3K27 tri-methylation marks to interrogate the role of Ezh2 in lung epithelial cells. Lung cells isolated from Ezh2-deficient and control mice at embryonic day E16.5 were sorted into epithelial and mesenchymal populations based on EpCAM expression. This enabled us to dissect the transcriptional and epigenetic changes induced by the loss of Ezh2 specifically in the lung epithelium. Here we provide a detailed description of the analysis of the RNA-seq and ChIP-seq data, including quality control, read mapping, differential expression and differential binding analyses, as well as visualisation methods used to present the data. These data can be accessed from the Gene Expression Omnibus database (super-series accession number GSE57393).

19.
Development ; 142(8): 1458-69, 2015 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-25790853

RESUMEN

Epigenetic mechanisms involved in the establishment of lung epithelial cell lineage identities during development are largely unknown. Here, we explored the role of the histone methyltransferase Ezh2 during lung lineage determination. Loss of Ezh2 in the lung epithelium leads to defective lung formation and perinatal mortality. We show that Ezh2 is crucial for airway lineage specification and alveolarization. Using optical projection tomography imaging, we found that branching morphogenesis is affected in Ezh2 conditional knockout mice and the remaining bronchioles are abnormal, lacking terminally differentiated secretory club cells. Remarkably, RNA-seq analysis revealed the upregulation of basal genes in Ezh2-deficient epithelium. Three-dimensional imaging for keratin 5 further showed the unexpected presence of a layer of basal cells from the proximal airways to the distal bronchioles in E16.5 embryos. ChIP-seq analysis indicated the presence of Ezh2-mediated repressive marks on the genomic loci of some but not all basal genes, suggesting an indirect mechanism of action of Ezh2. We found that loss of Ezh2 de-represses insulin-like growth factor 1 (Igf1) expression and that modulation of IGF1 signaling ex vivo in wild-type lungs could induce basal cell differentiation. Altogether, our work reveals an unexpected role for Ezh2 in controlling basal cell fate determination in the embryonic lung endoderm, mediated in part by repression of Igf1 expression.


Asunto(s)
Diferenciación Celular/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Pulmón/citología , Pulmón/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Animales , Diferenciación Celular/genética , Inmunoprecipitación de Cromatina , Proteína Potenciadora del Homólogo Zeste 2 , Citometría de Flujo , Factor I del Crecimiento Similar a la Insulina/genética , Queratina-5/genética , Queratina-5/metabolismo , Pulmón/embriología , Ratones , Complejo Represivo Polycomb 2/genética , Reacción en Cadena de la Polimerasa
20.
Appl Opt ; 54(33): 9875-82, 2015 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-26836551

RESUMEN

Compressive spectral imaging (CSI) senses a scene by using two-dimensional coded projections such that the number of measurements is far less than that used in spectral scanning-type instruments. An architecture that efficiently implements CSI is the coded aperture snapshot spectral imager (CASSI). A physical limitation of the CASSI is the system resolution, which is determined by the lowest resolution element used in the detector and the coded aperture. Although the final resolution of the system is usually given by the detector, in the CASSI, for instance, the use of a low resolution coded aperture implemented using a digital micromirror device (DMD), which induces the grouping of pixels in superpixels in the detector, is decisive to the final resolution. The mismatch occurs by the differences in the pitch size of the DMD mirrors and focal plane array (FPA) pixels. A traditional solution to this mismatch consists of grouping several pixels in square features, which subutilizes the DMD and the detector resolution and, therefore, reduces the spatial and spectral resolution of the reconstructed spectral images. This paper presents a model for CASSI which admits the mismatch and permits exploiting the maximum resolution of the coding element and the FPA sensor. A super-resolution algorithm and a synthetic coded aperture are developed in order to solve the mismatch. The mathematical models are verified using a real implementation of CASSI. The results of the experiments show a significant gain in spatial and spectral imaging quality over the traditional grouping pixel technique.

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