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Objective Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed. Methods We screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient-derived fibroblasts. Results Twelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype-modifier variants. All the DOA-associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28-associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA-associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28-associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission-inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells. Interpretation This study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020 ANN NEUROL 2020;88:18-32.

Interpretation of variants of uncertain significance is an actual major challenge. We addressed this question on a set of OPA1 missense variants responsible for variable severity of neurological impairments. We used targeted metabolomics to explore the different signatures of OPA1 variants expressed in Opa1 deleted mouse embryonic fibroblasts (Opa1−/− MEFs), grown under selective conditions. Multivariate analyses of data discriminated Opa1+/+ from Opa1−/− MEFs metabolic signatures and classified OPA1 variants according to their in vitro severity. Indeed, the mild p.I382M hypomorphic variant was segregating close to the wild-type allele, while the most severe p.R445H variant was close to Opa1−/− MEFs, and the p.D603H and p.G439V alleles, responsible for isolated and syndromic presentations, respectively, were intermediary between the p.I382M and the p.R445H variants. The most discriminant metabolic features were hydroxyproline, the spermine/spermidine ratio, amino acid pool and several phospholipids, emphasizing proteostasis, endoplasmic reticulum (ER) stress and phospholipid remodeling as the main mechanisms ranking OPA1 allele impacts on metabolism. These results demonstrate the high resolving power of metabolomics in hierarchizing OPA1 missense mutations by their in vitro severity, fitting clinical expressivity. This suggests that our methodological approach can be used to discriminate the pathological significance of variants in genes responsible for other rare metabolic diseases and may be instrumental to select possible compounds eligible for supplementation treatment.

A pitangueira é fruteira nativa com potencial de mercado. Contudo, o rendimento de polpa pode ficar prejudicado pelo tamanho da semente do fruto. Na UTFPR tem-se um genótipo que produz frutos sem sementes que pode potencializar o uso desta espécie em pomares, sendo importante analisar a qualidade de seu fruto produzido. O objetivo deste estudo foi determinar a qualidade dos frutos de acessos pirênicos e apirênico de pitangueira (E. uniflora). Nos anos de 2012, 2013 e 2015, foram coletados 40 frutos maduros de 23 acessos de pitangueira, incluindo-se um genótipo apirênico. Os frutos foram levados ao laboratório e analisadas quanto ao peso total do fruto e da semente, diâmetro equatorial do fruto e semente, teor de sólidos solúveis totais (SST). O acesso 23 apresentou características físicas que se destacam dos demais acessos, porém, o maior tamanho da semente é fator indesejável, pois com a industrialização diminui-se o aproveitamento e rendimento da polpa. O acesso 19, correspondente à pitanga apirênica apresentou o menor diâmetro e peso da semente, sendo esta característica desejável. Este genótipo também apresentou as características físico-químicos considerados adequados para o processamento ou mercado in natura.

Chagas disease infects approximately seven million people worldwide. Benznidazole is effective only in the acute phase of the disease, with an average cure rate of 80% between acute and recent cases. Therefore, there is an urgent need to find new bioactive substances that can be effective against parasites without causing so many complications to the host. In this study, the triterpene 3β-6β-16β-trihydroxilup-20 (29)-ene (CLF-1) was isolated from Combretum leprosum, and its molecular structure was determined by NMR and infrared spectroscopy. The CLF-1 was also evaluated in vitro and in silico as potential trypanocidal agent against epimastigote and trypomastigote forms of Trypanosoma cruzi (Y strain). The CLF-1 demonstrated good results highlighted by lower IC50 (76.0 ± 8.72 µM, 75.1 ± 11.0 µM, and 70.3 ± 45.4 µM) for epimastigotes at 24, 48 and 72 h, and LC50 (71.6 ± 11.6 µM) for trypomastigotes forms. The molecular docking study shows that the CLF-1 was able to interact with important TcGAPDH residues, suggesting that this natural compound may preferentially exert its effect by compromising the glycolytic pathway in T. cruzi. The ADMET study together with the MTT results indicated that the CLF-1 is well-absorbed in the intestine and has low toxicity. Thus, this work adds new evidence that CLF-1 can potentially be used as a candidate for the development of new options for the treatment of Chagas disease. Communicated by Ramaswamy H. Sarma

Resumo A espécie Sus scrofa (javali) foi introduzida no Brasil, nos anos de 1904 e 1906, tornando-se uma ameaça à biodiversidade, à economia do setor agrícola e à sociedade. Neste trabalho, foi proposto identificar os impactos ambientais causados na região de Bagé, as ocorrências e danos na agricultura local, assim como o que vem sendo feito para o efetivo controle da espécie. Para obtenção dos resultados, foi realizado um levantamento de dados através de artigos, documentos on-line e instituições locais. Verificou-se que esta situação é originária do manejo realizado no passado, que ocasionou no aumento da população de javalis gerando este desequilíbrio. A proliferação desta espécie tem causado danos ambientais e danos econômicos ao ecossistema local e aos produtores. Nas lavouras de soja, milho, trigo e arroz já se estimaram prejuízos de diferentes montas, chegando a registrar perdas totais em pequenos cultivos. Com estes impactos crescentes, foram necessárias medidas ambientalmente seguras para reorganizar este ecossistema, pois com a ausência de predadores naturais, esta população tende a crescer, sendo necessária a implantação de uma política de controle. Como método de controle populacional, foi identificada a liberação da caça do javali a partir de um Cadastro Técnico Federal e certificação. Palavras-chave: Manejo; crescimento; javali; biodiversidade. Abstract An analysis of the environmental impacts of exotic species in the Pampa Biome: from proliferation to the necessary control of Sus scrofa populations The species Sus scrofa (wild boar) was introduced in Brazil, during 1904 and 1906, becoming a threat to biodiversity, to agricultural sector economy and to society. In this research, it was proposed to identify environmental impacts caused in the Bagé region, occurrences and damages in local agriculture, as well as what has been done for the species effective control. In order to obtain the results, a data survey was carried out through articles, online documents and local institutions. It was found that this situation originates from management carried out in the past, which caused an increase in the wild boar population, generating this imbalance. The proliferation of this species has caused environmental damage and economic damage to local ecosystem and to producers. In soybean, corn, wheat and rice crops, losses of different amounts have already been estimated, reaching total losses in small crops. With these growing impacts, environmentally safe measures were necessary to reorganize this ecosystem, as with the absence of natural predators this population tends to grow, requiring the implementation of a control policy. As a method of population control, the release of wild boar hunting from a Federal Technical Register and certification was identified. Keywords: Management; growth; boar; biodiversity. Resumen Un análisis sobre los impactos ambientales de las especies exóticas en el Bioma Pampa: de la proliferación al control necesario de las poblaciones de Sus scrofa La especie Sus scrofa (jabalí) fue introducida en Brasil en los años de 1904 y 1906, convirtiéndose en una amenaza para la biodiversidad, a la economía del sector agrícola y de la sociedad. En este trabajo se propuso identificar los impactos ambientales provocados en la región de Bagé, las ocurrencias y daños en la agricultura local, así como lo que se está haciendo para el efectivo control de la especie. Para la obtención de los resultados, se realizó una encuesta de datos a través de artículos, documentos en línea e instituciones locales. Se verificó que esta situación se origina en el manejo realizado en el pasado, que provocó en el aumento de la población de jabalíes, generando este desequilibrio. La proliferación de esta especie ha causado daños ambientales y económicos al ecosistema local y a los productores. En los cultivos de soya, maíz, trigo y arroz ya se han estimado pérdidas de diferentes cantidades, alcanzando registrar pérdidas totales en cultivos pequeños. Con estos impactos crecientes, fueron necesarias medidas ambientalmente seguras para reorganizar este ecosistema, ya que, con la ausencia de depredadores naturales, esta población tiende a crecer, requiriendo la implementación de una política de control. Como método de control de la población, fue identificada la liberación de la caza de jabalíes a partir de un Registro Técnico Federal y una certificación. Palabras clave: Gestión; crecimiento; jabali; biodiversidad.

Aleutian mink disease virus (AMDV) is one the most relevant pathogens of domestic mink, where it can cause significant economic losses, and wild species, which are considered a threat to mink farms. Despite their relevance, many aspects of the origin, evolution, and geographic and host spreading patterns of AMDV have never been investigated on a global scale using a comprehensive biostatistical approach. The present study, benefitting from a large dataset of sequences collected worldwide and several phylodynamic-based approaches, demonstrates the ancient origin of AMDV and its broad, unconstrained circulation from the initial intercontinental spread to the massive among-country circulation, especially within Europe, combined with local persistence and evolution. Clear expansion of the viral population size occurred over time until more effective control measures started to be applied. The role of frequent changes in epidemiological niches, including different hosts, in driving the high nucleotide and amino acid evolutionary rates was also explored by comparing the strengths of selective pressures acting on different populations. The obtained results suggest that the viral passage among locations and between wild and domesticated animals poses a double threat to farm profitability and animal welfare and health, which is particularly relevant for endangered species. Therefore, further efforts must be made to limit viral circulation and to refine our knowledge of factors enhancing AMDV spread, particularly at the wild-domestic interface.

The pomegranate (Punica granatum L.) presents potential for commercial exploitation as a fruit, ornamental or medicinal plant. However, for its usage in orchards, it is ideal that the seedlings come from vegetative propagation techniques. The aim of this work was to test the usage of indolebutyric acid (IBA) and substrates, at two harvesting times (before and after fruiting) in the cutting propagation of pomegranate. The work was carried out at UTFPR, Campus Dois Vizinhos. The experiments were installed in a randomized block design, in a 4 x 4 factorial scheme (IBA concentration x substrate), with four replications and ten cuttings per experimental unit. IAB was tested at concentrations 0; 1000; 2000 and 3000 mg L-1. The used substrates were Red Latosol, medium textured sand, commercial substrate MecPlant® and a mixture of Red Latosol + sand + commercial (1:1:1, v/v). The cuttings were placed in beds in a screened protected environment, with 50% shading. Irrigation was performed three times a day for 30 min., by a micro sprinkler. After 60 days, rooting (%), cuttings with callus (%), number of primary leaf and root shoots, length of the three largest roots and percentage of dead cuttings were evaluated. Cutting presented itself as a potential technique to be adopted for pomegranate, using sand, with the use of IBA at concentrations between 1600 and 1750 mg L-1. Cuttings must be collected before fruiting. However, rhizogenesis close to 50% was achieved at the time after such phenological stage.

A utilização de urina de vaca pode ser considerada uma prática de baixo custo para os produtores rurais do Sudoeste do Paraná. Assim objetivou-se com este trabalho avaliar o efeito da urina de vaca sobre o crescimento e produção de mudas de alface. O delineamento experimental utilizado foi em inteiramente casualizado, com quatro repetições. Foram analisados os efeitos de sete concentrações de urina de vaca (1,0; 2,0; 3,0; 4,0; 5,0; 6,0 e 7,0%) (v v-1). Nas condições do sudoeste paranaense, o melhor desenvolvimento da alface foi obtido com a aplicação da concentração de 5,0%. Os índices de clorofila (a e b), também foram superiores com a utilização da concentração de 5,0%.

By-products from the dairy industry and mining activities represent a great environmental overload, which justify research for value-added reuse of these by-products (dairy sludge and dacite rock powder). Dairy sludge is generated at a rate of about 0.2–10 l per liter of processed milk, and dacite powder, from rock mining extraction and processing, is generated for about 52,400 m3 per year in Nova Prata city, Southern Brazil. For both by-products, the compositions of calcium (Ca), magnesium (Mg), potassium (K) and phosphorous (P), arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb) were determined by using appropriate analytical techniques. A greenhouse experiment was conducted to determine release of macronutrients, such as Ca, K, Mg, and P, from by-products to support black oat (Avena strigosa) and maize nutrition. Twelve by-products doses were blended with a typic Hapludox soil and were applied to pots with five replications each. Black oat (first cultivation) and, sequentially, maize (second cultivation) were cultivated for 70 days each. Ameliorations in soil chemical attributes, leaf dry matter yield, and plant nutritional status were evaluated at the end of each cultivation. There was a significant (p < 0.05) increase in all parameters evaluated in a dose of 7251 kg ha-1 of dacite rock powder and 20,594 kg ha-1 of dairy sludge. Compared to the control treatments, both crops grew well better on all mixtures. The presence of potentially toxic elements in both by-products was irrelevant, indicating that effective blending of dacite rock powder along with dairy sludge could be a potential source of Ca, K, Mg, and P in agriculture without posing a risk of contamination to the environment.

Objective This study aimed to assess the characteristics of different designs of systematic reviews (SRs) registered in the International Prospective Register of Systematic Reviews (PROSPERO) about COVID‐19. Methods The search was performed in the PROSPERO database using the strategy proposed by the database and considered only human studies. The last date of the search was April 27, 2020. Full text of all records was accessed, and data were extracted by a single researcher, which was further double‐checked by another researcher. A descriptive analysis was performed considering record characteristics using tables. Results We included 564 records from which the vast majority were registered as SRs (n = 513, 91%). In general, we found poor reporting and missing or confusing information, since 84% of the records (n = 474) did not report the full search that would be adopted, 16% (n = 90) did not report clearly the databases that would be used, and 49.1% (n = 277) did not report the number of primary outcomes. The main focus of most of the records involved clinical, epidemiological, complication, and laboratory characteristics (n = 173, 30.7%) or the treatment of COVID‐19 (n = 138, 24.5%). Conclusion A large number of SRs about COVID‐19 have been conducted, and many of the assessed records were poorly reported and would be difficult to replicate. Besides, collected data points to an epidemic of redundant reviews on COVID‐19.

In this work, comminuted seedpods of the forest species Luehea divaricata (LDPR) and Inga laurina (ILPR) were used as alternative and environmental-friendly adsorbents for the methylene blue (MB) removal from aqueous solutions. Batch adsorption experiments were carried out at the native pH of the solution (pH = 8.7), with curves of removal and adsorption capacity crossed at 0.75 g L−1, having 125 mg g−1 for LDPR and 115 mg g−1 for ILPR. The kinetic models of pseudo-first-order (PFO) and HSDM-Crank were the most adequate to represent MB dye concentration decay data for both biosorbents. The equilibrium curves were better adjusted by the Langmuir model for both adsorbents, with maximum adsorption capacity increased from 279 to 325 mg g−1 for LDPR, and 199 to 233 mg g−1 for ILPR, as a function of an increase in temperature from 298 to 328 K. The thermodynamic parameters showed that both systems are spontaneous with a dominance of physisorption. Mass transfer analysis indicates that the external mass transfer is the limiting step, with Bi

This study aimed to assess root canal irrigants' effect on the bond strength between endodontic sealers and root canal dentin, through a systematic review. The study protocol is available online (h...

Pods of the forest species Caesalpinia echinata were used as an alternative adsorbent to remove bright blue (BB) and methylene blue (MB) dyes. The raw and acid-treated samples were characterized by techniques like SEM, XRD, and FTIR. The acid-treated pod sample was characterized by an amorphous structure containing several cavities, bumps, and functional groups. The Elovich model was the most satisfactory to describe the adsorption kinetic data. The isothermal studies were better described by the Langmuir model for BB dye, with a maximum capacity of 261 mg g−1, and Toth model for MB dye, giving a maximum capacity of 288 mg g−1. The thermodynamic study indicated a spontaneous and favorable process and endothermic nature for both dyes. In the treatment of two simulated effluents containing a mixture of different compounds such as dyes and salts, to simulate real wastewaters, the adsorbent was highly efficient, presenting around 80% of color removal for both effluents. Therefore, the acid-treated pods of Caesalpinia echinata have great potential to be applied as an alternative adsorbents in treating colored effluents in discontinuous systems.

Two novel ecological and low-cost adsorbents were prepared from seed residues of the tree species Anadenanthera macrocarpa and Cedrela fissilis for the removal of methylene blue dye in water. The materials were comminuted and characterized by different techniques. The particles of samples have a rough surface with cavities. The optimum dosage and pH for both materials were 1 g L−1 and pH 8. The pseudo-second-order model was the most suitable for describing the adsorption kinetics for both systems. The Anadenanthera macrocarpa presented a maximum experimental capacity of 228 mg g−1, while the Cedrela fissilis, a similar capacity of 230 mg g−1 at 328 K. The Toth model was proper for describing the equilibrium curves for both systems. The thermodynamic indicators show that the adsorption process is spontaneous and endothermic for both materials. The application of materials for the simulated effluent treatment showed 74 and 78% of color removal using Anadenanthera macrocarpa and Cedrela fissilis samples, respectively. Overall, seed residues of Anadenanthera macrocarpa and Cedrela fissilis could be potentially applied for adsorptive removal of colored contaminants in wastewater.

Diatoms are considered the main base of the Southern Ocean food web as they are responsible for more than 85% of its annual primary production and play a crucial role in the Antarctic trophic structure and in the biogeochemical cycles. Within this context, an intense diatom bloom reaching > 45 mg m−3 of chlorophyll a was registered in the Northern Antarctic Peninsula (NAP) during a late summer study in February 2016. Given that nutrient concentrations and grazing activities were not identified here as limiting factors on the bloom development, the aim of this study was to evaluate the effect of water column structure (stability and upper mixed layer depth) on the phytoplankton biomass and composition in the NAP. The diatom bloom, mainly composed by the large centric Odontella weissflogii (mostly > 70 μm in length), was associated with a local ocean carbon dioxide uptake that reached values greater than −60 mmol m−2 d−1. We hypothesize that the presence of a vertically large water column stability barrier, just below the pycnocline, was the main driver allowing for the development of the intense diatom bloom, particularly in the Gerlache Strait. Contrarily, a shift from diatoms to dinoflagellates (mainly Gymnodiniales

A powdered biosorbent was developed by the processing of mandacaru (Cereus jamacaru) leaves, and tested as an alternative material to treat solutions containing Basic Fuchsin dye (BF) in discontinuous and continuous systems. A simple model (ILE model) based in the Langmuir isotherm was developed to predict the continuous biosorption. PML was a fast and efficient biosorbent, attaining biosorption capacity near to 400 mg g−1. PML was also efficient to treat a simulated effluent, providing color removal percentages around 90%. In relation to the continuous operation using PML, an excellent bed performance was found, with breakthrough time of 14 h, and length of mass transfer zone of 1.48 cm. The ILE model was able to predict the breakthrough curve. It can be concluded that PML is a low cost and efficient biosorbent to be used for decolorization of liquid streams in discontinuous and continuous systems.

Data about phylogenetic classification of Escherichia coli colonizing calves, lambs and foals are routinely neglected and restricted to outdated methodologies, even in the context of antimicrobial susceptibility (AS) testing. Thus, the aim of this study was to determine the phylogenetic diversity and the AS profile of E. coli colony-forming units (CFUs) from faecal samples of healthy animals. Five CFUs of E. coli were randomly selected from each faecal culture of calves (n = 13), foals (n = 13) and lambs (n = 13), totalizing 195 CFUs phylo-typed by quadruplex PCR. The AS profile of five CFUs from 15 samples (five from each animal species; n = 75 isolates) against nine drugs was determined by agar diffusion test. We found E. coli belonging to all phylo-groups already described, except D group, with the predominance of B1 (65% CFUs; 126/195) in the three-animal species sampled. Most faecal samples of calves (77%; 10/13) and foals (69%; 9/13) harboured both pathogenic and nonpathogenic E. coli. All faecal samples showed CFUs with diverse AS profile, highlighting the ineffectiveness of tetracycline, sulphonamide and ampicillin. As a key point, our data reinforce the importance to select at least four E. coli CFUs for AS testing. Significance and Impact of the Study This study provides relevant data about the high phylogenetic and antimicrobial susceptibility diversity observed in Escherichia coli colony-forming units (CFUs) from a bacteriological culture of faeces from healthy calves, foals and lambs. The selection pressure exerted by the herd treatment may directly impact the intestinal microflora of animals that have never been treated. Finally, we emphasize the importance of Clinical Laboratory Standards Institute guidelines and we recommended to analyse at least four E. coli CFUs to determine, in particular, the antimicrobial susceptibility profile of faecal isolates, independent of the animal’s health status.

In the year 2000, the discovery of OPA1 mutations as causative for dominant optic atrophy (DOA) was pivotal to rapidly expand the field of mitochondrial dynamics and describe the complex machinery governing this pathway, with a multitude of other genes and encoded proteins involved in neurodegenerative disorders of the optic nerve. OPA1 turned out to be a much more complex protein than initially envisaged, connecting multiple pathways beyond its strict role in mitochondrial fusion, such as sensing of OXPHOS needs and mitochondrial DNA maintenance. As a consequence, an increasing need to investigate OPA1 functions at multiple levels has imposed the development of multiple tools and models that are here reviewed. Translational mitochondrial medicine, with the ultimate objective of translating basic science necessary to understand pathogenic mechanisms into therapeutic strategies, requires disease modeling at multiple levels: from the simplest, like in yeast, to cell models, including the increasing use of reprogrammed stem cells (iPSCs) from patients, to animal models. In the present review, we thoroughly examine and provide the state of the art of all these approaches.

Hepatozoon spp. is the causative agent of a vector-borne parasitic disease in many animal species. In felids, Hepatozoon felis, Hepatozoon canis and Hepatozoon silvestris have been molecularly isolated. Hepatozoonosis usually causes asymptomatic infections in domestic cats, but clinical cases have recently been reported in Europe. We describe the first Italian case of hepatozoonosis in a cat with an unusual presentation. An 11-year-old neutered European shorthair cat was urgently hospitalized for intestinal intussusception. Hematology, biochemistry, FIV-FeLV tests, blood smears and molecular investigation targeting the 18S rRNA gene of Hepatozoon spp. were performed on blood samples; in addition, histological and molecular investigations were performed to analyze surgical samples to identify Hepatozoon infection. Hepatozoon gamonts were detected in granulocytes in the blood smear, and Hepatozoon spp. DNA was confirmed by PCR on blood. The intussusception was caused by a sessile endoluminal nodule that was surgically removed. Histologically, many elements referring to parasitic tissue forms were identified in the intestinal cells, and then the specimens were molecularly confirmed to harbor H. silvestris. This is the first description of symptomatic hepatozoonosis in a domestic cat in Italy. Hepatozoon silvestris has been described in wild felids, which are usually resilient to the infection, whereas the domestic cat seems to be more susceptible. Indeed, H. silvestris in cats usually presents tropism for skeletal muscle and myocardium with subsequent clinical manifestations. This is the first description of a domestic cat with H. silvestris localized in the intestinal epithelium and associated with intussusception. Graphical abstract

"Flash forward genetics" refers to a genetic approach based on the functional interaction of a given factor with unknown partner(s) converging on shared targets across evolutionary boundaries. A study by Li et al (2021), published in this issue of EMBO Reports, illustrates the innovative potential of the approach. The authors applied it to identify interacting factors for FOXN1, a mammalian transcription factor with a highly specialized function in hair follicle morphogenesis and thymus. The authors express FOXN1 in the Drosophila eye to perform an unbiased genetic screen in a totally heterologous system. In a remarkable tour de force, the authors identify and characterize a factor so far known for its ubiquitous function in transcription elongation, AFF4. Li et al show that AFF4 plays also a specific role in hair follicle and thymus development in the mouse overlapping with that of FOXN1.

Ma et al. uncovers an essential role of AR signaling in melanoma cell expansion and tumorigenesis, with loss of AR activity inducing cellular senescence, genomic DNA breakage, a STING-dependent inflammatory cascade, and immune cell recruitment, providing an attractive venue for new combination approaches to disease management., Melanoma susceptibility differs significantly in male versus female populations. Low levels of androgen receptor (AR) in melanocytes of the two sexes are accompanied by heterogeneous expression at various stages of the disease. Irrespective of expression levels, genetic and pharmacological suppression of AR activity in melanoma cells blunts proliferation and induces senescence, while increased AR expression or activation exert opposite effects. AR down-modulation elicits a shared gene expression signature associated with better patient survival, related to interferon and cytokine signaling and DNA damage/repair. AR loss leads to dsDNA breakage, cytoplasmic leakage, and STING activation, with AR anchoring the DNA repair proteins Ku70/Ku80 to RNA Pol II and preventing RNA Pol II–associated DNA damage. AR down-modulation or pharmacological inhibition suppresses melanomagenesis, with increased intratumoral infiltration of macrophages and, in an immune-competent mouse model, cytotoxic T cells. AR provides an attractive target for improved management of melanoma independent of patient sex., Graphical Abstract

OPA1 mutations are the major cause of dominant optic atrophy (DOA) and the syndromic form DOA plus, pathologies for which there is no established cure. We used a ‘drug repurposing’ approach to identify FDA-approved molecules able to rescue the mitochondrial dysfunctions induced by OPA1 mutations. We screened two different chemical libraries by using two yeast strains carrying the mgm1I322M and the chim3P646L mutations, identifying 26 drugs able to rescue their oxidative growth phenotype. Six of them, able to reduce the mitochondrial DNA instability in yeast, have been then tested in Opa1 deleted mouse embryonic fibroblasts expressing the human OPA1 isoform 1 bearing the R445H and D603H mutations. Some of these molecules were able to ameliorate the energetic functions and/or the mitochondrial network morphology, depending on the type of OPA1 mutation. The final validation has been performed in patients’ fibroblasts, allowing to select the most effective molecules. Our current results are instrumental to rapidly translating the findings of this drug repurposing approach into clinical trial for DOA and other neurodegenerations caused by OPA1 mutations.

International audience; OPA1 is a GTPase that controls several functions, such as mitochondrial dynamics and energetics, mtDNA maintenance and cristae integrity. In the last years, there have been described other cellular pathways and mechanisms involving OPA1 directly or through its interaction. All this new information, by implementing our knowledge on OPA1 is instrumental to elucidating the pathogenic mechanisms of OPA1 mutations. Indeed, these are associated with dominant optic atrophy (DOA), one of the most common inherited optic neuropathies, and with an increasing number of heterogeneous neurodegenerative disorders. In this review, we overview all recent findings on OPA1 protein functions, on its dysfunction and related clinical phenotypes, focusing on the current therapeutic options and future perspectives to treat DOA and the other associated neurological disorders due to OPA1 mutations.

Knowledge on the presence of Cytauxzoon sp. and Hepatozoon spp. in Italy is scant and mostly limited to a few areas of Northern and Southern regions, respectively. The present study updated the current epidemiological scenario by investigating the occurrence of these protozoa in domestic cats from three broad regions of North-Eastern Italy. Blood samples from cats at risk of vector-borne diseases were processed by PCR to detect Cytauxzoon and Hepatozoon DNA. Blood smears were observed for haemoparasite inclusions. The influence of cat individual data (e.g., provenance, management, indoor/outdoor lifestyle) on the prevalence of haemoprotozoan infections was statistically evaluated. Among 158 cats, Cytauxzoon and Hepatozoon DNA were detected in 6 (3.8%) and 26 (16.5%) animals, respectively. No Hepatozoon gamonts were detected in blood smears, whereas all Cytauxzoon PCR-positive samples were microscopically positive, though with low levels of parasitaemia. Two species of Hepatozoon were identified, Hepatozoon felis (n = 10) and Hepatozoon silvestris (n = 16). Hepatozoon silvestris prevalence values were significantly (p &lt, 0.05) higher in the region Friuli Venezia Giulia and in stray cats. Cytauxzoon sp. was detected in 6/39 (15.4%) stray cats from Friuli Venezia Giulia (Trieste province). These data add new information on the occurrence of these neglected protozoa in domestic cats’ populations.

Schizolobium parahyba species can be found in all of South America, producing several residues that can be a major opportunity to develop activated carbon. This work presents the investigation regarding the development of a high specific surface activated carbon (981.55 m2 g−1) and its application in the adsorption of ketoprofen from the aqueous media. The ketoprofen molecules were better adhered to the adsorbent surface under acidic conditions (pH = 2), being the ideal adsorbent dosage determined as 0.7 g L−1, resulting in satisfactory values. It was found that the system reached equilibrium in 200 to 250 min depending on the initial concentration studied, achieving an adsorption capacity of 229 mg g−1. The general order was the most suitable model for describing the experimental data, with an R2 ≥ 0.9985 and MSR ≤ 63.40 (mg g−1)2. The equilibrium adsorption found that the temperature increases the adsorption capacity, achieving 447.35 mg g−1 at 328 K. Besides that, the Toth model was the most suitable for describing the isotherms R2 ≥ 0.9990 and MSR ≤ 25.67 (mg g−1)2, indicating a heterogeneous adsorbent. The thermodynamic values found that the adsorption of ketoprofen is spontaneous (average ΔG0 of − 32.79 kJ mol−1) and endothermic (ΔH0 10.44 kJ mol−1). The treatment of simulated effluent with the developed adsorbent was efficient, removing 90% of ketoprofen, ibuprofen, and salts. It was found that the adsorbent is reaming its adsorption capacity up to the 5th cycle, progressively decreasing the adsorption capacity until the adsorption does not occur past the 12th cycle. Overall, the results demonstrated that the activated carbon from residual biomass of the Schizolobium parahyba species could be an excellent alternative in obtaining an effective adsorbent to treat wastewater-containing drugs.

Dyes are widely used in many industrial sectors, many contain harmful substances to human health, and their release into the environment entails several environmental problems, generating a major worldwide concern as water resources are increasingly limited. The development of cheap and efficient biosorbents that remove these pollutants is of utmost importance. In this study, powdered seeds of the araticum fruit (Annona crassiflora) were used in the biosorption of crystal violet (CV) dye from aqueous solutions and simulated textile effluents. Through the characterization techniques, it can be observed that the material presented an amorphous structure, containing an irregular surface composed mainly by groups containing carbon, hydrogen, and oxygen. CV biosorption was favored at the natural pH of the solution (7.5) for a dosage of 0.7 g L−1 of araticum seed powder. The pseudo-second-order model was the most suitable to represent the biosorption kinetics in the removal of the CV. Biosorption capacity reached equilibrium in the first minutes at the lowest concentrations, and, at the highest, after 120 min. The equilibrium data were well represented by the Langmuir model, with a maximum biosorption capacity of 300.96 mg g−1 at 328 K. Biosorption had a spontaneous and endothermic nature. In the treatment of a simulated effluent, the biosorbent removed 87.8% of the color, proving to be efficient. Therefore, the araticum seeds powder (ASP) can be used as a low-cost material for the treatment of colored effluents containing the crystal violet (CV) dye.

A utilização das telas coloridas visa uma melhor proteção contra a radiação solar. Este trabalho teve como objetivo avaliar a influência de diferentes cores nas telas de sombreamento no desenvolvimento da alface americana. O experimento foi conduzido no município de São João, Paraná. O delineamento experimental foi em blocos casualizados (DBC) com 6 tratamentos e 4 repetições, sendo eles: T1: Testemunha (cultivo a céu aberto), T2: Tela de sombreamento azul, T3: Tela de sombreamento prata, T4: Tela de sombreamento preta, T5: Tela de sombreamento verde e T6: Tela de sombreamento vermelha. O desenvolvimento da alface foi avaliado quanto ao peso da raiz, comprimento da raiz, diâmetro da cabeça, número de folhas, massa fresca e peso da cabeça. A alface sem tela de sombreamento apresentou o melhor desenvolvimento, dentre as telas de sombreamento estudadas a tela vermelha obteve um destaque negativo, sempre com o pior desempenho agronômico.

The adsorption of acid red 97 dye (RED 97) by the waste of the filamentous fungus Beauveria bassiana was analyzed. The adsorbent was obtained as a waste of a fermentative process, and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT–IR), X–ray powder diffractometry (XRD), and specific surface area (BET). After the characterization, adsorption tests were carried out to determine the ideal conditions of pH, adsorbent mass, and contact time for the process. Adsorption isotherms, thermodynamic studies, and the treatment of textile effluent were also investigated. The adsorbent characterization allowed the visualization of its amorphous structure, with irregular and heterogeneous particles. The pore diameter was 51.9 nm and the surface area was 0.247 m2 g−1. 1.2 g L−1 of the adsorbent and pH of 2.0 were the ideal conditions for RED 97 adsorption. The pseudo–second–order kinetic model was the most appropriate to represent the experimental data, being the equilibrium reached in about 110 min. The Langmuir model was the most suitable to represent the equilibrium data, with maximum adsorption capacity of 194.1 mg g−1 at 45 °C. The adsorption processes was thermodynamically spontaneous, favorable, and exothermic. In the treatment of a real textile effluent, 5 g L−1 of the spores was capable to decolorize 70% of the solution. Therefore, spore wastes of Beauveria bassiana were promising for RED 97 adsorption.

Phenylketonuria (PKU) is a metabolic disorder accumulating phenylalanine (Phe) and its metabolites in plasma and tissues of the patients. Regardless of the mechanisms, which Phe causes brain impairment, are poorly understood, energy deficit may have linked to the neurotoxicity in PKU. It is widely recognized that creatine is involved in maintaining of cerebral energy homeostasis. Because of this, in a previous work, we incorporated it into liposomes and this increased the concentration of creatine in the cerebral cortex. Here, we examined the effect of creatine nanoliposomes on parameters of oxidative stress, enzymes of phosphoryl transfer network, and activities of the mitochondrial respiratory chain complexes (RCC) in the cerebral cortex of young rats chemically induced hyperphenylalaninemia (HPA). HPA was induced with L-phenylalanine (5.2 µmol/g body weight; twice a day; s.c.), and phenylalanine hydroxylase inhibitor, α-methylphenylalanine (2.4 µmol/g body weight; once a day; i.p.), from the 7th to the 19th day of life. HPA reduced the activities of pyruvate kinase, creatine kinase, and complex II + III of RCC in the cerebral cortex. Creatine nanoliposomes prevented the inhibition of the activities of the complexes II + III, caused by HPA, and changes oxidative profile in the cerebral cortex. Considering the importance of the mitochondrial respiratory chain for brain energy production, our results suggesting that these nanoparticles protect against neurotoxicity caused by HPA, and can be viable candidates for treating patients HPA.

The powdered biomass of paddle cactus (Tacinga palmadora), a rustic plant of great occurrence in the driest regions of Brazil, was evaluated as a low-cost adsorbent to treat textile effluents conta...

A monolayer model extended to two energy levels (monolayer model 2) has been developed to fit the adsorption isotherms of acid blue 9 on Spirulina platensis (Sp LEB-52). These isotherms were obtain...

In this article, a theoretical study was performed in order to elucidate the adsorption mechanism of methylene blue (MB) on Cortaderia selloana flower spikes (FSs) and on Cortaderia selloana flower spikes derived carbon fibers (CFs). For this objective, the Hill model developed using grand canonical ensemble was successfully applied. This model represents the general case of Langmuir model assuming that the receptor sites of CFs and FSs accepts a variable number of MB molecules and is defined by the number of molecules captured per adsorbent site (n). Based on the model parameters, the MB adsorption geometry was described at different temperatures indicating that the MB molecules were fixed by an angled position on the investigated adsorbents. The elucidation of the adsorption capacity showed that CFs was more effective for removing MB from wastewater than FSs. This behavior was detailed and corroborated by an energetic investigation. Moreover, the adsorption energy varies from 22.187 to 25.378 kJ mol−1 for FSs and from 24.503 to 27.412 kJ mol−1 for the CFs reflecting a physisorption process. Interestingly, and based on this energetic investigation, it was deduced that the adsorption mechanism of MB was endothermic. Excellent correlation between the number of molecules captured by the receptor site, the adsorption capacity, and the adsorption energy was observed.

Glial cells (astrocytes, oligodendrocytes and microglia) are critical for the central nervous system (CNS) in both physiological and pathological conditions. With this in mind, several studies have indicated that glial cells play key roles in the development and progression of CNS diseases. In this sense, gliotoxicity can be referred as the cellular, molecular, and neurochemical changes that can mediate toxic effects or ultimately lead to impairment of the ability of glial cells to protect neurons and/or other glial cells. On the other hand, glioprotection is associated with specific responses of glial cells, by which they can protect themselves as well as neurons, resulting in an overall improvement of the CNS functioning. In addition, gliotoxic events, including metabolic stresses, inflammation, excitotoxicity, and oxidative stress, as well as their related mechanisms, are strongly associated with the pathogenesis of neurological, psychiatric and infectious diseases. However, glioprotective molecules can prevent or improve these glial dysfunctions, representing glial cells-targeting therapies. Therefore, this review will provide a brief summary of types and functions of glial cells and point out cellular and molecular mechanisms associated with gliotoxicity and glioprotection, potential glioprotective molecules and their mechanisms, as well as gliotherapy. In summary, we expect to address the relevance of gliotoxicity and glioprotection in the CNS homeostasis and diseases.

Human populations of Black African ancestry have a relatively high risk of aggressive cancer types, including keratinocyte‐derived squamous cell carcinomas (SCCs). We show that primary keratinocytes (HKCs) from Black African (Black) versus White Caucasian (White) individuals have on average higher oncogenic and self‐renewal potential, which are inversely related to mitochondrial electron transfer chain activity and ATP and ROS production. HSD17B7 is the top‐ranked differentially expressed gene in HKCs and Head/Neck SCCs from individuals of Black African versus Caucasian ancestries, with several ancestry‐specific eQTLs linked to its expression. Mirroring the differences between Black and White HKCs, modulation of the gene, coding for an enzyme involved in sex steroid and cholesterol biosynthesis, determines HKC and SCC cell proliferation and oncogenicity as well as mitochondrial OXPHOS activity. Overall, the findings point to a targetable determinant of cancer susceptibility among different human populations, amenable to prevention and management of the disease., Differences in individuals' cancer susceptibility can be attributed, in part, to specific genetic and epigenetic variations. Human populations of Black African ancestry have a higher risk of aggressive cancer of various types, including keratinocyte‐derived squamous cell carcinomas (SCCs).

The aim of the present study was to investigate whether seeds from six native fruit species ofthe South Brazilian regionhad any type of dormancy, as well as, to verify if they havephotoblastism. The work was carried out at the Plant Physiology Laboratoryofthe Federal Technological University of Paraná –Câmpus Dois Vizinhos, Paraná State, Brazil. The influence of photoperiod factors and techniques for overcoming dormancy were tested on the germination of Eugenia uniflora L.(Surinan cherry), Plinia peruviana(native jabuticaba), Plinia cauliflora(hybrid jabuticaba), Eugenia involucrataDC. (Rio Grande cherry), Myrcianthes pungens(guabiju) and Campomanesia guazumifolia(sete capoteiro). The seeds were exposed in a condition of total darkness or photoperiod of 24 hours, being the levels of one of factors tested. The techniques for breaking dormancy tested werethe immersion in gibberellic acid solution (200 mg L-1); stratification at 5°C for 30 days; immersion in water at room temperature for 24 hours; immersion in hot water (80°C) for five minutes; immersion in sulfuric acid solution (96%) for five minutes; and manual physical scarification with 120 grit sandpaper. The seeds were also tested without using any technique, making up the controlstreatments with or without light. The experimental design was completely randomized, in a 2 x 7 factorial scheme (luminosity x treatment for breaking dormancy), with four replications of 100 seeds. After 60 days, germination (%), percentage of accumulated germination, germination speed index and average germination time were analyzed. The seeds of most of the studied native species do not present dormancy or the effect of photoblastism, except for “sete capoteiro”seedswho are supposed to have morphophysiological dormancy, with negative photoblastism. The use of hot water or sulfuric acid in the seeds of native fruit trees is not recommended.

In this work, a novel and effective hydrochar was prepared by hydrothermal treatment of Prunus serrulata bark to remove the pesticide atrazine in river waters. The hydrothermal treatment has generated hydrochar with a rough surface and small cavities, favoring the atrazine adsorption. The adsorption equilibrium time was not influenced by different atrazine concentrations used, being reached after 240 min. The Elovich adsorption kinetic model presented the best adjustment to the kinetic data. The Langmuir model presented the greatest compliance to the isotherm data and indicated a higher affinity between atrazine and hydrochar, reaching a maximum adsorption capacity of 63.35 mg g-1. Thermodynamic parameters showed that the adsorption process was highly spontaneous, endothermic, and favorable, with a predominance of physical attraction forces. In treating three real river samples containing atrazine, the adsorbent showed high removal efficiency, being above 70 %. The hydrochar from Prunus serrulata bark waste proved highly viable to remove atrazine from river waters due to its high efficiency and low precursor material cost.

Exposure to different organisms (bacteria, mold, virus, protozoan, helminths, among others) can induce epigenetic changes affecting the modulation of immune responses and consequently increasing the susceptibility to inflammatory diseases. Epigenomic regulatory features are highly affected during embryonic development and are responsible for the expression or repression of different genes associated with cell development and targeting/conducting immune responses. The well-known, “window of opportunity” that includes maternal and post-natal environmental exposures, which include maternal infections, microbiota, diet, drugs, and pollutant exposures are of fundamental importance to immune modulation and these events are almost always accompanied by epigenetic changes. Recently, it has been shown that these alterations could be involved in both risk and protection of allergic diseases through mechanisms, such as DNA methylation and histone modifications, which can enhance Th2 responses and maintain memory Th2 cells or decrease Treg cells differentiation. In addition, epigenetic changes may differ according to the microbial agent involved and may even influence different asthma or allergy phenotypes. In this review, we discuss how exposure to different organisms, including bacteria, viruses, and helminths can lead to epigenetic modulations and how this correlates with allergic diseases considering different genetic backgrounds of several ancestral populations.

Human cells produce thousands of lipids that impact a wide range of biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation events and also varies across individual cells of the same type. Yet, the precise differences in lipid composition that directly affect cell phenotypes remain unknown. Here we have measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We found that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in wound repair and in skin cancer growth. Sphingolipid composition defined fibroblast subpopulations while sphingolipid metabolic rewiring drove cell state transitions. These data uncover a role for cell-to-cell lipid heterogeneity in the determination of cell states and reveal a new regulatory component to the homeostasis and self-organization of multicellular systems.

We present a generalized Chao (GC) estimator based on a subject-occasion-specific design matrix. We then extend the GC estimator to (i) external information, in the form of non-linear constraints on subpopulation sizes and (ii) measurement error. For the first, we propose a reparameterization of the estimating equations. As a result, the constrained MLE can be found with no additional computational efforts. For the second we generalize SIMEX procedure to multiple measurement methods. In simulation we show that (even incorrect) external information can substantially decrease the MSE. We illustrate with an application to a whale shark (Rhincodon typus) population, where mostly jouvenile males are observed. We use external information on gender ratio of whale sharks to correct for low catchability of females, and our multivariate SIMEX procedure to correct for measurement error in assessment of shark length. The resulting population size estimates are about 60% larger than the unconstrained–uncorrected counterparts.

Incomplete penetrance characterizes the two most frequent inherited optic neuropathies, Leber's Hereditary Optic Neuropathy (LHON) and dominant optic atrophy (DOA), due to genetic errors in the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA), respectively. For LHON, compelling evidence has accumulated on the complex interplay of mtDNA haplogroups and environmental interacting factors, whereas the nDNA remains essentially non informative. However, a compensatory mechanism of activated mitochondrial biogenesis and increased mtDNA copy number, possibly driven by a permissive nDNA background, is documented in LHON; when successful it maintains unaffected the mutation carriers, but in some individuals it might be hampered by tobacco smoking or other environmental factors, resulting in disease onset. In females, mitochondrial biogenesis is promoted and maintained within the compensatory range by estrogens, partially explaining the gender bias in LHON. Concerning DOA, none of the above mechanisms has been fully explored, thus mtDNA haplogroups, environmental factors such as tobacco and alcohol, and further nDNA variants may all participate as protective factors or, on the contrary, favor disease expression and severity. Next generation sequencing, complemented by transcriptomics and proteomics, may provide some answers in the next future, even if the multifactorial model that seems to apply to incomplete penetrance in mitochondrial optic neuropathies remains problematic, and careful stratification of patients will play a key role for data interpretation. The deep understanding of which factors impinge on incomplete penetrance may shed light on the pathogenic mechanisms leading to optic nerve atrophy, on their possible compensation and, thus, on development of therapeutic strategies.

The ability of microalgae to sequester carbon and at the same time synthesise valuable compounds with potential applications in nutraceutical, pharmaceutical and cosmetic industries makes them attractive for commercial deployment, especially in view of a blue bioeconomy. Among microalgae, the diatom Phaeodactylum tricornutum is considered as an important potential source of omega-3 polyunsaturated fatty acids, such as eicosapentanoic acid, an essential polyunsaturated fatty acid with anti-inflammatory and antimicrobial properties. The aim of this study was to perform the Life Cycle Assessment of the cultivation of P. tricornutum - at semi-industrial scale in photobioreactor - for the production of high-quality bioactive compounds comparing synthetic carbon dioxide supply to a supply with waste carbon dioxide from a biogas upgrading process hypothesizing industrial symbiosis network. The effect of renewable energy use instead of the European electricity mix was also examined. Primary data on the production process, including the stages of cleaning and sterilisation, cultivation, harvesting and freeze-drying, were used. The midpoint impact categories recommended in the ILCD Handbook were used for performing the impact assessment. A sensitivity analysis was also performed on algal productivity, culture medium recirculation factor and amount of solvents per cleaning cycle. Firstly, results indicate in general cultivation and freeze-drying as the most contributing stages to the impacts. Secondly, they demonstrate in the comparative assessment that the use of carbon dioxide from the biogas upgrading is a feasible and attractive alternative to the synthetic one, as it allows for the improvement of the environmental performance of the production process in all the analysed impact categories. Finally, sensitivity analysis suggests that the environmental performance could be further improved by acting on other key factors, such as electricity source, nutrients culture medium and cleaning solutions.

ADCA-DN and HSN-IE are rare neurodegenerative syndromes caused by dominant mutations in the replication foci targeting sequence (RFTS) of the DNA methyltransferase 1 (DNMT1) gene. Both phenotypes resemble mitochondrial disorders, and mitochondrial dysfunction was first observed in ADCA-DN. To explore mitochondrial involvement, we studied the effects of DNMT1 mutations in fibroblasts from four ADCA-DN and two HSN-IE patients. We documented impaired activity of purified DNMT1 mutant proteins, which in fibroblasts results in increased DNMT1 amount. We demonstrated that DNMT1 is not localized within mitochondria, but it is associated with the mitochondrial outer membrane. Concordantly, mitochondrial DNA failed to show meaningful CpG methylation. Strikingly, we found activated mitobiogenesis and OXPHOS with significant increase of H2O2, sharply contrasting with a reduced ATP content. Metabolomics profiling of mutant cells highlighted purine, arginine/urea cycle and glutamate metabolisms as the most consistently altered pathways, similar to primary mitochondrial diseases. The most severe mutations showed activation of energy shortage AMPK-dependent sensing, leading to mTORC1 inhibition. We propose that DNMT1 RFTS mutations deregulate metabolism lowering ATP levels, as a result of increased purine catabolism and urea cycle pathways. This is associated with a paradoxical mitochondrial hyper-function and increased oxidative stress, possibly resulting in neurodegeneration in non-dividing cells.

Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology.

Changes of quantity and/or morphology of cell mitochondria are often associated with metabolic modulation, pathology, and apoptosis. Exogenous fluorescent probes used to investigate changes in mitochondrial content and dynamics are strongly dependent, for their internalization, on the mitochondrial membrane potential and composition, thus limiting the reliability of measurements. To overcome this limitation, genetically encoded recombinant fluorescent proteins, targeted to different cellular districts, were used as reporters. Here, we explored the potential use of mitochondrially targeted red fluorescent probe (mtRFP) to quantify, by flow cytometry, mitochondrial mass changes in cells exposed to different experimental conditions. We first demonstrated that the mtRFP fluorescence intensity is stable during cell culture and it is related with the citrate synthase activity, an established marker of the mitochondrial mass. Incidentally, the expression of mtRFP inside mitochondria did not alter the oxygen consumption rate under both state 3 and 4 respiration conditions. In addition, using this method, we showed for the first time that different inducers of mitochondrial mass change, such as hypoxia exposure or resveratrol treatment of cells, could be consistently detected. We suggest that transfection and selection of stable clones expressing mtRFP is a reliable method to monitor mitochondrial mass changes, particularly when pathophysiological or experimental conditions change &Delta, &Psi, m, as it occurs during mitochondrial uncoupling or hypoxia/anoxia conditions.

4 Pags.- 1 Fig. Esta obra está licenciada com uma Licença Creative Commons Atribuição-NãoComercial-CompartilhaIgual 4.0 Internacional., [EN] Pitangueira (E. uniflora) is considered a diploid species with n = 11 and 2n = 22 chromosomes, in genotypes with the presence of seeds in the fruits. With the pitangueira production of apyrenic fruits existence, such behavior may be related to the ploidy level. The objective of this study was to determine the ploidy level of the pitangueira accessions producing fruit with and without seed, as well as to observe the meiotic behavior and possible chromosomal abnormalities. To check the ploidy level of the pitangueira, freshly expanded mature leaves were collected from the pyrenic pitangueira and from two pyrenic accessions, with suspensions of intact nuclei being prepared. Samples were analyzed in a flow cytometer equipped with multiple parameters data acquisition and UV laser. All analyses were performed using peak-height detection (>6000 fluorescent events, for example, nuclei, were analyzed per sample) and logarithmic amplification. The data were presented as histograms of the number of nuclei along the y-axis and the relative fluorescence intensity on the x-axis. The pyrenean pitangueira and other two pyrenic accessions were characterized as diploid., [PO] A pitangueira (E. uniflora) é considerada espécie diplóide com n=11 e 2n=22 cromossomos, em genótipos com presença de sementes nos frutos. Com a existência de pitangueira produtora de frutos apirênicos, tal comportamento pode estar relacionado ao nível de ploidia. O objetivo deste estudo foi determinar o nível de ploidia dos acessos de pitangueira produtora de frutos sem e com semente, bem como, observar o comportamento meiótico e possíveis anormalidades cromossômicas. Para verificar o nível de ploidia da pitangueira, folhas maduras recém-expandidas foram coletadas da pitangueira apirênica e de dois acessos pirênicos, sendo preparados suspensões de núcleos intactos. As amostras foram analisadas em citômetro de fluxo equipado com aquisição de dados de múltiplos parâmetros e de laser UV. Todas as análises foram realizadas utilizando detecção de pico-altura (>6000 eventos fluorescentes, por exemplo, núcleos, foram analisados por amostra) e amplificação logarítmica. Os dados foram apresentados como histogramas do número de núcleos ao longo do eixo-y e a intensidade da fluorescência relativa no eixo-x. A pitangueira apirênica e outros dois acessos pirênicos, foram caracterizadas como diplóides.

In this work, endocarp of the species Butia capitata was employed as precursor material to prepare a novel activated carbon with intrinsic properties to remove ketoprofen and paracetamol from water efficiently. The activated carbon presented a predominantly microporous structure, with an average pore diameter of 1.23 nm, a total pore volume of 0.449 cm3 g−1, and a high specific surface area, 820 m2 g−1. The adsorption kinetics showed a rapid initial decay for both pharmaceuticals, with the system entering equilibrium after 120 min for ketoprofen and 180 min for paracetamol. The pseudo-second-order model presented the best fit for ketoprofen and the Elovich model for paracetamol. The adsorption equilibrium data show that temperature can increase or decrease the adsorption capacity, being found a maximum adsorption capacity of 108.79 and 100.60 mg g−1 for the ketoprofen and paracetamol, respectively. The Freundlich and Langmuir models presented the best statistical adjustments for the adsorption of ketoprofen and paracetamol, respectively. The thermodynamic analysis confirmed an endothermic process for ketoprofen (ΔH0 = 11.98 kJ mol−1) and exothermic for paracetamol (ΔH0 = -13.37 kJ mol−1). The recycle tests revealed that the adsorbent has an average decrease for removal percentage of only 1.88 % for ketoprofen and 1.57 % for paracetamol. Estimations costs indicate that the price of 1 kg of activated carbon costs is 2.39 USD at minimum. Last, the material presented a highly efficient adsorptive activity to treat a synthetic mixture containing several pharmaceutical compounds and salts, reaching 84.82% removal.

In this work, a high porous activated carbon from Jacaranda mimosifolia was developed and employed for ketoprofen adsorption. After the pyrolysis process at 973.15 K, the material presented cavities with different sizes allocated on the particle surface. The material presented a pH at the point of zero charge of 4.1 with the best adsorption at pH 2. The best adsorbent dosage was 0.72 g L−1, corresponding to a removal of 96%. The system reached the adsorption equilibrium after 120 min and was described by the linear driving force model. The isotherms revealed that the adsorption capacity decreased with the temperature and followed the Langmuir model, with a maximum adsorption capacity of 303.9 mg g−1. This high capacity can be associated with the high surface area (928 m2 g−1) and pore volume (0.521 cm3 g−1) values. The thermodynamic values indicated that the adsorption system is spontaneous and exothermic. The enthalpy value indicates that the interactions between the adsorbent and adsorbate are physical. Regeneration tests showed a decreasing percentage of removal of 7.86% after 5 cycles. Finally, the adsorbent showed efficiency when treating a simulated effluent containing drugs and inorganic salts, showing the removal of 71.43%.

IntroductionAsteroid (65803) Didymos is an S-type [1] Apollo binary system characterized by a 780±30 m size primary, called Didymos, and a 164±18 m size secondary, called Dimorphos, orbiting at a distance of ~1.19 km [2]. The primary rotation period is 2.26 h [2], close to the 2.2 h disruption spin barrier [3], while the period of revolution of Dimorphos around the primary is 11.9217+0.0002 h [4]. This asteroid has been selected as the target of the Double Asteroid Redirection Test (DART, [5]), whose main goal is to impact Dimorphos at a speed of 6.6 km/s on September 30, 2022, thereby demonstrating the kinetic impactor technique and evaluating the resulting impulsive deflection.The scientific camera onboard DART is called DRACO, i.e. the Didymos Reconnaissance and Asteroid Camera for Op-nav [6]: its main goals are to image Didymos for optical navigation, to resolve the two bodies and support the spacecraft autonomous navigation to the target, and to locate the impact site precisely and characterize its local surface features. To complement such observations, the Light Italian Cubesat for Imaging of Asteroids (LICIACube, [7]) will be released from DART ten days before the impact, and autonomously guided through a flyby with closest approach distance of ~55 km from the target. LICIACube cameras LEIA (LICIACube Explorer Imaging for Asteroid - narrow angle camera) and LUKE (LICIACube Unit Key Explorer – wide angle camera) will then safely witness the redirection test in-situ, while its crater, as well as the ejecta and plume are being formed.Boulders SFD on Didymos systemBoulders/large blocks on asteroids are mainly interpreted as produced by target fragmentation and excavation due to high-velocity impact processes. They are the largest fragments excavated during an impact and are typically found within the crater or in its proximity, because they have not reached the escape velocity [8]. Instead, on rubble-pile asteroids boulders (typically the largest ones) are products of the reaccumulation process that formed the minor body itself, and may not be correlated to the observed craters [9]. For both cases, these blocks provide information on impact cratering processes occurring on low gravity bodies or on their parent body disruption event: their size-frequency distribution (SFD) fitting indices are therefore pivotal to provide hints on the fragment/boulder formation and/or degradation processes.Deriving boulder SFD and the corresponding power/exponential-law indices has been an important scientific topic addressed in several fly-by and orbital missions to minor bodies [e.g. 10-12]: it will be accomplished on the Didymos system as well.Four minutes before the impact the last image that contains all of Didymos will be taken by DRACO, with an expected spatial scale of 7 m/pixel. 120 seconds before impact, the last DRACO image containing any part of Dydimos will be taken, with a maximum resolution of 3.5 m [13]. DRACO will image all of Dimorphos ~50 cm/pixel ~17 seconds before impact and plans to return at least one higher-resolution image before impact. These final image(s) will have pixel scales At closest approach (CA), LICIACube/LEIA will image the surface of Dimorphos at 1.4 m/px [7]. If the DART crater will be observed through LEIA (it may be close to the limb during CA, hence the challenging imaging condition), we will be able to identify all boulders larger than 4.0-7.0 m located on the impacted side of Dimorphos, discerning those that have been generated/fragmented/moved after the DART impact from the ones previously imaged through DRACO. In addition, LEIA will image the non-impacted side of Dimorphos (not observed by DRACO) with resolutions ranging from 1.5 to 5 m: this will enable the characterization of the boulders SFD of the secondary down to 4.5 m.By comparing both the pre-, post- and non-impacted surface areas we will have the unique opportunity to witness how the boulders SFDs and densities/m2 will change as a result of a well characterized, hypervelocity impact. We will therefore test if the generation of a crater results in a different power-law distribution of boulders than the one observed on other S-type asteroids, such as (433) Eros and (25143) Itokawa [8,9], as well as recently observed carbonaceous asteroids, (101955) Bennu [12] and (162173) Ryugu [15].Acknowledgments: This research was supported by the Italian Space Agency (ASI) within the LICIACube project (ASI-INAF agreement AC n. 2019-31-HH.0).References: [1] de León, J. et al. (2010) Astron. Astrophys, 517, A23. [2] Naidu, S.P. et al. (2020) Icarus, 348, 113777. [3] Pravec P. and Harris A.W. (2000) Icarus, 148, 12-20. [4] Pravec, P. et al. (2006) Icarus, 181, 63. [5] Cheng A. F. et al. (2016) Planet. Space Sci., 121, 27-35. [6] Fletcher, Z.J. et al. (2016) 3rd Inst. Planetary Missions, 4043. [7] Dotto, E. et al., (submitted), Planet. Space Sci. [8] Thomas, P.C., et al. (2001) Nature 413, 394. [9] Michikami, T. et al. (2008), Earth Planets Space, 60, 13-20. [10] Lee, S.W., et al. (1986) Icarus 68, 77. [10] Geissler, P., et al. (1996) Icarus 120, 140. [11] Pajola, M. et al. (2015), Astron. Astrophys. 583, A37. [12] DellaGiustina, D. et al. (2019), Nat.Astron. 3, 341-351. [13] Cheng, A. F. et al. (2018) Planet. Space Sci., 157, 104-115. [14] Barnouin, O. et al. (2019). LPSC 50 abst. 2448. [15] Watanabe, S. et al. (2019), Science, 364, 6437, 268-272.

This scoping review study aimed to map the evidence about solvents' use for gutta-percha dissolution and removal during endodontic retreatments. The study protocol followed the Joanna Briggs Institute guidelines, available online (https://osf.io/5vy8n/). Reporting was based on PRISMA Extension for Scoping Reviews. We selected dentistry studies that considered the effectiveness of solvents in gutta-percha dissolution in endodontic retreatments and compared their performance to the use of instrumentation techniques without solvents. The search and study screening were performed in PubMed and Scopus databases by two independent researchers. A descriptive analysis considered the study design, method/technique used for obturation, method/technique used for instrumentation during retreatment, solvent solutions tested, exposure time, and main findings. A total of 41 studies were included. Despite that, most studies suggested that solvents' use may complicate root canal cleanliness, regardless of the type of instrumentation used, and facilitate the presence of gutta-percha remnants in the root surface. Thus, the use of solvents should be avoided and its use should only be considered if the previous working length was not possible to access without it. Despite that, high heterogeneity was observed, further studies are still encouraged comparing the performance and effects of different solvents in different clinical scenarios.

This study investigates, for the first time, the applicability of seed pods from Capparis flexuosa as an alternative biosorbent to remove methylene blue and bright blue from aqueous medium using continuous and batch systems. The biosorbent was characterized by different techniques, whose particles presented rough surface and large pores and functional groups existing on its surface. In the batch system, an adsorptive capacity of 96.40 mg g-1 and 80% of methylene blue removal was reached with 0.9 g L-1 of adsorbent at pH 10, whereas 109.7 mg g-1 and 83% of bright blue removal was observed using 0.8 g L-1 of adsorbent at pH 2.0. The Elovich model adjusted the experimental data satisfactorily for both dyes. Toth model for the MB best described the equilibrium data, and the Langmuir model for the bright blue both favored by the increase of temperature and dyes' concentration. The maximum capacities obtained were 280.78 mg g-1 and 342.85 mg g-1 for methylene blue and bright blue, respectively. The thermodynamic parameters indicated spontaneous processes, with endothermic behavior for both dyes. The fixed adsorption experiments using Capparis flexuosa seed pods showed adsorptive capacities of 158.65 and 205.81 mg g-1 for the methylene blue and bright blue, respectively. The overall results indicated that the pods of the Capparis flexuosa could be an ecological, effective, and economical alternative in the removal of dyes for both continuous and batch systems.