Finding a Needle in a Haystack: Producing Antimicrobial Cutin-Derived Oligomers from Tomato Pomace.

Agro-industrial residues comprise a rich diversity of plant polymers and bioactive compounds, constituting promising sources for the development of materials, including bioplastics, and food supplements, among other applications. In particular, the polyester cutin is abundant in fruit peel, a plentiful constituent of pomace agro-industrial residues. The potential of diverse fruit pomaces as a source for the development of cutin-derived materials/products has been extensively sought out. This study expands the established knowledge: it sets proof of concept for the production of antimicrobial oligomers from cutin-rich materials isolated in a single step from tomato pomaces generated by two remote agro-industries. Specifically, it first analyzed how the chemical signature (nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS)) of a pomace (and of its major constituents) mirrors that of the corresponding cutin-rich material isolated using an ionic liquid extractant. The cutin-rich materials were then deconstructed (using mild hydrolyses), and the resultant mixtures were chemically characterized and screened for bactericidal activity against Escherichia coli and Staphylococcus aureus. The presence of esterified structures, linear and/or branched, likely comprising dioic acids as a major building block (but not exclusively) is a prerequisite for activity against E. coli but not against S. aureus that was susceptible to monomers as well. Further studies are required to optimize the production of broad bactericidal oligomers from any cutin-rich pomace source, moving ahead toward their circular usage.

merlin, an improved framework for the reconstruction of high-quality genome-scale metabolic models.

Genome-scale metabolic models have been recognised as useful tools for better understanding living organisms' metabolism. merlin (https://www.merlin-sysbio.org/) is an open-source and user-friendly resource that hastens the models' reconstruction process, conjugating manual and automatic procedures, while leveraging the user's expertise with a curation-oriented graphical interface. An updated and redesigned version of merlin is herein presented. Since 2015, several features have been implemented in merlin, along with deep changes in the software architecture, operational flow, and graphical interface. The current version (4.0) includes the implementation of novel algorithms and third-party tools for genome functional annotation, draft assembly, model refinement, and curation. Such updates increased the user base, resulting in multiple published works, including genome metabolic (re-)annotations and model reconstructions of multiple (lower and higher) eukaryotes and prokaryotes. merlin version 4.0 is the only tool able to perform template based and de novo draft reconstructions, while achieving competitive performance compared to state-of-the art tools both for well and less-studied organisms.

Reconstruction of tissue-specific genome-scale metabolic models for human cancer stem cells.

Cancer Stem Cells (CSCs) contribute to cancer aggressiveness, metastasis, chemo/radio-therapy resistance, and tumor recurrence. Recent studies emphasized the importance of metabolic reprogramming of CSCs for the maintenance and progression of the cancer phenotype through both the fulfillment of the energetic requirements and the supply of substrates fundamental for fast-cell growth, as well as through metabolite-induced epigenetic regulation. Therefore, it is of paramount importance to develop therapeutic strategies tailored to target the metabolism of CSCs. In this work, we built computational Genome-Scale Metabolic Models (GSMMs) for CSCs of different tissues. Flux simulations were then used to predict metabolic phenotypes, identify potential therapeutic targets, and spot already-known Transcription Factors (TFs), miRNAs and antimetabolites that could be used as part of drug repurposing strategies against cancer. Results were in accordance with experimental evidence, provided insights of new metabolic mechanisms for already known agents, and allowed for the identification of potential new targets and compounds that could be interesting for further in vitro and in vivo validation.

Quantification of Structure-Property Relationships for Plant Polyesters Reveals Suberin and Cutin Idiosyncrasies.

Polyesters, as they exist in planta, are promising materials with which to begin the development of "green" replacements. Cutin and suberin, polyesters found ubiquitously in plants, are prime candidates. Samples enriched for plant polyesters, and in which their native backbones were largely preserved, were studied to identify "natural" structural features; features that influence critical physical properties. Quantitative nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and X-ray scattering methods were used to quantify structure-property relationships in these polymeric materials. The degree of esterification, namely, the presence of acylglycerol linkages in suberin and of secondary esters in cutin, and the existence of mid-chain epoxide groups defining the packing of the aliphatic chains were observed. This packing determines polymer crystallinity, the resulting crystal structure, and the melting temperature. To evaluate the strength of this rule, tomato cutin from the same genotype, studying wild-type plants and two well-characterized mutants, was analyzed. The results show that cutin's material properties are influenced by the amount of unbound aliphatic hydroxyl groups and by the length of the aliphatic chain. Collectively, the acquired data can be used as a tool to guide the selection of plant polyesters with precise structural features, and hence physicochemical properties.

ViralFP: A Web Application of Viral Fusion Proteins.

Viral fusion proteins are attached to the membrane of enveloped viruses (a group that includes Coronaviruses, Dengue, HIV and Influenza) and catalyze fusion between the viral and host membranes, enabling the virus to insert its genetic material into the host cell. Given the importance of these biomolecules, this work presents a centralized database containing the most relevant information on viral fusion proteins, available through a free-to-use web server accessible through the URL https://viralfp.bio.di.uminho.pt/. This web application contains several bioinformatic tools, such as Clustal sequence alignment and Weblogo, including as well a machine learning-based tool capable of predicting the location of fusion peptides (the component of fusion proteins that inserts into the host's cell membrane) within the fusion protein sequence. Given the crucial role of these proteins in viral infection, their importance as natural targets of our immune system and their potential as therapeutic targets, this web application aims to foster our ability to fight pathogenic viruses.

Risk Factors, Length of Stay and In-Hospital Mortality of Methicillin-Resistant Staphylococcus aureus Infections: A Case-Control Study.

INTRODUCTION: The emergence of strains of methicillin-resistant Staphylococcus aureus is a serious therapeutic challenge in healthcare provision. With this study, we aimed to investigate the risk factors and clinical outcomes (mortality and length of hospital stay) associated with methicillin-resistant Staphylococcus aureus infections in patients admitted to a district hospital in Portugal. MATERIAL AND METHODS: A case-control study was performed in 96 cases and 122 controls, selected, respectively, as function of antibiotic resistance or sensitivity to methicillin. Data were obtained through consultation of clinical records and subjected to multivariate statistical analysis. RESULTS: We identified the following independent risk factors for the occurrence of methicillin-resistant Staphylococcus aureus infection: urinary catheter (aOR = 10.62, 95% CI 3.66 - 30.78), prior use of antibiotics in the last 30 days (aOR = 5.60, 95% CI 2.15 - 14.62), exposure to 5 - 7 days of hospitalization (aOR = 4.99, 95% CI 1.20 - 20.79) or to ≥ 8 days (aOR = 5.34, 95% CI 1.18 - 24.22), chronic obstructive pulmonary disease (aOR = 4.27, 95% CI 1.64 - 11.13) and recent hospitalization (aOR = 2.66, 95% CI 1.14 - 6.23). Compared to infections due to methicillin-susceptible Staphylococcus aureus, we found increased probability of having a longer hospital stay (aHR = 1.74, 95% CI 1.11 - 2.71) and in-hospital mortality was significantly higher (p = 0.001) between patients infected by methicillin-resistant Staphylococcus aureus. DISCUSSION: The results demonstrate that methicillin resistance is associated with an increased clinical risk to patients infected by Staphylococcus aureus, in particular, a raised mortality and prolonged hospitalization. CONCLUSION: Our study underlines the additional burden imposed by methicillin resistance in Staphylococcus aureus infections. This highlights an urgent need to reinforce and optimize prevention, control, timely detection and effective treatment strategies for multidrug--resistant Staphylococcus aureus strains.

Introdução: A emergência de estirpes de Staphylococcus aureus resistentes à meticilina constitui um sério desafio terapêutico na prestação de cuidados de saúde. Com esta investigação, pretendeu-se estudar os fatores de risco e os resultados clínicos (mortalidade e tempo de internamento) associados a infeções por Staphylococcus aureus resistentes à meticilina em doentes internados numa unidade hospitalar em Portugal. Material e Métodos: Realizou-se um estudo caso-controlo. Integraram o estudo 96 casos e 122 controlos, selecionados, respetivamente, em função da resistência ou sensibilidade antibiótica à meticilina. Os dados obtidos, por consulta de registos clínicos, foram alvo de análise estatística multivariada. Resultados: Identificaram-se os seguintes fatores de risco independentes para desenvolvimento de infeção por Staphylococcus aureus resistentes à meticilina: cateter urinário (aOR = 10,62, IC 95% 3,66 ­ 30,78), antibioterapia nos últimos 30 dias (aOR = 5,60, IC 95% 2,15 ­ 14,62), exposição a cinco a sete dias de internamento (aOR = 4,99, IC 95% 1,20 ­ 20,79) ou a oito ou mais dias (aOR = 5,34, IC 95% 1,18 ­ 24,22), doença pulmonar obstrutiva crónica (aOR = 4,27, IC 95% 1,64 ­ 11,13) e internamento hospitalar recente (aOR = 2,66, IC 95% 1,14 ­ 6,23). Comparativamente a infeções por Staphylococcus aureus sensíveis à meticilina, constatou-se uma probabilidade acrescida de prolongamento do internamento (aHR = 1,74, IC 95% 1,11 ­ 2,71) e uma mortalidade intra-hospitalar significativamente superior (p = 0,001) em doentes infetados por Staphylococcus aureus resistentes à meticilina. Discussão: Os resultados demonstram que a resistência à meticilina se encontra associada a um risco clínico acrescido para os doentes infetados por Staphylococcus aureus, com tradução no aumento da mortalidade e no prolongamento do tempo de internamento. Conclusão: Este estudo salienta a sobrecarga adicional associada à resistência à meticilina em infeções por Staphylococcus aureus. Urge, portanto, reforçar e optimizar estratégias de controlo, prevenção, deteção atempada e tratamento efetivo de estirpes multirresistentes de Staphylococcus aureus.

Development of an information retrieval tool for biomedical patents.

BACKGROUND AND OBJECTIVE: The volume of biomedical literature has been increasing in the last years. Patent documents have also followed this trend, being important sources of biomedical knowledge, technical details and curated data, which are put together along the granting process. The field of Biomedical text mining (BioTM) has been creating solutions for the problems posed by the unstructured nature of natural language, which makes the search of information a challenging task. Several BioTM techniques can be applied to patents. From those, Information Retrieval (IR) includes processes where relevant data are obtained from collections of documents. In this work, the main goal was to build a patent pipeline addressing IR tasks over patent repositories to make these documents amenable to BioTM tasks. METHODS: The pipeline was developed within @Note2, an open-source computational framework for BioTM, adding a number of modules to the core libraries, including patent metadata and full text retrieval, PDF to text conversion and optical character recognition. Also, user interfaces were developed for the main operations materialized in a new @Note2 plug-in. RESULTS: The integration of these tools in @Note2 opens opportunities to run BioTM tools over patent texts, including tasks from Information Extraction, such as Named Entity Recognition or Relation Extraction. We demonstrated the pipeline's main functions with a case study, using an available benchmark dataset from BioCreative challenges. Also, we show the use of the plug-in with a user query related to the production of vanillin. CONCLUSIONS: This work makes available all the relevant content from patents to the scientific community, decreasing drastically the time required for this task, and provides graphical interfaces to ease the use of these tools.

A Model Integration Pipeline for the Improvement of Human Genome-Scale Metabolic Reconstructions.

Metabolism has been a major field of study in the last years, mainly due to its importance in understanding cell physiology and certain disease phenotypes due to its deregulation. Genome-scale metabolic models (GSMMs) have been established as important tools to help achieve a better understanding of human metabolism. Towards this aim, advances in systems biology and bioinformatics have allowed the reconstruction of several human GSMMs, although some limitations and challenges remain, such as the lack of external identifiers for both metabolites and reactions. A pipeline was developed to integrate multiple GSMMs, starting by retrieving information from the main human GSMMs and evaluating the presence of external database identifiers and annotations for both metabolites and reactions. Information from metabolites was included into a graph database with omics data repositories, allowing clustering of metabolites through their similarity regarding database cross-referencing. Metabolite annotation of several older GSMMs was enriched, allowing the identification and integration of common entities. Using this information, as well as other metrics, we successfully integrated reactions from these models. These methods can be leveraged towards the creation of a unified consensus model of human metabolism.

Giardia duodenalis and soil-transmitted helminths infections in children in São Tomé and Príncipe: do we think Giardia when addressing parasite control?

Giardia duodenalis prevalence is commonly as high as soil-transmitted helminths (STH), nevertheless is not considered for large-scale chemotherapy through mass drug administration (MDA) due to its short incubation period and frequent reinfections, its control being associated to improving access to water and sanitation. A study enrolling 444 children attending preschools was conducted in May 2011 during a deworming campaign. Faecal samples were obtained and analysed through microscopy of wet mounting and after Kato-Katz and formol-ether concentration techniques. The majority of children were infected with at least one pathogenic parasite (86.7%, 385 of 444). Ascaris lumbricoides and Trichuris trichiura (56.3%, 250 of 444 and 52.5%, 233 of 444, respectively) were the most frequent parasites followed by G. duodenalis infecting 41.7% (185 of 444) of the children. The present work aimed at obtaining updated information concerning intestinal parasite infections in children attending preschools in São Tomé and Príncipe and to contribute for the adequate management of the enteric infections.

Molecular and Clinical Characterization of Giardia duodenalis Infection in Preschool Children from Lisbon, Portugal.

Giardia duodenalis is the most prevalent intestinal protozoan infection especially in children. In Portugal scarce data are available relative to this infection in preschoolers. The present study was conducted from April to July 2009 in public preschools in Lisbon enrolling 316 children. Stool examination was performed through microscopy. Molecular analysis was conducted in all positive samples for G. duodenalis in order to determine the assemblage and subassemblage of this parasite. Eight of the preschoolers studied children (2.5%, 8/316) were infected with G. duodenalis. Additionally the brother of one of the infected children was also infected. Genotyping analysis targeting ssu-rRNA and ß -giardin loci revealed six infections with assemblage A and 3 with assemblage B. Sub-assemblage determination was possible in four of the samples, with three A2 and one A3. The limited number of cases precluded an association of a determined symptom with an assemblage. The data presented here show the relevance of considering G. duodenalis analysis in children with intestinal complaints even in developed countries.

[Giardia duodenalis and chronic malnutrition in children under five from a rural area of Guinea-Bissau]. / Giardia Duodenalis e Desnutrição Crónica em Crianças Menores de Cinco Anos de uma Região Rural da Guiné-Bissau.

INTRODUCTION: Malnutrition and infections by intestinal parasites such as Giardia duodenalis coexist in the same geographical regions, reaching the highest prevalence in developing countries. The cycle of malnutrition and infection implies that both conditions can aggravate each other and compromise the growth and development of children with special relevance for under-five. The aim of this study was to investigate the association between chronic malnutrition and infection by G. duodenalis in children under five in a rural community in Guinea-Bissau. MATERIAL AND METHODS: A case-control study that included 109 children aged 0 to 59 months of a rural community in Guinea-Bissau was conducted. The anthropometric assessment of children in the study identified 31 cases of chronic malnutrition (z-score height for age < -2) and 78 controls (z-score height for age = -2). Microscopic examination of stools was performed for detection and identification of G. duodenalis and other parasites. RESULTS: The microscopic analysis of stool samples revealed G. duodenalis infection in 29.0% (9/31) of cases and 35.9% (28/78) of controls. No association between the infection with G. duodenalis and chronic malnutrition in children under study could be established. DISCUSSION AND CONCLUSION: The results reinforce the interest in designing further studies exploring this association in different regions and epidemiological settings, while direct to the importance of the criteria for malnutrition definition which influences the subsequent analysis.

Introdução: A desnutrição e as infecções por parasitas intestinais como Giardia duodenalis coexistem nas mesmas regiões geográficas, atingindo maiores prevalências em países em desenvolvimento. O ciclo da desnutrição e infecção implica que ambas as condições se podem agravar mutuamente e comprometer o crescimento e desenvolvimento das crianças, com especial relevância para as menores de cinco anos. O objectivo do presente estudo foi investigar a associação entre a desnutrição crónica e a infecção por G. duodenalis em crianças de uma comunidade rural da Guiné-Bissau.Material e Métodos: Realizou-se um estudo de caso-controlo que incluiu 109 crianças com idades entre os 0 e os 59 meses de uma comunidade rural da Guiné-Bissau. A avaliação antropométrica das crianças em estudo permitiu identificar 31 casos de desnutrição crónica (z-score estatura para a idade < -2) e 78 controlos (z-score estatura para a idade ≥ -2). Foi realizado exame microscópico de fezes para a detecção e identificação de G. duodenalis e de outros parasitas.Resultados: Foi detectada infecção por G. duodenalis em 29,0% (9/31) dos casos e 35,9% (28/78) dos controlos. Não foi encontrada associação entre a infecção por G. duodenalis e a desnutrição crónica nas crianças em estudo.Discussão e Conclusão: Os resultados obtidos mantêm em aberto o interesse em desenhar estudos que explorem esta associação em diferentes regiões e contextos epidemiológicos, apontando para a reflexão sobre a importância dos critérios de definição de desnutrição e concomitantemente da análise subsequente.

Aortografía a contracorriente por inyección de contraste en arteria periférica / Countercurrent aortography with contrast injection in peripheral artery

Se practicó una aortografía a contracorriente, por inyección de contraste en la arteria radial izquierda, en 8 niños con edades entre 27 días y 42 meses de edad. Con ello fué posible evaluar anastomosis sistémico-pulmonares en 3 e 4 casos, incluyendo uno de 42 meses de edad. En otros 3 casos se pudo visualizar una coartación de la aorta. En el último caso con sospecha clínica de anillo vascular, la aortografía evidenció una arteria subclavia derecha anómala. Concluimos, que el procedimiento es seguro y muy útil para estudiar algunas patologías que comprometen la aorta torácica incluso en niños mayores