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1.
NPJ Syst Biol Appl ; 10(1): 41, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632240

RESUMEN

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has significantly impacted global health, stressing the necessity of basic understanding of the host response to this viral infection. In this study, we investigated how SARS-CoV-2 remodels the landscape of small non-coding RNAs (sncRNA) from a large collection of nasopharyngeal swab samples taken at various time points from patients with distinct symptom severity. High-throughput RNA sequencing analysis revealed a global alteration of the sncRNA landscape, with abundance peaks related to species of 21-23 and 32-33 nucleotides. Host-derived sncRNAs, including microRNAs (miRNAs), transfer RNA-derived small RNAs (tsRNAs), and small nucleolar RNA-derived small RNAs (sdRNAs) exhibited significant differential expression in infected patients compared to controls. Importantly, miRNA expression was predominantly down-regulated in response to SARS-CoV-2 infection, especially in patients with severe symptoms. Furthermore, we identified specific tsRNAs derived from Glu- and Gly-tRNAs as major altered elements upon infection, with 5' tRNA halves being the most abundant species and suggesting their potential as biomarkers for viral presence and disease severity prediction. Additionally, down-regulation of C/D-box sdRNAs and altered expression of tinyRNAs (tyRNAs) were observed in infected patients. These findings provide valuable insights into the host sncRNA response to SARS-CoV-2 infection and may contribute to the development of further diagnostic and therapeutic strategies in the clinic.


Asunto(s)
COVID-19 , MicroARNs , ARN Pequeño no Traducido , Humanos , SARS-CoV-2/genética , ARN Pequeño no Traducido/genética , Pandemias , MicroARNs/genética
2.
Viruses ; 16(3)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38543710

RESUMEN

The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of respiratory viruses in bronchoalveolar lavage and induced sputum samples in PLHIV and correlate their presence with lung function. A prospective cohort of adults hospitalized in Medellín between September 2016 and December 2018 included three groups: group 1 = people diagnosed with HIV and a diagnosis of community-acquired pneumonia (CAP), group 2 = HIV, and group 3 = CAP. People were followed up with at months 1, 6, and 12. Clinical, microbiological, and spirometric data were collected. Respiratory viruses were detected by multiplex RT-PCR. Sixty-five patients were included. At least 1 respiratory virus was identified in 51.9%, 45.1%, and 57.1% of groups 1, 2 and 3, respectively. Among these, 89% of respiratory viruses were detected with another pathogen, mainly Mycobacterium tuberculosis (40.7%) and Pneumocystis jirovecii (22.2%). The most frequent respiratory virus was rhinovirus (24/65, 37%). On admission, 30.4% of group 1, 16.6% of group 2, and 50% of group 3 had airflow limitation, with alteration in forced expiratory volume at first second in both groups with pneumonia compared to HIV. Respiratory viruses are frequent in people diagnosed with HIV, generally coexisting with other pathogens. Pulmonary function on admission was affected in patients with pneumonia, improving significantly in the 1st, 6th, and 12th months after CAP onset.


Asunto(s)
Infecciones por VIH , Neumonía , Virus , Adulto , Humanos , Estudios Prospectivos , Estudios de Seguimiento , Neumonía/epidemiología , Virus/genética , Pulmón , Infecciones por VIH/complicaciones
3.
Biomedicines ; 12(3)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38540133

RESUMEN

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

4.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1535407

RESUMEN

Introducción: La pandemia por COVID-19 trajo consigo grandes cambios a nivel socioeconómico, producto de las medidas tomadas para mitigar su expansión, que implicó cierre de colegios y dificultad para el acceso a servicios de salud. Sin embargo, no se cuenta con mucha información respecto al impacto que estas medidas han tenido en la salud y el bienestar de niños y adolescentes, por lo cual se desarrolló una encuesta virtual para conocer la dimensión de los efectos de la pandemia en el bienestar integral de los menores y sus familias. Metodología: Estudio observacional de corte transversal que se realizó mediante la aplicación de una encuesta en formato electrónico a padres de familia de niños y adolescentes del Área Metropolitana de Bucaramanga. Resultados: Se obtuvieron 960 respuestas. El 25,63 % de los encuestados refieren cancelación de citas médicas. El 98 % de los estudiantes pudo continuar las actividades académicas durante el aislamiento. El factor económico fue la principal causa de preocupación en el periodo de la encuesta. Discusión: Durante el periodo de aislamiento, los problemas de salud mental, las dificultades para el acceso a herramientas para la educación virtual y las barreras para la atención, propias de la emergencia sanitaria, causaron efectos significativos en la calidad de vida de los menores. Conclusiones: Ante emergencias sanitarias, se deben mantener los servicios de atención en salud de la misma forma que se hacía previo a la ocurrencia del evento, como los programas de vacunación, crecimiento y desarrollo, promoción y prevención, además de la continuidad de la escolaridad.


Introduction: The COVID-19 pandemic has brought great changes along with, some of those were at the socioeconomic level, as a result of the actions taken to mitigate the virus expansion, which involved the closure of schools and restriction in accessing to some health services. However, there is not much information regarding the impact that these measures have had on the health and well-being of children and adolescents, for this reason, a virtual survey was developed to find out the dimension of the pandemic's effect on the comprehensive welfare of minors and families. Methodology: Cross-sectional observational study, which was carried out by applying a survey in electronic format to parents of children and adolescents in the Metropolitan Area of Bucaramanga. Results: A total of 960 responses were obtained. Of those surveyed, 25,63% refer cancellation of medical appointments. The 98% of students were able to continue academic activities during isolation. The economic factor was the main cause of concern in the survey period. Discussion: During the isolation period, mental health problems, difficulties in accessing tools for virtual education and barriers to care, typical of the health emergency, caused a significant effects on the quality of life of youngsters. Conclusions: In the event of health emergencies, health care services should be maintained in the same way as before the occurrence of the event, such as vaccination, growth and development, promotion and prevention programs, in addition to the continuity of schooling.

5.
Front Neuroanat ; 17: 1227933, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37662477

RESUMEN

Macroscopic staining in anatomical samples of the central nervous system is a technique that has been used for decades to achieve better differentiation of multiple gray matter structures, such as the cortex, basal ganglia, and cerebellar nuclei. Staining methods are based on using the different components of the brain, mainly the lipids present in the white matter. These techniques have been progressively forgotten while computer renderings are increasing; however, as a primary exposure to surgical anatomy, stained brain specimens are considered a helpful tool. We aim to summarize different staining techniques, their principles, and their current applications for neuroanatomy learning purposes. In total, four gray matter staining protocol descriptions (Mulligan's, Roberts's, Alston's, and Prussian Blue) were performed, as well as Likert scale surveys of second-year medical students about their perceptions of the stained sections. The results showed that the different macroscopic stains for brain tissue are based on lipid and reactant interactions, intending to increase the white matter (WM) and gray matter (GM) contrast. The search also showed that most staining protocols would take 2 days to develop. Efficient preservation options include submerging the sections in formaldehyde solutions, formaldehyde-free solutions, ethanol, or applying plastination techniques. Based on the student's perspective, the stained slices seem to be a valuable alternative to facilitate the study and identification of the basal ganglia and their relationships with the white matter (from 51.2 to 72% based on the Likert scale) compared with the non-stained sections. In conclusion, macroscopic staining of brain tissue continues to be a valuable tool for comprehensively studying the brain. Further research is needed to determine the efficacy of stained specimens as teaching tools.

6.
J Wrist Surg ; 12(4): 377-382, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37564625

RESUMEN

Background Synovial cysts (SCs) are the most frequent wrist tumors; the arthroscopic treatment presents good results when surgery is indicated for symptomatic or patients with cosmetic concerns. The tumoral lesion should be arthroscopically decompressed or drained toward the inside of the joint through pedicle opening and resection of a small portion of the capsule. Hence, the cyst pedicle must be found for the success of this technique. Description of Technique Some tricks have already been described to facilitate SC location during arthroscopy. We describe an indirect technique that employs an 18-G needle to enhance SC pedicle location and drainage. The technique involves a puncture on the interval of the carpal extrinsic ligaments where the pedicle is suspected to be remain. When found, cyst is drained with a single-puncture motion of the need which promotes cyst content extravasation due to pressure toward the joint. Patients and Methods This method has been employed in 16 patients, including 9 with dorsal cysts, and seven with volar cysts. Results All patients presented complete recovery and symptom improvement in up to 30 days, with total disappearance of the cyst. There were no relapses or severe complications within the 12-month follow-up. Conclusion This is a safe, useful technique that facilitates location of intra-articular cyst pedicle, thus avoiding unnecessary damage in healthy tissues with no increased costs.

7.
Plant Cell Environ ; 46(9): 2909-2927, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37378473

RESUMEN

Viroids are circular RNAs of minimal complexity compelled to subvert plant-regulatory networks to accomplish their infectious process. Studies focused on the response to viroid-infection have mostly addressed specific regulatory levels and considered specifics infection-times. Thus, much remains to be done to understand the temporal evolution and complex nature of viroid-host interactions. Here we present an integrative analysis of the temporal evolution of the genome-wide alterations in cucumber plants infected with hop stunt viroid (HSVd) by integrating differential host transcriptome, sRNAnome and methylome. Our results support that HSVd promotes the redesign of the cucumber regulatory-pathways predominantly affecting specific regulatory layers at different infection-phases. The initial response was characterised by a reconfiguration of the host-transcriptome by differential exon-usage, followed by a progressive transcriptional downregulation modulated by epigenetic changes. Regarding endogenous small RNAs, the alterations were limited and mainly occurred at the late stage. Significant host-alterations were predominantly related to the downregulation of transcripts involved in plant-defence mechanisms, the restriction of pathogen-movement and the systemic spreading of defence signals. We expect that these data constituting the first comprehensive temporal-map of the plant-regulatory alterations associated with HSVd infection could contribute to elucidate the molecular basis of the yet poorly known host-response to viroid-induced pathogenesis.


Asunto(s)
Cucumis sativus , Virus de Plantas , Viroides , Viroides/genética , Multiómica , Transcriptoma , Cucumis sativus/genética , Enfermedades de las Plantas
9.
Arch Virol ; 168(5): 135, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37043016

RESUMEN

Tomato brown rugose fruit virus (ToBRFV) has become a cause of great concern in the global tomato agro-industry since its first report in Israel in 2014. Global tomato production is affected by ToBRFV, and management practices are being evaluated. We tested seed lots from international producers as well as greenhouse substrates and water wells as possible sources of virus contamination. We identified a second introduction of ToBRFV in Mexico by a strain closely resembling isolates from the Netherlands and the Middle East. ToBRFV was detected by RT-PCR in seed coats and epicotyls (from commercial seeds and seedlings obtained from infected tomato plants), indicating a transmission rate of 9%. Virus-like particles (VLPs) were found in wells used for irrigation in greenhouses, but these exhibited low infectivity. These findings suggest that water sources could serve as ToBRFV reservoirs. We evaluated four chemical and six thermal methods for sanitizing substrates, plasticware, and other greenhouse utensils, using detached leaf bioassays in Nicotiana rugosa. The most effective chemical sanitization method was treatment with glutaraldehyde plus quaternary ammonium salts and pentapotassium salts. The most effective heat treatment was at 92°C for 30 minutes, which inactivated the virus. Tomato producers could implement these sanitization methods to control ToBRFV.


Asunto(s)
Frutas , Solanum lycopersicum , México , Sales (Química) , Bioensayo
10.
Semin Ultrasound CT MR ; 44(2): 71-80, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37055142

RESUMEN

The facial nerve is the seventh cranial nerve and consists of motor, parasympathetic and sensory branches, which arise from the brainstem through 3 different nuclei (1). After leaving the brainstem, the facial nerve divides into 5 intracranial segments (cisternal, canalicular, labyrinthine, tympanic, and mastoid) and continues as the intraparotid extracranial segment (2). A wide variety of pathologies, including congenital abnormalities, traumatic disorders, infectious and inflammatory disease, and neoplastic conditions, can affect the facial nerve along its pathway and lead to ​​weakness or paralysis of the facial musculature (1,2). The knowledge of its complex anatomical pathway is essential to clinical and imaging evaluation to establish if the cause of the facial dysfunction is a central nervous system process or a peripheral disease. Both computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice for facial nerve assessment, each of them providing complementary information in this evaluation (1).


Asunto(s)
Oído Interno , Neoplasias , Humanos , Nervio Facial/anatomía & histología , Nervio Facial/patología , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética
11.
Biomedicines ; 11(3)2023 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-36979922

RESUMEN

Heterotopic ossification (HO) is the abnormal growth of bone in soft connective tissues that occurs as a frequent complication in individuals with traumatic brain injury (TBI) and in rare genetic disorders. Therefore, understanding the mechanisms behind ectopic bone formation in response to TBI is likely to have a significant impact on identification of novel therapeutic targets for HO treatment. In this study, we induced repetitive mild TBI (mTBI) using a weight drop model in mice and then stimulated HO formation via a local injury to the Achilles tendon or fibula. The amount of ectopic bone, as evaluated by micro-CT analyses, was increased by four-fold in the injured leg of mTBI mice compared to control mice. However, there was no evidence of HO formation in the uninjured leg of mTBI mice. Since tissue injury leads to the activation of hypoxia signaling, which is known to promote endochondral ossification, we evaluated the effect of IOX2, a chemical inhibitor of PHD2 and a known inducer of hypoxia signaling on HO development in response to fibular injury. IOX2 treatment increased HO volume by five-fold compared to vehicle. Since pericytes located in the endothelium of microvascular capillaries are known to function as multipotent tissue-resident progenitors, we determined if activation of hypoxia signaling promotes pericyte recruitment at the injury site. We found that markers of pericytes, NG2 and PDGFRß, were abundantly expressed at the site of injury in IOX2 treated mice. Treatment of pericytes with IOX2 for 72 h stimulated expression of targets of hypoxia signaling (Vegf and Epo), as well as markers of chondrocyte differentiation (Col2α1 and Col10α1). Furthermore, serum collected from TBI mice was more effective in promoting the proliferation and differentiation of pericytes than control mouse serum. In conclusion, our data show that the hypoxic state at the injury site in soft tissues of TBI mice provides an environment leading to increased accumulation and activation of pericytes to form endochondral bone.

12.
Entropy (Basel) ; 25(3)2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36981383

RESUMEN

Chaotic systems are hard to synchronize, and no general solution exists. The presence of hidden attractors makes finding a solution particularly elusive. Successful synchronization critically depends on the control strategy, which must be carefully chosen considering system features such as the presence of hidden attractors. We studied the feasibility of fuzzy control for synchronizing chaotic systems with hidden attractors and employed a special numerical integration method that takes advantage of the oscillatory characteristic of chaotic systems. We hypothesized that fuzzy synchronization and the chosen numerical integration method can successfully deal with this case of synchronization. We tested two synchronization schemes: complete synchronization, which leverages linearization, and projective synchronization, capitalizing on parallel distributed compensation (PDC). We applied the proposal to a set of known chaotic systems of integer order with hidden attractors. Our results indicated that fuzzy control strategies combined with the special numerical integration method are effective tools to synchronize chaotic systems with hidden attractors. In addition, for projective synchronization, we propose a new strategy to optimize error convergence. Furthermore, we tested and compared different Takagi-Sugeno (T-S) fuzzy models obtained by tensor product (TP) model transformation. We found an effect of the fuzzy model of the chaotic system on the synchronization performance.

13.
J Orthop Res ; 41(7): 1471-1481, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36448182

RESUMEN

The increasing incidence of physiologic/pathologic conditions that impair the otherwise routine healing of endochondral bone fractures and the occurrence of severe bone injuries necessitate novel approaches to enhance clinically challenging bone fracture repair. To promote the healing of nonunion fractures, we tested an approach that used two small molecules to sequentially enhance cartilage development and conversion to the bone in the callus of a murine femoral segmental defect nonunion model of bone injury. Systemic injections of smoothened agonist 21k (SAG21k) were used to stimulate chondrogenesis through the activation of the sonic hedgehog (SHH) pathway early in bone repair, while injections of the prolyl hydroxylase domain (PHD)2 inhibitor, IOX2, were used to stimulate hypoxia signaling-mediated endochondral bone formation. The expression of SHH pathway genes and Phd2 target genes was increased in chondrocyte cell lines in response to SAG21k and IOX2 treatment, respectively. The segmental defect responded to sequential systemic administration of these small molecules with increased chondrocyte expression of PTCH1, GLI1, and SOX9 in response to SAG and increased expression of hypoxia-induced factor-1α and vascular endothelial growth factor-A in the defect tissues in response to IOX2. At 6 weeks postsurgery, the combined SAG-IOX2 therapy produced increased bone formation in the defect with the bony union over the injury. Clinical significance: This therapeutic approach was successful in promoting cartilage and bone formation within a critical-size segmental defect and established the utility of a sequential small molecule therapy for the enhancement of fracture callus development in clinically challenging bone injuries.


Asunto(s)
Condrogénesis , Factor A de Crecimiento Endotelial Vascular , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Hedgehog/metabolismo , Cartílago , Callo Óseo/metabolismo , Osteogénesis , Curación de Fractura/fisiología
14.
Virus Res ; 323: 198958, 2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36209921

RESUMEN

Post-transcriptional modifications of RNA bases are widespread across all the tree of life and have been linked to RNA maturation, stability, and molecular interactions. RNA modifications have been extensively described in endogenous eukaryotic mRNAs, however, little is known about the presence of RNA modifications in plant viral and subviral RNAs. Here, we used a computational approach to infer RNA modifications in plant-pathogenic viruses and viroids using high-throughput annotation of modified ribonucleotides (HAMR), a software that predicts modified ribonucleotides using high-throughput RNA sequencing data. We analyzed datasets from representative members of different plant viruses and viroids and compared them to plant-endogenous mRNAs. Our approach was able to predict potential RNA chemical modifications (RCMs) in all analyzed pathogens. We found that both DNA and RNA viruses presented a wide range of RCM proportions while viroids had lowest values. Furthermore, we found that for viruses with segmented genomes, some genomic RNAs had a higher proportion of RCM. Interestingly, nuclear-replicating viroids showed most of the predicted modifications located in the pathogenesis region, pointing towards a possible functional role of RCMs in their infectious cycle. Thus, our results strongly suggest that plant viral and subviral RNAs might contain a variety of previously unreported RNA modifications, thus opening a new perspective in the multifaceted process of plant-pathogen interactions.

15.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1536392

RESUMEN

Introducción: La integración de la investigación científica y la vinculación es clave para la contribución de las universidades a la solución de los problemas de la sociedad mediante la transferencia de conocimientos y la innovación. Objetivo: Caracterizar el proceso de integración entre vinculación e investigación en la carrera de Medicina de UNIANDES. Método: Se realizó una investigación predominantemente cualitativa y descriptiva con la utilización del análisis documental y la entrevista. Se revisaron documentos rectores, lineamientos, y políticas, aplicadas en la carrera de Medicina. Se aplicaron entrevistas a los coordinadores en la carrera para buscar volumen informativo acerca de estas dos actividades y las proyecciones concretas de transversalización. Resultados: Se denotó una debilidad en cuanto a la gestión de la vinculación con la sociedad, ausencia de una visión más amplia de una gestión integral donde no solo se imbrique vinculación con docencia en las prácticas preprofesionales sino en los proyectos integradores y la existencia de la voluntad de los directivos institucionales en gestar desde la investigación una verdadera vinculación universidad-sociedad. Conclusiones: Falta una visión más amplia de la integración entre los tres procesos claves universitarios, se evidencia solo la relación entre docencia y vinculación a partir de las prácticas preprofesionales, dejando fuera la base y génesis que deben ser los proyectos integradores de saberes. En aras del perfeccionamiento de esta integración se deben proponer proyectos de innovación social donde se unan vinculación e investigación, garantizar la publicación de los resultados de los proyectos de innovación social en las revistas internas de UNIANDES y en otras de impacto regional o mundial.


Introduction: The integration of scientific research and linkage is key for the contribution of universities to the solution of society's problems through the transfer of knowledge and innovation. Objective: Characterize the integration process between linkage and research in the UNIANDES Medicine degree. Method: A predominantly qualitative and descriptive research was carried out with the use of documentary analysis and interviews. Governing documents, guidelines, and policies applied in the Medicine career were reviewed. Interviews were carried out with the coordinators in the program to search for volume of information about these two activities and the specific projections of mainstreaming. Results: A weakness was noted in terms of the management of the link with society, absence of a broader vision of comprehensive management where not only linkage with teaching is intertwined in pre-professional practices but also in integrative projects and the existence of will of institutional directors to create a true university-society link through research. Conclusions: A broader vision of the integration between the three key university processes is missing, only the relationship between teaching and connection is evident from pre-professional practices, leaving out the basis and genesis that knowledge-integrating projects should be. In order to perfect this integration, social innovation projects must be proposed where linkage and research come together, guaranteeing the publication of the results of social innovation projects in the internal journals of UNIANDES and in others with regional or global impact.


Introdução: A integração e articulação da investigação científica é fundamental para a contribuição das universidades na solução dos problemas da sociedade através da transferência de conhecimento e inovação. Objetivo: Caracterizar o processo de integração entre vinculação e pesquisa na graduação em Medicina da UNIANDES. Método: Foi realizada uma pesquisa predominantemente qualitativa e descritiva com utilização de análise documental e entrevistas. Foram revisados documentos normativos, diretrizes e políticas aplicadas à carreira de Medicina. Foram realizadas entrevistas com os coordenadores do programa para buscar volume de informações sobre essas duas atividades e as projeções específicas de mainstreaming. Resultados: Constatou-se uma fragilidade na gestão do vínculo com a sociedade, ausência de uma visão mais ampla de uma gestão integral onde não só o vínculo com o ensino esteja entrelaçado nas práticas pré-profissionais, mas também nos projetos integradores e na existência de vontade de instituições diretores para criar um verdadeiro vínculo universidade-sociedade através da pesquisa. Conclusões: Falta uma visão mais ampla da integração entre os três principais processos universitários, apenas a relação entre ensino e conexão é evidente nas práticas pré-profissionais, deixando de fora a base e a gênese que os projetos integradores de conhecimento deveriam ser. Para aperfeiçoar esta integração, devem ser propostos projetos de inovação social onde a articulação e a investigação se unam, garantindo a publicação dos resultados dos projetos de inovação social nas revistas internas da UNIANDES e em outras com impacto regional ou global.

17.
Elife ; 112022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36342465

RESUMEN

Pathological obesity and its complications are associated with an increased propensity for bone fractures. Humans with certain genetic polymorphisms at the kinase suppressor of ras2 (KSR2) locus develop severe early-onset obesity and type 2 diabetes. Both conditions are phenocopied in mice with Ksr2 deleted, but whether this affects bone health remains unknown. Here we studied the bones of global Ksr2 null mice and found that Ksr2 negatively regulates femoral, but not vertebral, bone mass in two genetic backgrounds, while the paralogous gene, Ksr1, was dispensable for bone homeostasis. Mechanistically, KSR2 regulates bone formation by influencing adipocyte differentiation at the expense of osteoblasts in the bone marrow. Compared with Ksr2's known role as a regulator of feeding by its function in the hypothalamus, pair-feeding and osteoblast-specific conditional deletion of Ksr2 reveals that Ksr2 can regulate bone formation autonomously. Despite the gains in appendicular bone mass observed in the absence of Ksr2, bone strength, as well as fracture healing response, remains compromised in these mice. This study highlights the interrelationship between adiposity and bone health and provides mechanistic insights into how Ksr2, an adiposity and diabetic gene, regulates bone metabolism.


Our bones are living tissues which constantly reshape and renew themselves. This ability relies on stem cells present in the marrow cavity, which can mature into the various types of cells needed to produce new bone material, marrow fat, or other components. Obesity and associated conditions such as type 2 diabetes are often linked to harmful changes in the skeleton. In particular, these metabolic conditions are associated with weight-bearing bones becoming more prone to facture and healing poorly. Mice genetically modified to model obesity and diabetes could help researchers to study exactly how these conditions ­ and the genetic changes that underlie them ­ impact bone health. Gomez et al. aimed to address this question by focusing on KSR2, a gene involved in energy consumption and feeding behavior. Children who carry certain KSR2 mutations are prone to obesity and type 2 diabetes; mice lacking the gene also develop these conditions due to uncontrolled eating. Closely examining mutant mice in which Ksr2 had been deactivated in every cell revealed that the weight-bearing bones of these animals were also more likely to break, and the fractures then healed more slowly. This was the case even though these bones had higher mass and less marrow fat compared to healthy mice. Non-weight bearing bones (such as the spine) did not exhibit these changes. Further experiments revealed that, when expressed normally in the skeleton, Ksr2 skews the stem cell maturation process towards marrow fat cells instead of bone-creating cells. This suggests a new role for Ksr2, which therefore seems to independently regulate both feeding behavior and bone health. In addition, the work by Gomez et al. demonstrate that Ksr2 mutant mice could be a useful model to better understand how obesity and diabetes affect human bones, and to potentially develop new therapies.


Asunto(s)
Adiposidad , Médula Ósea , Hueso Esponjoso , Animales , Humanos , Ratones , Adiposidad/genética , Médula Ósea/metabolismo , Hueso Esponjoso/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ratones Noqueados , Obesidad/metabolismo , Osteoblastos/metabolismo , Proteínas Serina-Treonina Quinasas
18.
J. health med. sci. (Print) ; 8(4): 247-257, oct.2022.
Artículo en Español | LILACS | ID: biblio-1443240

RESUMEN

INTRODUCION Estos últimos años la Educación Superior ha tenido que incorporar en su curricular el desarrollo de habilidades comunicacionales, siendo actualmente considerada por la Asociación de Colegios Médicos Americanos (AAMC), Asociación Americana de Escuelas de Medicina(AAME) y Escuela de aprendizaje, conductual y de habilidades (EACH) como una competencia básica del profesional del área salud y que en ocasiones determina el éxito o fracaso del proceso asistencial, existiendo evidencia que el proceso comunicativo que se da en los centros de atención médica referida a la interacción médico-paciente determina la precisión del diagnóstico, toma de decisiones y adherencia del tratamiento que permite una excelente práctica médica. Frente a esta necesidad las Universidades han implementado diversas actividades realizadas en países anglosajones que deben ser ajustadas a las necesidades y contexto social chileno.


In recent years, Higher Education has had to incorporate in its curriculum the development of communication skills, being currently considered by the Association of American Medical Colleges (AAMC), American Association of Medical Schools (AAME) and School of Learning, Behavioral and Skills (EACH) as a basic competence of the health professional and that sometimes determines the success or failure of the care process, there is evidence that the communicative process that occurs in health care centers related to doctor-patient interaction determines the accuracy of diagnosis, decision making and adherence to treatment that allows excellent medical practice. Faced with this need, the Universities have implemented various activities carried out in Anglo Saxon countries that must be adjusted to the needs and social context of Chile


Asunto(s)
Humanos , Relaciones Médico-Paciente , Estudiantes de Medicina , Comunicación en Salud , Chile , Curriculum , Educación Médica
19.
Plant J ; 112(1): 284-293, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35916236

RESUMEN

Gene silencing for functional studies in plants has been largely facilitated by manipulating viral genomes with inserts from host genes to trigger virus-induced gene silencing (VIGS) against the corresponding mRNAs. However, viral genomes encode multiple proteins and can disrupt plant homeostasis by interfering with endogenous cell mechanisms. To try to circumvent this functional limitation, we have developed a silencing method based on the minimal autonomously-infectious nucleic acids currently known: viroids, which lack proven coding capability. The genome of Eggplant latent viroid, an asymptomatic viroid, was manipulated with insertions ranging between 21 and 42 nucleotides. Our results show that, although larger insertions might be tolerated, the maintenance of the secondary structure appears to be critical for viroid genome stability. Remarkably, these modified ELVd molecules are able to induce systemic infection promoting the silencing of target genes in eggplant. Inspired by the design of artificial microRNAs, we have developed a simple and standardized procedure to generate stable insertions into the ELVd genome capable of silencing a specific target gene. Analogously to VIGS, we have termed our approach viroid-induced gene silencing, and demonstrate that it is a promising tool for dissecting gene functions in eggplant.


Asunto(s)
MicroARNs , Solanum melongena , Viroides , Silenciador del Gen , MicroARNs/genética , MicroARNs/metabolismo , Nucleótidos/metabolismo , Enfermedades de las Plantas/genética , Plantas/metabolismo , ARN Circular/genética , ARN Viral/genética , Solanum melongena/genética , Viroides/genética , Viroides/metabolismo
20.
Viruses ; 14(8)2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-36016425

RESUMEN

To uncover novel genes associated with the Sugarcane mosaic virus (SCMV) response, we used RNA-Seq data to analyze differentially expressed genes (DEGs) and transcript expression pattern clusters between a tolerant/resistant (CI-RL1) and a susceptible (B73) line, in addition to the F1 progeny (CI-RL1xB73). A Gene Ontology (GO) enrichment of DEGs led us to propose three genes possibly associated with the CI-RL1 response: a heat shock 90-2 protein and two ABC transporters. Through a clustering analysis of the transcript expression patterns (CTEPs), we identified two genes putatively involved in viral systemic spread: the maize homologs to the PIEZO channel (ZmPiezo) and to the Potyvirus VPg Interacting Protein 1 (ZmPVIP1). We also observed the complex behavior of the maize eukaryotic factors ZmeIF4E and Zm-elfa (involved in translation), homologs to eIF4E and eEF1α in A. thaliana. Together, the DEG and CTEPs results lead us to suggest that the tolerant/resistant CI-RL1 response to the SCMV encompasses the action of diverse genes and, for the first time, that maize translation factors are associated with viral interaction.


Asunto(s)
Potyvirus , Zea mays , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas/genética , Potyvirus/genética
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