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Narrative abilities are an important part of communication, academic success, and healthy relationships. These abilities involve complex language and cognitive skills, such as precise vocabulary, control of the coherence markers, relations of cause-effect, and planning. They are also relevant during the elementary school years and interact with the socio-emotional skills necessary to understand different points of view. Oral narrative production develops dramatically from 3 to 5 years of age and is a key factor in a child's ability to communicate about the world. During this period narratives are a product of increasing linguistic sophistication over the preschool period and there is a complex relationship between early narratives and language proficiency. So far, most research about this topic has been pursued in populations other than Latin American preschoolers. At the same time, a considerably lesser number of studies about narrative abilities development have been carried out comparing typically developing children from different socioeconomic backgrounds. To our knowledge, there are no studies in Uruguay that assess the narrative abilities development in typically developing preschool children who grow up in vulnerable contexts. It is therefore of the utmost relevance to produce empirical evidence for this population. For these reasons, this study aimed at characterizing and comparing narrative abilities and receptive vocabulary in a group of a total of 54 Uruguayan preschoolers from different socioeconomic backgrounds (middle and low socioeconomic status, SES). Children were assessed in receptive vocabulary and narrative abilities across two task conditions: (1) narrative comprehension through a story retelling task which included some final questions about the story; (2) narrative production elicited from a set of thematically related puppets. The examiner gives a child a puppet set and asks him/her to elaborate a narrative using them. After that, puppets are removed and the child is asked to retell the story without puppets. Children's oral productions were video-taped and then transcribed and categorized using the ELAN software (Max Planck Institute for Psycholinguistics, 2019). The verbal information was categorized according to Stein and Glenn's (1979) story grammar and considering the microstructural aspects (productivity and complexity). Analyses showed that both groups performed according to their stage of development in both narrative task conditions. With regards to the narrative comprehension task, no differences in the number of recovered categories, extension, or narrative complexity were observed. Concerning the narrative production task, there were no differences between the groups in narrative sequences, nor in the number of completed episodes in conditions neither with puppets nor without puppets. Results showed that children who grow up in poverty perform more poorly than their peers from middle-income families in receptive vocabulary, in the number of recovered episodes, ask-answer items of narrative comprehension tasks. Moreover, concerning the microstructural parameters analyses showed that children from middle socioeconomic backgrounds scored better in syntactic complexity in the without puppets condition. No differences between the groups were observed in syntactic complexity in the puppets condition. Taken together these results indicate a complex link between vocabulary and narrative abilities. It is worth noting that important differences in vocabulary did not reflect in the children's narrative performance. These findings are also relevant as a contribution to an ongoing debate about the role of vocabulary in the development of narrative abilities. Furthermore, these results could inform the discussion about the ecological validity of the test of cognitive and linguistic development. Finally, to provide some additional evidence to Uruguayan Spanish language about the relationships between oral language and cognitive development allows to carry out early interventions before formal schooling sets children for success in school and life. [ABSTRACT FROM AUTHOR]

The eukaryotic chaperonin TRiC/CCT is a large ATP-dependent complex essential for cellular protein folding. Its subunit arrangement into two stacked eight-membered hetero-oligomeric rings is conserved from yeast to man. A recent breakthrough enables production of functional human TRiC (hTRiC) from insect cells. Here, we apply a suite of mass spectrometry techniques to characterize recombinant hTRiC. We find all subunits CCT1-8 are N-terminally processed by combinations of methionine excision and acetylation observed in native human TRiC. Dissociation by organic solvents yields primarily monomeric subunits with a small population of CCT dimers. Notably, some dimers feature non-canonical inter-subunit contacts absent in the initial hTRiC. This indicates individual CCT monomers can promiscuously re-assemble into dimers, and lack the information to assume the specific interface pairings in the holocomplex. CCT5 is consistently the most stable subunit and engages in the greatest number of non-canonical dimer pairings. These findings confirm physiologically relevant post-translational processing and function of recombinant hTRiC and offer quantitative insight into the relative stabilities of TRiC subunits and interfaces, a key step toward reconstructing its assembly mechanism. Our results also highlight the importance of assigning contacts identified by native mass spectrometry after solution dissociation as canonical or non-canonical when investigating multimeric assemblies. [ABSTRACT FROM AUTHOR]

How the essential eukaryotic chaperonin TRiC/CCT assembles from eight distinct subunits into a unique double-ring architecture remains undefined. We show TRiC assembly involves a hierarchical pathway that segregates subunits with distinct functional properties until holocomplex (HC) completion. A stable, likely early intermediate arises from small oligomers containing CCT2, CCT4, CCT5, and CCT7, contiguous subunits that constitute the negatively charged hemisphere of the TRiC chamber, which has weak affinity for unfolded actin. The remaining subunits CCT8, CCT1, CCT3, and CCT6, which comprise the positively charged chamber hemisphere that binds unfolded actin more strongly, join the ring individually. Unincorporated late-assembling subunits are highly labile in cells, which prevents their accumulation and premature substrate binding. Recapitulation of assembly in a recombinant system demonstrates that the subunits in each hemisphere readily form stable, noncanonical TRiC-like HCs with aberrant functional properties. Thus, regulation of TRiC assembly along a biochemical axis disfavors the formation of stable alternative chaperonin complexes. [Display omitted] • TRiC assembles hierarchically through defined intermediates along a biochemical axis • Subcomplexes of adjacent subunits CCT2-4-5-7 nucleate concurrent double-ring assembly • Monomeric CCT8 and labile CCT1, CCT3, and CCT6 join individually to form final complex • Hierarchical regulation disfavors alternate CCT arrangements with aberrant function Moreira et al. show that TRiC/CCT chaperonin assembly involves a hierarchical pathway of intermediates segregating subunit properties along a biochemical axis with subunits CCT2, CCT4, CCT5, and CCT7 nucleating assembly while CCT8, CCT1, CCT3, and CCT6 join the ring individually. Unassembled oligomers and subunits are degraded by proteasomal and lysosomal pathways, preventing the assembly of noncanonical chaperonin arrangements with aberrant functions. [ABSTRACT FROM AUTHOR]

This study researched the influence of learning and practising chess on two executive functions (planning and flexibility) in childhood. The performance of a group of child chess players was compared to a group of children who did not play chess through a planning test (Tower of London) and a cognitive flexibility test (Wisconsin Card Sorting Test). The results showed a better performance in planning by the group of child chess players and suggested certain differences in flexibility (in favour of the group of chess players). This study adds evidence to the hypothesis that highly complex games like chess can favour the development of executive functions in childhood. [ABSTRACT FROM AUTHOR]

The results from a study that administered the Vygotsky-Sakharov artificial concept formation task (Hanfmann & Kasanin administration and scoring system) to children aged 8, 11 and 15 years who attend classes at urban schools in middle and very low socioeconomic status (SES) neighbourhoods of Montevideo, Uruguay, are presented. Videotaped interviews were used to perform a microgenetic analysis of the solving process. The overall results showed a performance improvement related to age, increased ability to benefit from information provided during the task, the role of language in the problem solving process and the prominence of the Vygotskian description of phases in the development of generalization structures. The results suggested that there are differences between subjects from different socioeconomic contexts; however, further research is required. [ABSTRACT FROM AUTHOR]

Identifying enhancers regulating gene expression remains an important and challenging task. While recent sequencing-based methods provide epigenomic characteristics that correlate well with enhancer activity, it remains onerous to comprehensively identify all enhancers across development. Here we introduce a computational framework to identify tissue-specific enhancers evolving under purifying selection. First, we incorporate high-confidence binding site predictions with target gene functional enrichment analysis to identify transcription factors (TFs) likely functioning in a particular context. We then search the genome for clusters of binding sites for these TFs, overcoming previous constraints associated with biased manual curation of TFs or enhancers. Applying our method to the placenta, we find 33 known and implicate 17 novel TFs in placental function, and discover 2,216 putative placenta enhancers. Using luciferase reporter assays, 31/36 (86%) tested candidates drive activity in placental cells. Our predictions agree well with recent epigenomic data in human and mouse, yet over half our loci, including 7/8 (87%) tested regions, are novel. Finally, we establish that our method is generalizable by applying it to 5 additional tissues: heart, pancreas, blood vessel, bone marrow, and liver. [ABSTRACT FROM AUTHOR]

Eisosomes are stable domains at the plasma membrane of the budding yeast Saccharomyces cerevisiae and have been proposed to function in endocytosis. Eisosomes are composed of two main cytoplasmic proteins, Pil1 and Lsp1, that form a scaffold around furrow-like plasma membrane invaginations. We show here that the poorly characterized eisosome protein Seg1/Ymr086w is important for eisosome biogenesis and architecture. Seg1 was required for efficient incorporation of Pil1 into eisosomes and the generation of normal plasma membrane furrows. Seg1 preceded Pil1 during eisosome formation and established a platform for the assembly of other eisosome components. This platform was further shaped and stabilized upon the arrival of Pil1 and Lsp1. Moreover, Seg1 abundance controlled the shape of eisosomes by determining their length. Similarly, the Schizosaccharomyces pombe Seg1-like protein Sle1 was necessary to generate the filamentous eisosomes present in fission yeast. The function of Seg1 in the stepwise biogenesis of eisosomes reveals striking architectural similarities between eisosomes in yeast and caveolae in mammals. [ABSTRACT FROM AUTHOR]

The protein and lipid composition of eukaryotic plasma membranes is highly dynamic and regulated according to need. The sphingolipid-responsive Pkh kinases are candidates for mediating parts of this regulation, as they affect a diverse set of plasma membrane functions, such as cortical actin patch organization, efficient endocytosis, and eisosome assembly. Eisosomes are large protein complexes underlying the plasma membrane and help to sort a group of membrane proteins into distinct domains. In this study, we identify Nce102 in a genome-wide screen for genes involved in eisosome organization and Pkh kinase signaling. Nce102 accumulates in membrane domains at eisosomes where Pkh kinases also localize. The relative abundance of Nce102 in these domains compared with the rest of the plasma membrane is dynamically regulated by sphingolipids. Furthermore, Nce102 inhibits Pkh kinase signaling and is required for plasma membrane organization. Therefore, Nce102 might act as a sensor of sphingolipids that regulates plasma membrane function. [ABSTRACT FROM AUTHOR]

Learning to read transforms lives. Reading contributes to knowledge acquisition, cultural engagement, and success in the school. The unequal distribution of literacy skills in a society is associated with economic and social inequalities as a result, children with a poor foundation in literacy before entering formal schooling are more likely to struggle academically and to drop out of school. For these reasons, there has been an intense scientific interest for decades in understanding how children learn to read. It is well established that in the early stages of reading development, phonological awareness, letter namesounds knowledge, and the naming speed are three independent longitudinal predictors of children's later word-reading skills in alphabetic-writing systems. Phonological awareness constitutes the ability to recognize and manipulate the sounds of their own language, meanwhile letter knowledge promotes the discovery of systematic relationships between writing and oral language. As early readers develop some level of phonological awareness and some level of letter knowledge, they can recognize written words through phonological recoding processes, in which graphemes are recoded as phonemes and assembled to pronounce words. In addition, rapid naming expresses the speed at which phonological information is accessed from a graphic label. Phonological processing and letter knowledge are powerfully affected by the experience, stimulation, and support that children receive before beginning formal education. Most children acquire these abilities relatively effortlessly during early childhood. However, there is a significant number of children in Latin America who experience difficulties in their pre-literacy skills development. This study examined the cognitive profiles of a total of 50 Uruguayan preschoolers from different socioeconomic backgrounds from two public schools in Montevideo, Uruguay. Twenty-six children from low-income households were compared to peers from middle-income. At the end of the pre-schooling period (time 1) receptive vocabulary, phonological awareness, letter name-sounds knowledge, and object naming speed tests were administered to children. One year later (time 2), word -reading of a subgroup of children was measured. Significant correlations were observed between all predictors at time 1; between predictors at time 1 and word reading at time 2; and between all measured abilities and socioeconomic status. Comparative analysis between children of different socioeconomic status showed that children growing up in poverty contexts performed more poorly than their peers from middle-income families in all the tests. Nonetheless, both groups performed poorly in word reading. Descriptive statistics indicated that, out of a total of 26 words, low SES children correctly read a total of 7 words per minute, and medium SES children a total of 14 words. Finally, regression analyses indicated that phonological awareness contributed 30 % variance in predicting the total score achieved in a reading-word test in children of low-income families, meanwhile letter name knowledge contributed 74 % variance in predicting the total score achieved in a reading-word test in their peers from middle-income families. In general terms, results of pre-reading skills and reading performance seem to indicate that children of different socioeconomic status use different word recognition strategies according to their level of letter-knowledge of and phonological processing. Discussion considers international literature pointing out that children who enter elementary school with limited reading-related skills are unlikely to be able to keep pace with their peers. These findings warn about the importance to elaborate systematic and high-quality educational proposals to try to reduce the gap in reading development for children from low-income families. Developing literacy and language skills before formal schooling sets a child up for success in school and life. Results also suggest the importance of analyzing the variables that affect reading development in populations that are not the majority described. [ABSTRACT FROM AUTHOR]

In 1982 and 1986, Lyons and co-authors defined secretinite as one of the two types of sclerotinite (the other being funginite) and established its origin based on its occurrence inside the secretory ducts of medullosan seed ferns. However, in 2001, the International Committee for Coal and Organic Petrology implicitly classified many materials whose derivation is not clear (e.g. inertinite discrete structureless bodies (IDSBs)) as secretinite. By using a combination of coal petrography and micro-Raman spectroscopy (MRS), fusinite, secretinite, IDSBs, and 'ovoid' bodies infilling fusinite were compared in a set of coals within the same rank. Coal petrography allows to identify and quantify macerals of the basis of their shape, internal structure, reflectance, relief, and size. The reflectance of these materials can be determined and then calculate the reflectance indicating surfaces (RIS) main axes (i.e. R MAX , R INT , and R MIN) and parameters (i.e. R am and R ev); moreover, the Raman spectra and parameters (i.e. the full width at half maximum intensity of the G band (FWHM G) and the integrated intensity ratio of the S band to G band (I S /I G)) reflect changes in their structures. Many of the results obtained from the analysis of secretinite did not correspond to those of fusinite and IDSBs. These data suggest different origins/derivations for these materials and justify further discussions about the classification of secretinite and macrinite. The results obtained for the 'ovoid' bodies indicate that their reflectance and Raman parameters can vary within a broad range. We infer that such bodies could represent sclereids; however, when they occur disassociated from fusinite, they should represent IDSBs. • Inertinite study using petrography and microRaman spectroscopy. • Secretinite definition is too broad, whereas macrinite is limited. • Discrete structureless bodies studied properties overlap with fusinite, not with secretinite. [ABSTRACT FROM AUTHOR]

High amounts of coal combustion products, such as fly ash and bottom ash, are generated every year; however, only 64% are used, which means that a significant part is landfilled despite containing valuable materials such as ferrospheres, which may be used as catalysts, substituting critical raw materials (e.g., platinoids). In commercial coals, pyrite contents are reduced as a pre-combustion S-emissions control measure, so low amounts of ferrospheres are expected in the respective ashes. However, given the large amounts of ash being generated from these coals, it may provide a reliable source of catalysts, with ferrospheres being easily recovered via magnetic separation. Several studies have been conducted regarding these morphotypes; however, there is a lack of investigation considering the ash derived from highly beneficiated coals and the variations with location and time. In this study, bottom ash, economizer grits, and fly ash samples from a Portuguese power plant burning Colombian commercial coal were fractionated using ferrite (Fe-MC fraction) and Nd (Nd-MC fraction) magnets, and a multi-technique approach was used to assess their properties (magnetic parameters, particle size distribution, mineralogy, particle morphology, microtexture, and chemical composition). The Fe-MC presented higher Fe concentrations (up to 44 wt.% Fe2O4) than the Nd-MC (up to 7 wt.% Fe2O4). Once it was a sequential process, Nd magnets essentially collected Fe-bearing aluminosilicate glass, and Fe-bearing minerals were residual when compared to the Fe-MC, where magnetite, magnesioferrite, hematite, and maghemite accounted for up to 30 wt.%. Among the Fe-MC, the sample collected from electrostatic precipitator fly ash (ESP FA), despite having a lower yield, presented higher Fe concentrations than the ones from bottom ash and economizer grits, which was related to the mode of occurrence of Fe-bearing phases: in the Fe-MC from ESP FA, discrete ferrospheres predominated, while in the remaining Fe-bearing phases, they were often embedded in aluminosilicate glass. All Fe-MC samples showed an increase of Fe-substituting elements (e.g., Mn and Ni) and their concentration tended to increase with decreasing particle size along with Fe. The integrated study of cross-sections enabled the identification of oxidation rims, martitization aspects, and the co-existence of hematite and magnesioferrite. [ABSTRACT FROM AUTHOR]

Oxidative stress has been linked to a pathological mechanism that contributes to the initiation and progression of hepatic injury during Ichthyophthirius multifiliis infection. Thus, natural compounds with antioxidant and free radical scavenger properties, such as the Melaleuca alternifolia essential oil (TTO), might help to prevent or reduce hepatic damage. Thus, the aim of this study was to investigate whether TTO is capable of preventing or reducing hepatic oxidative damage in silver catfish naturally infected with I. multifiliis. After a TTO bath treatment of 1 h/day for 4 days, the number of trophonts on the skin of catfish was reduced by 94.87% compared to the control group. Hepatic samples from fish infected by I. multifiliis showed increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation levels, while catalase (CAT) activity decreased compared to uninfected and untreated animals. Moreover, the histopathology analyses demonstrated the presence of necrosis, nuclear lateralization and cariorrexis, as well as swelling and vacuolization of cytoplasm. Treatment with TTO reduced hepatic TBARS and protein carbonylation levels and ameliorated the antioxidant system of infected fish, as well as preserve the hepatocytes morphology, but not prevented the occurrence of necrosis. Based on our findings, we propose that TTO is an alternative therapeutic option for silver catfish infected with I. multifiliis . Moreover, TTO treatment is a useful approach for avoiding or minimizing the hepatic oxidative stress caused by I. multifiliis, thus improving the hepatic antioxidant system. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to evaluate service user (SU) and clinician acceptability of video care, including future preferences to inform mental health practice during COVID-19, and beyond. Design/methodology/approach: Structured questionnaires were co-developed with SUs and clinicians. The SU online experience questionnaire was built into video consultations (VCs) via the Attend Anywhere platform, completed between July 2020 and March 2021. A Trust-wide clinician experience survey was conducted between July and October 2020. Chi-squared test was performed for any differences in clinician VC rating by mental health difficulties, with the content analysis used for free-text data. Findings: Of 1,275 SUs completing the questionnaire following VC, most felt supported (93.4%), and their needs were met (90%). For future appointments, 51.8% of SUs preferred video, followed by face-to-face (33%), with COVID-related and practical reasons given. Of 249 clinicians, 161 (64.7%) had used VCs. Most felt the therapeutic relationship (76.4%) and privacy (78.7%) were maintained. Clinicians felt confident about clinical assessment and management using video. However, they were less confident in assessing psychotic symptoms and initiating psychotropic medications. There were no significant differences in clinician VC rating by mental health difficulties. For future, more SUs preferred using video, with a quarter providing practical reasons. Originality/value: The study provides a real-world example of video care implementation. In addition to highlighting clinician needs, support at the wider system/policy level, with a focus on addressing inequalities, can inform mental health care beyond COVID-19. [ABSTRACT FROM AUTHOR]

Natural graphite is a critical raw material and its substitution in some applications will contribute to reduce its supply risk. Coal ash, which is still produced in high amounts, contains a carbonaceous solid residue (char) that may be a substitute of natural graphite. For this purpose, char may be graphitized and used in electrocatalysis reactions, however char properties depend on coal rank, composition and combustion conditions that affect the graphitization process. Research on industrial coal char graphitization is limited, resulting in restricted comprehension of the contributing factors. In order to provide novel insights, industrial residual chars (derived from Poland, Portugal, Romania and South Africa) subjected to high-temperature treatments (carbonization at 1000 °C followed by treatment at 2600 °C under environmental pressure) were examined regarding their microstructural and microtextural transformations. The samples were studied by focussing on its heterogeneity, namely its specific properties and interactions, including elemental composition, optical character, and structure. Furthermore, the evolution of structural order of selected char morphotypes in samples derived from coal of similar rank was assessed using Raman microspectroscopy. The results highlighted a set of aspects that could have influenced the transformations experienced by the different chars during high temperature treatments (graphitization). It was found that Hydrogen might play a role in the graphitization ability of isotropic chars derived from low rank coal. The prior preferential orientation of the Basic Structural Units (BSU) contributes to achieve a higher graphitization degree, but it can be enhanced or hindered by other factors, e.g., hydrogen content. Raman microspectroscopy showed that char morphotypes from the same group underwent different transformations during graphitization, indicating that morphotypes or sections with unfused optical character may be more prone to graphitization. However, the existence of disordered domains and specific microtextures, such as polyhedral pores identified under TEM, likely hindered further graphitization. Further research on this topic is needed. [ABSTRACT FROM AUTHOR]

Abstract Citrobacter freundii is a fish pathogen known for its ability to cause injury and high mortality. There have been no studies reporting the effect of this bacterium on hematological parameters and internal organ histology in silver catfish (Rhamdia quelen). Therefore, the aim of this study is to evaluate the hematological and histopathological effects of an experimentally induced C. freundii infection in silver catfish. Twenty fish were divided into healthy and infected groups. The fish of the infected group were inoculated intramuscularly with 100 μL of bacterial suspension (6.4 × 108 CFU mL−1), while healthy control animals received 100 μL of sterile saline. On day 18 post-infection, blood and tissues (cephalic kidneys, livers, and spleens) were collected for histological analysis. The infected animals presented high mortality, as well as hematological and histological changes. In relation to hematology, the infected fish presented aregenerative anemia, protein loss, leukopenia with neutropenia, lymphocytosis, and leukoblastosis. Regarding histology, there was liver degeneration, decrease in the amount of renal hematopoietic tissue, and the presence of melanomacrophage centers (MMCs) in the spleen and cephalic kidney of infected fish. In summary, these alterations may contribute to disease pathophysiology, contributing to high mortality of affected fish. Highlights • Citrobacter freundii infection affects hematological parameters of silver catfish. • There was also liver degeneration, decrease in the renal hematopoietic tissue, and presence of MMCs in the spleen and kidney. • These alterations may contribute to disease pathophysiology, contributing to high mortality of affected fish. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo or erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. Aim of the study To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. Materials and methods The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400 mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS Results Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400 mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200 mg/kg and 400 mg/kg of the extract. Conclusions The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats. [ABSTRACT FROM AUTHOR]

It is known that the cytotoxic effects of aflatoxin B 1 (AFB 1 ) in endothelial cells of the blood–brain barrier (BBB) are associated with behavioral dysfunction. However, the effects of a diet contaminated with AFB 1 on the behavior of silver catfish remain unknown. Thus, the aim of this study was to evaluate whether an AFB 1 -contaminated diet (1177 ppb kg feed −1 ) impaired silver catfish behavior, as well as whether disruption of the BBB and alteration of neurotransmitters in brain synaptosomes are involved. Fish fed a diet contaminated with AFB 1 presented a behavioral impairment linked with hyperlocomotion on days 14 and 21 compared with the control group (basal diet). Neurotransmitter levels were also affected on days 14 and 21. The permeability of the BBB to Evans blue dye increased in the intoxicated animals compared with the control group, which suggests that the BBB was disrupted. Moreover, acetylcholinesterase (AChE) activity in brain synaptosomes was increased in fish fed a diet contaminated with AFB 1 , while activity of the sodium-potassium pump (Na + , K + -ATPase) was decreased. Based on this evidence, the present study shows that silver catfish fed a diet containing AFB 1 exhibit behavioral impairments related to hyperlocomotion. This diet caused a disruption of the BBB and brain lesions, which may contribute to the behavioral changes. Also, the alterations in the activities of AChE and Na + , K + -ATPase in brain synaptosomes may directly contribute to this behavior, since they may promote synapse dysfunction. In addition, the hyperlocomotion may be considered an important macroscopic marker indicating possible AFB 1 intoxication. [ABSTRACT FROM AUTHOR]

The precise coupling of spatially separated intracellular adenosine triphosphate (ATP)-producing and ATP-consuming, catalyzed by creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), is a critical process in the bioenergetics of tissues with high energy demand, such as the branchial tissue. The effects of Citrobacter freundii infection on gills remain poorly understood, limited only to histopathological studies. Thus, the aim of this study was to evaluate whether experimental infection by C. freundii impairs the enzymes of the phosphoryl transfer network in gills of silver catfish ( Rhamdia quelen ). The CK (cytosolic and mitochondrial) and AK activities decreased in infected compared to uninfected animals, while the PK activity did not differ between groups. The gill histopathology of infected animals revealed extensive degeneration with fusion and necrosis of secondary lamellae, detachment of superficial epithelium, aneurysm, vessel congestion and inflammatory process. Based on these evidences, the inhibition and absence of an efficient communication between CK compartments caused the impairment of the branchial bioenergetics homeostasis, which was not compensated by the augmentation on branchial AK activity in an attempt to restore energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to branchial tissue in animals infected with C. freundii. [ABSTRACT FROM AUTHOR]

It has been recognized that the cholinergic and adenosinergic systems, through the enzymes acetylcholinesterase (AChE) and adenosine deaminase (ADA), exert an important role in the immune and inflammatory responses during bacterial fish diseases. The immune response against Aeromonas caviae remains poorly understood, and the involvement of these systems, through the anti-inflammatory molecules acetylcholine (ACh) and adenosine (Ado), has not been studied. Thus, the aim of this study was to evaluate the involvement of cholinergic and adenosinergic systems on the inflammatory and immune responses in peripheric and splenic lymphocytes of fish experimentally infected with A . caviae . AChE and ADA activities in peripheric and splenic lymphocytes increased in infected animals on day 4 post-infection compared to uninfected animals, while the ACh and Ado levels decreased. Moreover, spleen histopathology revealed an increase in the number of melano-macrophage centers, as well as lipid inclusions and cellular debris in the ellipsoids. This evidence indicates that infection by A . caviae alters the cholinergic and adenosinergic systems, suggesting the involvement of AChE and ADA activities in the impairment of the immune system, since infection leads to a reduction in ACh and Ado levels, respectively. In summary, the upregulation of AChE and ADA activities in peripheric and splenic lymphocytes exerts a pro-inflammatory profile, contributing to systemic and tissue inflammatory damage, and consequently to disease pathogenesis. [ABSTRACT FROM AUTHOR]

It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish ( Rhamdia quelen ). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is a final enzyme of purine metabolism linked with initiation and progression of infectious diseases, since is considered an important source of reactive oxygen species (ROS) and nitric oxide (NO), developing a pro-oxidant and pro-inflammatory profile in some infectious diseases. Thus, the aim of this study was to evaluate the involvement of XO activity in the renal oxidative and inflammatory damage, as well as the interplay with ROS and metabolites of nitric oxide (NOx) levels in silver catfish experimentally infected with Streptococcus agalactiae. Xanthine oxidase activity, and uric acid, ROS and NOx levels increased in renal tissue of infected animals compared to uninfected animals. Moreover, the histopathological analyses revealed the presence of necrosis, generalized edema and nuclear degeneration of renal tubules. Based on these evidences, the upregulation on renal XO activity exerts a pro-oxidant and pro-inflammatory profile in kidney of fish infected with S. agalactiae. The excessive uric acid levels induced the release of oxidative and inflammatory mediators, such as ROS and NOx, that directly contribute to renal oxidative and inflammatory damage. In summary, the upregulation on XO activity may be considered a pathway involved in the renal injury during S. agalactiae infection. [ABSTRACT FROM AUTHOR]

Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na + , K + -ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na + , K + -ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Some studies have demonstrated that xanthine oxidase activity, through the regulation of uric acid levels, exerts a pro-inflammatory profile during infectious diseases. It has been recognized that uric acid induces the release of pro-inflammatory mediators, such as reactive oxygen species (ROS) and nitric oxide (NO), which contribute to inflammatory processes. Considering this, the aim of this study was to evaluate whether upregulation of branchial xanthine oxidase activity may be considered a pathway involved in ROS and nitric oxide (NOx) metabolites production in experimentally infected Rhamdia quelen (silver catfish) with Streptococcus agalactiae . Xanthine oxidase activity, and uric acid, ROS and NOx levels increased in gills of infected animals compared to uninfected animals. Moreover, a positive Pearson correlation was observed between uric acid and ROS levels, and between uric acid and NOx levels. Histopathology revealed the presence of necrosis, hyperplasia and vein congestion in gills of animals infected with S . agalactiae . Based on this evidence, the upregulation of xanthine oxidase activity induces a pro-inflammatory and oxidative profile in the gills of fish infected with S . agalactiae . The excessive uric acid levels induce the release of pro-inflammatory mediators, such as ROS and NOx, which contribute to disease pathogenesis. In summary, the upregulation of xanthine oxidase activity may be considered a pathway involved in ROS and NOx production. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that fish are able to mount protective immune responses against various parasites, including Ichthyophthirius multifiliis, an economically important protozoosis in freshwater aquaculture. Although the immune response against this parasite have been partly elucidated in the literature, the involvement of the cholinergic and adenosinergic systems, through the anti-inflammatory molecules acetylcholine (ACh) and adenosine (Ado), has not been studied. Thus, the aim of this study was to evaluate the involvement of the cholinergic and adenosinergic systems in the immune and inflammatory responses in the immune lymphatic organs of silver catfish, Rhamdia quelen , naturally infected with I. multifiliis. Acetylcholinesterase (AChE) activity increased, while adenosine deaminase (ADA) activity decreased in the head kidney and spleen of silver catfish naturally infected with I. multifiliis compared to the uninfected control group. Moreover, the levels of ACh in the head kidney and spleen decreased in infected animals, while the Ado levels increased compared to the uninfected control group. A negative and significant Pearson correlation was observed between AChE activity and ACh levels, as well as between ADA activity and Ado levels. Therefore, the cholinergic system exerts a pro-inflammatory profile due to upregulation of AChE activity and a consequent reduction in ACh levels, which contributes to inflammatory damage. Conversely, the adenosinergic system plays an anti-inflammatory profile via downregulation of ADA activity and consequent augmentation of Ado levels, which may contribute to restricting the inflammatory process and improving the immune response during ichthyophthiriasis. [ABSTRACT FROM AUTHOR]

It has long been recognized that there are several infectious diseases linked to the impairment of enzymatic complexes of the mitochondrial respiratory chain, with consequent production of reactive oxygen species (ROS), that contribute to disease pathogenesis. In this study, we determined whether the inhibition on mitochondrial respiratory chain might be considered a pathway involved in the production of ROS in gills of Rhamdia quelen experimentally infected by P. aeruginosa. The animals were divided into two groups with six fish each: uninfected (the negative control group) and infected (the positive control group). On day 7 post-infection (PI), animals were euthanized and the gills were collected to assess the activities of complexes I-III, II and IV of the respiratory chain, as well as ROS levels. The activities of complexes I-III, II and IV of the respiratory chain in gills decreased, while the ROS levels increased in infected compared to uninfected animals. Moreover, a significant negative correlation was found between enzymatic activity of the complexes I-III and IV related to ROS levels in P. aeruginosa infected animals, corroborating to our hypothesis that inhibition on complexes of respiratory chain leads to ROS formation. Also, microscopic severe gill damage and destruction of primary and secondary lamellae were observed in infected animals, with the presence of hyperplasia, leukocytic infiltration and telangiectasia. In summary, we have demonstrated, for the first time, that experimental infection by P. aeruginosa inhibits the activities of mitochondrial complexes of respiratory chain and, consequently, impairs the cellular energy homeostasis. Moreover, the inhibition on mitochondrial complexes I-III and IV are linked to the ROS production, contributing to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for gills bioenergetics, since this tissue plays an important role in the respiratory energy metabolism. The effects of bacterial infection on gills remain poorly understood, limited only to histopathological analyses. Thus, the aim of this study was to investigate whether experimental infection by Pseudomonas aeruginosa strain PA01 alters the enzymes of the phosphoryltransfer network (adenylate kinase (AK), pyruvate kinase (PK) and cytosolic and mitochondrial creatine kinase (CK)) in gills of silver catfish ( Rhamdia quelen ). The animals were divided into two groups with six fish each: uninfected (negative control) and infected (positive control). On day 7 post-infection (PI), animals were euthanized and the gills collected. AK, PK, and cytosolic and mitochondrial CK activities in gills decreased in infected compared to uninfected animals. Also, severe gill damage and destruction in the primary and secondary lamellae was observed in the infected animals. Therefore, we have demonstrated, for the first time, that experimental infection by P. aeruginosa inhibits key enzymes linked to the production and utilization of metabolic energy in silver catfish, and consequently, impairs cellular energy homeostasis, which may contribute to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Interleukin-4 ( IL-4) and IL-13 are critical drivers of immune activation and inflammation in ulcerative colitis, asthma and other diseases. Because these cytokines may have redundant function, dual targeting holds promise for achieving greater efficacy. We have recently described a bifunctional therapeutic targeting IL-4 and IL-13 developed on a novel protein scaffold, generated by combining specific binding domains in an optimal configuration using appropriate linker regions. In the current study, the bifunctional IL-4/ IL-13 antagonist was evaluated in the murine oxazolone-induced colitis model, which produces disease with features of ulcerative colitis. The bifunctional IL-4/ IL-13 antagonist reduced body weight loss throughout the 7-day course of the model, and ameliorated the increased colon weight and decreased colon length that accompany disease. Colon tissue gene expression was modulated in accordance with the treatment effect. Concentrations of serum amyloid P were elevated in proportion to disease severity, making it an effective biomarker. Serum concentrations of the bifunctional IL-4/ IL-13 antagonist were inversely proportional to disease severity, colon tissue expression of pro-inflammatory genes, and serum amyloid P concentration. Taken together, these results define a panel of biomarkers signifying engagement of the IL-4/ IL-13 pathway, confirm the T helper type 2 nature of disease in this model, and demonstrate the effectiveness of dual cytokine blockade. [ABSTRACT FROM AUTHOR]

Eisosomes help sequester a subgroup of plasma membrane proteins into discrete membrane domains that colocalize with sites of endocytosis. Here we show that the major eisosome component Pil1 in vivo is a target of the long-chain base (LCB, the biosynthetic precursors to sphingolipids)-signaling pathway mediated by the Pkh-kinases. Eisosomes disassemble if Pil1 is hyperphosphorylated (i) upon overexpression of Pkh-kinases, (ii) upon reducing LCB concentrations by inhibiting serine-palmitoyl transferase in lcb1-mutant cells or by poisoning the enzyme with myriocin, and (iii) upon mimicking hyperphosphorylation in pil1-mutant cells. Conversely, more Pil1 assembles into eisosomes if Pil1 is hypophosphorylated (i) upon reducing Pkh-kinase activity in pkh1 pkh2-mutant cells, (ii) upon activating Pkh-kinases by addition of LCBs, and (iii) upon mimicking hypophosphorylation in pil1-mutant cells. The resulting enlarged eisosomes show altered organization. Other data suggest that Pkh signaling and sphingolipids are important for endocytosis. Taken together with our previous results that link eisosomes to endocytosis, these observations suggest that Pkh-kinase signaling relayed to Pil1 may help regulate endocytic events to modulate the organization of the plasma membrane. [ABSTRACT FROM AUTHOR]

Phosphate rocks are a critical resource for the European Union, and alternative sources to assure the future production of a new generation of fertilizers are to be assessed. In this study, a statistical approach, combined with a sustainability evaluation for the recovery of materials from waste containing phosphorus (P), is presented. This work proposes a strategy to recover P and silica (SiO2) from rice husk poultry litter ash (RHPLA). The design of experiment (DoE) method was applied to maximize the P extraction using hydrochloric acid (HCl), with the aim to minimize the contamination that can occur by leachable heavy metals present in RHPLA, such as zinc (Zn). Two independent variables, the molar concentration of the acid, and the liquid-to-solid ratio (L/S) between the acid and RHPLA, were used in the experimental design to optimize the operating parameters. The statistical analysis showed that a HCl concentration of 0.34 mol/L and an L/S ratio of 50 are the best conditions to recover P with low Zn contamination. Concerning the SiO2, its content in RHPLA is too low to consider the proposed recovery process as advantageous. However, based on our analysis, this process should be sustainable to recover SiO2 when its content in the starting materials is more than 80%. [ABSTRACT FROM AUTHOR]

Coal ash char concentrates from four countries (Portugal, Poland, Romania, and South Africa) were prepared, characterised, and graphitized under the scope of the Charphite project (Third ERA-MIN Joint Call (2015) on the Sustainable Supply of Raw Materials in Europe). Coal ash chars may be a secondary raw material to produce synthetic graphite and could be an alternative to natural graphite, which is a commodity with a high supply risk. The char concentrates and the graphitized material derived from the char concentrates were characterised using proximate analysis, X-ray fluorescence, X-ray diffraction (structural), Raman microspectroscopy, solid-state nuclear magnetic resonance, scanning electron microscopy, and petrographic analyses to determine if the graphitization of the char was successful, and which char properties enhanced or hindered graphitization. Char concentrates with a lower proportion of anisotropic particles and a higher proportion of mixed porous particles showed greater degrees of graphitization. It is curious to see that embedded Al2O3 minerals, such as glass and clay, influenced graphitization, as they most likely acted as catalysts for crystal growth in the basal direction. However, the graphitized samples, as a whole, do not compare well against a reference natural graphite sample despite some particles in select char concentrates appearing to be graphitized following graphitization. [ABSTRACT FROM AUTHOR]