Search

Infections with certain types of papillomavirus, such as the human papillomavirus 16 (HPV16), are associated with the development of preneoplastic lesions and cancers of the anogenital, and head and neck regions. Cytinus hypocistis (L.) L. extracts are composed of substances presenting antiproliferative, antioxidant, anti-inflammatory and antibacterial properties, which might be promising as new therapeutic compounds. This study analysed the influence of topical application of an extract obtained from C. hypocistis (CH) on K14-HPV16 and FVB/n mice to evaluate its therapeutic and toxicological properties. To achieve the study goals, 30 female mice, 33–37 weeks old, were divided into six groups (n=5/group): I (HPV+CH3.1); II (HPV+CH6.2); III (HPV+CH12.4); IV (FVB/n+CH12.4); V (HPV+control) and VI (FVB/n+-control). CH was applied topically to both ears for 28 days. After this period, all animals were sacrificed for samples collection. Skin lesions were classified histologically. Toxicological parameters included haematological and biochemical blood markers, and hepatic oxidative stress analysis. Transgenic animals showed a decrease in mean body weight regardless of the concentration of extract applied. The extract had no influence on physiological parameters, organ weight, or biochemical and oxidative stress parameters. Histology demonstrated the presence of proliferative epithelial lesions in the skin and oral mucosa of K14-HPV16 mice, with no association with the application of this extract. Overall, the application of CH extract had no influence on the skin lesions and was well tolerated by the animals in these concentrations., Infekcije određenim vrstama papiloma virusa, poput humanog papiloma virusa 16 (HPV16), povezane su s razvojem preneoplastičnih lezija i karcinoma anogenitalnog područja i područja glave i vrata. Ekstrakti Cytinus hypocistis (CH) sadrže tvari koje pokazuju antiproliferativna, antioksidativna, protuupalna i antibakterijska svojstva te bi stoga mogle predstavljati nove, obećavajuće terapijske spojeve. Cilj je ovog rada bio analizirati utjecaj topikalne primjene ekstrakta dobivenog iz C. hypocistis (L.) L. na K14-HPV16 i FVB/n miševima za procjenu njegovih terapijskih i toksikoloških svojstava. Za postizanje ciljeva istraživanja, trideset ženki miševa starosti 33-37 tjedana podijeljeno je u šest skupina (n=5/ skupini): I (HPV+CH3,1); II (HPV+CH6,2); III (HPV+CH12,4); IV (FVB/n+CH12,4); V (HPV+kontrola) i VI (FVB/n+kontrola). CH je tijekom 28 dana topikalno primijenjen na oba uha. Nakon tog razdoblja sve životinje su žrtvovane u svrhu prikupljanja rezulata. Lezije kože su histološki klasificirane. Toksikološki parametri uključivali su hematološke i biokemijske markere krvi te analizu oksidativnog stresa jetre. Transgenične životinje pokazale su smanjenje srednje tjelesne mase, bez obzira na primijenjenu koncentraciju ekstrakta. Ekstrakt nije utjecao na fiziološke parametre, masu organa ili parametre biokemijskog i oksidativnog stresa. Histološki je dokazana prisutnost proliferativnih epitelnih lezija na koži i oralnoj sluznici K14-HPV16 miševa, bez povezanosti s primjenom ovog ekstrakta. Općenito, primjena CH ekstrakta nije utjecala na lezije kože te su ga životinje dobro podnosile u primijenjenim koncentracijama.

Funding: This study was financially supported by the Virology Laboratory from the Pathology Department of the Portuguese Oncology Institute of Lisboa IUIC/1168, with contributions by the Research Center of the Portuguese Oncology Institute of Porto (project no. PI86-CI-IPOP-66-2017), by Base Funding-UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology, and Energy—LEPABE—funded by national funds through the FCT/MCTES (PIDDAC), and Project 2SMART-engineered Smart materials for Smart citizens, with reference NORTE-01- 0145-FEDER-000054, supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). PIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status and patient survival. A meta-analysis of scientific literature also revealed widely different mutation rates in cohorts from different world regions and a trend towards improved prognosis among patients with PIK3CA mutations. DNA samples were available from 95 patients diagnosed with HNSCC at the Portuguese Institute of Oncology in Lisbon between 2010 and 2019. HPV status was established based on viral DNA detected using real-time PCR. The evaluation of PIK3CA gene mutations was performed by real-time PCR for four mutations (H1047L; E542K, E545K, and E545D). Thirty-seven cases were found to harbour PIK3CA mutations (39%), with the E545D mutation (73%) more frequently detected. There were no significant associations between the mutational status and HPV status (74% WT and 68% MUT were HPV (+); p = 0.489) or overall survival (OS) (3-year OS: WT 54% and MUT 65%; p = 0.090). HPV status was the only factor significantly associated with both OS and disease-free survival (DFS), with HPV (+) patients having consistently better outcomes (3-year OS: HPV (+) 65% and HPV (-) 36%; p = 0.007; DFS HPV (+) 83% and HPV (-) 43%; p = 0.001). There was a statistically significant interaction effect between HPV status and PIK3CA mutation regarding DFS (Interaction test: p = 0.026). In HPV (+) patients, PIK3CA wild-type is associated with a significant 4.64 times increase in the hazard of recurrence or death (HR = 4.64; 95% CI 1.02-20.99; p = 0.047). Overall, PIK3CA gene mutations are present in a large number of patients and may help define patient subsets who can benefit from therapies targeting the PI3K pathway. The systematic assessment of PIK3CA gene mutations in HNSCC patients will require further methodological standardisation. publishersversion published

The execution and learning of diverse movements involve neuronal networks distributed throughout the nervous system. The brainstem and basal ganglia are key for processing motor information. Both harbour functionally specialized populations stratified on the basis of axonal projections, synaptic inputs and gene expression, revealing a correspondence between circuit anatomy and function at a high level of granularity. Neuronal populations within both structures form multistep processing chains dedicated to the execution of specific movements; however, the connectivity and communication between these two structures is only just beginning to be revealed. The brainstem and basal ganglia are also embedded into wider networks and into systems-level loops. Important networking components include broadcasting neurons in the cortex, cerebellar output neurons and midbrain dopaminergic neurons. Action-specific circuits can be enhanced, vetoed, work in synergy or competition with others, or undergo plasticity to allow adaptive behaviour. We propose that this highly specific organization of circuits in the motor system is a core ingredient for supporting behavioural specificity, and at the same time for providing an adequate substrate for behavioural flexibility.

Gait and balance abnormalities develop commonly in Parkinson's disease and are among the motor symptoms most disabling and refractory to dopaminergic or other treatments, including deep brain stimulation. Efforts to develop effective therapies are challenged by limited understanding of these complex disorders. There is a major need for novel and appropriately targeted research to expedite progress in this area. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society has charged a panel of experts in the field to consider the current knowledge gaps and determine the research routes with highest potential to generate groundbreaking data. © 2021 International Parkinson and Movement Disorder Society. ispartof: MOVEMENT DISORDERS vol:37 issue:2 pages:253-263 ispartof: location:United States status: published

Despite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated. Here, we aimed to test whether focal brain lesions in lesional mania are more often right- than left-sided, and if lesions converge on areas relevant to mood regulation. We thus performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflect diagnoses and structures of interest, as well as lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, selecting reports of adult-onset hypomania, mania or mixed state following a focal brain lesion, for pooled-analyses of individual patient data. Eligible lesion images were manually traced onto the corresponding MNI space slices, and lesion topography analyzed using standard brain atlases. Using this approach, data from 211 lesional mania patients was extracted from 114 reports. Among 201 cases with focal lesions, more patients had lesions involving exclusively the right (60.7%) than exclusively the left (11.4%) hemisphere. In further analyses of 56 eligible lesion images, while findings should be considered cautiously given the potential for selection bias of published lesion images, right-sided predominance of lesions was confirmed across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, and several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions. Such pooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected. publishersversion published

We are constantly faced with the trade-off between exploiting past actions with known outcomes and exploring novel actions whose outcomes may be better. The balance between exploitation and exploration has been hypothesized to rely on multiple neuromodulator systems, namely dopaminergic neurons of the substantia nigra pars compacta (SNc) and noradrenergic neurons of the locus coeruleus (LC). However, little is known about the dynamics of these neuromodulator systems during exploitative and exploratory states, or how they interact. We developed a novel behavioral paradigm to capture exploitative and exploratory behavioral states, and imaged calcium dynamics in genetically-identified dopaminergic SNc neurons and noradrenergic LC neurons during the transitions between these states. We found dichotomous changes in sustained activity in SNc and LC during exploitative bouts of action-reward, with SNc showing higher and LC showing lower sustained activity. Exploitative states were also marked by a lengthening of positive SNc response plateaus and negative LC response depressions, as well as hysteretic dynamics in SNc networks. Chemogenetic enhancement of dopaminergic and noradrenergic excitability favored exploitative and exploratory states, respectively. Together, these data suggest that opponent changes in dopaminergic and noradrenergic activity states modulate the transitions between exploitative and exploratory behavioral states, with important implications for downstream circuit dynamics.

31st European Society for Comparative Biochemistry and Physiology (ESCPB), Shifting Biological Landscapes: from molecules to mechanisms, 9-12 September 2018, Porto, Portugal, The present study aimed to assess the effects caused by an non-steroidal inflammatory drug, Diclofenac, and an antimicrobial and antifungal agent, Triclosan, in the clams Ruditapes philippinarum and Ruditapes decussatus, and to evaluate if the impacts induced were dependent on pH and temperature. Initially organisms were exposed for 30 days at two different temperature and pH (control: pH 8.0, 17ºC; test condition: pH 7.7, 20ºC) in the absence of drugs (experimental period I) followed by a 7 days exposure under the former same physical parameters but in the absence or presence of the drugs (at 1 µg/L of each contaminant, experimental period II). Biochemical responses comprising oxidative stress and metabolic capacity biomarkers were evaluated in clams after both experimental periods. The results obtained showed that under control pH and temperature, R. philippinarum individuals exposed to both pharmaceuticals presented higher lipid peroxidation and enhanced antioxidant activities compared to non-contaminated clams. When exposed to low pH and high temperature a similar response was observed in contaminanted specimens, but, in this case clams strongly increased their metabolic activities probably to fight the stress caused by the combination of both physical and chemical stressors. R. decussatus exposed to pH and temperature control conditions increased their cellular damages and antioxidant defenses when exposed to the drugs, and these same clams under low pH and high temperature showed limited oxidative stress impacts. Overall, both species presented identical responses to Diclofenac and Triclosan, although R. decussatus seemed to be less impacted by these drugs when under low pH and high temperature

31st European Society for Comparative Biochemistry and Physiology (ESCPB), Shifting Biological Landscapes: from molecules to mechanisms, 9-12 September 2018, Porto, Portugal, The lack of knowledge upon the impacts induced by pharmaceutcals under predicted climate change scenarios leads to the concern on their potential toxicity to non-target organisms. The present study aimed to assess the effects caused by an non-steroidal inflammatory drug, Diclofenac, and an antimicrobial and antifungal agent, Triclosan, in the mussel species Mytilus galloprovincialis, when organisms were exposed to different temperature and salinity conditions. The experiment consisted on the exposure of organisms to two different temperatures (17 and 21 ºC) at control salinity (30) and two different salinities (25 and 35) under control temperature (17 ºC), in absence and presence of each drug. Biochemical responses, including oxidative status, metabolic capacity and neurotoxicity, were evaluated after 28 days of exposure. The results obtained demonstrated that exposure to Diclofenac andTriclosan , especially when under salinity and temperature chalenges, induced oxidative damages in mussels, which probably resulted from the lack of efficient antioxidant defenses, if compared to mussels mantained under control conditions. The exposure to Diclofenac and Triclosan also reduced mussels metabolism, which may explain their lack of capacity to activate defense mechanisms when exposed to stressors. The exposure to both drugs further induced neurotoxicity, especially noticed at the lowest salinity when mussels were exposed to Triclosan and at the highest temperature when mussels were exposed to Diclofenac. Overall, similar responses were induced by both drugs, especially noticiable when mussels were under salinity and temperature challenges. Our findings also indicate that the most stressulful condition resulted from the exposure to low salinity

Dolphins' positions in the Pool to be used with the software link available in the manuscript.

D-Track is a suite of software used to track an object in 3D based on the 3D schematics of a scene. These set of software was used to calculate and analyse the 3D position of a dolphin in a pool inZoomarine @ Portugal.

What is a habit? One problem with the concept of habit has been that virtually everyone has their own ideas of what is meant by such a term. Whilst not eschewing folk psychology, it is useful to re-examine dictionary definitions of 'habit'. The Oxford Dictionary of English defines habit as "a settled or regular tendency or practice, especially one that is hard to give up" and also "an automatic reaction to a specific situation". The latter, reassuringly, is not too far from what has come to be known as stimulus-response theory.

What is a habit? One problem with the concept of habit has been that virtually everyone has their own ideas of what is meant by such a term. Whilst not eschewing folk psychology, it is useful to re-examine dictionary definitions of 'habit'. The Oxford Dictionary of English defines habit as "a settled or regular tendency or practice, especially one that is hard to give up" and also "an automatic reaction to a specific situation". The latter, reassuringly, is not too far from what has come to be known as stimulus-response theory.

In this report the magnetic, atomic structures and spin-lattice coupling have been thoroughly studied through high magnetic field magnetometry, Synchrotron X-ray diffraction under applied magnetic field and magnetostriction measurements in the Tb5Ge4 compounds. A field induced phase transition from an antiferromagnetic towards a ferromagnetic ordering was confirmed but with absence of structural transformation. This absence has been confirmed experimentally through synchrotron x-ray diffraction under applied field (up to 30 T). Moreover, this absence was explained via a thermodynamic free energy model: first principles calculations determined a large energy gap (ΔE=0.65 eV) between the two possible structures, O(I) and O(II). From magnetic and structural properties, a H-T phase diagram has been proposed for Tb5Ge4. Finally it was observed a large magnetostriction (up to 600 ppm) induced by ∆H=7 T., Work partially supported by the projects FEDER/POCTI no. 155/94, PTDC/CTM/NAN/5414/2014 from Fundacao para a Ciencia e Tecnologia (FCT), Portugal. J.H.B. Silva and M. B. Barbosa thanks FCT for the Grant SFRH/BD/88440/2012 and SFRH/BD/97591/2013, respectively. C.M. acknowledges the support of the Fundación ARAID. This work was supported by the Spanish Ministry of Science (through Project Nos. MAT2014- 51982-C2-R and C1-R, including FEDER funding) and the Aragon Regional government (Project No. E26). Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Offce of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. Use of the High Magnetic Field Laboratory at Nijmegen was supported by contract no: NMA01-111.

In this report, a successful thermodynamical model was employed to understand the structural transition in Er$_5$Si$_4$, able to explain the decoupling of the magnetic and structural transition. This was achieved by the DFT calculations which were used to determine the energy differences at 0 K, using a LSDA+U approximation. It was found that the M structure as the stable phase at low temperatures as verified experimentally with a $\Delta F_0 = -$0.262 eV. Finally, it was achieved a variation of Seebeck coefficient ($\sim$ 6 $\mu$V) at the structural transition which allow to conclude that the electronic entropy variation is negligible in the transition., Comment: 17 pages, 3 figures, 1 table

In this report, a successful thermodynamical model was employed to understand the structural transition in Er5Si4, able to explain the decoupling of the magnetic and structural transition. This was achieved by DFT calculations, which were used to determine the energy differences at 0 K, using a LSDA + U approximation. It was found that the M structure is the stable phase at low temperatures, as verified experimentally with a value of ΔF0 = −0.262 eV. Finally, a variation of Seebeck coefficient (∼6 μV) was determined at the structural transition, which allows to conclude that the electronic entropy variation is negligible in the transition., This work was partially supported by the projects FEDER/POCTI n0155/94, PTDC/CTM/NAN/5414/2014 from Fundação para a Ciência e Tecnologia (FCT), Portugal. The authors thank the Portuguese Foundation for Science and Technology (FCT) for grants SFRH/BD/88440/2012 (JHB) and SFRH/BD/97591/2013 (MSB), SFRH/BD/97591/2013 (MBB), SFRH/BPD/82059/2011 (JNG), IF/01089/2015 (JSA). This work was developed within the scope of the project CICECO‐Aveiro Institute of Materials, POCI‐01‐0145‐FEDER‐007679 (FCT Ref. UID /CTM /50011/2013), financed by national funds through the FCT/MEC and when appropriate co‐financed by FEDER under the PT2020 Partnership Agreement. C.M. acknowledges the support of the Fundación ARAID. This work was supported by the Spanish Ministry of Science (through Project Nos. MAT2014‐ 51982‐C2‐R and C1‐R, including FEDER funding) and the Aragon Regional government (Project No. E26).

Aim: Comparison between transplant glomerulopathy (TG) and de novo thrombotic microangiopathy (TMA) in renal allograft biopsies in a 10 -year retrospective analysis. Results: Out of a total of 627 biopsies, TG (6.2%) was diagnosed at a later stage (6.9 �± 5.9 vs. 3.5 �± 6.5 years, p = 0.01) and presented higher proteinuria (4.0 �± 3.6 vs. 2.3 �± 1.6 gr/24h, p = 0.02), advanced glomerulosclerosis, interstitial fibrosis/tubular atrophy and interstitial plasma cells (30.8% vs. 0%, p = 0.02). De novo TMA (2.2%) was associated to worse graft disfunction (sCr 4.9 ± 1.8 vs. 2.7 �± 0.2mg/dl, p < 0.01), older donors (53 �± 10 vs. 41 �± 17 years, p = 0.04), PRA levels ≥ 25% (16.7% vs. 3.1%, p = 0.07) and previous rejection events (21.4% vs. 5.3%, p = 0.08). Diffuse glomerular lesions were observed in all TMA cases, with capillary congestion (100 vs. 35.1%, p < 0.01), microthrombi (50% vs. 5.4, p = 0.01), schistocytes (42.8% vs. 7.7%, p = 0.01) and mesangiolysis (85.7% vs. 29.7%, p < 0.01). Positive C4d in de novo TMA cases was similar to TG (71.4% vs. 53.8%, p = ns) but presented arteriolar C4d deposition (35.7 % vs. 8.7%, p = 0.042). Donor -specific antibodies detection was equally found (TG: 41.6%; TMA: 57.1%, p = ns), mainly anti-HLA Class II. In ultrastructural analysis only TG cases presented glomerular basement membrane (GBM) multilayering. Graft loss was similar, but de novo MAT cases had worst first year survival (73.3% vs. 97%, p = 0.013). Conclusion: Both pathologies belong within the spectrum of microcirculatory injury: TG results from subclinical lesion, presenting chronic cyclic accommodation, de novo TMA represents severe form of lytic endothelial lesion Objectivo: Comparação retrospectiva entre a glomerulopatia de transplante (GT) e microangiopatia trombótica (MAT) de novo num período de 10 anos de biópsias de enxertos renais. Resultados: No total de 627 biopsias, GT (6,2%) foi diagnosticada mais tardiamente (6.9 ± 5.9 vs. 3.5 �± 6.5 anos, p = 0.01), com maior grau de proteinúria (4.0 ± 3.6 vs. 2.3 ± 1.6 gr/24h, p = 0.02), glomeruloesclerose, fibrose intersticial e atrofia tubular mais severas e presença de plasmócitos intersticiais (30.8% vs. 0%, p = 0.02). Os casos de MAT de novo >(2,2%) apresentavam disfunção do enxerto mais severa (sCr 4.9 ± 1.8 vs. 2.7 ± 0.2mg/dl, p < 0.01) e associação com dadores mais velhos (53 ± 10 vs. 41 ± 17 anos, p = 0.04), níveis de PRA ≥ 25% (16.7% vs. 3.1%, p = 0.07) e episódios prévios de rejeição aguda (21.4% vs. 5.3%, p = 0.08). Lesões glomerulares difusas foram detectadas em todos os casos de MAT, especialmente com congestão capilar (100% vs>. 35.1%, p < 0.01) e predomínio de presença de microtrombos (50% vs>. 5.4 %, p = 0.01), esquizócitos (42.8% vs. 7.7%, p = 0.01) e mesangiólise (85.7% vs. 29.7%, p < 0.01). Positividade para C4D em MAT de novo e TG foi semelhante (71.4% vs. 53.8%, p = ns) mas a deposição arteriolar de C4d foi mais frequente em MAT de novo (35.7 % vs. 8.7%, p = 0.042). A detecção de anticorpos anti -dador foi similar entre os dois grupos (GT: 41.6%; MAT: 57.1%, p = ns) e constituído maioritariamente por anticorpos anti-HLA Classe II. Apenas a GT apresentava multilaminação da membrana basal glomerular na microscopia electrónica. A perda do enxerto foi semelhante entre as duas patologias mas MAT de novo apresentou pior sobrevida renal ao primeiro ano (73.3% vs>. 97%, p = 0.013). Conclusão: GT e MAT de novo são expressões histológicas que se incluem num espectro de lesão da microcirculação: a GT resulta de lesão subclínica, apresentando acomodação crónica cíclica e a MAT de novo expressa uma forma severa de lise endotelial

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety of brain disorders. To better understand the mechanisms by which brain circuits react to an animal's experience requires the ability to monitor the experience-dependent molecular changes in a given set of neurons, over a prolonged period of time, in the live animal. While experience and associated neural activity is known to trigger gene expression changes in neurons most of the methods to detect such changes do not allow repeated observation of the same neurons over multiple days or do not have sufficient resolution to observe individual neurons. Here, we describe a method that combines in vivo two-photon microscopy with a genetically encoded fluorescent reporter to track experience-dependent gene expression changes in individual cortical neurons over the course of day-to-day experience. One of the well-established experience-dependent genes is Activity-regulated cytoskeletal associated protein (Arc). The transcription of Arc is rapidly and highly induced by intensified neuronal activity and its protein product regulates the endocytosis of glutamate receptors and long-term synaptic plasticity. The expression of Arc has been widely used as a molecular marker to map neuronal circuits involved in specific behaviors. In most of those studies, Arc expression was detected by in situ hybridization or immunohistochemistry in fixed brain sections. Although those methods revealed that the expression of Arc was localized to a subset of excitatory neurons after behavioral experience, how the cellular patterns of Arc expression might change with multiple episodes of repeated or distinctive experiences over days was not investigated. In vivo two-photon microscopy offers a powerful way to examine experience-dependent cellular changes in the living brain. To enable the examination of Arc expression in live neurons by two-photon microscopy, we previously generated a knock-in mouse line in which a GFP reporter is placed under the control of the endogenous Arc promoter. This protocol describes the surgical preparations and imaging procedures for tracking experience-dependent Arc-GFP expression patterns in neuronal ensembles in the live animal. In this method, chronic cranial windows were first implanted in Arc-GFP mice over the cortical regions of interest. Those animals were then repeatedly imaged by two-photon microscopy after desired behavioral paradigms over the course of several days. This method may be generally applicable to animals carrying other fluorescent reporters of experience-dependent molecular changes.

In the European context, several methodologies have been developed to assess the ecological status and, specifically, the hydromorphological status of running surface waters. Although these methodologies have been widely used, few studies have focused on hydrologically altered water bodies and the factors that may determine their status. In this study, the Serpis River was divided into 16 segments from the Beniarr'es dam (40 km from the river mouth) to the sea, all of which are affected by flow regulation, but with different severity. In each segment, an inventory of the flora was conducted, and hydromorphological indices (QBR, Riparian Habitat Quality Index; and IHF, River Habitat Index) were applied. The objectives of the study were (A) to identify relationships between floristic composition and QBR components and (B) between instream habitat characteristics and IHF components as well as (C) to determine the main factors controlling the floristic composition and riparian habitat quality (QBR) and the factors controlling instream habitat characteristics and heterogeneity (IHF). A cluster analysis allowed grouping sites according to their floristic composition and instream habitat characteristics, and non-metric multidimensional scaling (NMDS) was used to ordinate the sites, obtaining the biotic and instream habitat characteristics, as well as the QBR and IHF subindices, which better explained the spatial patterns. Finally, a canonical correspondence analysis (CCA) with predictor variables (geographical, hydrological, geomorphological and human pressures) indicated the main factors controlling the spatial patterns of the floristic composition, instreamhabitat characteristics, riparian habitat quality and instream habitat heterogeneity. A gradient of riparian and instream habitat quality was identified. Our results suggest that physical constraints (presence of a gorge) have protected sites from severe human impacts, resulting in good ecological quality, despite hydrological alteration. This area, where there is geomorphological control, could be potentially reclassified into a different ecotype because regular monitoring could be using incorrect references for index scores, and naturally high scores could be confused with recovery from hydrological alteration or other pressures. The sites with the worst quality were near the river mouth and were characterised by an artificial and highly variable flow regime (related to large autumnal floods and frequent human-induced periods of zero flow). This artificial flow variability as well as the presence of lateral structures in the river channel and geomorphological characteristics were identified as the main factors driving the hydromorphological and floristic pattern in this regulated river. Diversas metodologías han sido desarrolladas en el contexto europeo para evaluar el estado ecológico, y específicamente el estado hidromorfológico de las aguas superficiales. Aunque éstas han sido ampliamente utilizadas, pocos estudios se han centrado en masas de agua hidrológicamente alteradas y en los factores que condicionan su estado. En este estudio, el río Serpis fue dividido en 16 segmentos desde la presa de Beniarrés (a 40 km de la desembocadura) hasta el mar, todos ellos afectados por la regulación de caudales con distinta severidad. En cada segmento se realizó un inventario florístico y se aplicaron índices hidromorfológicos (QBR, Calidad del Bosque de Ribera, e IHF, Índice de Hábitat Fluvial). Los objetivos del estudio fueron (A) identificar relaciones entre la composición florística y los componentes del QBR, (B) entre las caracteríısticas del hábitat fluvial y los componentes del IHF, (C) determinar los principales factores que controlan la composición florística y la calidad del hábitat ripario (QBR), y las características del hábitat fluvial y su heterogeneidad (IHF). Un cluster permitió agrupar los puntos de muestreo según su composición florística y las características del hábitat fluvial, y un escalado multidimensional no-métrico (NMDS) fue usado para ordenar los puntos, obteniendo las variables bióticas y características del hábitat y los subindices del QBR e IHF, respectivamente, que explicaban mejor los patrones espaciales. Finalmente, un análisis de correspondencias canónicas (CCA) con variables predictoras (geográficas, hidrológicas, geomorfológicas y presiones humanas) indicó los principales factores que controlan los patrones espaciales de la composición florística, las características del hábitat fluvial, la calidad del hábitat ripario y la heterogeneidad del hábitat fluvial. Se identificó un gradiente de calidad del hábitat ripario y fluvial. Los resultados sugieren que las limitaciones físicas (presencia de un cañón) han protegido a los tramos de impactos humanos severos, resultando en una buena calidad ecológica a pesar de la alteración hidrológica. Esta zona podría potencialmente ser reclasificada en un ecotipo diferente, ya que un monitoreo regular podría estar usando referencias incorrectas para los índices y sus altas puntuaciones naturales se podrían estar confundiendo con una recuperación de la alteración hidrológica o de otras presiones. Los puntos de muestreo con peor calidad estuvieron cerca de la desembocadura y tuvieron un régimen de caudales alterado y muy variable. Esta variabilidad artificial del caudal, junto con la presencia de estructuras laterales en el cauce y las características geomorfológicas fueron identificadas como los principales factores determinantes del patrón hidromorfológico y florístico en este río regulado.

XII congresso da Associação Espanhola de Limnologia/IV Congresso Ibérico de Limnologia, organizado pela Associação Espanhola de Limnologia, de 5 a 9 de Julho de 2004 no Porto, Portugal. A ilha de São Miguel é a maior ilha do arquipélago dos Açores, com aproximadamente 747 km2 de superfície. Nesta ilha existem mais de 30 lagoas e lagoeiros (Constância et al., 1997). Os maiores ecossistemas lacustres da ilha são as lagoas do Fogo, das Sete Cidades e das Furnas. Nestas duas últimas lagoas existe um problema de eutrofização das massas de água resultante das actividades antropogénicas desenvolvidas nas bacias hidrográficas, em especial as explorações agro-pecuárias, o qual constitui um dos problemas mais graves de degradação da qualidade bio-físico-química da água. Uma das consequências do aumento de nutrientes é a proliferação da biomassa de fitoplâncton.

XII congresso da Associação Espanhola de Limnologia/IV Congresso Ibérico de Limnologia, organizado pela Associação Espanhola de Limnologia, de 5 a 9 de Julho de 2004 no Porto, Portugal. A qualidade da água de um sistema lacustre de baixa profundidade não deve ser avaliada apenas segundo a concentração de nutrientes, uma vez que esses sistemas podem existir em dois estados alternativos: um de água transparente, dominado por macrófitos, e outro de água turva dominado por fitoplâncton.

XII congresso da Associação Espanhola de Limnologia/IV Congresso Ibérico de Limnologia, organizado pela Associação Espanhola de Limnologia, de 5 a 9 de Julho de 2004 no Porto, Portugal. A ilha de S. Miguel é dotada de lagoas e ribeiras abundantes em espécies piscícolas que levaram ao desenvolvimento da pesca desportiva. Todas as espécies existentes nas lagoas foram introduzidas por acção humana.

Submitted by Ana Costa (apcosta@porto.ucp.pt) on 2011-07-14T10:41:26Z No. of bitstreams: 1 Application of image analysis to the study.pdf: 2342766 bytes, checksum: 07ed9e3a79000c90ea1c1babd2cccfe2 (MD5) Made available in DSpace on 2011-09-13T15:57:25Z (GMT). No. of bitstreams: 1 Application of image analysis to the study.pdf: 2342766 bytes, checksum: 07ed9e3a79000c90ea1c1babd2cccfe2 (MD5) Previous issue date: 1997

XII Expedição Científica do Departamento de Biologia - Pico 2005. Submitted by Duarte Furtado (dfurtado@uac.pt) on 2010-11-22T17:49:36Z No. of bitstreams: 1 Contribuição para a caracterização das águas interiores de superfície da ilha do Pico.pdf: 314025 bytes, checksum: 2b7564fb59f7f6cf6fafa90fd60028c7 (MD5) Made available in DSpace on 2010-11-29T11:25:46Z (GMT). No. of bitstreams: 1 Contribuição para a caracterização das águas interiores de superfície da ilha do Pico.pdf: 314025 bytes, checksum: 2b7564fb59f7f6cf6fafa90fd60028c7 (MD5) Previous issue date: 2006-06

Submitted by Isabel Murta (isamurta@itqb.unl.pt) on 2020-05-20T15:31:49Z No. of bitstreams: 1 NUNO_LOUREIRO_THESIS.pdf: 13834923 bytes, checksum: 088ada4c6bf037e5855e47ac7e2f2270 (MD5) Made available in DSpace on 2020-05-20T15:31:49Z (GMT). No. of bitstreams: 1 NUNO_LOUREIRO_THESIS.pdf: 13834923 bytes, checksum: 088ada4c6bf037e5855e47ac7e2f2270 (MD5) Previous issue date: 2020-01-16

Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the ventral tegmental area (VTA) are activated by the omission of the aversive unconditioned stimulus (US) during fear extinction. This dopamine signal occurred specifically during the beginning of extinction when the US omission is unexpected, and correlated strongly with extinction learning. Furthermore, temporally-specific optogenetic inhibition or excitation of dopamine neurons at the time of the US omission revealed that this dopamine signal is both necessary for, and sufficient to accelerate, normal fear extinction learning. These results identify a prediction error-like neuronal signal that is necessary to initiate fear extinction and reveal a crucial role of DA neurons in this form of safety learning., eLife digest To survive, animals must identify and react to stimuli in their environment that signal danger. But they must also adapt their behavior when those stimuli no longer signal danger – hiding whenever you hear a loud noise might keep you safe, but it also prevents you from searching for food. In the laboratory, we can study this form of learning using procedures called fear conditioning and extinction. During fear conditioning, animals learn that a stimulus, such as a tone, signals that an unpleasant event is about to occur. That event might involve receiving a mild shock to the foot, for example. After experiencing the tone and shock paired together multiple times, animals will initially show signs of fear – such as freezing – when they hear the tone. But if later the tone occurs without being followed by the shock, these fear responses fade. This fading process is called extinction. Extinction does not involve erasing the old memory about the tone-shock relationship. That is, it is not a form of forgetting. Instead, the animals learn that the tone no longer signals an impending shock. By monitoring brain activity in mice trained to associate a shock with a tone, Salinas-Hernández et al. reveal how the brain begins to learn that the shock no longer follows the tone. When the mice do not receive the anticipated shock to the foot, a group of brain cells that produce the chemical dopamine increase their activity. These neurons also fire whenever animals receive a reward, particularly one that exceeds their expectations. The more the dopamine neurons fire, the faster the mice reduce their fear responses to the tone. Preventing the neurons from increasing their activity prevents the mice from extinguishing their fear memory. By contrast, activating the neurons speeds up the extinction process. Understanding how the brain extinguishes learned fear responses has therapeutic implications. Many anxiety disorders, such as post-traumatic stress disorder, involve impaired fear extinction learning. Indeed, exposure therapy – used to treat anxiety disorders such as phobias – is a form of fear extinction. Manipulating the activity of dopamine neurons during extinction could therefore help to treat anxiety disorders.

RESUMO: Decidir quando nos movemos é essencial para a nossa sobrevivência. A perda de neurónios dopaminérgicos (DANs) na substantia nigra pars compacta (SNc), a alteração patológica característica da doença de Parkinson (PD), causa deficits na iniciação do movimento e lentificação do movimento. A teoria dominante é que o papel dos DANs da SNc no movimento deve-se a mudanças mantidas da atividade destes neurónios (atividade tónica) enquanto as alterações fásicas da atividade estão envolvidas na aprendizagem baseada na recompensa. No entanto, foi demonstrado que a atividade fásica dos DANs da SNc se correlaciona com o início e terminação de uma sequência de ações aprendida. Contudo, continua por esclarecer se esta atividade é ou não necessária para a iniciação ‘self-paced’ de sequências de ações. A maioria dos estudos anteriores que incidiram sobre movimento ou iniciação de ações utilizaram lesões crónicas ou fármacos para manipular a via nigro-estriada. Estes métodos não são ideais para estudar o papel de populações neuronais específicas devido a limitações tais como a baixa resolução temporal e a baixa especificidade destas manipulações. Devido a isto, o papel dos DANs da SNc na iniciação de movimentos/ações ‘self-paced’ continua a ser pouco claro. Para resolver esta questão nós utilizámos uma abordagem optogenética para gravar, visualizar e manipular a atividade de DANs da SNc com uma elevada especificidade neuronal e resolução temporal. Descobrimos que quando murganhos se movimentavam livremente num ‘open field’, os DANs da SNc aumentavam a sua atividade de forma transitória, antes do início do movimento. Para testar se este aumento de atividade era ou não necessário para a iniciação do movimento, expressámos uma opsina inibitória (ArchT) nos DANs da SNc dos murganhos. Utilizando esta estratégia foto-inibimos estes neurónios transitoriamente e descobrimos que conseguíamos perturbar a probabilidade e o vigor das iniciações de movimento mas não conseguíamos modificar a aceleração dos animais quando estes já se encontravam em movimento. Em seguida quisemos saber se uma breve activação destes neurónios era suficiente para promover a iniciação de movimento. Para conseguirmos isto expressámos ChR2 nos DANs da SNc e ativámos transitoriamente estes neurónios enquanto os murganhos se moviam livremente. Ao contrário da experiência de inibição, esta breve ativação promoveu a iniciação do movimento quando os murganhos se encontravam imóveis, e de uma forma semelhante não modificou a aceleração dos murganhos quando estes já se encontravam em movimento. Quando treinámos os murganhos para realizarem uma sequência de acções (recompensando-os se eles pressionassem uma alavanca 8 vezes) descobrimos que os DANs da SNc aumentavam a sua actividade transitoriamente imediatamente antes do início e o final da sequência. Para além disto, estes neurónios na sua maioria correspondiam a uma população que não respondia à recompensa. Quando inibimos transitoriamente os DANs da SNC imediatamente antes do inicio da sequência os murganhos exibiram um aumento da latência para iniciarem a sequência. Contudo, não conseguimos perturbar a execução da sequência quando fizemos a mesma inibição após a sequência ter sido iniciada. Os nossos resultados demonstram que a actividade dos DANs da SNc modulam não apenas a probabilidade mas também o vigor dos movimentos futuros mas não modula o movimento durante a sua execução. Isto sugere que o ‘gating’ de iniciações ‘selfpaced’ acontece através de efeitos permissivos da dopamina nos circuitos estriatais que por sua vez recebem a informação relativa a que ações iniciar de outros ‘inputs’. A depleção de dopamina na PD é crónica. Os estudos sobre o papel da dopamina no movimento utilizando modelos animais de depleção crónica são bastante importantes mas têm uma utilidade limitada para a compreensão do papel dinâmico dos DANs da SNc nos circuitos para os quais projetam. O nosso trabalho, ao demonstrar a relevância da atividade transitória destes neurónios imediatamente antes do início de movimentos ‘self-paced’, sugere que poderá ser benéfico desenvolver terapêuticas que providenciem modulações transitórias dos circuitos dos gânglios da base quando os doentes com PD querem iniciar uma ação (e.g. estimulação cerebral profunda em ‘closed–loop’ despoletada por atividade cortical nas áreas relacionadas com o planeamento motor). ABSTRACT: Deciding if and when to move is critical for survival. Loss of dopamine neurons (DANs) in substantia nigra pars compacta (SNc), the pathological hallmark of Parkinson’s disease (PD), causes deficits in movement initiation and slowness of movement. The dominant theory is that the role of SNc DANs in movement is mainly due to sustained changes in their firing (tonic changes) while phasic changes are involved in rewardbased learning. Nevertheless, phasic activity of SNc DANs has been found to correlate with the start and finish of a learned action sequence. However, it remains unclear whether this activity is necessary for self-paced action initiation. The majority of previous studies on movement/action initiation have used chronic lesions or drugs to manipulate the nigrostriatal pathway. These methods are not ideal to study the role of specific neuron populations due to constraints such as temporal resolution and/or specificity of the manipulations. Thus, the role of SNc DANs in self-paced movement/action initiation remains unsettled. To tackle this question we used an optogenetic approach to record, image and manipulate the activity of genetically identified SNc DANs with high specificity and temporal resolution. We found that when mice were freely moving in an open field SNc DANs transiently increased their activity just before self-paced movements were initiated. To test whether this transient increase in activity was necessary for movement initiation we expressed an inhibitory opsin (ArchT) in SNc DANs of mice. We proceeded to briefly photoinhibit these neurons and found that we could disturb the probability and vigor of movement initiations but we could not change mice's acceleration when they were already moving. Next we wanted to know whether brief activation of SNc DANs was sufficient to promote movement initiation. To achieve this we expressed ChR2 in mice's SNc DANs and briefly activated these neurons while mice were freely moving. Contrary to the inhibition experiment, this brief activation promoted movement initiation when mice were immobile and in a similar way it did not change significantly mice's acceleration when they were already moving. When we trained mice to perform a learned action sequence (by rewarding them if they pressed a lever 8 times) we found that SNc DANs increased their activity transiently just before the start and finish of the action sequence. Furthermore, these neurons were largely non-overlapping with reward related DANs. When we briefly inhibited SNc DANs just before the action sequence, mice increased their latency to initiate the sequence. However, inhibition of these neurons when mice had already started the action sequence did not change their performance. Our results show that the activity of SNc DANs modulates not only the probability but also the vigor of future movements but that it does not modulate movements once they have been initiated. This suggests that the gating of self-paced initiation happens by permissive effects of dopamine on downstream striatal circuits that would receive information about which plans to execute from other inputs. Dopamine depletion in PD is chronic. Studies of the role of dopamine in movement in chronic models of depletion are very valuable, but have limited our understanding of the dynamic role of SNc DAN activity in downstream circuits. Our work, by highlighting the relevance of transient activity of these neurons before self-paced movement initiation, suggests that it could be beneficial to pursue treatments aimed at providing transient modulations of basal ganglia circuitry when patients initiate movements, e.g. via closed-loop deep brain stimulation triggered by activity in cortical areas related to motor planning.

Learning novel actions and skills is a prevalent ability across multiple species and a critical feature for survival and competence in a constantly changing world. Novel actions are generated and learned through a process of trial and error, where an animal explores the environment around itself, generates multiple patterns of behavior and selects the ones that increase the likelihood of positive outcomes. Proper adaptation and execution of the selected behavior requires the coordination of several biomechanical features by the animal. Cortico-basal ganglia circuits and loops are critically involved in the acquisition, learning and consolidation of motor skills.(...) Fundação para a Ciência e a Tecnologia

Short-term memory requires the coordination of sub-processes like encoding, retention, retrieval and comparison of stored material to subsequent input. Neuronal oscillations have an inherent time structure, can effectively coordinate synaptic integration of large neuron populations and could therefore organize and integrate distributed sub-processes in time and space. We observed field potential oscillations (14–95 Hz) in ventral prefrontal cortex of monkeys performing a visual memory task. Stimulus-selective and performance-dependent oscillations occurred simultaneously at 65–95 Hz and 14–50 Hz, the latter being phase-locked throughout memory maintenance. We propose that prefrontal oscillatory activity may be instrumental for the dynamical integration of local and global neuronal processes underlying short-term memory.