ABSTRACT
T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM-1 has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles. We found that TIM-1 on the surface of host cells significantly reduced CHIKV release efficiency in comparison to other entry factors. Removal of cell surface TIM-1 through direct cellular knock-out or altering the cellular lipid distribution enhanced CHIKV release. Over the course of infection, CHIKV was able to counteract the tethering effect by gradually decreasing the surface levels of TIM-1 in a process mediated by the nonstructural protein 2. This study highlights the importance of phosphatidylserine receptors in mediating not only the entry of CHIKV but also its release and could aid in developing cell lines capable of enhanced vaccine production. IMPORTANCE: Chikungunya virus (CHIKV) is an enveloped alphavirus transmitted by the bites of infectious mosquitoes. Infection with CHIKV results in the development of fever, joint pain, and arthralgia that can become chronic and last for months after infection. Prevention of this disease is still highly focused on vector control strategies. In December 2023, a new live attenuated vaccine against CHIKV was approved by the FDA. We aimed to study the cellular factors involved in CHIKV release, to better understand CHIKV's ability to efficiently infect and spread among a wide variety of cell lines. We found that TIM-1 receptors can significantly abrogate CHIKV's ability to efficiently exit infected cells. This information can be beneficial for maximizing viral particle production in laboratory settings and during vaccine manufacturing.
ABSTRACT
T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of Chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce Chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles. We found that TIM-1 on the surface of host cells significantly reduced CHIKV release efficiency in comparison to other entry factors. Removal of cell surface TIM-1 through direct cellular knock-out or altering the cellular lipid distribution enhanced CHIKV release. Over the course of infection, CHIKV was able to counteract the tethering effect by gradually decreasing the surface levels of TIM-1 in a process that appears to be mediated by the nonstructural protein 2. This study highlights the importance of phosphatidylserine receptors in mediating not only the entry of CHIKV but also its release and could aid in developing cell lines capable of enhanced vaccine production.
ABSTRACT
BACKGROUND: About half of people living with dementia have not received a diagnosis, delaying access to treatment, education, and support. We previously developed a tool, eRADAR, which uses information in the electronic health record (EHR) to identify patients who may have undiagnosed dementia. This paper provides the protocol for an embedded, pragmatic clinical trial (ePCT) implementing eRADAR in two healthcare systems to determine whether an intervention using eRADAR increases dementia diagnosis rates and to examine the benefits and harms experienced by patients and other stakeholders. METHODS: We will conduct an ePCT within an integrated healthcare system and replicate it in an urban academic medical center. At primary care clinics serving about 27,000 patients age 65 and above, we will randomize primary care providers (PCPs) to have their patients with high eRADAR scores receive targeted outreach (intervention) or usual care. Intervention patients will be offered a "brain health" assessment visit with a clinical research interventionist mirroring existing roles within the healthcare systems. The interventionist will make follow-up recommendations to PCPs and offer support to newly-diagnosed patients. Patients with high eRADAR scores in both study arms will be followed to identify new diagnoses of dementia in the EHR (primary outcome). Secondary outcomes include healthcare utilization from the EHR and patient, family member and clinician satisfaction assessed through surveys and interviews. CONCLUSION: If this pragmatic trial is successful, the eRADAR tool and intervention could be adopted by other healthcare systems, potentially improving dementia detection, patient care and quality of life.
Subject(s)
Alzheimer Disease , Delivery of Health Care, Integrated , Dementia , Aged , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/therapy , Brain , Dementia/diagnosis , Dementia/therapy , Electronic Health Records , Quality of Life , Pragmatic Clinical Trials as Topic , AlgorithmsABSTRACT
Microplastics (MPs) are plastic sediments that are released into the environment by various sources, their abundance and distribution increase as their size decreases, they represent a risk to ecological processes and their abundance is related to their proximity to human activities and The Anthropocene era, in addition to the Covid-19 pandemic, has exacerbated the emitting sources of plastics such as face masks, disinfectant container bottles, among others, all due to all the biosafety measures required globally. Over time, the transformation of plastics into microplastics generates particles transported by atmospheric and water dynamics, being accumulated in soils, bodies of water and incorporated into ecosystems and the food chains of organisms, including humans. Marine-coastal environments such as coastal lagoons, which in addition to hosting strategic ecosystems, being areas of convergence of different ecological flows and with important ecosystem services, have also become sinks for MP particles, putting their productivity and value at risk. Socio-ecological that they have. The purpose of this research is to evaluate and zone the environmental risks derived from contamination by microplastics in a coastal lagoon system, since once the MPs enter the environment they can cause harmful effects, in this case in the Caribbean Sea and in the lagoon complex. To this end, a comprehensive study of planetary systems was carried out to better understand their disturbances due to the presence of microplastics.
Subject(s)
COVID-19 , Microplastics , Humans , Plastics , Ecosystem , Colombia , Pandemics , Caribbean Region , Food ChainABSTRACT
RESUMEN Esta revisión presenta una metodología de análisis espacial de las principales interrelaciones entre los componentes ambientales: atmosférico, geosférico, hidrosférico, biosférico y antroposférico y la variabilidad climática de temperatura y precipitación, que se proyectan hasta el 2100, en la cuenca Torca, en Bogotá, D.C., Colombia. Los humedales de la cuenca son de importancia local, nacional e internacional, por los servicios ecosistémicos de soporte de flora y fauna. Para ello, mediante los sistemas de información geográfica (SIG), se establecieron apreciaciones prospectivas con resultados ya establecidos, desde 2011 al 2040, desde 2041 hasta 2070 y desde 2071 al 2100. Se identificaron, relaciones de interconectividad entre los sistemas naturales y humanos, para entender las capacidades de adaptación a las variaciones de temperatura y de precipitación, que se proyectan en la Cuenca. Uno de los resultados más relevantes está asociado a que los análisis prospectivos multitemporales, a escalas regionales, necesitan más detalle, para generar planes de acción concretos en los ecosistemas estratégicos, como lo son los humedales de la Cuenca. Adicionalmente, la Estructura Ecológica Principal, de la cual, hace parte la cuenca Torca, que aun cumple sus funciones de regulación, pero se encuentra en peligro de degradación, debido al acelerado crecimiento de Bogotá y el fenómeno de conurbación con los municipios aledaños, como Chía, Sopó y Cajicá, lo que disminuiría sus capacidades de adaptabilidad a la variabilidad climática proyectada.
ABSTRACT This review presents a methodology for the spatial analysis of the main interrelationships between the environmental components: atmospheric, geospheric, hydrospheric, biospheric and anthropospheric, and the climatic variability of temperature and precipitation that are projected until the year 2100, in the Torca basin in the city from Bogota, Colombia. The wetlands of the basin are of local, national and international importance, due to the ecosystem services that support flora and fauna. Then, through geographic information systems (GIS), prospective appraisals were established with results already established from 2011 to 2040, from 2041 to 2070 and from 2071 to 2100. Interconnectivity relationships between natural and human systems were identified, to understand the capacities to adapt to variations in temperature and precipitation that are projected in the Basin. One of the most relevant results is associated with the fact that multitemporal prospective analyzes at regional scales need more detail to generate concrete plans of action in strategic ecosystems, such as the wetlands of the Basin. Additionally, the Main Ecological Structure, of which the Torca basin is part, which still fulfills its regulatory functions, but is in danger of degradation due to the rapid growth of the city of Bogotá and the phenomenon of conurbation with neighboring municipalities such as Chía, Sopó and Cajicá, which would decrease their adaptability capacities to the projected climate variability.
