A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection.

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases.

RNA Regulatory Networks 2.0.

The central role of RNA molecules in cell biology has been an expanding subject of study since the proposal of the "RNA world" hypothesis 60 years ago [...].

Transcriptomic Analysis of Acetaminophen Biodegradation by Penicillium chrysogenum var. halophenolicum and Insights into Energy and Stress Response Pathways.

(1) Background: Acetaminophen (APAP), an active component of many analgesic and antipyretic drugs, is one of the most concerning trace contaminants in the environment and is considered as an emergent pollutant of marine and aquatic ecosystems. Despite its biodegradability, APAP has become a recalcitrant compound due to the growth of the global population, the ease of availability, and the inefficient wastewater treatment applied. (2) Methods: In this study, we used a transcriptomic approach to obtain functional and metabolic insights about the metabolization of APAP by a phenol-degrading fungal strain, Penicillium chrysogenum var. halophenolicum. (3) Results: We determined that the transcriptomic profile exhibited by the fungal strain during APAP degradation was very dynamic, being characterized by an abundance of dysregulated transcripts which were proportional to the drug metabolization. Using a systems biology approach, we also inferred the protein functional interaction networks that could be related to APAP degradation. We proposed the involvement of intracellular and extracellular enzymes, such as amidases, cytochrome P450, laccases, and extradiol-dioxygenases, among others. (4) Conclusions: Our data suggested that the fungus could metabolize APAP via a complex metabolic pathway, generating nontoxic metabolites, which demonstrated its potential in the bioremediation of this drug.

Use of a mobile platform in rheumatology by undergraduate medical students during the COVID-19 pandemic / Uso de uma plataforma móvel em reumatologia por acadêmicos de Medicina durante a pandemia por Covid-19

Abstract: Introduction: Mobile applications are considered relevant in the health area. As rheumatology is a complex and prevalent specialty in clinical practice, the development of tools that favor learning becomes necessary. Objective: To evaluate the impact of a mobile platform on learning, obtaining the degree of satisfaction with the teaching tool and the effects on different scenarios of educational practice, including performance evaluation regarding questions about the theoretical contents of the platform. Methods: Quantitative, descriptive study, carried out in Christus University Center, located in Fortaleza, Brazil. Questionnaires prepared by the authors were used to assess the impact on the different active methodologies used in the institution and the degree of student satisfaction regarding their use. The estimate of the students' cognitive gain was measured through pre-test and post-test, using the multiple-choice format. Results: The questionnaires were applied to 71 students to assess the effects and satisfaction. A total of 90 students participated in the pre-test and 32 in the post-test phase. The platform showed a positive perception of learning for 83.1% of the students, with greater impact on lectures, although there was a greater impact on the simulation scenarios in the eighth semester. A good degree of satisfaction was observed in 94.4% of the answers, with improved performance in the tests, increasing from 43.7% to 63.3% (P < 0.001). Conclusions: The development and application of the mobile platform in rheumatology showed excellent results, with favorable effects on the teaching of the specialty, disclosing a good degree of satisfaction regarding its use and better performance on the questioning about the theoretical contents of the platform.

Resumo: Introdução: Aplicativos móveis são considerados relevantes na área da saúde. Sendo a reumatologia uma especialidade complexa e prevalente na prática clínica, torna-se necessário o desenvolvimento de ferramentas que favoreçam a aprendizagem. Objetivo: Este estudo teve como objetivo avaliar o impacto no aprendizado que uma plataforma móvel proporcionou, obtendo o grau de satisfação com a ferramenta de ensino e a repercussão nos diferentes cenários de prática educacional, incluindo avaliação de performance quanto a questionamentos do conteúdo teórico da plataforma. Método: Trata-se de estudo transversal com delineamento descritivo e abordagem quantitativa do tipo analítico, realizado no Centro Universitário Christus, localizado em Fortaleza, Brasil. Pesquisaram-se, por meio de questionários elaborados pelos autores, a repercussão nas diferentes metodologias ativas presentes na instituição e o grau de satisfação dos alunos quanto ao uso. A estimativa do ganho cognitivo dos alunos foi mensurada por meio de pré-teste e pós-teste, no formato de múltiplas escolhas. Resultado: Participaram 71 alunos durante do questionário sobre a repercussão e a satisfação. Nas questões de múltiplas escolhas, 90 alunos participaram do pré-teste e 32 do pós-teste. A plataforma apresentou percepção positiva na aprendizagem para 83,1% dos alunos, havendo maior impacto nas aulas expositivas, embora no oitavo semestre tenha havido maior repercussão nos cenários de simulação. Houve boa satisfação em 94,4% das respostas, com melhora no aproveitamento quanto às questões de múltiplas escolhas, evoluindo de 43,7% para 63,3% (p < 0,001). Conclusão: A elaboração e a aplicação da plataforma móvel em reumatologia obtiveram excelentes resultados, com repercussão favorável no ensino da especialidade e boa satisfação quanto ao uso e melhor performance no que concerne ao questionamento sobre os conteúdos teóricos da plataforma.

Comemoração do jubileu de ouro da Academia Brasileira de Medicina de Reabilitação - ABMR

Noticiamos com muita alegria o cinquentenário da Academia de Medicina de Reabilitação - ABMR, ocasião que todos os médicos Fisiatras prestam uma homenagem ao fundador reproduzindo a historia desta Academia.

The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response.

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function of viral components versus the cellular defenses. Non-coding RNAs (ncRNAs) are important cellular modulators, either promoting or preventing the progression of viral infections. Among these ncRNAs, the long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators of the cellular response during infection of human host cells by single stranded RNA viruses. However, the role of host lncRNAs in the infection by human RNA coronaviruses such as SARS-CoV-2 remains uncharacterized. Methods: In the present work, we have performed a transcriptomic study of a cohort of patients with different SARS-CoV-2 viral load and analyzed the involvement of lncRNAs in supporting regulatory networks based on their interaction with RNA-binding proteins (RBPs). Results: Our results revealed the existence of a SARS-CoV-2 infection-dependent pattern of transcriptional up-regulation in which specific lncRNAs are an integral component. To determine the role of these lncRNAs, we performed a functional correlation analysis complemented with the study of the validated interactions between lncRNAs and RBPs. This combination of in silico functional association studies and experimental evidence allowed us to identify a lncRNA signature composed of six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, and U62317.2 - associated with the regulation of SARS-CoV-2 infection. Conclusions: We propose a competition mechanism between the viral RNA genome and the regulatory lncRNAs in the sequestering of specific RBPs that modulates the interferon response and the regulation of RNA surveillance by nonsense-mediated decay (NMD).

A Structural View of miRNA Biogenesis and Function.

Micro-RNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of gene expression. Since their discovery in 1993, they have been the subject of deep study due to their involvement in many important biological processes. Compared with other ncRNAs, miRNAs are generated from devoted transcriptional units which are processed by a specific set of endonucleases. The contribution of structural biology methods for understanding miRNA biogenesis and function has been essential for the dissection of their roles in cell biology and human disease. In this review, we summarize the application of structural biology for the characterization of the molecular players involved in miRNA biogenesis (processors and effectors), starting from the X-ray crystallography methods to the more recent cryo-electron microscopy protocols.

Recovery of ß-galactosidase produced by Kluyveromyces lactis by ion-exchange chromatography: Influence of pH and ionic strength parameters.

The use of ß-galactosidase in food products has been a major focus of the industry. Therefore, the development of efficient and inexpensive methodologies to purify it is essential. Thus, this study aimed to recover the enzyme ß-galactosidase (ß-gal) by ion-exchange chromatography in a fixed-bed column. Batch adsorption tests were performed using four types of adsorbents. The ß-gal adsorption capacity in batch mode using Streamline DEAE resin presented the best performance, with a retention capacity of 18.77 ± 0.14 U/g at pH 6.0. A 22 experimental design was applied to optimize the ß-gal recovery using an AKTA Start system, evaluating the ionic strength and the pH as process parameters. The results showed that ionic strength exerted a greater influence on fold purification (FP). The ß-gal fraction in elution using 0.1-0.4 M of NaCl showed a yield of 51.65 ± 0.17% and FP of 2.00 ± 0.43. Electrophoresis confirmed the ß-gal recovery, where an evident band with a molecular weight between 60 and 120 kDa was observed. These results point to the recovery of a stable ß-gal of K. lactis with potential industrial applications.

Imperfect mimicry of host begging calls by a brood parasitic cuckoo: a cue for nestling rejection by hosts?

Coevolutionary interactions between avian brood parasites and their hosts often lead to the evolution of discrimination and rejection of parasite eggs or chicks by hosts based on visual cues, and the evolution of visual mimicry of host eggs or chicks by brood parasites. Hosts may also base rejection of brood parasite nestlings on vocal cues, which would in turn select for mimicry of host begging calls in brood parasite chicks. In cuckoos that exploit multiple hosts with different begging calls, call structure may be plastic, allowing nestlings to modify their calls to match those of their various hosts, or fixed, in which case we would predict either imperfect mimicry or divergence of the species into host-specific lineages. In our study of the little bronze-cuckoo (LBC) Chalcites minutillus and its primary host, the large-billed gerygone Gerygone magnirostris, we tested whether: (1) hosts use nestling vocalizations as a cue to discriminate cuckoo chicks; (2) cuckoo nestlings mimic the host begging calls throughout the nestling period; and (3) the cuckoo begging calls are plastic, thereby facilitating mimicry of the calls of different hosts. We found that the begging calls of LBCs are most similar to their gerygone hosts shortly after hatching (when rejection by hosts typically occurs) but become less similar as cuckoo chicks get older. Begging call structure may be used as a cue for rejection by hosts, and these results are consistent with gerygone defenses selecting for age-specific vocal mimicry in cuckoo chicks. We found no evidence that LBC begging calls were plastic.

Systematic Structure-Based Search for Ochratoxin-Degrading Enzymes in Proteomes from Filamentous Fungi.

(1) Background: ochratoxins are mycotoxins produced by filamentous fungi with important implications in the food manufacturing industry due to their toxicity. Decontamination by specific ochratoxin-degrading enzymes has become an interesting alternative for the treatment of contaminated food commodities. (2) Methods: using a structure-based approach based on homology modeling, blind molecular docking of substrates and characterization of low-frequency protein motions, we performed a proteome mining in filamentous fungi to characterize new enzymes with potential ochratoxinase activity. (3) Results: the proteome mining results demonstrated the ubiquitous presence of fungal binuclear zinc-dependent amido-hydrolases with a high degree of structural homology to the already characterized ochratoxinase from Aspergillus niger. Ochratoxinase-like enzymes from ochratoxin-producing fungi showed more favorable substrate-binding pockets to accommodate ochratoxins A and B. (4) Conclusions: filamentous fungi are an interesting and rich source of hydrolases potentially capable of degrading ochratoxins, and could be used for the detoxification of diverse food commodities.

Non-Random Genome Editing and Natural Cellular Engineering in Cognition-Based Evolution.

Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that permits purposive genetic adjustments as cellular problem-solving. CBE upholds that the cornerstone of biology is the intelligent measuring cell. Since all biological information that is available to cells is ambiguous, multicellularity arises from the cellular requirement to maximize the validity of available environmental information. This is best accomplished through collective measurement purposed towards maintaining and optimizing individual cellular states of homeorhesis as dynamic flux that sustains cellular equipoise. The collective action of the multicellular measurement and assessment of information and its collaborative communication is natural cellular engineering. Its yield is linked cellular ecologies and mutualized niche constructions that comprise biofilms and holobionts. In this context, biological variation is the product of collective differential assessment of ambiguous environmental cues by networking intelligent cells. Such concerted action is enabled by non-random natural genomic editing in response to epigenetic impacts and environmental stresses. Random genetic activity can be either constrained or deployed as a 'harnessing of stochasticity'. Therefore, genes are cellular tools. Selection filters cellular solutions to environmental stresses to assure continuous cellular-organismal-environmental complementarity. Since all multicellular eukaryotes are holobionts as vast assemblages of participants of each of the three cellular domains (Prokaryota, Archaea, Eukaryota) and the virome, multicellular variation is necessarily a product of co-engineering among them.

Structural Insights into Carboxylic Polyester-Degrading Enzymes and Their Functional Depolymerizing Neighbors.

Esters are organic compounds widely represented in cellular structures and metabolism, originated by the condensation of organic acids and alcohols. Esterification reactions are also used by chemical industries for the production of synthetic plastic polymers. Polyester plastics are an increasing source of environmental pollution due to their intrinsic stability and limited recycling efforts. Bioremediation of polyesters based on the use of specific microbial enzymes is an interesting alternative to the current methods for the valorization of used plastics. Microbial esterases are promising catalysts for the biodegradation of polyesters that can be engineered to improve their biochemical properties. In this work, we analyzed the structure-activity relationships in microbial esterases, with special focus on the recently described plastic-degrading enzymes isolated from marine microorganisms and their structural homologs. Our analysis, based on structure-alignment, molecular docking, coevolution of amino acids and surface electrostatics determined the specific characteristics of some polyester hydrolases that could be related with their efficiency in the degradation of aromatic polyesters, such as phthalates.

Kinetic study and characterization of surfactin production by Bacillus subtilis UFPEDA 438 using sugarcane molasses as carbon source.

The present study evaluated the surfactin production by Bacillus subtilis UFPEDA 438 using sugarcane molasses as a substrate. The effects of the cultivation conditions (temperature, agitation and aeration ratio) on the biosurfactant production and kinetic parameters were investigated. Characteristics of the biosurfactant were obtained after analyses of the emulsification index (EI) and critical micellar concentration (CMC) of the fermentation broth. The results showed that in relation to the product its formation kinetics is strongly affected by operational conditions. It was also observed that surfactin production can be partially dependent or fully independent on microbial growth. The maximum values of surfactin concentration (199.45 ± 0.13 mg/L) and productivity (8,187 mg/L.h) were obtained in the culture under cultivation time of 24 h, temperature of 36 °C, agitation of 100 rpm and aeration ratio of 0.4. Under optimal conditions, the fermentation broth achieved good emulsification capacity (EI >40%) and CMC value of 20.73 mg/L. The results revealed that Bacillus subtilis UFPEDA 438 is a good producer of biosurfactant and that sugarcane molasses is a viable substrate for the production of surfactin.

Sex role similarity and sexual selection predict male and female song elaboration and dimorphism in fairy-wrens.

Historically, bird song complexity was thought to evolve primarily through sexual selection on males; yet, in many species, both sexes sing and selection pressure on both sexes may be broader. Previous research suggests competition for mates and resources during short, synchronous breeding seasons leads to more elaborate male songs at high, temperate latitudes. Furthermore, we expect male-female song structure and elaboration to be more similar at lower, tropical latitudes, where longer breeding seasons and year-round territoriality yield similar social selection pressures in both sexes. However, studies seldom take both types of selective pressures and sexes into account. We examined song in both sexes in 15 populations of nine-fairy-wren species (Maluridae), a Southern Hemisphere clade with female song. We compared song elaboration (in both sexes) and sexual song dimorphism to latitude and life-history variables tied to sexual and social selection pressures and sex roles. Our results suggest that song elaboration evolved in part due to sexual competition in males: male songs were longer than female songs in populations with low male survival and less male provisioning. Also, female songs evolved independently of male songs: female songs were slower paced than male songs, although only in less synchronously breeding populations. We also found male and female songs were more similar when parental care was more equal and when male survival was high, which provides strong evidence that sex role similarity correlates with male-female song similarity. Contrary to Northern Hemisphere latitudinal patterns, male and female songs were more similar at higher, temperate latitudes. These results suggest that selection on song can be sex specific, with male song elaboration favored in contexts with stronger sexual selection. At the same time, selection pressures associated with sex role similarity appear to favor sex role similarity in song structure.

A avaliação da vítima de trauma em contexto pré e intra-hospitalar: a criação de um instrumento de avaliação terciária / The assessment of the trauma victim in the pre- and intra-hospital context: the creation of a tertiary assessment tool

Objetivo: Obtenção do grau de mestre em Enfermagem e proposta à aquisição do título especialista em Enfermagem Médico-Cirúrgica: A pessoa em situação Crítica através do aprimoramento de competências clínicas. Metodologia: O relatório é fundamentado por pesquisa descritiva. A intervenção profissional major tem substrução na metodologia de projeto, tendo como produto final a criação de um instrumento de avaliação terciária da vítima de trauma num serviço de cuidados intensivos. Resultados: O estágio final foi realizado em contexto pré-hospitalar, num serviço de urgência polivalente e numa unidade de cuidados intensivos. Estes contextos para além de permitirem o desenvolvimento da temática abordada: a avaliação da vítima de trauma; permitiram o planeamento e realização de atividades com o intento da aquisição de competências de Enfermeiro Especialista e de Mestre em Enfermagem. Reconheceu-se a inexistência de um instrumento auxiliar na avaliação da vítima de trauma, destacando-se a pertinência da sua formulação através de uma revisão sistemática da literatura. Conclusão: Consumou-se uma reflexão sistematizada das atividades desenvolvidas com enfoque à aquisição e desenvolvimento das competências em questão, a qual permitiu consagrar a efetividade do projeto e atingir os objetivos definidos.

Purpose: Obtaining a master's degree in nursing and the skills to propose for the title of specialist nurse in the medical and surgical areas with an emphasis to the critically ill patient. Methodology: This paper has a descriptive methodology. The professional intervention is based on project methodology, and its outcome is the creation of an assessment tool of trauma patient in an Intensive Care Unit (ICU). Results: The final placement occurred in a pre-hospital context, in an emergency department and in an ICU. These contexts despite allowing the development of the study subject: the trauma patient assessment; also allowed the development of the Nursing Specialist's and the Nursing Master's competences. The nonexistence of an assessment tool of the trauma patient was recognized, leading to its formulation throughout a systematic review. Conclusion: A review of the developed activities was conducted with focus on the achievement and development of the related skills. These activities allowed the implementation of the project and the achievement of the proposed goals.

Potential of "coalho" cheese whey as lactose source for ß-galactosidase and ethanol co-production by Kluyveromyces spp. yeasts.

The present study evaluated the co-production of ß-galactosidase and ethanol by Kluyveromyces marxianus ATCC 36907 and Kluyveromyces lactis NRRL Y-8279 using as carbon source the lactose found on "coalho" cheese whey. Cheese whey was subjected to partial deproteinization, and physicochemical parameters were assessed. Cultivations were carried out in an shaker to evaluate two carbon/nitrogen (C:N) ratios. The best C:N ratio (1.5:1) was carried to 1.5-L bioreactor cultivation in order to increase co-production yields. The stability of ß-galactosidase was assessed against different temperatures and pH, and in the presence of metal ions. Concerning the co-production of ß-galactosidase and ethanol, K. lactis proved to be more efficient in both the C:N ratios, reaching 21.09 U·mL-1 of activity and 7.10 g·L-1 of ethanol in 16 h. This study describes the development of a viable and value-adding biotechnological process using a regional cheese by-product from Northeast Brazil for co-production of biomolecules of industrial interest.

Interspecies Communication in Holobionts by Non-Coding RNA Exchange.

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

Use of plasmids for expression of proteins from the genus Leishmania in Escherichia coli: current state and perspectives.

Leishmaniosis is caused by the protozoa of the genus Leishmania with a wide spectrum of clinical and epidemiological manifestations which are characterized into four clinical groups: cutaneous, mucocutaneous, diffuse cutaneous, and visceral. American visceral leishmaniosis (AVL) or visceral leishmaniosis (VL) has been known as the most severe form of the disease. However, despite the growing number of people exposed to the infection risk and the great effort done by the scientific community worldwide to significantly increase the knowledge about these diseases, there is no vaccine capable of preventing VL in humans. In this short review, we present some of the plasmids used for the expression of recombinant protein by Escherichia coli strains used mainly for the second generation of vaccines for leishmaniosis. It can be emphasized that currently, these vectors and hosts play an important role in developing vaccine strategies against the disease. Indeed, use of the E. coli BL21 (DE) strain is remarkable mainly due to its characteristics for being a stable protein producer as well as the use of histidine tags for antigen purification. KEY POINTS: • Plasmid vectors and E. coli will continue being important for studies about leishmaniosis. • Protein purification exploiting histidine tags is a key technique.

Si vis pacem para bellum: A prospective in silico analysis of miRNA-based plant defenses against fungal infections.

Fungal pathogens are an important threat for plant crops, being responsible for important reductions of production yields and a consequent economic impact. Among the molecular mediators of fungal infections of plant crops, non-coding RNAs (ncRNAs) have been described as relevant players either in the plant immune responses and mechanism of defense or in the colonization of plant tissues by fungi. Acting as a mechanism of defense, some plant small ncRNAs such as miRNAs and tasiRNAs can be secreted by cells and directed to target the transcriptome of pathogenic fungi, triggering an RNAi-like interference mechanism able to silence the expression of specific fungal genes. The detailed knowledge of this mechanism of defense against fungal pathogens could open new possibilities for the protection of human important crops. To infer putative functional relationships mediated by ncRNA communication, we performed a prospective analysis to determine potential plant miRNAs able to target the genome of fungal pathogens, which resulted in the description of enriched specific plant miRNA families and their putative fungal targets that could be further studied in the context of plant-fungi interactions. The expression profile of specific members of the enriched miRNAs families showed an infection-dependent behavior in laboratory models of infection. Plant miRNAs showed sequence complementarity with coding genes of their cognate fungal pathogens. Plant miRNAs could potentially target fungal genes belonging to functional families related to stress response, membrane architecture, vacuolar transport, membrane traffic, and anabolic processes. Families of specific infection-responsive miRNAs are included in the putative plant defense mechanism.