DisProt in 2022: improved quality and accessibility of protein intrinsic disorder annotation.

The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.

Impact of protein conformational diversity on AlphaFold predictions.

MOTIVATION: After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here, we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm. RESULTS: Using a curated collection of apo-holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in ∼70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions. AVAILABILITY AND IMPLEMENTATION: Data and code used in this manuscript are publicly available at https://gitlab.com/sbgunq/publications/af2confdiv-oct2021. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Structural and optical characterisation of silanised Dy-doped-Gd2O3 NPs.

In this work, we studied the optical properties of Dy-doped Gd2O3 nanoparticles (NPs) before and after their APTES functionalisation. We obtained luminescent Dy@Gd2O3 NPs (0.5, 1, and 5% mol) using a modified polyol method. Our work describes their detailed structural analysis using FT-IR, XRD, HRTEM, TGA and XAS techniques. The results show that these systems present a crystalline structure with a body-centred cubic cell and particle sizes of 10 nm. The dopant position was inferred as substitutional, through XAS analysis at the M4,5-edges of Gd and Dy and K-edge of O, and in C2 sites, based on photoluminescence studies. There was sensitization of the luminescence by the matrix as shown by the emission increase of the hypersensitive transition (6F9/2 → 6H13/2, 572 nm) and also a broadband appears around 510 nm attributed to defects in Gd2O3. An enhanced emissive lifetime of 398 µs was found for the sample doped at 1%. We functionalised the Dy@Gd2O3 (at 1%) NPs with 3-aminopropiltrietoxisilane (APTES) for further application as a biomarker sensor. We found that these NPs conserved their luminescence after adding the surface agent (avoiding quenching effects) making them potential materials for biosensing.

Enterobiasis and its risk factors in urban, rural and indigenous children of subtropical Argentina.

A cross-sectional survey to assess the prevalence of Enterobius vermicularis infection and its associated factors among the child population of infant, preschool and school age in the urban, rural and indigenous population of Iguazú city, in subtropical Argentina was presented. Additionally, the status of enterobiasis at country level was reviewed and analysed. Enterobius vermicularis presence was assessed employing an oviscopic serial sampling technique. Statistical analysis of socio-demographic determinants was performed by generalized linear mixed models at individual, household and community levels. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used to gather national information about E. vermicularis prevalence spanning the decade 2010­2020. A total of 916 children from 470 families participated. Overall prevalence was 29.8%, with 25.3, 30.7 and 34.2% detected for children inhabiting urban, rural and indigenous villages, respectively. The multi-level analysis showed that the presence of E. vermicularis was mostly determined by individual (e.g. age, playing habits, previous pinworm infection) and household-level factors (e.g. family size, overcrowding conditions). Interestingly, WASH variables, such as waste disposal, analysed at community level were also important. Data were analysed to provide eco-epidemiological features of enterobiasis in a heterogeneous subtropical child population in the same territory but with different socio-sanitary realities. The importance of promoting multi-level actions against the determinants identified, to control this public health problem integratively was evidenced. The scoping review of national data updated the state of knowledge of this parasitosis, identifying risk determinants and gaps in knowledge at country level.

Diphyllobothrium sp. in Canis familiaris from the subtropical area of Argentina (Puerto Iguazú, Misiones).

This paper reports the first finding of Diphyllobothrium sp. eggs in Canis familiaris (domestic dog) from Puerto Iguazú, a subtropical city of Misiones province, Argentina. In 2013, two positive cases of Diphyllobothrium sp. eggs were detected during an annual parasitological survey of dogs. Dog feces were collected in vials containing 10% formalin and processed using Telemann's sedimentation and Sheather's flotation techniques. The two cases were detected in rural areas of the municipality. Since Misiones is not a part of the endemic area of diphyllobothriasis and given the fact that it is located in the three-border area of Argentina, Brazil and Paraguay, we consider this finding of great importance to public health. We stress the need for updating the current knowledge about the life cycle of these parasites considering the range of intermediate and definitive hosts, their zoonotic potential, and the epidemiological situation in non-endemic areas.

RhNPs supported on N-functionalized mesoporous silica: effect on catalyst stabilization and catalytic activity.

Amine and nicotinamide groups grafted on ordered mesoporous silica (OMS) were investigated as stabilizers for RhNPs used as catalysts in the hydrogenation of several substrates, including carbonyl and aryl groups. Supported RhNPs on functionalized OMS were prepared by controlled decomposition of an organometallic precursor of rhodium under dihydrogen pressure. The resulting materials were characterized thoroughly by spectroscopic and physical techniques (FTIR, TGA, BET, SEM, TEM, EDX, XPS) to confirm the formation of spherical rhodium nanoparticles with a narrow size distribution supported on the silica surface. The use of nicotinamide functionalized OMS as a support afforded small RhNPs (2.3 ± 0.3 nm), and their size and shape were maintained after the catalyzed acetophenone hydrogenation. In contrast, amine-functionalized OMS formed RhNP aggregates after the catalytic reaction. The supported RhNPs could selectively reduce alkenyl, carbonyl, aryl and heteroaryl groups and were active in the reductive amination of phenol and morpholine, using a low concentration of the precious metal (0.07-0.18 mol%).

Twice upon a time: The progression of canine visceral leishmaniasis in an Argentinean city.

Canine Visceral Leishmaniasis (CVL) prevalence, spatial distribution and associated factors were assessed in four locations in Iguazú department in 2014 and in Puerto Iguazú city again in 2018. The city areas were divided into a grid of 400x400m cells. All cells were sampled in 2014 and a random subsampling was developed in 2018. In each cell, five dogs clustered in a 'critical scenario' (prone to have vectors) were sampled. A rapid immunochromatographic dipstick was used to detect antibodies against Leishmania infantum, confirming by lymph node smears observation and PCR. For Puerto Iguazú, Generalized Linear Models (GLMs) were constructed considering environmental, dog and clinical variables. Pearson's Chi square and Fisher's exact tests were employed to evaluate the association between CVL, dog clinical signs and infestation with other parasites. Cartographic outputs were made and Moran's I indices were calculated as spatial autocorrelation indicators. CVL prevalence rates were 26.18% in 2014 and 17.50% in 2018. No associations were established in environmental models, but dog age and repellent use were significant when running 2014 dog models. Clinical models showed significant associations between seropositive dogs and ophthalmological, dermal signs and onychogryphosis in 2014. In 2018, only adenomegaly was associated. The results of global Moran´s I were not significant but regarding local analysis, six sites in 2014 and one in 2018 presented autocorrelation with neighboring sites. The decrease in CVL prevalence may be associated to transmission stabilization, which could explain the lack of associations with dog-related variables. Further, spatial distribution of CVL is a poor evidence for design of transmission control measures but could be important in case of intensive parasite circulation or when the first autochthonous cases appear. For control success, sensitivity of diagnostic methods, political will and adequate material resources remain critical. Modeling of multiple variables will be required to identify factors that drive disease stabilization/destabilization.

Environmental and socio-demographic individual, family and neighborhood factors associated with children intestinal parasitoses at Iguazú, in the subtropical northern border of Argentina.

BACKGROUND: Intestinal parasitoses are a major concern for public health, especially in children from middle and low-income populations of tropical and subtropical areas. We examined the presence and co-infection of parasites in humans as well as parasitic environmental contamination in Puerto Iguazú, Argentina. We explored the environmental and socio-demographic characteristics of the persistence of parasites in children and their environment. METHODOLOGY/PRINCIPAL FINDINGS: This cross-section survey was conducted among children population comprised into the area of the public health care centers of Iguazú during June 2013 to May 2016. Copro-parasitological status of 483 asymptomatic children was assessed. Simultaneously, a design-based sampling of 744 soil samples and 530 dog feces was used for characterize the environmental contamination. The 71.5% of these sites were contaminated. Sixteen genera were detected in the environment being hookworms (62.0%) the main pathogens group detected followed by Toxocara spp (16.3%), Trichuris spp (15.2%) and Giardia (6.5%). Total children prevalence raised 58.8%, detecting twelve genera of parasite with Giardia intestinalis as the most prevalent pathogen (29.0%) followed by Enterobius vermicularis (23.0%), Hymenolepis nana (12.4%) and hookworms (4.4%). Through questionnaires and census data, we characterized the socio-demographics conditions at an individual, family and neighborhood levels. A multi-level analysis including environmental contamination data showed that the ´presence of parasites´ was mostly determined by individual (e.g. age, playing habits, previous treatment) and household level (e.g. UBN, WASH, mother's literacy) determinants. Remarkably, to define the level of 'parasite co-infection', besides individual and household characteristics, environmental factors at a neighborhood level were important. CONCLUSION/SIGNIFICANCE: Our work represents the major survey of intestinal parasites in human and environmental samples developed in the region. High prevalence was detected in the children population as well as in their environment. This work shows the importance of considering and promoting multi-level actions over the identified determinants to face this public health problem from integrative approaches.

Echinococcus oligarthrus in the subtropical region of Argentina: First integration of morphological and molecular analyses determines two distinct populations.

Echinococcosis is a parasitic zoonosis that is considered as a neglected disease by the World Health Organization. The species Echinococcus oligarthrus is one of the causative agents of Neotropical echinococcosis, which is a poorly understood disease that requires a complex medical examination, may threaten human life, and is frequently associated with a low socioeconomic status. Morphological and genetic diversity in E. oligarthrus remains unknown. The aim of this work is to identify and characterize E. oligarthrus infections in sylvatic animals from the Upper Paraná Atlantic Forest in the province of Misiones, Argentina, by following an integrative approach that links morphological, genetic and ecological aspects. This study demonstrates, for the first time, one of the complete life cycles of E. oligarthrus in an important ecoregion. The Upper Paraná Atlantic Forest constitutes the largest remnant continuous forest of the Atlantic Forest, representing 7% of the world's biodiversity. This is the first molecular determination of E. oligarthrus in Argentina. In addition, the agouti (Dasyprocta azarae), the ocelot (Leopardus pardalis) and the puma (Puma concolor) were identified as sylvatic hosts of Neotropical echinococcosis caused by E. oligarthrus. Mitochondrial and nuclear molecular marker analyses showed a high genetic diversity in E. oligarthrus. Moreover, the genetic distance found among E. oligarthrus isolates is higher than the one observed among Echinococcus granulosus genotypes, which clearly indicates that there are at least two different E. oligarthrus populations in Argentina. This study provides valuable information to understand the underlying conditions that favour the maintenance of E. oligarthrus in sylvatic cycles and to evaluate its zoonotic significance for devising preventive measures for human and animal wellbeing.

First report of parasitism by Hexametra boddaertii (Nematoda: Ascaridae) in Oxyrhopus guibei (Serpentes: Colubridae).

The current study summarizes the postmortem examination of a specimen of Oxyrhopus guibei (Serpentes, Colubridae) collected in Iguazu National Park (Argentina), and found deceased a week following arrival to the serpentarium of the National Institute of Tropical Medicine (Argentina). Although the snake appeared to be in good health, a necropsy performed following its death identified the presence of a large number of roundworms in the coelomic cavity, with indications of peritonitis and serosal adherence. Additional observations from the necropsy revealed small calcifications in the mesothelium of the coelomic cavity; solid and expressive content in the gallbladder; massive gastrointestinal obstruction due to nematodes; and lung edema and congestion. Histopathological analyses of lung sections also showed proliferative heterophilic and histiocytic pneumonia. Parasites isolated from both the intestine and coelomic cavity were identified as Hexametra boddaertii by a combination of light and scanning electron microscopic examination. Results from this necropsy identify O. guibei as a new host for H. boddaertii, and is the first report of a natural infection by Hexametra in Argentina. Since Hexametra parasites may contribute to several pathological conditions in humans, and with the recent availability of O. guibei specimens through the illegal pet trade, it is necessary to consider the possibility of zoonotic helminth transmission of Hexametra from snake to human.

Diphyllobothrium sp. en Canis familiares de la región del subtrópico argentino (Puerto Iguazú, Misiones) / Diphyllobothrium sp. in Canis familiaris from the subtropical area of Argentina (Puerto Iguazú, Misiones)

En este trabajo se informa el hallazgo de huevos de Diphyllobothrium sp. en ejemplares de Canis familiaris (perro doméstico) de Puerto Iguazú, una ciudad subtropical de la provincia de Misiones, Argentina. Durante 2013, en el marco de un relevamiento de la fauna parasitológica de los perros de Puerto Iguazú, se detectaron dos casos positivos en la búsqueda de huevos de Diphyllobothrium sp. La materia fecal de los perros fue recolectada en frascos con formol al 10% y procesada mediante las técnicas de sedimentación de Telemann y de flotación de Sheather. Dado que Misiones no forma parte de la zona endémica de difilobotriasis y considerando, además, su ubicación fronteriza, este hallazgo reviste gran importancia para la salud pública. Se señala la necesidad de actualizar el estado de conocimiento sobre el ciclo de vida de estos parásitos identificando el rango de hospederos intermediarios y definitivos, su potencial zoonótico y la situación epidemiológica en áreas no endémicas

This paper reports the first finding of Diphyllobothrium sp. eggs in Canis familiaris (domestic dog) from Puerto Iguazú, a subtropical city of Misiones province, Argentina. In 2013, two positive cases of Diphyllobothrium sp. eggs were detected during an annual parasitological survey of dogs. Dog feces were collected in vials containing 10% formalin and processed using Telemann's sedimentation and Sheather's flotation techniques. The two cases were detected in rural areas of the municipality. Since Misiones is not a part of the endemic area of diphyllobothriasis and given the fact that it is located in the three-border area of Argentina, Brazil and Paraguay, we consider this finding of great importance to public health. We stress the need for updating the current knowledge about the life cycle of these parasites considering the range of intermediate and definitive hosts, their zoonotic potential, and the epidemiological situation in non-endemic areas

[Prescription of drugs in family medicine: on the trail of efficiency]. / Prescripción de medicamentos en medicina de familia: tras las pistas de la eficiencia.

OBJECTIVE: To analyse the effect of various factors on the efficiency of drug prescription by general practitioners (GPs). DESIGN: Descriptive, cross-sectional study. SETTING: Primary care in Murcia, Cartagena, and Lorca, in which 535 GPs work in the care of 921,281 people. Murcia Region (Spain).Participants. Prescriptions issued by the 288 GPs who were working constantly and continuously in May-June 1998 and who were away from work for no longer than 10% of the time (53.8%). MAIN MEASUREMENTS: We measured their efficiency with two general indicators--potential saving (PS) and prescription of generics (PG)--and 3 specific indicators: efficiency of prescription of omeprazole (EO), enalapril (EE), and ranitidine (ER). We analysed their relationship with structural-organisational factors and with the population attended, the doctor and his/her action. Bivariate and multivariate analyses (logistic regression) were used. RESULTS: There was an association with programmed consultation (PC); a weak inverse relationship with age of doctor, years qualified, pensioners allocated, case load and inter-consultations conducted; and a direct correlation with the length of the consultation. PG was related to rural environment, being non-permanent, specialist in family medicine, belonging to a primary care team. In the multivariate analysis PC was related to all the indicators: PS (OR=1.96), PG (OR=2.10), EO (OR=2.63), ER (OR=2.84), EE (OR=2.06); and the inter-consultations conducted with general efficiency of PS (OR=1.70), PG (OR=1.91). Rural environment was the worst for PS (OR=2.43). CONCLUSIONS: The main factors related to the efficiency of GPs prescription can be changed. The most important is the existence of PC. A lot of inter-consultations and working in a rural environment means worse general efficiency.

[Effectiveness of a personalized information system on the quality of family doctors' medical prescription]. / Efectividad de un sistema de información personalizada sobre la calidad de prescripción de medicamentos en médicos de familia.

OBJECTIVES: To evaluate the effectiveness of a system of personalised prescription information (PPI) to improve prescription habits of family doctors (FD); to examine how useful PPI is in maintaining these habits, and to analyse its influence through factors of the doctor and his/her environment. DESIGN: Cross-sectional, descriptive pilot study to analyse conditioning factors and possible confusion; quasi-experimental intervention study to assess the effectiveness of PPI, with two groups (experimental and control) and 4 determinations (before the PPI and after: short, medium and long-term).Setting. Family doctors in the Murcia Region. SUBJECTS OF STUDY: The prescriptions of all family doctors in the Murcia region which started before PPI and which continued until the end of the study and without absences of over 10% at each measurement.Intervention. The family doctors from the Murcia city area formed the experimental group: they received PPI with specific proposals for improvement. The FDs of Cartagena and Lorca, who did not receive PPI, made up the control group. Statistical analysis. Logistical regression to identify conditioning factors. Z comparison of proportions contrasted with one-tail hypothesis to check the effectiveness of PPI. LIMITATIONS OF THE DESIGN: Non-randomised allocation to groups made comparison difficult: conditioning factors for stratification or adjustment were studied. PRACTICAL APPLICATION: Confirmation of PPI s effectiveness justifies its dissemination. If there is no such confirmation, it will have to be perfected. Isolating the factors conditioning prescription that can be modified helps find ways to improve PPI.