Design, synthesis, and biological evaluation of new thalidomide–donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation

A new series of eight multifunctional thalidomide–donepezil hybrids were synthesized based on the multi target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the N-benzylpiperidine pharmacophore of donepezil and the isoindoline 1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC50 value of 3.15 μM, which was predicted by docking studies as interacting with the enzyme in the same orientation observed in the AChE–donepezil complex and a similar profile of interaction. Additionally, compound 3g significantly decreased iNOS and IL-1β levels by 43% and 39%, respectively, after 24 h of incubation with lipopolysaccharide. In vivo data confirmed the ability of 3g to prevent locomotor impairment and changes in feeding behavior elicited by lipopolysaccharide. Moreover, the PAMPA assay evidenced adequate blood–brain barrier and gastrointestinal tract permeabilities with an Fa value of 69.8%. Altogether, these biological data suggest that compound 3g can treat the inflammatory process and oxidative stress resulting from the overexpression of iNOS and therefore the increase in reactive nitrogen species, and regulate the release of pro-inflammatory cytokines such as IL-1β. In this regard, compound PQM-189 (3g) was revealed to be a promising neuroprotective and anti-neuroinflammatory agent with an innovative thalidomide–donepezil-based hybrid molecular architectur

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests

The seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positively to precipitation when rainfall is  < 2000 mm yr⁻¹ (water-limited forests) and to radiation otherwise (light-limited forests). On the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest productivity in a drier climate in water-limited forest, and in current light-limited forest with future rainfall  < 2000 mm yr⁻¹

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Neurofibroma subungueal solitário: relato de um caso inédito no sexo masculino Solitary subungual neurofibroma: a previously unreported finding in a male patient

Neurofibroma é uma proliferação hamartomatosa de origem neuromesenquimal. Pode ser encontrado associado à neurofibromatose ou como tumor solitário, sendo sua apresentação subungueal solitária bastante rara. É mais frequente em pacientes do sexo feminino e a cirurgia é o tratamento de escolha. Relatase um caso de um paciente masculino, com lesão tumoral subungueal no pododáctilo, cuja biópsia e imuno-histoquímica foram compatíveis com neurofibroma. Até a presente data, menos de dez casos sobre neurofibromas subungueais sem associação com doença de Von Recklinhausen foram documentados, sendo este o primeiro caso relatado no Brasil e o único no sexo masculino no mundo<br>A neurofibroma is a hamartomatous proliferation of neuromesenchymal origin. It may be found in combination with neurofibromatosis or in the form of a solitary tumor. Clinical presentation as a solitary subungual tumor is very rare. Neurofibroma is more common in females and surgery is the treatment of choice. The present paper reports the case of a male patient with a subungual tumor on his toe. Biopsy and immunohistochemistry findings were compatible with a neurofibroma. To date, fewer than ten cases of subungual neurofibromas unassociated with von Recklinghausen's disease have been documented, this being the first case to be reported in Brazil and the only report worldwide to have described this condition in a male patien

Desenvolvimento de prematuros com baixo peso ao nascer nos primeiros dois anos de vida Development of low birth weight preterm infants during the first two years of life

OBJETIVO: Analisar e descrever o desenvolvimento neuropsicomotor de prematuros com baixo peso ao nascer nos dois primeiros anos de vida. MÉTODOS: Estudo transversal realizado com prematuros entre quatro e 24 meses, no Ambulatório de Alto Risco Neonatal do Hospital Universitário da Universidade Federal de Santa Catarina, avaliados em três momentos: 8, 11 e 14 meses de idade cronológica. A amostra, composta inicialmente por 69 indivíduos, teve caráter intencional, segundo os critérios de inclusão e exclusão estabelecidos. A Escala de Brunet e Lèzine foi usada para avaliar o desenvolvimento nas seguintes áreas: coordenação óculo-motriz, linguagem, postura e sociabilidade. Os dados foram analisados por meio de estatística descritiva e inferencial. RESULTADOS: A idade gestacional média foi de 31 semanas e o peso ao nascer foi de 1236g. O quociente de desenvolvimento global apresentou melhora da primeira para a última avaliação, alcançando 85% de escores dentro da normalidade na terceira avaliação. As áreas específicas da coordenação óculo-motriz e da linguagem tiveram os piores resultados iniciais, contrapondo-se à postural, que apresentou os melhores escores. Foi encontrada correlação entre o peso ao nascer e as áreas da postura, linguagem e sociabilidade na primeira avaliação e sociabilidade e coordenação óculo-motriz na terceira avaliação. CONCLUSÕES: O desenvolvimento neuropsicomotor desta população apresentou déficits mais evidentes nos primeiros meses de vida. Embora o seguimento não tenha mostrado diferenças estatísticas entre a primeira e a última avaliação, houve melhora em todas as áreas do desenvolvimento.<br>OBJECTIVE: To analyze and describe the neuropsychomotor development of low birth weight preterm infants in the first two years of life. METHODS: This cross-sectional study enrolled preterm infants between 4 and 24 months old at the follow up clinic of Universidade Federal de Santa Catarina, Florianópolis, Brazil. The children were assessed in three moments: 8, 11 and 14 months (chronological age). The sample, initially composed by 69 individuals, was chosen intentionally according to the inclusion and exclusion criteria. The Brunet and Lèzine's Scale was used to evaluate development in the following areas: hand-eye coordination, language, posture and sociability. Data were analyzed using descriptive and inferential statistics. RESULTS: The average gestational age was 31 weeks and the birth weight, 1236g. The global development quotient improved from the first to the last assessment, reaching 85% of scores within the normal range in the third assessment. The specific areas of hand-eye coordination and language had the worst initial results, while posture had the best scores. Correlation was found between birth weight and posture, language and social areas at the first assessment and between birth weight and social and hand-eye coordination at the third assessment. CONCLUSION: Deficits of neuromotor development of the studied population were more evident in the first months of life. Although the follow-up did not show statistic differences between the first and last assessment, there was an improvement in all areas of development