Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases.

Cassava brown streak disease (CBSD), dubbed the "Ebola of plants", is a serious threat to food security in Africa caused by two viruses of the family Potyviridae: cassava brown streak virus (CBSV) and Ugandan (U)CBSV. Intriguingly, U/CBSV, along with another member of this family and one secoviridae, are the only known RNA viruses encoding a protein of the Maf/ham1-like family, a group of widespread pyrophosphatase of non-canonical nucleotides (ITPase) expressed by all living organisms. Despite the socio-economic impact of CDSD, the relevance and role of this atypical viral factor has not been yet established. Here, using an infectious cDNA clone and reverse genetics, we demonstrate that UCBSV requires the ITPase activity for infectivity in cassava, but not in the model plant Nicotiana benthamiana. HPLC-MS/MS experiments showed that, quite likely, this host-specific constraint is due to an unexpected high concentration of non-canonical nucleotides in cassava. Finally, protein analyses and experimental evolution of mutant viruses indicated that keeping a fraction of the yielded UCBSV ITPase covalently bound to the viral RNA-dependent RNA polymerase (RdRP) optimizes viral fitness, and this seems to be a feature shared by the other members of the Potyviridae family expressing Maf/ham1-like proteins. All in all, our work (i) reveals that the over-accumulation of non-canonical nucleotides in the host might have a key role in antiviral defense, and (ii) provides the first example of an RdRP-ITPase partnership, reinforcing the idea that RNA viruses are incredibly versatile at adaptation to different host setups.

Synthetic Corpus Generation for Deep Learning-Based Translation of Spanish Sign Language.

Sign language serves as the primary mode of communication for the deaf community. With technological advancements, it is crucial to develop systems capable of enhancing communication between deaf and hearing individuals. This paper reviews recent state-of-the-art methods in sign language recognition, translation, and production. Additionally, we introduce a rule-based system, called ruLSE, for generating synthetic datasets in Spanish Sign Language. To check the usefulness of these datasets, we conduct experiments with two state-of-the-art models based on Transformers, MarianMT and Transformer-STMC. In general, we observe that the former achieves better results (+3.7 points in the BLEU-4 metric) although the latter is up to four times faster. Furthermore, the use of pre-trained word embeddings in Spanish enhances results. The rule-based system demonstrates superior performance and efficiency compared to Transformer models in Sign Language Production tasks. Lastly, we contribute to the state of the art by releasing the generated synthetic dataset in Spanish named synLSE.

Use of Bacterial Toxin-Antitoxin Systems as Biotechnological Tools in Plants.

Toxin-antitoxin (TA) systems in bacteria are key regulators of the cell cycle and can activate a death response under stress conditions. Like other bacterial elements, TA modules have been widely exploited for biotechnological purposes in diverse applications, such as molecular cloning and anti-cancer therapies. However, their use in plants has been limited, leaving room for the development of new approaches. In this study, we examined two TA systems previously tested in plants, MazEF and YefM-YoeB, and identified interesting differences between them, likely related to their modes of action. We engineered modifications to these specific modules to transform them into molecular switches that can be activated by a protease, inducing necrosis in the plant cells where they are expressed. Finally, we demonstrated the antiviral potential of the modified TA modules by using, as a proof-of-concept, the potyvirus plum pox virus as an activator of the death phenotype.

A survey of gene expression meta-analysis: methods and applications.

The increasing use of high-throughput gene expression quantification technologies over the last two decades and the fact that most of the published studies are stored in public databases has triggered an explosion of studies available through public repositories. All this information offers an invaluable resource for reuse to generate new knowledge and scientific findings. In this context, great interest has been focused on meta-analysis methods to integrate and jointly analyze different gene expression datasets. In this work, we describe the main steps in the gene expression meta-analysis, from data preparation to the state-of-the art statistical methods. We also analyze the main types of applications and problems that can be approached in gene expression meta-analysis studies and provide a comparative overview of the available software and bioinformatics tools. Moreover, a practical guide for choosing the most appropriate method in each case is also provided.

Vaccination against SARS-CoV-2 and its relationship with public interest in mental health: a study between 2020-2022 in Spain.

The possible relationship between vaccination against SARS-CoV-2 (COVID-19) and mental health has been largely unexplored. We investigated variations in public interest in mental health issues between the different periods of the vaccination campaign against SARS-CoV-2 in Spain and before the initiation of the campaign. Using Google Trends, we explored the relative search volume (RSV) for the terms 'anxiety', 'depression', 'stress', 'insomnia', and 'suicide' between 03/01/2020 and 01/15/2022. The RSV was compared for these terms with respect to four periods: the pre-vaccination pandemic period; the period running from initiation of vaccination until 50% of the population was fully vaccinated (FV); the period running from 50% FV to 70% FV; and the period after 70% FV. Differences in the RSV indices were observed between the studied periods for 'anxiety'(F = 6.07; p = 0.001; ƞ2 = 0.16), 'stress' (F = 7.77; p < 0.001; ƞ2 = 0.19), and 'insomnia' (F = 3.80; p = 0.013; ƞ2 = 0.11). A lower RSV was found for 'anxiety', 'stress', and 'insomnia' after 70% FV compared to the two previous vaccination periods. A lower RSV was also found for 'stress' after achieving the milestone of 70% FV in relation to the period prior to initiation of the campaign. In conclusion, there is less need for information on specific mental health topics in the period after 70% FV. In Spain, reaching this vaccination milestone may have had a positive impact on anxiety, stress, and insomnia levels in the population, as reflected in fewer web searches for information on these psychopathological processes. The promotion of the COVID-19 vaccination campaign could take into account the changes observed in this preliminary study with respect to public interest in stress, anxiety, and insomnia once a large percentage of the population has been vaccinated.

Neuropsychological functioning and suicidal behaviours in patients with first-episode psychosis: A systematic review.

INTRODUCTION: Suicidal behaviour is particularly frequent in patients with psychosis. Therefore, prevention is a key objective of mental health policies. The aim of the current work is to systematically review the association between neurocognitive functioning and suicidal behaviour in patients with first-episode psychosis (FEP). MATERIAL AND METHODS: Of the 3051 studies reviewed, only 7 met the inclusion criteria. Documents in English from their earliest date of coverage until January 2022 were searched for in the following databases: PubMed, Science Direct, Web of Science, Cochrane Library, PsycINFO (ProQuest), and Springerlink. We used the PICO strategy to collect and categorize the data from each selected manuscript. RESULTS: Overall, the results showed that the risk of suicidal behaviour is higher for FEP patients in the presence of a number of factors: poorer general neuropsychological functioning (except for working memory), poorer social cognition, more depressive symptoms, longer duration of untreated psychosis, higher awareness of the illness, poorer premorbid adjustment, and more frequent cannabis use. DISCUSSION: Comprehensive general neuropsychology and assessment of social cognition, together with routine clinical record keeping, may help to identify FEP patients at a greater risk of attempting suicide.

Analysis of aerosol production and aerosol dispersion during otologic surgery.

BACKGROUND: As a respiratory disease, the transmission of Coronavirus disease (COVID-19) is mainly caused by small droplets and aerosols. Healthcare personnel are particularly exposed during otologic surgery given the continuity with the nasopharynx, where the viral load is high, and the use of high-speed instruments. The purpose of the present study is to test a model of droplet dispersion produced in the performance of a drilling procedure on human bone to provide information about its distribution and size of the deposit in similar conditions to those of an operating theatre, to design different preventive measures. MATERIAL AND METHOD: A mastoidectomy and trans-labyrinthine approach were performed on an embalmed human corpse using for irrigation during drilling methylene blue dye in physiological saline solution (pss) at a concentration of 0.324 mg/mL. The distribution of the drops was stablished using semi-absorbent papers of size 52 cm × 42 cm covering the area around the dissection field to a radius of 150 cm and on the corpse at different heights to check vertical dispersion. The collected deposit material was analysed with the microscope at different magnification objectives. RESULTS: Droplets between 2 µm and 2.6 cm were obtained. The visualization of the coloured droplets in the horizontal plane at a magnification of 1.5 was detected at 150 cm from the focus of emission of milling particles. DISCUSSION: According to our study, bone drilling with high speed motors under continuous saline irrigation in a haemorrhagic surgical field increases the amount of aerosols exposing healthcare personnel to additional airbone particles. This risk does not end in the operating rooms as particles smaller than 2 µm can be suspended in the air for hours and could exit the operating theatre due to the use of positive pressure systems. Thus, the use of N95, FFP2, FFP3 or PAPRS should be considered and the development of hood systems to prevent the dispersion of aerosols during these procedures should be considered.

Cadmium (Cd) and Lead (Pb) topsoil levels and incidence of childhood leukemias.

There are few well-established risk factors for childhood leukemias. While the frequency of childhood leukemias might be partially attributable to some diseases (accounting for a small fraction of cases) or ionizing radiation, the role of heavy metals has not been assessed. The objective of our study was to assess the potential association between levels of cadmium (Cd) and lead (PB) in soil and childhood leukemias incidence. We conducted a population-based case-control study of childhood leukaemia in Spain, covering 2897 incident cases gathered from the Spanish Registry of Childhood Tumours and including 14 Spanish Regions with a total population of 5,307,433 children (period 1996-2015). Cd and Pb bioavailable levels at every children's home address were estimated using data from the Geochemical Atlas of Spain. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (95%CIs); we included as covariates: sex, rurality, employment rate and socioeconomic status. Metal levels were analysed according to two definitions: as continuous variable assuming linearity and as categorical variables to explore a potentially nonlinear association (quantiles). Increases in both Cd and Pb topsoil levels were associated with increased probability of childhood leukemias incidence. The results for the models with the continuous variables showed that a unit increase on the topsoil level was associated with an OR of 1.11 for Cd (95%CI 1.00-1.24) and an OR of 1.10 for Pb (95%CI 0.99-1.21). Our study may point towards a possible link between residential Cd and Pb topsoil levels and the probability of childhood leukemias incidence. Residing in a location with the highest concentrations of these heavy metals compared to those locations with the lowest could increase the risk around a 20%, for both Cd and Pb.

Revisiting the original Akin technique: A comparative analysis of radiographic outcome.

BACKGROUND: The Akin osteotomy is widely used to correct the hallux valgus and different fixation techniques have been proposed. Currently most of these procedures coexist, with disagreement on which offers the best results. The aim of this study is to compare the radiological outcome of the original Akin's technique with one in which a staple was used to stabilize the osteotomy. We also assessed whether other factors unrelated to the osteosynthesis could influence the radiological outcome. METHODS: We retrospectively reviewed data from 118 patients who underwent a scarf and Akin osteotomy. In 60 patients the Akin osteotomy was fixed with a staple and in 58 cases no staple was used. Hallux valgus angle (HVA), distal articular set angle (DASA), interphalangeal angle (IPA) and tibial sesamoid position were measured. The presence of lateral cortex disruption of the phalanx was also included in the analysis. RESULTS: Six variables significantly influenced the radiological results of the Akin osteotomy: preoperative HVA, IPA and tibial sesamoid position, laterality, postoperative cortical disruption and use of a staple. CONCLUSION: Ours results suggest that the original Akin's technique seems to offer equal or better results than a variation in which a staple is added to stabilize the osteotomy. LEVEL OF EVIDENCE: This is a level III retrospective case-control study.

Review of the questionnaries used to detect alcohol consumption during pregnancy and the Green Page. / Revisión de los cuestionarios utilizados para la detección del consumo de alcohol durante el embarazo y la Hoja Verde.

Alcohol consumption during pregnancy is a leading cause of fetal alcohol spectrum disorder (FASD). Maternal reporting in childbearing women or pregnant women is the standard for the early detection of alcohol consumption. The Green Page (GP) is a screening questionnaire of environmental health which includes the alcohol intake record during pregnancy and/or lactation period. The aim of this paper is to review the features of the different questionnaires for the detection of alcohol consumption during the gestation period and the GP, as well as to make a comparison between them. Review of the scientific literature published over the last 10 years of indexed articles in Medline. Combined searching strategy with MeSH descriptors: 'pregnancy, alcohol drinking, surveys and/or questionnaires. AUDIT, AUDIT-C and SURP-P are mainly self-administered and do not require training. SURP-P and 4P´s are validated in pregnant women. Others detect quantity and frequency of exposure, need specific training and are administered face to face: TLFB, RD, ACOG antepartum record and the GP. ACOG antepartum record and GP are specific for pregnant population. GP detects alcohol consumption at the beginning of pregnancy in both women and their partner on a holistic and global environmental health approach. A careful face-to-face recording of alcohol exposure with trained staff, with an integrative and global environmental health focus throughout pregnancy, may help improve prevention and screening of pregnancy at risk for FASD.

El consumo de alcohol en el embarazo es la causa del trastorno del espectro alcohólico fetal (TEAF). La información aportada por las mujeres en edad fértil o embarazadas es el estándar para la detección temprana del consumo de alcohol. La Hoja Verde (HV) es una herramienta de cribado de salud medioambiental que incluye el registro de la ingesta de alcohol durante el embarazo y/o lactancia. El objetivo del presente trabajo es revisar las características de los distintos cuestionarios de detección del consumo de alcohol durante la gestación y de la HV, así como hacer una comparación entre ellos. Revisión de la literatura científica publicada en los últimos 10 años de los artículos indexados en Medline. Estrategia de búsqueda combinada con los descriptores MeSH: 'pregnancy, alcohol drinking, surveys and/or questionnaires'. AUDIT, AUDIT-C y SUPR-P se realizan mayoritariamente autoadministrados y no requieren entrenamiento. SUPR-P y 4P´s Plus están validados en embarazadas. Otros detectan cantidad y frecuencia, requieren entrenamiento previo y se realizan cara a cara: TLFB, RD, ACOG antepartum record y la HV. ACOG antepartum record y la HV son específicos para embarazadas. La HV detecta el consumo de alcohol al inicio del embarazo tanto en la gestante como en su pareja con un enfoque holístico y global de la salud medioambiental. Un cuidadoso registro de la ingesta de alcohol de forma presencial, con profesionales entrenados y con un enfoque holístico y global de la salud medioambiental durante el embarazo ayudaría a mejorar la prevención y cribado de embarazos en riesgo de TEAF.

A comprehensive database for integrated analysis of omics data in autoimmune diseases.

BACKGROUND: Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. RESULTS: Here, we present Autoimmune Diseases Explorer ( https://adex.genyo.es ), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis. CONCLUSIONS: This is the first omics database focused on autoimmune diseases. This resource incorporates homogeneously processed data to facilitate integrative analyses among studies.

Molecular Plant-Plum Pox Virus Interactions.

Plum pox virus, the agent that causes sharka disease, is among the most important plant viral pathogens, affecting Prunus trees across the globe. The fabric of interactions that the virus is able to establish with the plant regulates its life cycle, including RNA uncoating, translation, replication, virion assembly, and movement. In addition, plant-virus interactions are strongly conditioned by host specificities, which determine infection outcomes, including resistance. This review attempts to summarize the latest knowledge regarding Plum pox virus-host interactions, giving a comprehensive overview of their relevance for viral infection and plant survival, including the latest advances in genetic engineering of resistant species.

Phosphorylation-Related Crosstalk Between Distant Regions of the Core Region of the Coat Protein Contributes to Virion Assembly of Plum Pox Virus.

Eukaryotic proteins are often targets of posttranslational modifications (PTMs). Capsid protein (CP) of plum pox virus (PPV), a member of genus Potyvirus, has been reported to be prone to phosphorylation in four serines at the N-terminal region. CP phosphorylation has been proposed to influence PPV infection by regulating CP accumulation in coordination with a second PTM, O-GlcNAcylation. In this study, a further proteomic characterization of PPV CP phosphorylation revealed additional phospho-targets, thus evidencing even greater complexity of the network of PTMs affecting this protein. In particular, two new phosphorylation targets, T254 and T313, at protein distal core, appear to be highly relevant for infection. Although abolishing phosphorylation at these positions does not have a severe effect on infectivity or viral accumulation, phospho-mimicking at either of these targets disrupts cell-to-cell movement. Strand-specific reverse transcription-quantitative PCR analysis and fractionation by centrifugation in a continuous sucrose gradient enabled us to conclude that such a deleterious effect is not related to failures in replication but is a consequence of inaccurate virion assembly. The analysis of spontaneous compensatory mutations at the CP core identified in a multiple phospho-mimicking mutant disclosed a functional dialogue between distant phospho-targets, which was further supported by an in silico PPV virion model, built on the watermelon mosaic virus atomic structure. Therefore, whereas joint and opposite action of O-GlcNAcylation and phosphorylation at the N-terminal disordered protrusion of CP appears to regulate protein stability, we propose that phosphorylations at the core region control assembly and disassembly of viral particles.

A Functional Link between RNA Replication and Virion Assembly in the Potyvirus Plum Pox Virus.

Accurate assembly of viral particles in the potyvirus Plum pox virus (PPV) has been shown to depend on the contribution of the multifunctional viral protein HCPro. In this study, we show that other viral factors, in addition to the capsid protein (CP) and HCPro, are necessary for the formation of stable PPV virions. The CP produced in Nicotiana benthamiana leaves from a subviral RNA termed LONG, which expresses a truncated polyprotein that lacks P1 and HCPro, together with HCPro supplied in trans, was assembled into virus-like particles and remained stable after in vitro incubation. In contrast, deletions in multiple regions of the LONG coding sequence prevented the CP stabilization mediated by HCPro. In particular, we demonstrated that the first 178 amino acids of P3, but not a specific nucleotide sequence coding for them, are required for CP stability and proper assembly of PPV particles. Using a sequential coagroinfiltration assay, we observed that the subviral LONG RNA replicates and locally spreads in N. benthamiana leaves expressing an RNA silencing suppressor. The analysis of the effect of both point and deletion mutations affecting RNA replication in LONG and full-length PPV demonstrated that this process is essential for the assembly of stable viral particles. Interestingly, in spite of this requirement, the CP produced by a nonreplicating viral RNA can be stably assembled into virions as long as it is coexpressed with a replication-proficient RNA. Altogether, these results highlight the importance of coupling encapsidation to other viral processes to secure a successful infection.IMPORTANCE Viruses of the family Potyviridae are among the most dangerous threats for basically every important crop, and such socioeconomical relevance has made them a subject of many research studies. In spite of this, very little is currently known about proteins and processes controlling viral genome encapsidation by the coat protein. In the case of Plum pox virus (genus Potyvirus), for instance, we have previously shown that the multitasking viral factor HCPro plays a role in the production of stable virions. Here, by using this potyvirus as a model, we move further to show that additional factors are also necessary for the efficient production of potyviral particles. More importantly, a comprehensive screening for such factors led us to the identification of a functional link between virus replication and packaging, unraveling a previously unknown connection of these two key events of the potyviral infection cycle.

Sterol isomerase HYDRA1 interacts with RNA silencing suppressor P1b and restricts potyviral infection.

Plants use RNA silencing as a strong defensive barrier against virus challenges, and viruses counteract this defence by using RNA silencing suppressors (RSSs). With the objective of identifying host factors helping either the plant or the virus in this interaction, we have performed a yeast two-hybrid screen using P1b, the RSS protein of the ipomovirus Cucumber vein yellowing virus (CVYV, family Potyviridae), as a bait. The C-8 sterol isomerase HYDRA1 (HYD1), an enzyme involved in isoprenoid biosynthesis and cell membrane biology, and required for RNA silencing, was isolated in this screen. The interaction between CVYV P1b and HYD1 was confirmed in planta by Bimolecular Fluorescence Complementation assays. We demonstrated that HYD1 negatively impacts the accumulation of CVYV P1b in an agroinfiltration assay. Moreover, expression of HYD1 inhibited the infection of the potyvirus Plum pox virus, especially when antiviral RNA silencing was boosted by high temperature or by coexpression of homologous sequences. Our results reinforce previous evidence highlighting the relevance of particular composition and structure of cellular membranes for RNA silencing and viral infection. We report a new interaction of an RSS protein from the Potyviridae family with a member of the isoprenoid biosynthetic pathway.

Complete genome sequence of a novel member of the family Potyviridae isolated from Phellodendron amurense Rupr. in Liaoning, China.

In September 2017, Phellodendron amurense Rupr. plants showing yellow ringspots on leaves were observed in Liaoning, China. Flexuous filamentous particles (~1000 × 13 nm) were observed in the sap prepared from symptomatic leaves. A virus was detected in the symptomatic leaves by sequencing small RNAs and assembling the genome sequence. The complete genomic RNA was found to be 10,457 nucleotides in length excluding the poly(A) tail and to have the closest phylogenetic relationship to rose yellow mosaic virus (RoYMV), the sole member of newly established genus Roymovirus in the family Potyviridae. The coat protein gene (CP) of this virus shares 49.2% nucleotide and 55.1% amino acid sequence identity with that of RoYMV. These results suggest that this virus, which was named "phellodendron yellow ringspot-associated virus" (PYRaV) is a new member of the genus Roymovirus.

An Integrative Screening Tool of Alcohol Exposure During Early Pregnancy: Combining of the CDT Biomarker with Green Page Questionnaire.

AIMS: In current clinical practice, prenatal alcohol exposure is usually assessed by interviewing the pregnant woman by applying questionnaires. An alternative method for detecting alcohol use is to measure the biomarker carbohydrate-deficient transferrin (CDT). However, few studies measure CDT during pregnancy. This study examines the utility of CDT biomarker in the screening of alcohol exposure during early pregnancy. METHODS: A cohort of 91, first-trimester pregnant women assigned to a public reference maternity hospital, was screened using the Green Page (GP) questionnaire, an environmental exposure tool. CDT levels and other biomarkers of alcohol use were measured and compared with questionnaire data. RESULTS: About 70% of the mothers in the study consumed alcohol during early pregnancy and 22% met high-risk criteria for prenatal exposure to alcohol. CDT measurement showed a statistically significant area under the receiver operating characteristic curve with a value of 0.70. For a value of 0.95% of CDT, a specificity of 93% was observed. The most significant predictors of CDT were the number of binge drinking episodes, women's body mass index and European white race. CONCLUSION: Pregnant women with a CDT value >0.95% would be good candidates for the performance of the GP questionnaire during early pregnancy in order to detect potential high-risk pregnancy due to alcohol exposure.

Metagenomic insights into zooplankton-associated bacterial communities.

Zooplankton and microbes play a key role in the ocean's biological cycles by releasing and consuming copious amounts of particulate and dissolved organic matter. Additionally, zooplankton provide a complex microhabitat rich in organic and inorganic nutrients in which bacteria thrive. In this study, we assessed the phylogenetic composition and metabolic potential of microbial communities associated with crustacean zooplankton species collected in the North Atlantic. Using Illumina sequencing of the 16S rRNA gene, we found significant differences between the microbial communities associated with zooplankton and those inhabiting the surrounding seawater. Metagenomic analysis of the zooplankton-associated microbial community revealed a highly specialized bacterial community able to exploit zooplankton as microhabitat and thus, mediating biogeochemical processes generally underrepresented in the open ocean. The zooplankton-associated bacterial community is able to colonize the zooplankton's internal and external surfaces using a large set of adhesion mechanisms and to metabolize complex organic compounds released or exuded by the zooplankton such as chitin, taurine and other complex molecules. Moreover, the high number of genes involved in iron and phosphorus metabolisms in the zooplankton-associated microbiome suggests that this zooplankton-associated bacterial community mediates specific biogeochemical processes (through the proliferation of specific taxa) that are generally underrepresented in the ambient waters.