Updating functional brain units: Insights far beyond Luria.

This paper reviews Luria's model of the three functional units of the brain. To meet this objective, several issues were reviewed: the theory of functional systems and the contributions of phylogenesis and embryogenesis to the brain's functional organization. This review revealed several facts. In the first place, the relationship/integration of basic homeostatic needs with complex forms of behavior. Secondly, the multi-scale hierarchical and distributed organization of the brain and interactions between cells and systems. Thirdly, the phylogenetic role of exaptation, especially in basal ganglia and cerebellum expansion. Finally, the tripartite embryogenetic organization of the brain: rhinic, limbic/paralimbic, and supralimbic zones. Obviously, these principles of brain organization are in contradiction with attempts to establish separate functional brain units. The proposed new model is made up of two large integrated complexes: a primordial-limbic complex (Luria's Unit I) and a telencephalic-cortical complex (Luria's Units II and III). As a result, five functional units were delineated: Unit I. Primordial or preferential (brainstem), for life-support, behavioral modulation, and waking regulation; Unit II. Limbic and paralimbic systems, for emotions and hedonic evaluation (danger and relevance detection and contribution to reward/motivational processing) and the creation of cognitive maps (contextual memory, navigation, and generativity [imagination]); Unit III. Telencephalic-cortical, for sensorimotor and cognitive processing (gnosis, praxis, language, calculation, etc.), semantic and episodic (contextual) memory processing, and multimodal conscious agency; Unit IV. Basal ganglia systems, for behavior selection and reinforcement (reward-oriented behavior); Unit V. Cerebellar systems, for the prediction/anticipation (orthometric supervision) of the outcome of an action. The proposed brain units are nothing more than abstractions within the brain's simultaneous and distributed physiological processes. As function transcends anatomy, the model necessarily involves transition and overlap between structures. Beyond the classic approaches, this review includes information on recent systemic perspectives on functional brain organization. The limitations of this review are discussed.

Chemical characteristics and valuation of sewage sludge from four different wastewater treatment plants.

Sewage sludge contains plant nutrients and organic matter in its composition, making it a potential partial substitute for mineral fertilizers if it meets environmental, agronomic, and sanitary standards. The objective was to evaluate the content of nutrients and heavy metals in the sludge generated in four wastewater treatment stations (WWTPs) in Rio de Janeiro state and assess its potential value and usefulness. The samples of 19 batches from the WTTPs Alegria, Barra da Tijuca, Ilha do Governador, and Sarapuí were analyzed. The WWTPs differ in methods and processes used for treating sewage and sludge. The total contents of C, N, P, K, Ca, Mg, Fe, Al, Na, Co, Mn, As, Ba, Cd, Cr, Cu, Ni, Se, Pb, and Zn were evaluated, as well as the ratio C/N, pH, organic matter content, and electrical conductivity. The grouping of sludge samples was assessed using principal components (PCA) and cluster analysis. The economic valuation of sludge was conducted utilizing the substitute goods method, which compared the sludge's N-P-K contents with the prices of consolidated nutrient sources. All the evaluated sludge batches exhibited concentrations of heavy metals below the limits allowed by Brazilian law, along with high levels of nutrients and organic matter. Considering the chemical characteristics, all evaluated materials showed potential for agricultural use, but it is crucial to evaluate the microbiological characteristics of sludge batches before agriculture application. PCA and cluster analysis demonstrated that sludge samples from the same WWTP clustered close to each other, demonstrating higher similarity among themselves than with samples from other WWTPs. The sludge had an average added value of U$ 88.46 per megagram, considering the total contents of N, P, and K in its composition. Land application of sewage sludge can reduce the need to purchase mineral fertilizers, thereby supporting the feasibility of reusing this material in the agricultural sector.

[Comment on articule "Bibliometric analysis of scientific publications on COVID-19 elaborated by staff of the Instituto Mexicano del Seguro Social"]. / Comentario al artículo "Análisis bibliométrico de las publicaciones científicas sobre COVID-19 realizadas por personal IMSS".

In this letter to the editor, some doubts are expressed about the methodology used in the article Bibliometric analysis of scientific publications on COVID-19 elaborated by staff of the Instituto Mexicano del Seguro Social with the purpose of clarifying them and strengthening the scientific rigor with which it was carried out the investigation. The replicability of the studies is essential for other researchers to be able to assess the quality of the study and the validity of its results, in addition to ensuring the transparency of the science.

En esta carta al editor se plasman algunas dudas sobre la metodología empleada en el artículo "Análisis bibliométrico de las publicaciones científicas sobre COVID-19 realizadas por personal IMSS" con la finalidad de que sean aclaradas y se fortalezca la riguridad científica con la que se realizó la investigación. La replicabilidad de los estudios es fundamental para que otros investigadores estén en posibilidad de evaluar la calidad de éste y la validez de sus resultados, además de que asegura la transparencia de la ciencia.

Family Attitudes towards Multilingualism in Bilingual Education Programs and Their Relationship with Academic Performance.

This article reports on a large-scale study investigating the overall perception of multilingualism in the family environment of children enrolled in an English immersion program in primary schools across Spain and the potential relationship between these attitudes and the student's academic performance. One thousand and one families participated in the study, based on a tailored questionnaire that evaluated three main aspects: (1) parents' and guardians' ratings of their children's language skills; (2) language practices in the home, especially with respect to time allocated to different languages and multilingual practices such as code-switching; and (3) attitudes and general perception of the benefits and drawbacks of multilingualism in socio-economic, cultural, cognitive and professional terms. The complex results from this questionnaire, in addition to providing a more accurate picture of the family environment of students enrolled in these programs, show some significant correlations with academic performance, which we discuss here, with some reference to their educational implications.

Environment Context Variability and Incidental Word Learning: A Virtual Reality Study.

Previous research has shown that changes in the scenarios in which something is learned and recalled, respectively, may result in a subpar performance in memory recollection. The current study aimed to evaluate how changes in the visuo-perceptual environmental learning context impact incidental vocabulary learning. To this end, a highly immersive virtual reality setting was created, and participants were required to read eight distinct stories visually presented to them. A novel word was delivered twice in every paragraph and embedded in each story. Stories could be displayed either in a high variability condition, where each paragraph was shown in a new environment context (four different classrooms) or in a low variability condition, where each paragraph was shown in the same context. The findings obtained across four assessment tasks (free recall, recognition, picture matching, and sentence completion) demonstrated that significant visuo-perceptual variability did not bring about any disadvantages in word learning. Thus, perceptual information from a physically diverse environment could provide a variety of instructional and educational beneficial possibilities in the absence of a learning disadvantage.

CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase.

Pyruvate carboxylase (PC) is a tetrameric enzyme that contains two active sites per subunit that catalyze two consecutive reactions. A mobile domain with an attached prosthetic biotin links both reactions, an initial biotin carboxylation and the subsequent carboxyl transfer to pyruvate substrate to produce oxaloacetate. Reaction sites are at long distance, and there are several co-factors that play as allosteric regulators. Here, using cryoEM we explore the structure of active PC tetramers focusing on active sites and on the conformational space of the oligomers. The results capture the mobile domain at both active sites and expose catalytic steps of both reactions at high resolution, allowing the identification of substrates and products. The analysis of catalytically active PC tetramers reveals the role of certain motions during enzyme functioning, and the structural changes in the presence of additional cofactors expose the mechanism for allosteric regulation.

Sewage sludge as substrate in Schinus terebinthifolia raddi seedlings commercial production.

Schinus terebinthifolia Raddi is a species with several potential uses; selecting the proper substrate and fertilizer rate can be vital for seedling production in a nursery environment. This study aims to evaluate two substrates, namely: (i) sewage sludge (SS) from Ilha WWTP; (ii) a commercial substrate (CS) made of organic materials (mainly sphagnum peat). Increasing rates of controlled-release fertilizer - CRF (0, 3, 6, and 12 kg m-3) were applied. The experiment was completely randomized with a factorial 2 × 4 scheme (substrates × rates). The seedlings' growth, biomass, and quality were evaluated. The treatments were compared by Tukey test and regression analysis, where linear, quadratic, and cubic models were considered. Principal components analysis (PCA) and cluster analysis were performed. The CRF rates showed non-significant effects for most of the investigated variables in the SS substrate. In the CS, a 7.8 kg m-3 rate of CRF showed the best growth performance. The multivariate analysis of the morphological parameters proved suitable as a complementary approach to evaluate the seedlings' quality. Seedlings reached recommended values for height, diameter, and quality in the 100% SS substrate without chemical fertilizers; thus, Schinus terebinthifolia production in the SS from Ilha is recommended. Besides the growth advantage, the SS can promote nursery cost savings with commercial substrates and chemical fertilizers.

Trombo intracardíaco neonatal de hallazgo casual / Neonatal intracardiac thrombus as a casual finding

No disponible

Forms and Methods for Interferon's Encapsulation.

Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been marketed for more than 30 years with considerable impact on the global therapeutic protein market thanks to their diversity in terms of biological activities. They have been used as single agents or with combination treatment regimens, demonstrating promising clinical results, resulting in 22 different formulations approved by regulatory agencies. The 163 clinical trials with currently active IFNs reinforce their importance as therapeutics for human health. However, their application has presented difficulties due to the molecules' size, sensitivity to degradation, and rapid elimination from the bloodstream. For some years now, work has been underway to obtain new drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. Although different research groups have presented various formulations that encapsulate IFNs, to date, there is no formulation approved for use in humans. The current review exhibits an updated summary of all encapsulation forms presented in the scientific literature for IFN-α, IFN-ß, and IFN-γ, from the year 1996 to the year 2021, considering parameters such as: encapsulating matrix, route of administration, target, advantages, and disadvantages of each formulation.

3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme.

Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs180) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs180 in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH180 (mL-GDH180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH180 involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs.

A conserved rRNA switch is central to decoding site maturation on the small ribosomal subunit.

While a structural description of the molecular mechanisms guiding ribosome assembly in eukaryotic systems is emerging, bacteria use an unrelated core set of assembly factors for which high-resolution structural information is still missing. To address this, we used single-particle cryo-electron microscopy to visualize the effects of bacterial ribosome assembly factors RimP, RbfA, RsmA, and RsgA on the conformational landscape of the 30S ribosomal subunit and obtained eight snapshots representing late steps in the folding of the decoding center. Analysis of these structures identifies a conserved secondary structure switch in the 16S ribosomal RNA central to decoding site maturation and suggests both a sequential order of action and molecular mechanisms for the assembly factors in coordinating and controlling this switch. Structural and mechanistic parallels between bacterial and eukaryotic systems indicate common folding features inherent to all ribosomes.

On the status of transfer in adult third language acquisition of early bilinguals.

The study of linguistic transfer-understood here in terms of the copying of previous linguistic representations-seeks to reveal how domain-relevant prior language knowledge impacts the acquisition and development of new mental representations more generally. Studying sequential multilingualism offers a natural laboratory to observe cognitive-economical mechanisms that avoid redundancy in language learning. One of the key dividing questions between theories of transfer in sequential multilingualism is the extent of transfer, that is, whether a whole previous grammar is transferred (full transfer) or a potentially different source language is selected for each linguistic property (property-by-property transfer). We adopted a novel methodological approach to this question, examining four different linguistic properties from unrelated domains of grammar across the three languages of a heterogeneous population of highly proficient, early Catalan/Spanish bilinguals with different degrees of language dominance and order of acquisition, at the very beginning of (adult) L3 English. Results are variably complex across the different properties, but compatible with a scenario where one of the previous languages, Catalan, was selected as the basis for the initial L3 English grammar of these speakers. We discuss the theoretical implications of these findings.

Polymeric nanoencapsulation of alpha interferon increases drug bioavailability and induces a sustained antiviral response in vivo.

Polymeric nanoparticulate systems allow the encapsulation of bio-active substances, giving them protection against external agents and increasing the drug's bioavailability. The use of biocompatible and biodegradable polymers usually guarantees the harmless character of the formulation, and a controlled drug release is also assured. A relatively easy procedure to obtain polymeric formulations of bioactive agents is ionotropic gelation, which allows the synthesis of chitosan (CS) - sodium tri-polyphosphate nanoparticles (NPs) loading encapsulated proteins. In this work, Bovine serum albumin (BSA) model protein and a recombinant porcine alpha interferon variant were used to obtain nanoparticulate formulations. The internalization of the encapsulated material by cells was studied using a BSA-fluorescein system; the fluorescent conjugate was observable inside the cells after 20 h of incubation. The therapeutic CS-alpha interferon formulation showed a maximum of protein released in vitro at around 90 h. This system was found to be safe in a cytotoxicity assay, while biological activity experiments in vitro showed antiviral protection of cells in the presence of encapsulated porcine alpha interferon. In vivo experiments in pigs revealed a significant and sustained antiviral response through overexpression of the antiviral markers OAS2 and PKR. This proves the preservation of porcine alpha interferon biological activity, and also that a lasting response was obtained. This procedure is an effective and safe method to formulate drugs in nanoparticulate systems, representing a significant contribution to the search for more effective drug delivery strategies.

Multicentre prospective study of drug-eluting bead chemoembolisation safety using tightly calibrated small microspheres in non-resectable hepatocellular carcinoma.

PURPOSE: To assess the safety and tolerability of transarterial drug-eluting bead chemoembolisation (DEB-TACE) using tightly calibrated 100-µm microspheres in hepatocellular carcinoma (HCC). METHOD: This multicentre prospective study included 131 patients with a 2-year follow-up. All patients had Child-Pugh scores ≤ B7, a good performance status, and Barcelona Clinic Liver Cancer stage A or B. Beads were loaded with 50 mg of doxorubicin per millilitre. Overall, 223 nodules were treated (mean size: 27.6 mm, average number of nodules per patient: 1.7). Toxicity was assessed using Common Terminology Criteria for Adverse Events 4.03 and response according to the modified Response Evaluation Criteria in Solid Tumours. The primary endpoint was safety. Secondary endpoints included technical success, post-embolisation syndrome (PES), local tumour response, and 2-year survival. RESULTS: A total of 214 DEB-TACE procedures were performed (mean per patient: 1.64), with a technical success rate of 97.6 % and a PES rate of 9.3 %. Major complications occurred in 6.8 % of patients and 4.1 % of procedures. There were no treatment-related deaths. Doxorubicin dose was an independent predictor of complications (p = 0.01). Four patients were lost to follow-up and 18 received liver transplants. Objective response rates were 74.6 %, 45.7 %, and 44.1 % at 6, 12, and 24 months, respectively. The cumulative 24-month overall survival rate was 55.96 %. Median survival was 22 months (interquartile range = 13-24). Co-morbidities and tumour response were independent predictors of survival (p = 0.0012 and 0.0052, respectively). Complications did not affect survival (p = 0.24). CONCLUSIONS: DEB-TACE with tightly calibrated 100-µm beads is safe and not associated with increases in biliary toxicity or complications. Tumour response and survival are in the expected range for chemoembolisation therapy. (Clinical trials ID: NCT02670122).

Caracterização de biossólido e potencial de uso na produção de mudas de Schinus terebinthifolia Raddi / Characterization of biosolids and potential use in the production of seedlings of Schinus terebinthifolia Raddi

RESUMO O presente trabalho teve como objetivo caracterizar técnica, química e biologicamente o biossólido proveniente da estação de tratamento de esgoto (ETE) de Alegria, Rio de Janeiro, e inferir sobre sua aptidão como componente do substrato para produção de mudas de Schinus terebinthifolia Raddi (aroeira pimenteira). Foram coletadas amostras significativas do biossólido, submetidas às análises química e biológica em um laboratório especializado, atendendo às especificações da legislação vigente (Resolução CONAMA nº 375/2006). No viveiro, foram testadas quatro diferentes formulações de substrato, compostas de diferentes proporções volumétricas de substrato comercial (SC) e biossólido (BIO), consistindo nos seguintes tratamentos: T1 (100% SC + 0% BIO); T2 (75% SC + 25% BIO); T3 (50% SC + 50% BIO); e T4 (0% SC + 100% BIO). O delineamento experimental foi o inteiramente casualizado, com 4 tratamentos, 4 repetições de 18 mudas. O biossólido atendeu às especificações da legislação quanto à sua composição. Aos 120 dias após a semeadura foram mensuradas a altura da parte aérea e o diâmetro do coleto, observando que o crescimento das mudas foi diretamente proporcional à concentração de biossólido no substrato. O biossólido da ETE Alegria atende à legislação de uso agrícola e mostrou ser viável tecnicamente para a produção de mudas de aroeira pimenteira.

ABSTRACT This study aimed to technically, chemically and biologically characterize the biosolids from the Sewage Treatment Plant (STP) of Alegria, Rio de Janeiro, Brazil, and infer about their aptitude as a substrate component for the seedlings production of Anadenanthera macrocarpa (Benth.) Brenan. Significant samples of biosolid were collected and submitted to chemical and biological analysis in a specialized laboratory, according to the specifications of the current Brazilian law (CONAMA Resolution nº 375/2006). In the forest nursery, four different formulations of substrate, composed by different volumetric proportions of commercial substrate (CS) and biosolids (BIO) were tested, consisting of the following treatments: T1 (100% SC + 0% BIO); T2: (75% SC + 25% BIO); T3: (50% SC + 50% BIO); e T4: (0% SC + 100% BIO). The experimental design was CRD, each of the four treatments having four replications of eighteen seedlings. The biosolid met the legal specifications concerning its composition. Fifty days after sowing, shoot height and stem diameter were measured. It was observed, for both characteristics, that seedling growth was directly proportional to the concentration of sewage sludge in the substrate. Finally, the Alegria ETE's biosolid attends the legislation and shows a technically viable alternative for the production of angico vermelho seedlings.