Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses

Unlike their counterparts in bacterial and higher eukaryotic hosts, most fungal viruses are transmitted intracellularly and lack an extracellular phase. Here we determined the cryo-EM structure at 3.7 Å resolution of Rosellinia necatrix quadrivirus 1 (RnQV1), a fungal double-stranded (ds)RNA virus. RnQV1, the type species of the family Quadriviridae, has a multipartite genome consisting of four monocistronic segments. Whereas most dsRNA virus capsids are based on dimers of a single protein, the ~450-Å-diameter, T = 1 RnQV1 capsid is built of P2 and P4 protein heterodimers, each with more than 1000 residues. Despite a lack of sequence similarity between the two proteins, they have a similar α-helical domain, the structural signature shared with the lineage of the dsRNA bluetongue virus-like viruses. Domain insertions in P2 and P4 preferential sites provide additional functions at the capsid outer surface, probably related to enzyme activity. The P2 insertion has a fold similar to that of gelsolin and profilin, two actin-binding proteins with a function in cytoskeleton metabolism, whereas the P4 insertion suggests protease activity involved in cleavage of the P2 383-residue C-terminal region, absent in the mature viral particle. Our results indicate that the intimate virus-fungus partnership has altered the capsid genome-protective and/or receptor-binding functions. Fungal virus evolution has tended to allocate enzyme activities to the virus capsid outer surface

Four-Dimensional Characterization of the Babesia divergens Asexual Life Cycle, from the Trophozoite to the Multiparasite Stage

Babesia is an apicomplexan parasite of significance that causes the disease known as babesiosis in domestic and wild animals and in humans worldwide. Babesia infects vertebrate hosts and reproduces asexually by a form of binary fission within erythrocytes/red blood cells (RBCs), yielding a complex pleomorphic population of intraerythrocytic parasites. Seven of them, clearly visible in human RBCs infected with Babesia divergens, are considered the main forms and named single, double, and quadruple trophozoites, paired and double paired pyriforms, tetrad or Maltese Cross, and multiparasite stage. However, these main intraerythrocytic forms coexist with RBCs infected with transient parasite combinations of unclear origin and development. In fact, little is understood about how Babesia builds this complex population during its asexual life cycle. By combining cryo-soft X-ray tomography and video microscopy, main and transitory parasites were characterized in a native whole cellular context and at nanometric resolution. The architecture and kinetics of the parasite population was observed in detail and provide additional data to the previous B. divergens asexual life cycle model that was built on light microscopy. Importantly, the process of multiplication by binary fission, involving budding, was visualized in live parasites for the first time, revealing that fundamental changes in cell shape and continuous rounds of multiplication occur as the parasites go through their asexual multiplication cycle. A four-dimensional asexual life cycle model was built highlighting the origin of several transient morphological forms that, surprisingly, intersperse in a chronological order between one main stage and the next in the cycle. IMPORTANCE Babesiosis is a disease caused by intraerythrocytic Babesia parasites, which possess many clinical features that are similar to those of malaria. This worldwide disease is increasing in frequency and geographical range and has a significant impact on human and animal health. Babesia divergens is one of the species responsible for human and cattle babesiosis causing death unless treated promptly. When B. divergens infects its vertebrate hosts, it reproduces asexually within red blood cells. During its asexual life cycle, B. divergens builds a population of numerous in-traerythrocytic (IE) parasites of difficult interpretation. This complex population is largely unexplored, and we have therefore combined three- and four-dimensional imaging techniques to elucidate the origin, architecture, and kinetics of IE parasites. Unveiling the nature of these parasites has provided a vision of the B. divergens asexual cycle in unprecedented detail and is a key step to develop control strategies against babesiosis

The effects of spatial survey bias and habitat suitability on predicting the distribution of threatened species living in remote areas

Knowledge of a species’ potential distribution and the suitability of available habitat are fundamental for effective conservation planning and management. However, the quality of information on the distribution of species and their required habitats is highly variable in terms of accuracy and availability across taxa and regions, particularly in tropical landscapes where accessibility is especially challenging. Species distribution models (SDMs) provide predictive tools for addressing gaps for poorly surveyed species, but they rarely consider biases in geographical distribution of records and their consequences. We applied SDMs and variation partitioning analyses to investigate the relative importance of habitat characteristics, human accessibility, and their joint effects in the global distribution of the Critically Endangered Blue-throated Macaw Ara glaucogularis, a species endemic to the Amazonian flooded savannas of Bolivia. The probability of occurrence was skewed towards more accessible areas, mostly secondary roads. Variability in observed occurrence patterns was mostly accounted for by the pure effect of habitat characteristics (76.2%), indicating that bias in the geographical distribution of occurrences does not invalidate species-habitat relationships derived from niche models. However, observed spatial covariation between land-use at a landscape scale and accessibility (joint contribution: 22.3%) may confound the independent role of land-use in the species distribution. New surveys should prioritise collecting data in more remote (less accessible) areas better distributed with respect to land-use composition at a landscape scale. Our results encourage wider application of partitioning methods to quantify the extent of sampling bias in datasets used in habitat modelling for a better understanding of species-habitat relationships, and add insights into the potential distribution of our study species and opportunities for its conservation

Implementation of COGNIVITRA, an Information- and Communications-Technology-Based Solution for Dual-Task Training, in Patients at Risk of Cognitive Impairment

Mild cognitive impairment (MCI) is characterized by a modest decline in cognitive function that, while noticeable, does not severely impact daily life, allowing individuals to maintain their independence—a key factor distinguishing it from dementia. Currently, there are no treatments available that can modify the course of the disease, although cognitive and physical activities have shown potential in slowing its progression. In response to the need for more accessible cognitive care, COGNIVITRA, an information- and communications-technology-based solution, was developed to extend cognitive training into the home environment. This platform not only facilitates communication between patients and care providers but also holds promise for enhancing cognitive care accessibility and potentially influencing the economic aspects of healthcare institutions. To evaluate the usability, impact, and effectiveness of COGNIVITRA, a 12-week (6 mandatory + 6 voluntary) multicenter study was conducted, with an expected total sample size of 20 professionals, 90 patients and 20 caregivers and involving two settings (clinical and home settings) and the collection of various data types at baseline and after 6 or 12 weeks of training, including sociodemographic information, cognitive assessments, and usability metrics. These metrics included the System Usability Scale (SUS), the International Classification of Functioning-Based Usability Scales (ICF-US I and II), the Unified Theory of Acceptance and Use of Technology (UTAUT), health-related quality of life measures such as the EQ-5D-5L, cognitive domain assessments via the Montreal Cognitive Assessment (MoCA), and physical assessments such as the Timed 25-Foot Walk (T25-FW) test. The study included 22 patients, 2 caregivers, and 24 professionals. The usability evaluation revealed that patients, particularly those participating in the home study, showed improved SUS scores, suggesting an enhanced user experience with the platform. The ICF-US I results further supported this finding by indicating that COGNIVITRA was particularly effective as a supportive tool in terms of satisfaction and ease of learning. Despite a higher incidence of errors during the home study, the observational grid questionnaire demonstrated high success rates for task completion. Professionals involved in the study also reported high SUS scores and provided positive feedback regarding device usability. Overall, the participants expressed increased satisfaction with the platform, as reflected in their responses. The UTAUT analysis confirmed a generally positive attitude toward the use of COGNIVITRA. However, when assessing effectiveness, the analysis revealed a noninferiority positive trend in the EQ-5D-5L, T25-FW, and MoCA scores, indicating that while there were positive changes, they were not statistically significant. © 2024 by the authors.This project has received funding from the European Union under the AAL programme through project CogniViTra (Grant No. AAL-2018-5-115-CP), with national funding support from Fundação para a Ciência e a Tecnologia (FCT), Instituto de Salud Carlos III (ISCIII) and Luxembourg National Research Fund (FNR). This presentation reflects the authors’ views and neither AAL nor the National Funding Agencies are responsible for any use that may be made of the information

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly

D.A.C. was supported by the Nicolás Monardes program of the Andalusian Ministry of Health (C-0015-2014) and by a grant from the Andalusian Ministry of Science and Innovation (CTS-7478). A.S-M and A.L.C were supported by grants from the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI12/0143 and PI13/02043, respectively) and the Andalusian Regional Government (CTS-444) and a grant from Pfizer Spain. R.L.C. was supported by a grant from Andalusian Ministry of Health (PI0302-2012). R.M.L. was supported by grants from Proyecto de Investigación en Salud (FIS) PI13- 00651 (funded by Instituto de Salud Carlos III), CTS-1406, PI-0639-2012, BIO-0139 (funded by Junta de Andalucía) and by Ayuda Merck Serono 2013. J. P. C. was funded by a grant (BFU2013-43282-R) from Ministerio de Economía y Competitividad. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. J.F.M.R. is supported by the “Sara Borrell” program from the Instituto de Salud Carlos III. R.M. Luque and J.P. Castaño have received grants and lecture fees from Ipsen and Novartis. E. Venegas-Moreno and A. Soto-Moreno received grants and lecture fees from Ipsen, Novartis and Pfizer. A. Leal-Cerro received grants from Novartis and Pfizer. David Cano received a grant from Novartis