A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.

A Phakopsora pachyrhizi Effector Suppresses PAMP-Triggered Immunity and Interacts with a Soybean Glucan Endo-1,3-ß-Glucosidase to Promote Virulence.

Asian soybean rust, caused by the fungus Phakopsora pachyrhizi, is one of the most important diseases affecting soybean production in tropical areas. During infection, P. pachyrhizi secretes proteins from haustoria that are transferred into plant cells to promote virulence. To date, only one candidate P. pachyrhizi effector protein has been characterized in detail to understand the mechanism by which it suppresses plant defenses to enhance infection. Here, we aimed to extend understanding of the pathogenic mechanisms of P. pachyrhizi based on the discovery of host proteins that interact with the effector candidate Phapa-7431740. We demonstrated that Phapa-7431740 suppresses pathogen-associated molecular pattern-triggered immunity (PTI) and that it interacts with a soybean glucan endo-1,3-ß-glucosidase (GmßGLU), a pathogenesis-related (PR) protein belonging to the PR-2 family. Structural and phylogenetic characterization of the PR-2 protein family predicted in the soybean genome and comparison to PR-2 family members in Arabidopsis thaliana and cotton, demonstrated that GmßGLU is a type IV ß-1,3-glucanase. Transcriptional profiling during an infection time course showed that the GmßGLU mRNA is highly induced during the initial hours after infection, coinciding with peak of expression of Phapa-7431740. The effector was able to interfere with the activity of GmßGLU in vitro, with a dose-dependent inhibition. Our results suggest that Phapa-7431740 may suppress PTI by interfering with glucan endo-1,3-ß-glucosidase activity. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.

A single unidirectional piRNA cluster similar to the flamenco locus is the major source of EVE-derived transcription and small RNAs in Aedes aegypti mosquitoes.

Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster.

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models.

Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future.

Relationship between gut microbiota, probiotics, and type 2 diabetes mellitus.

The worldwide prevalence of type 2 diabetes mellitus (T2DM) is constantly increasing, and it has become a major concern, with several implications for public health, economy, and social well-being. It is well-known that several factors such as lifestyle, increased intake of fat and sugar-rich foods, and host genetics can lead to T2DM. Some recent studies have suggested that the composition of the intestinal microbiota can trigger T2DM. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and T2DM, as well as the role of probiotics in modulation of intestinal microbiota. This mini-review summarizes the major findings and discusses the close relationship between intestinal microbiota, probiotics, and T2DM.

Standardization of DNA extraction from sand flies: Application to genotyping by next generation sequencing.

Standardization of the methods for extraction of DNA from sand flies is essential for obtaining high efficiency during subsequent molecular analyses, such as the new sequencing methods. Information obtained using these methods may contribute substantially to taxonomic, evolutionary, and eco-epidemiological studies. The aim of the present study was to standardize and compare two methods for the extraction of genomic DNA from sand flies for obtaining DNA in sufficient quantities for next-generation sequencing. Sand flies were collected from the municipalities of Campo Grande, Camapuã, Corumbá and Miranda, state of Mato Grosso do Sul, Brazil. Three protocols using a silica column-based commercial kit (ReliaPrep™ Blood gDNA Miniprep System kit, Promega®), and three protocols based on the classical phenol-chloroform extraction method (Uliana et al., 1991), were compared with respect to the yield and quality of the extracted DNA. DNA was quantified using a Qubit 2.0 fluorometer. The presence of sand fly DNA was confirmed by PCR amplification of the IVS6 region (constitutive gene), followed by electrophoresis on a 1.5% agarose gel. A total of 144 male specimens were analyzed, 72 per method. Significant differences were observed between the two methods tested. Protocols 2 and 3 of phenol-chloroform extraction presented significantly better performance than all commercial kit extraction protocols tested. For phenol-chloroform extraction, protocol 3 presented significantly better performance than protocols 1 and 2. The IVS6 region was detected in 70 of 72 (97.22%) samples extracted with phenol, including all samples for protocols 2 and 3. This is the first study on the standardization of methods for the extraction of DNA from sand flies for application to next-generation sequencing, which is a promising tool for entomological and molecular studies of sand flies.

Extracellular Hydrolysis of Adenine Nucleotides and Nucleoside Adenosine is Higher in Patients with ST Elevation than Non-ST Elevation in Acute Myocardial Infarction.

BACKGROUND: The hydrolysis of adenine nucleotide linked to the membrane of the platelets is changed in acute myocardial infarction (AMI) probably due to a greater arterial blockage and cell damage in patients with ST elevation (STEMI) than in those without ST segment elevation (NSTEM). METHODS: This study aimed to compare the extracellular hydrolysis of adenine nucleotides on the platelet surface of STEMI and NSTEMI patients. This study was carried out with 50 patients with AMI (STEMI and NSTEMI). The extracellular hydrolysis of adenine nucleotides and nucleoside adenosine as well as the expression of NTPDase were verified in platelets. RESULTS: The results demonstrated that STEMI patients had significantly higher extracellular hydrolysis of adenine nucleotides (p < 0.001), ADA (adenosine deaminase) activity (p < 0.05), as well as troponin levels (p < 0.0001) when compared to NSTEMI patients. CONCLUSIONS: Findings suggest that the extracellular hydrolysis of adenine nucleotides and increase in the ADA activity are higher in patients with STEMI than in those with NSTEMI probably because there was a blockage in this major arterial with a large area of damaged tissue.

cirCodAn: A GHMM-based tool for accurate prediction of coding regions in circRNA.

Studies focusing on characterizing circRNAs with the potential to translate into peptides are quickly advancing. It is helping to elucidate the roles played by circRNAs in several biological processes, especially in the emergence and development of diseases. While various tools are accessible for predicting coding regions within linear sequences, none have demonstrated accurate open reading frame detection in circular sequences, such as circRNAs. Here, we present cirCodAn, a novel tool designed to predict coding regions in circRNAs. We evaluated the performance of cirCodAn using datasets of circRNAs with strong translation evidence and showed that cirCodAn outperformed the other tools available to perform a similar task. Our findings demonstrate the applicability of cirCodAn to identify coding regions in circRNAs, which reveals the potential of use of cirCodAn in future research focusing on elucidating the biological roles of circRNAs and their encoded proteins. cirCodAn is freely available at https://github.com/denilsonfbar/cirCodAn.

High-throughput sequencing of small RNA transcriptomes reveals critical biological features targeted by microRNAs in cell models used for squamous cell cancer research.

BACKGROUND: The implication of post-transcriptional regulation by microRNAs in molecular mechanisms underlying cancer disease is well documented. However, their interference at the cellular level is not fully explored. Functional in vitro studies are fundamental for the comprehension of their role; nevertheless results are highly dependable on the adopted cellular model. Next generation small RNA transcriptomic sequencing data of a tumor cell line and keratinocytes derived from primary culture was generated in order to characterize the microRNA content of these systems, thus helping in their understanding. Both constitute cell models for functional studies of microRNAs in head and neck squamous cell carcinoma (HNSCC), a smoking-related cancer. Known microRNAs were quantified and analyzed in the context of gene regulation. New microRNAs were investigated using similarity and structural search, ab initio classification, and prediction of the location of mature microRNAs within would-be precursor sequences. Results were compared with small RNA transcriptomic sequences from HNSCC samples in order to access the applicability of these cell models for cancer phenotype comprehension and for novel molecule discovery. RESULTS: Ten miRNAs represented over 70% of the mature molecules present in each of the cell types. The most expressed molecules were miR-21, miR-24 and miR-205, Accordingly; miR-21 and miR-205 have been previously shown to play a role in epithelial cell biology. Although miR-21 has been implicated in cancer development, and evaluated as a biomarker in HNSCC progression, no significant expression differences were seen between cell types. We demonstrate that differentially expressed mature miRNAs target cell differentiation and apoptosis related biological processes, indicating that they might represent, with acceptable accuracy, the genetic context from which they derive. Most miRNAs identified in the cancer cell line and in keratinocytes were present in tumor samples and cancer-free samples, respectively, with miR-21, miR-24 and miR-205 still among the most prevalent molecules at all instances. Thirteen miRNA-like structures, containing reads identified by the deep sequencing, were predicted from putative miRNA precursor sequences. Strong evidences suggest that one of them could be a new miRNA. This molecule was mostly expressed in the tumor cell line and HNSCC samples indicating a possible biological function in cancer. CONCLUSIONS: Critical biological features of cells must be fully understood before they can be chosen as models for functional studies. Expression levels of miRNAs relate to cell type and tissue context. This study provides insights on miRNA content of two cell models used for cancer research. Pathways commonly deregulated in HNSCC might be targeted by most expressed and also by differentially expressed miRNAs. Results indicate that the use of cell models for cancer research demands careful assessment of underlying molecular characteristics for proper data interpretation. Additionally, one new miRNA-like molecule with a potential role in cancer was identified in the cell lines and clinical samples.

Ectoenzymes and cholinesterase activity and biomarkers of oxidative stress in patients with lung cancer.

We aimed to examine the nucleoside triphosphate diphosphohydrolases (NTPDase) in lymphocytes; adenosine deaminase (ADA) and butyrylcholinesterase (BChE) in serum; and acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT) activity in whole blood; since these enzymes are involved in inflammation responses as well as in oxidative stress conditions. We also checked the levels of total thiols (T-SH), non-protein thiols (NPSH), and thiobarbituric acid reactive substances (TBARS) in serum of patients with lung cancer. We collected blood samples from patients (n = 31) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). The results showed a significant increase in the hydrolysis of ATP, ADP, and adenosine in patients when compared with the control group. The activity of AChE, SOD, and CAT as well as the T-SH and NPSH levels were higher in patients group and TBARS levels were lower in patients compared with the control group. These findings demonstrated that the enzymes activity involved in the control of inflammatory and immune processes as well as the oxidative stress parameters are altered in patients with lung cancer.

Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons.

Profile hidden Markov models (HMMs) are a powerful way of modeling biological sequence diversity and constitute a very sensitive approach to detecting divergent sequences. Here, we report the development of protocols for the rational design of profile HMMs. These methods were implemented on TABAJARA, a program that can be used to either detect all biological sequences of a group or discriminate specific groups of sequences. By calculating position-specific information scores along a multiple sequence alignment, TABAJARA automatically identifies the most informative sequence motifs and uses them to construct profile HMMs. As a proof-of-principle, we applied TABAJARA to generate profile HMMs for the detection and classification of two viral groups presenting different evolutionary rates: bacteriophages of the Microviridae family and viruses of the Flavivirus genus. We obtained conserved models for the generic detection of any Microviridae or Flavivirus sequence, and profile HMMs that can specifically discriminate Microviridae subfamilies or Flavivirus species. In another application, we constructed Cas1 endonuclease-derived profile HMMs that can discriminate CRISPRs and casposons, two evolutionarily related transposable elements. We believe that the protocols described here, and implemented on TABAJARA, constitute a generic toolbox for generating profile HMMs for the highly sensitive and specific detection of sequence classes.

Coffee fermentation process: A review.

In recent years, the importance of controlling coffee fermentation in the final quality of the beverage has been recognized. The literature review was conducted in the Science Direct and Springer databases, considering studies published in the last ten years, 74 references were selected. Several studies have been developed to evaluate and propose fermentation conditions that result in sensory improvements in coffee. So, this review aims to describe detailed the different protocols for conducting the coffee fermentation step and how they could influence the sensory quality of coffee based on the Specialty Coffee Association protocol. We propose a new way to identify coffee post-harvest processing not based on the already known wet, dry and semi-dry processing. The new identification is focused on considering fermentation as a step influenced by the coffee fruit treatment, availability of oxygen, water addition, and starter culture utilization. The findings of this survey showed that each type of coffee fermentation protocol can influence the microbiota development and consequently the coffee beverage. There is a migration from the use of processes in open environments to closed environments with controlled anaerobic conditions. However, it is not possible yet to define a single process capable of increasing coffee quality or developing a specific sensory pattern in any environmental condition. The use of starter cultures plays an important role in the sensory differentiation of coffee and can be influenced by the fermentation protocol applied. The application of fermentation protocols well defined is essential in order to have a good product also in terms of food safety. More research is needed to develop and implement environmental control conditions, such as temperature and aeration, to guarantee the reproducibility of the results.

Major proliferation of transposable elements shaped the genome of the soybean rust pathogen Phakopsora pachyrhizi.

With >7000 species the order of rust fungi has a disproportionately large impact on agriculture, horticulture, forestry and foreign ecosystems. The infectious spores are typically dikaryotic, a feature unique to fungi in which two haploid nuclei reside in the same cell. A key example is Phakopsora pachyrhizi, the causal agent of Asian soybean rust disease, one of the world's most economically damaging agricultural diseases. Despite P. pachyrhizi's impact, the exceptional size and complexity of its genome prevented generation of an accurate genome assembly. Here, we sequence three independent P. pachyrhizi genomes and uncover a genome up to 1.25 Gb comprising two haplotypes with a transposable element (TE) content of ~93%. We study the incursion and dominant impact of these TEs on the genome and show how they have a key impact on various processes such as host range adaptation, stress responses and genetic plasticity.

A Bioinformatics Tool for Efficient Retrieval of High-Confidence Terpene Synthases (TPS) and Application to the Identification of TPS in Coffea and Quillaja.

Terpenoids are a class of compounds that are found in all living organisms. In plants, some terpenoids are part of primary metabolism, but most terpenes found in plants are classified as specialized metabolites, encoded by terpene synthases (TPS). It is not obvious how to assign the putative product of a given TPS using bioinformatics tools. Phylogenetic analyses easily assign TPS into families; however members of the same TPS family can synthetize more than one terpenoid-and, in many biotechnological applications, researchers are more interested in the product of a given TPS rather than its phylogenetic profile. Automated protein annotation can be used to classify TPS based on their products, despite the family they belong to. Here, we implement an automated bioinformatics method, search_TPS, to identify TPS proteins that synthesize mono, sesqui and diterpenes in Angiosperms. We verified the applicability of the method by classifying wet lab validated TPS and applying it to find TPS proteins in Coffea arabica, C. canephora, C. eugenioides, and Quillaja saponaria. Search_TPS is a computational tool based on PERL scripts that carries out a series of HMMER searches against a curated database of TPS profile hidden Markov models. The tool is freely available at https://github.com/liliane-sntn/TPS .

Parasite species variation and impact of spatial displacement of the population on cutaneous leishmaniasis in Rio de Janeiro, Brazil.

BACKGROUND: Cutaneous leishmaniasis results from complex interactions between human beings, vectors and the environment. Parasitic species differ in epidemiological and geographical contexts. METHODS: We studied a retrospective cohort of 696 patients with cutaneous leishmaniasis treated at a reference centre in the state of Rio de Janeiro, Brazil, between 2000 and 2015. We analysed displacements due to work, leisure and migrations with identification of Leishmania species. RESULTS: The geographic distribution of autochthonous cases showed that >95% of infections occurred in urban areas. In the state of Rio de Janeiro, most cases were concentrated in the cities surrounding forest parks and nature conservation areas. The same applies to the city of Rio de Janeiro, where these infections occurred in the neighbourhoods surrounding some mountain and forest areas. The non-displacement group included 575 (82.6%) patients and the displacement group included 121 (17.4%) patients. Leishmania (Viannia) braziliensis predominated in both groups. Other species were found in the displacement group. CONCLUSIONS: The disordered urbanization of the state of Rio de Janeiro in recent decades has created conditions for the emergence of urban foci of transmission close to forest areas. Changes in the environment, movement of infected individuals and adaptation of sandflies may have contributed to this.

Telehealth for Parkinson disease patients during the COVID-19 pandemic: the TeleParkinson study.

BACKGROUND: Telemedicine allows Parkinson disease (PD) patients to overcome physical barriers to access health care services and increases accessibility for people with mobility impairments. OBJECTIVE: To investigate the feasibility indicators of a telehealth intervention for PD patients, including patient recruitment, attendance, technical issues, satisfaction, and benefits on levels of physical activity and sleep. METHODS: We conducted a single-center, single-arm study of telehealth video consultations using WhatsApp (Meta Platforms, Inc., Menlo Park, CA, USA). Also, we collected the feasibility indicators as the primary endpoints. All the patients in the study were previously evaluated in person by the same team. RESULTS: Patient recruitment, attendance, and technical issues rates were 61.3%, 90.5%, and 13.3%, respectively, with good scores of patient acceptance and satisfaction with the study intervention. The telehealth intervention improved physical activity, including the number of walks for at least 10 continuous minutes (p = 0.009) and the number of moderate-intensity activities lasting at least 10 continuous minutes (p = 0.001). The Pittsburgh sleep quality index (PSQI) scores also improved for one of its components: perceived sleep duration (p < 0.001) and for total Pittsburgh score (p < 0,001). The average travel time saving was 289.6 minutes, and money-saving was R$106.67 (around USD 18; almost 10% of the current minimum wage in Brazil). CONCLUSIONS: Direct-to-patient telehealth video consultations proved to be feasible and effective and had a positive impact on physical activity levels and sleep in PD patients.

ANTECEDENTES: A telemedicina permite que pacientes com doença de Parkinson (DP) superem barreiras físicas para acessar serviços de saúde e aumenta a acessibilidade para pessoas com mobilidade reduzida. OBJETIVO: Investigar indicadores de viabilidade de uma intervenção em telessaúde para pacientes com DP, incluindo recrutamento, atendimento, aderência, problemas técnicos, satisfação e benefícios nos níveis de atividade física e sono. MéTODOS: Foi conduzido um estudo de centro e braço únicos baseado em consultas por telessaúde com utilização do WhatsApp (Meta Platforms, Inc., Menlo Park, CA, EUA). Foram calculados indicadores de viabilidade como desfechos primários. RESULTADOS: As taxas de recrutamento, atendimento e problemas técnicos foram 61,3%, 90,5% e 13,3%, respectivamente, com bons escores de aceitação e satisfação com a intervenção. A intervenção melhorou os níveis de atividade física, incluindo o número de passos por pelo menos 10 minutos contínuos (p = 0,009) e o número de atividades intensas e moderadas com duração de pelo menos 10 minutos contínuos (p = 0,001). O Índice de Qualidade do Sono de Pittsburgh melhorou nos seguintes componentes: duração percebida do sono (p < 0,001) e escore total (p < 0,001). A média do tempo de viagem médio poupado foi de 289,6 minutos, e a economia financeira foi de R$ 106,67 reais (por volta de USD 18; quase 10% do salário mínimo atual do Brasil). CONCLUSõES: As consultas por vídeo provaram ser viáveis e efetivas, com impacto positivo nos níveis de atividade física e sono de pacientes com DP.

High Gravity and Very High Gravity Fermentation of Sugarcane Molasses by Flocculating Saccharomyces cerevisiae: Experimental Investigation and Kinetic Modeling.

Substantial progress has been made in ethanol fermentation technology under high gravity (HG) and very high gravity (VHG), which offer environmental and economic benefits. HG and VHG processes increase the productivity of ethanol, reduce distillation costs, and enable higher yields. The aim of the present study was to evaluate the use of sugarcane molasses as the medium component along with flocculating yeasts for fermentation in a fed-batch process employing this promising technology. We evaluated fed-batch fermentation, HG, and VHG involving a molasses-based medium with high concentrations of reducing sugars (209, 222, and 250 g/L). Fermentation of 222 g/L of total reducing sugars achieved 89.45% efficiency, with a final ethanol concentration of 104.4 g/L, whereas the highest productivity (2.98 g/(L.h)) was achieved with the fermentation of 209 g/L of total reducing sugars. The ethanol concentration achieved with the fermentation of 222 g/L of total reducing sugars was close to the value obtained for P'max (105.35 g/L). The kinetic model provided a good fit to the experimental data regarding the fermentation of 222 g/L. The results revealed that sugarcane molasses and flocculating yeasts can be efficiently used in HG fermentation to reduce the costs of the process and achieve high ethanol titers.

A Practical Guide on Computational Tools and Databases for Transposable Elements in Plants.

In the age of big data, obtaining precise information about the research topic of interesting is extremely important. Keeping this in mind, this chapter focuses on providing a practical knowledge guide about computational tools and databases of transposable elements (TE) in plants. For that, we organize and present this text in three sections: (1) a discussion about tools and databases on this theme; (2) hands-on of how to use a few of them; (3) an exploratory data analysis on public TE data. Finally, we are going deep to present the main challenges and possible solutions to improve resources and tools.

Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization.

Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert less selection pressure. We identified promising adhesion inhibitors by screening a library of 4208 compounds for their capacity to inhibit S. aureus adhesion to A-549 epithelial cells in vitro in a novel automated, imaging-based assay. The assay quantified DAPI-stained nuclei of the host cell; attached bacteria were stained with an anti-teichoic acid antibody. The most promising candidate, aurintricarboxylic acid (ATA), was evaluated in a novel persistent S. aureus nasal colonization model using a mouse-adapted S. aureus strain. Colonized mice were treated intranasally over 7 days with ATA using a wide dose range (0.5-10%). Mupirocin completely eliminated the bacteria from the nose within three days of treatment. In contrast, even high concentrations of ATA failed to eradicate the bacteria. To conclude, our imaging-based assay and the persistent colonization model provide excellent tools to identify and validate new drug candidates against S. aureus nasal colonization. However, our first tested candidate ATA failed to induce S. aureus decolonization.

Computational Analysis of Transposable Elements and CircRNAs in Plants.

This chapter provides two main contributions: (1) a description of computational tools and databases used to identify and analyze transposable elements (TEs) and circRNAs in plants; and (2) data analysis on public TE and circRNA data. Our goal is to highlight the primary information available in the literature on circular noncoding RNAs and transposable elements in plants. The exploratory analysis performed on publicly available circRNA and TEs data help discuss four sequence features. Finally, we investigate the association on circRNAs:TE in plants in the model organism Arabidopsis thaliana.