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1.
Rev Cardiovasc Med ; 25(9): 320, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39355596

RESUMO

Heart-failure (HF) is a severe medical condition. Physicians need new tools to monitor the health status of their HF patients outside the hospital or medical supervision areas, to better know the evolution of their patients' main biomarker values, necessary to evaluate their health status. Bioimpedance (BI) represents a good technology for sensing physiological variables and processes on the human body. BI is a non-expensive and non-invasive technique for sensing a wide variety of physiological parameters, easy to be implemented on biomedical portable systems, also called "wearable devices". In this systematic review, we address the most important specifications of wearable devices based on BI used in HF real-time monitoring and how they must be designed and implemented from a practical and medical point of view. The following areas will be analyzed: the main applications of BI in heart failure, the sensing technique and impedance specifications to be met, the electrode selection, portability of wearable devices: size and weight (and comfort), the communication requests and the power consumption (autonomy). The different approaches followed by biomedical engineering and clinical teams at bibliography will be described and summarized in the paper, together with results derived from the projects and the main challenges found today.

2.
Rev Cardiovasc Med ; 25(9): 315, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39355607

RESUMO

Background: Heart failure (HF) represents a frequent cause of hospital admission, with fluid overload directly contributing to decompensations. Bioimpedance (BI), a physical parameter linked to tissue hydration status, holds promise in monitoring congestion and improving prognosis. This systematic review aimed to assess the clinical relevance of BI-based wearable devices for HF fluid monitoring. Methods: A systematic review of the published literature was conducted in five medical databases (PubMed, Scopus, Cochrane, Web of Science, and Embase) for studies assessing wearable BI-measuring devices on HF patients following PRISMA recommendations on February 4th, 2024. The risk of bias was evaluated using the ROBINS tool. Results: The review included 10 articles with 535 participants (mean age 66.7 ± 8.9 years, males 70.4%). Three articles identified significant BI value differences between HF patients and controls or congestive vs non-congestive HF patients. Four articles focused on the devices' ability to predict HF worsening-related events, revealing an overall sensitivity of 70.0 (95% CI 68.8-71.1) and specificity of 89.1 (95% CI 88.3-89.9). One article assessed prognosis, showing that R80kHz decrease was related to all-cause-mortality with a hazard ratio (HR) of 5.51 (95% CI 1.55-23.32; p = 0.02) and the composite all-cause-mortality and HF admission with a HR of 4.96 (95% CI 1.82-14.37; p = 0.01). Conclusions: BI-measuring wearable devices exhibit efficacy in detecting fluid overload and hold promise for HF monitoring. However, further studies and technological improvements are required to optimize their impact on prognosis compared to standard care before they can be routinely implemented in clinical practice. PROSPERO Registration: The search protocol was registered at PROSPERO (CRD42024509914).

3.
NMR Biomed ; : e5254, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358036

RESUMO

Calcium sulfate is an established carrier for localized drug delivery, but a means to non-invasively measure drug release, which would improve our understanding of localized delivery, remains an unmet need. We aim to quantitatively estimate the diffusion-controlled release of small molecules loaded into a calcium sulfate carrier through a gadobutrol-based contrast agent, which acts as a surrogate small molecule. A central cylindrical core made of calcium sulfate, either alone or within a metal scaffold, is loaded with contrast agents that release into agar. Multi-echo scans are acquired at multiple time points over 4 weeks and processed into R2* and quantitative susceptibility mapping (QSM) maps. Mean R2* values are fit to a known drug delivery model, which are then compared with the decrease in core QSM. Fitting R2* measurements of calcium sulfate core while constraining constants to a drug release model results in an R2-value of 0.991, yielding a diffusion constant of 4.59 × 10-11 m2 s-1. Incorporating the carrier within a metal scaffold results in a slower release. QSM shows the resulting loss of susceptibility in the non-metal core but is unreliable around metal. R2* characterizes the released gadobutrol, and QSM detects the resulting decrease in core susceptibility. The addition of a porous metal scaffold slows the release of gadobutrol, as expected.

4.
Viruses ; 16(9)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39339861

RESUMO

Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus species, shows intrinsic genetic stability. While the virus appears to have some mechanism that limits the accumulation of single-nucleotide variants, the production of defective viral genomes (DVGs) during virus infection has been reported for certain variants of CTV. The intra-host diversity generated during plant infection with variant T36 (CTV-T36) remains unclear. To address this, we analyzed the RNA species accumulated in the initially infected and systemic leaves of Nicotiana benthamiana plants inoculated with an infectious cDNA clone of CTV-T36, which warranted that infection was initiated by a known, well-defined sequence variant of the virus. CTV-T36 limited the accumulation of single-nucleotide mutants during infection. With that, four types of DVGs-deletions, insertions, and copy- and snap-backs-were found in all the samples, with deletions and insertions being the most common types. Hot-spots across the genome for DVG recombination and short direct sequence repeats suggest that sequence complementarity could mediate DVG formation. In conclusion, our study illustrates the formation of diverse DVGs during CTV-T36 infection. To the best of our knowledge, this is the first study that has analyzed the genetic variability and recombination of a well-defined sequence variant of CTV in an herbaceous host.


Assuntos
Closterovirus , Variação Genética , Genoma Viral , Nicotiana , Doenças das Plantas , RNA Viral , Nicotiana/virologia , Closterovirus/genética , Closterovirus/classificação , Doenças das Plantas/virologia , RNA Viral/genética , Citrus/virologia , Folhas de Planta/virologia
5.
BMC Genomics ; 25(1): 897, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350047

RESUMO

BACKGROUND: Plant-virus interaction models propose that a virus's ability to infect a host genotype depends on the compatibility between virulence and resistance genes. Recently, we conducted an evolution experiment in which lineages of turnip mosaic virus (TuMV) were passaged in Arabidopsis thaliana genotypes carrying mutations in components of the DNA methylation and the histone demethylation epigenetic pathways. All evolved lineages increased infectivity, virulence and viral load in a host genotype-dependent manner. RESULTS: To better understand the underlying reasons for these evolved relationships, we delved into the transcriptomic responses of mutant and WT plant genotypes in mock conditions and infected with either the ancestral or evolved viruses. Such a comparison allowed us to classify every gene into nine basic expression profiles. Regarding the targets of viral adaptation, our analyses allowed the identification of common viral targets as well as host genotype-specific genes and categories of biological processes. As expected, immune response-related genes were found to be altered upon infection. However, we also noticed the pervasive over-representation of other functional groups, suggesting that viral adaptation was not solely driven by the level of expression of plant resistance genes. In addition, a significant association between the presence of transposable elements within or upstream the differentially expressed genes was observed. Finally, integration of transcriptomic data into a virus-host protein-protein interaction network highlighted the most impactful interactions. CONCLUSIONS: These findings shed extra light on the complex dynamics between plants and viruses, indicating that viral infectivity depends on various factors beyond just the plant's resistance genes.


Assuntos
Arabidopsis , Epigênese Genética , Potyvirus , Arabidopsis/virologia , Arabidopsis/genética , Potyvirus/patogenicidade , Potyvirus/genética , Potyvirus/fisiologia , Transcriptoma , Evolução Molecular , Doenças das Plantas/virologia , Doenças das Plantas/genética , Interações Hospedeiro-Patógeno/genética , Metilação de DNA , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genótipo
6.
Sci Adv ; 10(39): eadn5945, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331715

RESUMO

Orsay virus (OrV) is the only known natural virus affecting Caenorhabditis elegans, with minimal impact on the animal's fitness due to its robust innate immune response. This study aimed to understand the interactions between C. elegans and OrV by tracking the infection's progression during larval development. Four distinct stages of infection were identified on the basis of viral load, with a peak in capsid-encoding RNA2 coinciding with the first signs of viral egression. Transcriptomic analysis revealed temporal changes in gene expression and functions induced by the infection. A specific set of up-regulated genes remained active throughout the infection, and genes correlated and anticorrelated with virus accumulation were identified. Responses to OrV mirrored reactions to other biotic stressors, distinguishing between virus-specific responses and broader immune responses. Moreover, mutants of early response genes and defense-related processes showed altered viral load progression, uncovering additional players in the antiviral defense response.


Assuntos
Caenorhabditis elegans , Interações Hospedeiro-Patógeno , Carga Viral , Animais , Caenorhabditis elegans/virologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/imunologia , Interações Hospedeiro-Patógeno/imunologia , Interações Hospedeiro-Patógeno/genética , Imunidade Inata , Nodaviridae/fisiologia , Perfilação da Expressão Gênica , Transcriptoma , Regulação da Expressão Gênica
7.
J Gen Virol ; 105(9)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39292505

RESUMO

Arabidopsis thaliana is more susceptible to certain viruses during its later developmental stages. The differential responses and the mechanisms behind this development-dependent susceptibility to infection are still not fully understood. Here we explored the outcome of a viral infection at different host developmental stages by studying the response of A. thaliana to infection with turnip mosaic virus at three developmental stages: juvenile vegetative, bolting, and mature flowering plants. We found that infected plants at later stages downregulate cell wall biosynthetic genes and that this downregulation may be one factor facilitating viral spread and systemic infection. We also found that, despite being more susceptible to infection, infected mature flowering plants were more fertile (i.e. produce more viable seeds) than juvenile vegetative and bolting infected plants; that is, plants infected at the reproductive stage have greater fitness than plants infected at earlier developmental stages. Moreover, treatment of mature plants with salicylic acid increased resistance to infection at the cost of significantly reducing fertility. Together, these observations support a negative trade-off between viral susceptibility and plant fertility. Our findings point towards a development-dependent tolerance to infection.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Doenças das Plantas , Potyvirus , Doenças das Plantas/virologia , Arabidopsis/virologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Potyvirus/fisiologia , Ácido Salicílico/metabolismo , Interações Hospedeiro-Patógeno/genética , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica
8.
Virus Evol ; 10(1): veae055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091990

RESUMO

The outcome of a viral infection depends on a complex interplay between the host physiology and the virus, mediated through numerous protein-protein interactions. In a previous study, we used high-throughput yeast two-hybrid (HT-Y2H) to identify proteins in Arabidopsis thaliana that bind to the proteins encoded by the turnip mosaic virus (TuMV) genome. Furthermore, after experimental evolution of TuMV lineages in plants with mutations in defense-related or proviral genes, most mutations observed in the evolved viruses affected the VPg cistron. Among these mutations, D113G was a convergent mutation selected in many lineages across different plant genotypes, including cpr5-2 with constitutive expression of systemic acquired resistance. In contrast, mutation R118H specifically emerged in the jin1 mutant with affected jasmonate signaling. Using the HT-Y2H system, we analyzed the impact of these two mutations on VPg's interaction with plant proteins. Interestingly, both mutations severely compromised the interaction of VPg with the translation initiation factor eIF(iso)4E, a crucial interactor for potyvirus infection. Moreover, mutation D113G, but not R118H, adversely affected the interaction with RHD1, a zinc-finger homeodomain transcription factor involved in regulating DNA demethylation. Our results suggest that RHD1 enhances plant tolerance to TuMV infection. We also discuss our findings in a broad virus evolution context.

9.
Biol Lett ; 20(8): 20240278, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39137892

RESUMO

The heat-shock response plays a key role in the immune defence against viruses across various organisms. Studies on model organisms have shown that inducing this response prior to viral exposure enhances host resistance to infections, while deficient responses make individuals more susceptible. Moreover, viruses rely on components of the heat-shock response for their own stability and viral infections improve thermal tolerance in plants, giving infected individuals an advantage in extreme conditions, which aids the virus in replication and transmission. Here, we examine the interaction between the nematode Caenorhabditis elegans and its natural pathogen the Orsay virus (OrV) under heat stress. We found that OrV infection leads to differential expression of heat-stress-related genes, and infected populations show increased resistance to heat-shock. This resistance correlates with increased expression of argonautes alg-1 and alg-2, which are crucial for survival after heat-shock and for OrV replication. Overall, our study suggests an environmental-dependent mutualistic relationship between the nematode and OrV, potentially expanding the animal's ecological niche and providing the virus with extra opportunities for replication and adaptation to extreme conditions.


Assuntos
Caenorhabditis elegans , Resposta ao Choque Térmico , Animais , Caenorhabditis elegans/virologia , Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/imunologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Interações Hospedeiro-Patógeno
10.
Matern Child Nutr ; : e13706, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186933

RESUMO

Prevalence studies about family meals, including large and representative samples of children and adolescents on this topic, are scarce. Therefore, the aim of this study was twofold: first, to determine the prevalence of daily family meals in large and representative samples of school-going children and adolescents from 43 countries, and second, to identify the sex, age, socioeconomic status (SES), family structure, immigrant status and parental labour market status inequalities associated with this prevalence. Using data from the 2017/2018 wave of the Health Behaviour in School-aged Children study, a total of 179,991 participants from 43 countries were involved in this cross-sectional study. Family meals were assessed by the following question: 'How often do you and your family usually have meals together?'. Participants had five different response options: 'every day', 'most days', 'about once a week', 'less often', and 'never'. The meta package was utilized for conducting a meta-analysis of single proportions, specifically applying the metaprop function. The analysis involved pooling the data using a random-effects model and presenting the outcomes through a forest plot generated using the inverse variance method. Moreover, we applied generalized linear mixed models to explore the relationships between the studied sociodemographic factors as fixed effects, country as a random effect and the status of daily family meals as an outcome. Overall, the prevalence of daily family meals was 49.12% (95% confidence interval [CI]: 45.00-53.25). A greater probability of having daily family meals was identified for children aged 10-12 years (61.55%; 95% CI: 57.44%-65.49%), boys (61.55%, 95% CI: 57.44%-65.49%), participants with high SES (64.66%, 95% CI: 60.65%-68.48%), participants with both parents at home (65.05%, 95% CI: 61.16%-68.74%) and those with both unemployed parents (61.55%, 95% CI: 57.44%-65.49%). In the present study, which included large representative samples of school-going children and adolescents from 43 countries, more than half of the participants did not have daily family meals.

11.
Infect Genet Evol ; 123: 105623, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901623

RESUMO

The discovery of Orsay virus (OrV), the first virus infecting wild populations of Caenorhabditis elegans, has boosted studies of viral immunity pathways in this nematode. Considering the many advantages that C. elegans offers for fundamental research in host-pathogen interactions, this pathosystem has high potential to become a model system for experimental virus evolution studies. However, the evolutionary constraints - i.e, the balance between genetic variation, selection, drift and historical contingency- operating in this pathosystem have barely been explored. Here we describe for the first time an evolution experiment of two different OrV strains in C. elegans. Comparison of the two ancestral strains showed differences in infectivity and sequence, and highlighted the importance of consistently normalize viral inocula for meaningful comparisons among strains. After 10 serial passages of evolution, we report slight changes in infectivity and non-synonymous mutations fixed in the evolved viral populations. In addition, we observed numerous minor variants emerging in the viral population. These minor variants were not randomly distributed along the genome but concentrated in polymorphic genomic regions. Overall, our work established the grounds for future experimental virus evolution studies using Caenorhabditis nematodes.


Assuntos
Caenorhabditis elegans , Animais , Caenorhabditis elegans/virologia , Evolução Molecular , Mutação , Vírus de RNA/genética , Interações Hospedeiro-Patógeno/genética , Variação Genética , Genoma Viral
12.
Sci Rep ; 14(1): 14644, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918479

RESUMO

Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe surrogate system to interrogate the function, evolution, and antigenicity of viral glycoproteins from viruses that are difficult to manipulate or those requiring high biosafety level containment. However, the production of recombinant VSV can be technically challenging. In this work, we present an efficient and robust plasmid-based system for the production of recombinant VSV encoding foreign glycoproteins. We validate the system using glycoproteins from different viral families, including arenaviruses, coronaviruses, and hantaviruses, as well as highlight their utility for studying the effects of mutations on viral fitness. Overall, the methods described herein can facilitate the study of both native and recombinant VSV encoding foreign glycoproteins and can serve as the basis for the production of VSV-based vaccines.


Assuntos
Glicoproteínas , Plasmídeos , Plasmídeos/genética , Glicoproteínas/genética , Glicoproteínas/imunologia , Animais , Humanos , Vesiculovirus/genética , Proteínas Virais/genética , Proteínas Virais/imunologia , Células HEK293
13.
JACC Case Rep ; 29(9): 102296, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38708431

RESUMO

Fontan pathway obstruction is a potentially serious complication characterized by an anatomical or functional narrowing anywhere in the cavo-pulmonary pathways. Here, we report the first case in the literature where an innovative Fontan conduit rehabilitation procedure with intravascular lithotripsy was used achieving a dramatic increase in the pathway size.

14.
Virus Evol ; 10(1): veae032, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779130

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can infect various human tissues and cell types, principally via interaction with its cognate receptor angiotensin-converting enzyme-2 (ACE2). However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study the adaptation of the SARS-CoV-2 spike to four human cell lines expressing different levels of key entry factors. After twenty passages of a spike-expressing recombinant vesicular stomatitis virus (VSV), cell-type-specific phenotypic changes were observed and sequencing allowed the identification of sixteen adaptive spike mutations. We used VSV pseudotyping to measure the entry efficiency, ACE2 affinity, spike processing, TMPRSS2 usage, and entry pathway usage of all the mutants, alone or in combination. The fusogenicity of the mutant spikes was assessed with a cell-cell fusion assay. Finally, mutant recombinant VSVs were used to measure the fitness advantage associated with selected mutations. We found that the effects of these mutations varied across cell types, both in terms of viral entry and replicative fitness. Interestingly, two spike mutations (L48S and A372T) that emerged in cells expressing low ACE2 levels increased receptor affinity, syncytia induction, and entry efficiency under low-ACE2 conditions. Our results demonstrate specific adaptation of the SARS-CoV-2 spike to different cell types and have implications for understanding SARS-CoV-2 tissue tropism and evolution.

15.
Contemp Clin Trials Commun ; 39: 101288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616815

RESUMO

Objectives: Radiation-induced dermatitis (RD) is one of the most common toxicities in radiation therapy (RT) patients. Corticosteroids, immunosuppressants, and natural products (NPs) have been used as treatment. The objective was to evaluate the efficacy of a NPs-based cream (Alantel®) to reduce the incidence of RD in women with breast cancer undergoing RT treatment. Design: We conducted a controlled, randomized, double-blind clinical trial. Setting: Radiation Oncology Unit of the Reina Sofía Hospital and 5 Primary Care centers of the Cordoba and Guadalquivir Health District (Spain). Interventions: Patients assigned to the experimental group (GTA) were treated with Alantel, while those in the control group (GTE) were treated with a moisturizer and emollient cream. Main outcome measures: The primary outcome variable was the incidence of RD. RD-free time, duration of RD, quality of life, and product safety were also assessed. Results: Seventy patients were included in the study, 35 in the GTA and 35 in the GTE. The incidence of RD was lower in the GTA (71.4%) than in the GTE (91.4%) after 4 weeks of follow-up (RR = 0.78; NNT = 5; p < 0.031). The Skindex-29 questionnaire showed differences in the statement: "My skin condition makes it hard to work or do hobbies" (17.1% in the GTE vs. 2.9% in GTA; p = 0.024). Conclusions: The higher efficacy of Alantel® compared to the control cream in reducing the incidence of RD in women with breast cancer has been demonstrated.

16.
mSystems ; 9(5): e0012424, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38651902

RESUMO

Invertebrates constitute the majority of animal species on Earth, including most disease-causing agents or vectors, with more diverse viromes when compared to vertebrates. Recent advancements in high-throughput sequencing have significantly expanded our understanding of invertebrate viruses, yet this knowledge remains biased toward a few well-studied animal lineages. In this study, we analyze invertebrate DNA and RNA viromes for 31 phyla using 417 publicly available RNA-Seq data sets from diverse environments in the marine-terrestrial and marine-freshwater gradients. This study aims to (i) estimate virome compositions at the family level for the first time across the animal tree of life, including the first exploration of the virome in several phyla, (ii) quantify the diversity of invertebrate viromes and characterize the structure of invertebrate-virus infection networks, and (iii) investigate host phylum and habitat influence on virome differences. Results showed that a set of few viral families of eukaryotes, comprising Retroviridae, Flaviviridae, and several families of giant DNA viruses, were ubiquitous and highly abundant. Nevertheless, some differences emerged between phyla, revealing for instance a less diverse virome in Ctenophora compared to the other animal phyla. Compositional analysis of the viromes showed that the host phylum explained over five times more variance in composition than its habitat. Moreover, significant similarities were observed between the viromes of some phylogenetically related phyla, which could highlight the influence of co-evolution in shaping invertebrate viromes.IMPORTANCEThis study significantly enhances our understanding of the global animal virome by characterizing the viromes of previously unexamined invertebrate lineages from a large number of animal phyla. It showcases the great diversity of viromes within each phylum and investigates the role of habitat shaping animal viral communities. Furthermore, our research identifies dominant virus families in invertebrates and distinguishes phyla with analogous viromes. This study sets the road toward a deeper understanding of the virome across the animal tree of life.


Assuntos
Invertebrados , Viroma , Animais , Viroma/genética , Invertebrados/virologia , Invertebrados/genética , Filogenia , Vírus/genética , Vírus/classificação
17.
Viruses ; 16(4)2024 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-38675984

RESUMO

Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When co-infected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can in some cases disrupt infectious virus replication, impact immune responses, and affect viral persistence or evolution. Understanding the dynamics of DVGs alongside standard viral genomes during infection remains unclear. To address this, we conducted a long-term experimental evolution of two betacoronaviruses, the human coronavirus OC43 (HCoV-OC43) and the murine hepatitis virus (MHV), in cell culture at both high and low multiplicities of infection (MOI). We then performed RNA-seq at regular time intervals, reconstructed DVGs, and analyzed their accumulation dynamics. Our findings indicate that DVGs evolved to exhibit greater diversity and abundance, with deletions and insertions being the most common types. Notably, some high MOI deletions showed very limited temporary existence, while others became prevalent over time. We observed differences in DVG abundance between high and low MOI conditions in HCoV-OC43 samples. The size distribution of HCoV-OC43 genomes with deletions differed between high and low MOI passages. In low MOI lineages, short and long DVGs were the most common, with an additional cluster in high MOI lineages which became more prevalent along evolutionary time. MHV also showed variations in DVG size distribution at different MOI conditions, though they were less pronounced compared to HCoV-OC43, suggesting a more random distribution of DVG sizes. We identified hotspot regions for deletions that evolved at a high MOI, primarily within cistrons encoding structural and accessory proteins. In conclusion, our study illustrates the widespread formation of DVGs during betacoronavirus evolution, influenced by MOI and cell- and virus-specific factors.


Assuntos
Coronavirus Humano OC43 , Vírus Defeituosos , Evolução Molecular , Genoma Viral , Vírus da Hepatite Murina , Replicação Viral , Animais , Humanos , Vírus Defeituosos/genética , Vírus da Hepatite Murina/genética , Coronavirus Humano OC43/genética , Camundongos , RNA Viral/genética , Linhagem Celular
18.
J Clin Med ; 13(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673481

RESUMO

Background: Cardiorespiratory fitness (CRF) is an important component of overall physical fitness and is associated with numerous health benefits, including a reduced risk of heart disease, diabetes, and obesity. However, direct measurement of CRF is time-consuming and therefore not feasible for screening purposes. Methods: A maximal treadmill exercise test with the Bruce protocol was performed to estimate VO2max in 1047 Spanish men and women aged 17 to 62 years. Weight, height, and heart rate were measured. Leisure-time physical activity (LTPA) was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. A multiple linear regression model was developed to predict exercise-based VO2max. The validity of the model was examined by correlation, concordance, Bland-Altman analysis, cross-validation, and construct validity analysis. Results: There was no significant difference between VO2max obtained by the Bruce protocol (43.56 mL/kg/min) or predicted by the equation (43.59 mL/kg/min), with R2 of 0.57, and a standard error of the estimate of 7.59 mL/kg/min. Pearson's product-moment correlation and Lin's concordance correlation between measured and predicted CRF values were 0.75 and 0.72, respectively. Bland-Altman analysis revealed a significant proportional bias of non-exercise eCRF, overestimating unfit and underestimating highly fit individuals. However, 64.3% of participants were correctly classified into CRF tertile categories, with an important 69.9% in the unfit category. Conclusions: The eCRF equation was associated with several cardiovascular risk factors in the anticipated directions, indicating good construct validity. In conclusion, the non-exercise eCRF showed a reasonable validity to estimate true VO2max, and it may be a useful tool for screening CRF.

19.
Cureus ; 16(4): e57602, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577166

RESUMO

Cone beam computed tomography (CBCT) technology is increasingly utilized in the head and neck region and is valuable in treatment planning for cleft palate patients, potentially enabling the creation of 3D-printed obturators to assist with feeding and speech. This technical report investigates the feasibility of using data from a 360-degree CBCT scan to accurately produce a cleft palate obturator and assesses whether a lower-dose 180-degree CBCT scan can achieve a comparable result. A simulated cleft palate was crafted on a dehydrated human skull, which was then scanned using both 360-degree and 180-degree CBCT scanning protocols. Two obturators were digitally designed based on the segmented images from each scan and subsequently 3D printed. Evaluation of the segmented images and 3D-printed obturators from both protocols demonstrated clear visualization of anatomical landmarks and identical scores across all parameters, suggesting that the 180-degree CBCT scan can produce an obturator of comparable quality to that of the 360-degree scan, with the added benefit of reduced radiation exposure.

20.
J Biol Chem ; 300(5): 107218, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522515

RESUMO

Virus genomes may encode overlapping or nested open reading frames that increase their coding capacity. It is not known whether the constraints on spatial structures of the two encoded proteins limit the evolvability of nested genes. We examine the evolution of a pair of proteins, p22 and p19, encoded by nested genes in plant viruses from the genus Tombusvirus. The known structure of p19, a suppressor of RNA silencing, belongs to the RAGNYA fold from the alpha+beta class. The structure of p22, the cell-to-cell movement protein from the 30K family widespread in plant viruses, is predicted with the AlphaFold approach, suggesting a single jelly-roll fold core from the all-beta class, structurally similar to capsid proteins from plant and animal viruses. The nucleotide and codon preferences impose modest constraints on the types of secondary structures encoded in the alternative reading frames, nonetheless allowing for compact, well-ordered folds from different structural classes in two similarly-sized nested proteins. Tombusvirus p22 emerged through radiation of the widespread 30K family, which evolved by duplication of a virus capsid protein early in the evolution of plant viruses, whereas lineage-specific p19 may have emerged by a stepwise increase in the length of the overprinted gene and incremental acquisition of functionally active secondary structure elements by the protein product. This evolution of p19 toward the RAGNYA fold represents one of the first documented examples of protein structure convergence in naturally occurring proteins.


Assuntos
Tombusvirus , Evolução Molecular , Fases de Leitura Aberta , Dobramento de Proteína , Estrutura Secundária de Proteína , Tombusvirus/genética , Tombusvirus/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Virais/química , Sequência de Aminoácidos , Homologia de Sequência de Aminoácidos , Modelos Psicológicos , Estrutura Terciária de Proteína
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