Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods

The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.H2020 -“la Caixa” Foundation(101003187

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Explorar novos secretomes para aplicações em medicina regenerativa para a doença de Parkinson

Dissertação de mestrado em Ciências da SaúdeParkinson’s Disease (PD) is a progressive neurodegenerative disease that is primarily characterized by the loss of dopaminergic neurons (DAn), mostly in the nigrostriatal pathway, leading to dopamine (DA) deficiency, thereby causing the appearance of the characteristic PD motor and non-motor symptoms. Current state of the art in the field is based on the use of pharmacotherapies. However, these just mitigate motor symptomatology instead of stoping/delaying the progression of the disease, whereby imposing an urgent need for innovative therapeutical approaches. Human Mesenchymal Stem Cells (hMSCs) secretome has been presented as a promising therapeutic option, given their ability to modulate DAn cell survival/differentiation. Apart from a direct effect in neuronal survival, recent studies showed the possibility of an interplay between hMSCs (secretome), glial cells and DAn. Indeed, glial cells have been regarded as potential targets and modulators of PD. Therefore, in the present thesis we aim to 1) determine the role of glial cells secretome and glial cells (preconditioned) with hMSCs secretome as modulators of in vitro neuronal survival and differentiation, and 2) investigate the effects of glial and hMSCs secretomes in a 6-hydroxydopamine (6-OHDA) rat model of PD. Our in vitro data revealed that hMSCs and glial cells secretome per se and glial cells (preconditioned with hMSCs secretome) secretome induced higher rates of neuronal differentiation. Curiously, in vivo, distinct effects between hMSCs and glial cells secretomes were observed. While hMSCs secretome induced a positive impact in the amelioration of PD motor symptoms (assessed by the rotarod and staircase tests), glial cells secretome had a more pronounced effect in ameliorating PD non-motor symptomatology, namely anxious and depressive-like behaviors. Overall, one can conclude that the use of different secretomes can differentially targets PD motor and non motor behavioral dimensions, thereby opening new avenues for the treatment of PDA Doença de Parkinson (DP) é uma doença neurodegenerativa progressiva caracterizada pela perda de neurónios dopaminérgicos (DAn), principalmente na via nigroestriatal, levando à deficiência de dopamina (DA), que causando perda motora e sintomas não motores. O tratamento padrão é baseado na farmacoterapia. No entanto, este apenas mitiga a sintomatologia motora em vez de parar/retardar a progressão da doença, o que leva a uma necessidade urgente de criar terapias inovadoras. O secretoma de células estaminais mesenquimatosas (MSCs) tem sido apresentado como uma opção terapêutica promissora, dada a sua capacidade em modular a sobrevivência/diferenciação dos DAn. Além de um efeito direto na sobrevivência neuronal, estudos recentes têm igualmente demonstrado uma possível interação entre as hMSCs (secretoma), as células gliais e os DAn. Na verdade, as células gliais, são hoje, consideradas potenciais alvos terapêuticos para o tratamento da DP. Assim, a presente tese teve como principais objetivos: 1) determinar o efeito do secretoma de células da glia (por si só, e precondicionadas com secretoma de MSCs) e MSCs como um modulador da sobrevivência e diferenciação neuronal in vitro, e 2) investigar os efeitos destes secretomas num modelo animal de degeneração dopaminérgica induzido pela injeção da neurotoxina 6-hidroxidopamina (6-OHDA). In vitro, verificou que o secretoma de MSCs e glias (por si só ou precondicionadas com secretoma de MSCs) induziram altas taxas de diferenciação neuronal. Curiosamente, in vivo, foram observados efeitos distintos entre o secretoma de hMSCs e o secretoma de células gliais. Enquanto que o secretoma de MSCsinduziu um efeito positivo na melhoria do desempenho motor (avaliada pelo rotarod e straircase), o secretoma das células gliais, apresentou, por seu lado, um impacto mais pronunciado na melhoria dos sintomas não-motores da doença, nomeadamente ansiedade e depressão. Em suma, podemos concluir que o uso de diferentes secretomas têm impactos distintos nos sintomas motores e não motores da DP, abrindo assim novas perspetivas para o seu tratamento.The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), Minho University. Financial support was provided from project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and funded by FEDER funds through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038

Fractionating stem cells secretome for Parkinson's disease modeling: Is it the whole better than the sum of its parts?

Human mesenchymal stem cells (hMSCs) secretome has been have been at the forefront of a new wave of possible therapeutic strategies for central nervous system neurodegenerative disorders, as Parkinson's disease (PD). While within its protein fraction, several promising proteins were already identified with therapeutic properties on PD, the potential of hMSCs-secretome vesicular fraction remains to be elucidated. Such highlighting is important, since hMSCs secretome-derived vesicles can act as biological nanoparticles with beneficial effects in different pathological contexts. Therefore, in this work, we have isolated hMSCs secretome vesicular fraction, and assessed their impact on neuronal survival, and differentiation on human neural progenitors' cells (hNPCs), and in a 6-hydroxydopamine (6-OHDA) rat model of PD when compared to hMSCs secretome (as a whole) and its protein derived fraction. From the results, we have found hMSCs vesicular fraction as polydispersity source of vesicles, which when applied in vitro was able to induce hNPCs differentiation at the same levels as the whole secretome, while the protein separated fraction was not able to induce such effect. In the context of PD, although distinct effects were observed, hMSCs secretome and its derived fractions displayed a positive impact on animals' motor and histological performance, thereby indicating that hMSCs secretome and its different fractions may impact different mechanisms and pathways. Overall, we concluded that the use of the secretome collected from hMSCs and its different fractions might be active modulators of different neuroregeneration mechanisms, which could open new therapeutical opportunities for their future use as a treatment for PD.Prémios Santa Casa Neurociências Prize Mantero Belard for Neurodegenerative Diseases Research (MB-28-2019). This work was supported by the European Regional Development Fund (FEDER), through the Competitiveness Internationalization Operational Programme (POCI), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of projects UIDB/50026/2020; UIDP/50026/2020 and POCI-01-0145-FEDER-029751. This article has also been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI–POCI-01-0145-FEDER-022122)info:eu-repo/semantics/publishedVersio

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved