6 research outputs found
Designing Interorganizational Logistic Networks - A simulation based interdisciplinary approach
No full textTechnology, Policy and Managemen
Depth-dependent scaling of axial distances in light microscopy
No full textIn volume fluorescence microscopy, refractive index matching is essential to minimize aberrations. There are, however, common imaging scenarios where a refractive index mismatch (RIM) between immersion and a sample medium cannot be avoided. This RIM leads to an axial deformation in the acquired image data. Over the years, different axial scaling factors have been proposed to correct for this deformation. While some reports have suggested a depth-dependent axial deformation, so far none of the scaling theories has accounted for a depth-dependent, non-linear scaling. Here, we derive an analytical theory based on determining the leading constructive interference band in the objective lens pupil under RIM. We then use this to calculate a depth-dependent re-scaling factor as a function of the numerical aperture (NA), the refractive indices n1 and n2, and the wavelength λ. We compare our theoretical results with wave-optics calculations and experimental results obtained using a measurement scheme for different values of NA and RIM. As a benchmark, we recorded multiple datasets in different RIM conditions, and corrected these using our depth-dependent axial scaling theory. Finally, we present an online web applet that visualizes the depth-dependent axial re-scaling for specific optical setups. In addition, we provide software that will help microscopists to correctly re-scale the axial dimension in their imaging data when working under RIM.ImPhys/Hoogenboom groupImPhys/Geertsema grou
An integrated in silico-in vitro approach for identifying therapeutic targets against osteoarthritis
No full textBackground: Without the availability of disease-modifying drugs, there is an unmet therapeutic need for osteoarthritic patients. During osteoarthritis, the homeostasis of articular chondrocytes is dysregulated and a phenotypical transition called hypertrophy occurs, leading to cartilage degeneration. Targeting this phenotypic transition has emerged as a potential therapeutic strategy. Chondrocyte phenotype maintenance and switch are controlled by an intricate network of intracellular factors, each influenced by a myriad of feedback mechanisms, making it challenging to intuitively predict treatment outcomes, while in silico modeling can help unravel that complexity. In this study, we aim to develop a virtual articular chondrocyte to guide experiments in order to rationalize the identification of potential drug targets via screening of combination therapies through computational modeling and simulations. Results: We developed a signal transduction network model using knowledge-based and data-driven (machine learning) modeling technologies. The in silico high-throughput screening of (pairwise) perturbations operated with that network model highlighted conditions potentially affecting the hypertrophic switch. A selection of promising combinations was further tested in a murine cell line and primary human chondrocytes, which notably highlighted a previously unreported synergistic effect between the protein kinase A and the fibroblast growth factor receptor 1. Conclusions: Here, we provide a virtual articular chondrocyte in the form of a signal transduction interactive knowledge base and of an executable computational model. Our in silico-in vitro strategy opens new routes for developing osteoarthritis targeting therapies by refining the early stages of drug target discovery. Graphical Abstract: [Figure not available: see fulltext.]Biomaterials & Tissue Biomechanic
Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: An updated review
No full textCOVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19. © 2020 The Author(s)
Enfoque “One Health” para la comprensión de las interacciones entre hospederos, garrapatas y Rickettsia spp. en Colombia
No full textArtículos, mapas, gráficas, tablas,Las enfermedades zoonóticas transmitidas por vectores representan una amenaza global para la salud humana y animal. Las garrapatas actúan como vectores de una gran variedad de patógenos, incluidas bacterias del género Rickettsia. Estas bacterias son responsables de las rickettsiosis, enfermedades desatendidas que suelen pasar inadvertidas o confundirse con otras patologías en regiones tropicales y subtropicales. Los ciclos de transmisión de rickettsias involucran vectores y hospederos vertebrados, donde algunos mamíferos silvestres pueden actuar como hospederos amplificadores. Frente a los desafíos que implican estas enfermedades, organizaciones internacionales promueven el enfoque "Una Salud" para integrar la salud humana, animal y del ecosistema en la lucha frente a estas enfermedades. Por lo anterior, el objetivo de esta investigación fue determinar las asociaciones entre garrapatas, hospederos vertebrados y bacterias del género Rickettsia en Colombia. Entre 2015 y 2023, se recolectaron garrapatas de la vegetación y parasitando animales silvestres, animales domésticos y humanos en siete departamentos de Colombia. Así mismo, se recolectaron muestras de suero y tejidos de mamíferos silvestres en los departamentos de Caldas y Risaralda. Se recolectaron 551 garrapatas pertenecientes a 23 especies de los géneros Amblyomma, Dermacentor, Ixodes, Ornithodoros y Rhipicephalus. Se realizó la detección e identificación de ADN de Rickettsia bellii, Rickettsia felis, Rickettsia parkeri cepa NOD, Rickettsia parkeri, Rickettsia cf. monacensis, Rickettsia rickettsii, 'Candidatus Rickettsia colombianensi', Candidatus Rickettsia andeanae y 'Candidatus Rickettsia tarasevichiae' en garrapatas o mamíferos silvestres. Así mismo, se detectaron anticuerpos contra Rickettsia (i.e., Rickettsia amblyommatis, R. bellii, R. parkeri, R. rickettsii y R. rhipicephali) en sueros de mamíferos silvestres. Los resultados evidencian la amplia diversidad de garrapatas y rickettsias en Colombia, y destacan el posible rol de la fauna silvestre en la circulación y transmisión de estas bacterias. Los hallazgos resaltan la importancia de promover investigaciones que refuercen la vigilancia y el control de la rickettsiosis en el país.Zoonotic vector-borne infectious diseases represent a global threat to human and animal health. Ticks act as vectors for a wide variety of pathogens, including bacteria from the Rickettsia genus. These bacteria are responsible for rickettsioses, neglected diseases that often go unnoticed or are misdiagnosed as other conditions in tropical and subtropical regions. Rickettsia transmission cycles involve vectors and vertebrate hosts, where some wild mammals serve as key amplifying hosts. In response to the challenges posed by these diseases, international organizations promote the "One Health" approach to integrate human, animal, and ecosystem health. Therefore, the objective of this research was to determine the associations between ticks, vertebrate hosts, and Rickettsia bacteria in Colombia. Between 2015 and 2023, ticks were collected from vegetation and actively feeding on wild and domestic animals and humans from seven departments of Colombia. Additionally, serum and tissue samples from wild mammals were collected in the departments of Caldas and Risaralda. A total of 551 ticks belonging to 23 species from the genera Amblyomma, Dermacentor, Ixodes, Ornithodoros, and Rhipicephalus were collected. DNA from Rickettsia bellii, R. felis, R. parkeri strain NOD, R. parkeri, R. cf. monacensis, R. rickettsii, ‘Candidatus Rickettsia colombianensi’, ‘Candidatus Rickettsia andeanae’, and ‘Candidatus Rickettsia tarasevichiae’ was detected in ticks or wild mammals. Antibodies against Rickettsia species (i.g., R. amblyommatis, R. bellii, R. parkeri, R. rickettsii, and R. rhipicephali) were also detected in wild mammal sera. The findings highlight the broad diversity of ticks and Rickettsia species in Colombia, emphasizing the potential role of wildlife in the circulation and transmission of these bacteria. The results underscore the importance of promoting research to strengthen the surveillance and control of rickettsiosis in the country.Ministerio de Ciencia Tecnología e Innovación - Programa Minciencias “Relación, distribución, taxonomía de especies de garrapatas asociadas a mamíferos silvestres en zonas endémicas de rickettsiosis en Colombia. Una aproximación al entendimiento de la relación patógeno-vector reservorio”INTRODUCCIÓN / Pregunta de investigación / Objetivos / Objetivo general / Objetivos específicos / MATERIALES Y MÉTODOS / Área de estudio / Identificación morfológica y molecular de garrapatas / Captura de mamíferos y toma de muestras / Detección de anticuerpos contra Rickettsia / Detección e identificación molecular de Rickettsia / Relaciones filogenéticas / RESULTADOS / CAPÍTULO I Interacciones entre rickettsias y garrapatas asociadas a hospederos vertebrados en Colombia / CAPÍTULO II Rickettsias en mamíferos silvestres de los Andes colombianos / CONSIDERACIONES FINALES / REFERENCIAS BIBLIOGRÁFICASMaestríaMagister en Ciencias Biológica
Human viral pathogens in the wastewater-source water-drinking water continuum: evidence, health risks, and lessons for future outbreaks in low-income settings
No full textHuman viral pathogens, including SARS-CoV-2 continue to attract public and research attention due to their disruption of society, global health, and the economy. Several earlier reviews have investigated the occurrence and fate of SARS-CoV-2 in wastewater, and the potential to use such data in wastewater-based epidemiology. However, comprehensive reviews tracking SARS-CoV-2 and other viral pathogens in the wastewater-water-drinking water continuum and the associated risk assessment are still lacking. Therefore, to address this gap, the present paper makes the following contributions: (1) critically examines the early empirical results to highlight the occurrence and stability of SARS-CoV-2 in the wastewater-source water-drinking water continuum, (2) discusses the anthropogenic and hydro(geo)logical processes controlling the circulation of SARS-CoV-2 in the wastewater-source water-drinking water continuum, (3) discusses the risky behaviour, drivers and high-risk settings in the wastewater-source water-drinking water continuum, (4) uses the available empirical data on SARS-CoV-2 occurrence in the wastewater-source water-drinking water continuum to discuss human health risks from multiple exposure pathways, gendered aspects of SARS-CoV-2 transmission via shared on-site sanitation systems, and (5) develops and risk mitigation strategy based on the available empirical evidence and quantitative human risk assessment data. Finally, it presents a comprehensive research agenda on SARS-CoV-2/COVID-19 to guide the mitigation of future similar outbreaks in low-income settings
