Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors

Epinephrine (EPI) strengthens contextual fear memories by acting on peripheral β2-adrenoceptors. Phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice are EPI-deficient mice and have reduced contextual fear learning. Our aim was to evaluate the molecular mechanisms by which peripheral EPI strengthens contextual fear memory and if a β2-adrenoceptor antagonist can erase contextual fear memories. Pnmt-KO and wild-type (WT) mice were submitted to fear conditioning (FC) procedure after treatment with EPI, norepinephrine (NE), EPI plus ICI 118,551 (selective β2-adrenoceptor antagonist), ICI 118,551 or vehicle (NaCl 0.9%). Catecholamines were separated and quantified by high performance liquid chromatography-electrochemical detection (HPLC-ED). Blood glucose was measured by coulometry. Real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of nuclear receptor 4a1 (Nr4a1), Nr4a2 and Nr4a3 in hippocampus samples. In WT mice, plasma EPI concentration was significantly higher after fear acquisition (FA) compared with mice without the test. NE did not increase in plasma after FA and did not strengthen contextual fear memory, contrary to EPI. Freezing induced by EPI was blocked by ICI 118,551 in Pnmt-KO mice. In WT mice, ICI 118,551 blocked blood glucose release into the bloodstream after FA and decreased contextual fear memory. Nr4a1, Nr4a2 and Nr4a3 mRNA expression decreased in Pnmt-KO mice compared with WT mice after FC procedure. In Pnmt-KO mice, EPI induced an increase in mRNA expression of Nr4a2 compared to vehicle. In conclusion, EPI increases in plasma after an aversive experience, possibly improving long-term and old memories, by acting on peripheral β2-adrenoceptors. Glucose could be the mediator of peripheral EPI in the central nervous system, inducing the expression of Nr4a transcription factor genes involved in consolidation of contextual fear memories

Assessment of the Transmission Dynamics of Clostridioides difficile in a Farm Environment Reveals the Presence of a New Toxigenic Strain Connected to Swine Production

The recent increase in community-acquired Clostridioides difficile infections discloses the shift in this bacterium epidemiology. This study aimed at establishing a transmission network involving One Health components, as well as assessing the zoonotic potential and genomic features of dominant clones. Samples were collected from different compartments of animal, human and environmental origin, from an animal production unit. C. difficile isolates were characterized for toxigenic profile by multiplex-PCR, while genetic diversity was evaluated by PCR-ribotyping and whole genome-based analysis. The overall C. difficile prevalence was 37.2% (70/188), and included samples from environmental (58.3%, 35/60) and animal (31.5%, 35/111) compartments; human samples (n = 17) taken from healthy workers were negative. A predominant clone from RT033 was found in almost 90% of the positive samples, including samples from all compartments connected to the pig production unit, with core-genome single nucleotide variant (SNV)-based Analysis supporting a clonal transmission between them (mean distance of 0.1 ± 0.1 core-SNVs). The isolates from this clone (herein designated PT RT033) were positive for all C. difficile toxin genes (tcdA, tcdB, cdtA/cdtB). The phyloGenetic positioning of this clone was clearly distinct from the classical RT033 cluster, suggesting a different evolutionary route. This new clone shares genomic features with several RTs from the clade 5 Sequence Type (ST) 11, including a complete pathogenicity locus (PaLoc) that is more similar to the one found in toxigenic strains and contrasting to the less virulent classical RT033 (tcdA-, tcdB-, cdtA + /cdtB +). The presence of a tcdA gene truncated into two ORFs, not previously described, requires further evaluation concerning toxin functionality. We hypothesize that the unique combination of genetic elements found in the PT RT033 clone may contribute to host tropism and environmental dissemination and maintenance. This study constitutes the first report of a toxigenic RT033 clone and adds to the overall knowledge on Clade 5 sequence type 11, considered the C. difficile evolutionary lineage with the highest zoonotic potential. The presence of this clone in all compartments associated with the pig production unit suggests a transmission chain involving these animals and contributes to unveil the role played by animal and environmental reservoirs in this pathogen epidemiology.This work was supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No. 773830: One Health European Joint Programme. FA and RC were recipients of fellowships from the same programme.info:eu-repo/semantics/publishedVersio

Movimentos de vertente no norte de Portugal: importância do comportamento hidrológico das formações superficiais = Slope Movements in Northern Portugal: Importance of Surficial Formations Hydrological Behavior

A ocorrência de movimentos de vertente no Norte de Portugal tem motivado o desenvolvimento de vários estudos de caso, ensaiando-se diversas metodologias que visam definir e caracterizar os factores condicionantes que maior influência exercem sobre os processos de instabilidade. Neste trabalho apresentam-se os resultados obtidos para o fluxo de detritos de Frades (Arcos de Valdevez), discutindo-se a importância do contexto morfo-estrutural, das formações superficiais e do seu comportamento hidrológico, analisados através de ensaios laboratoriais e in situ, designadamente, granulometria, composição mineralógica, condutividade hidráulica, resistência à penetração e refracção sísmica. O estudo desenvolvido, para além de demonstrar a existência de caminhos preferenciais da circulação interna da água, em associação com condicionamentos ligados às características das formações superficiais, revela que a rede de drenagem subsuperficial tem uma ligação evidente com o escoamento que se processa à superfície, embora possa sofrer alterações motivadas por estruturas subjacentes.The occurrence of landslides in northern Portugal has motivated the development of several case studies, rehearsing different methodologies that seek to defi ne and characterize the conditioning factors with the greatest infl uence over the geomorphologic instability processes. This paper presents the results obtained for Frades (Arcos de Valdevez) debris fl ow, discussing the importance of morphostructural context, surfi cial formations and their hydrological behavior, analyzed by in situ and laboratory tests, namely, grain size, mineralogy, hydraulic conductivity, penetration resistance and seismic refraction. The developed study shows the existence of preferential paths of internal water circulation, in combination with constraints linked to the characteristics of the surficial formations, revealing also that the subsurface drainage network has an obvious link with the fl ow that takes place at the surface, although it may present changes motivated by underlying structures

Attenuation of the cardiovascular and metabolic complications of obesity in CD14 knockout mice

Aims: Although toll-like receptors (TLR) are known to mediate the metabolic complications of obesity, the mechanisms underlying its activation remain largely unknown. The present study analyzed a model of dietinduced obesity in mice lacking the TLR4/TLR2 co-receptor CD14. Main methods: Six-week-old male mice lacking CD14 (n= 16) were allocated to either a control diet or a high-fat high-simple carbohydrate diet (5.4 kcal/g; 35% fat; 35% sucrose), and compared with C57BL/6 (WT; n = 15) controls. After 12 weeks, body composition, basal sympathetic activity, non-invasive blood pressure and glucose tolerance were evaluated. Hepatic and adipose tissues were collected for mRNA quantification, histology and LPS incubation. Key findings: In both WT and CD14 knockout mice, obesity was accompanied by TLR2 and TLR4 upregulation. However, obese mice lacking CD14 presented decreased lipid and macrophage content in hepatic and adipose tissues, lower urinary levels of noradrenaline, decreased systolic blood pressure, reduced fasting plasma glucose and blunted glucose intolerance, compared with obese WT group. In the presence of exogenous sCD14, adipose tissue incubation with LPS-induced TLR2 and TNF-alpha upregulation in both WT and CD14 knockout obese mice. Significance: In our model of diet-induced obesity, mice lacking CD14 showed lower adiposity and hepatic steatosis, improved glucose homeostasis, blunted sympathetic overactivity and reduced blood pressure elevation. This was observed in the presence of preserved TLR4 and TLR2 gene expression, and intact TLR4 signaling pathways. These results suggest that CD14-mediated TLR activation might contribute to the cardiovascular and metabolic complications of obesity

Movimentos de vertente no norte de Portugal: importância do comportamento hidrológico das formações superficiais

A ocorrência de movimentos de vertente no Norte de Portugal tem motivado o desenvolvimento de vários estudos de caso, ensaiando-se diversas metodologias que visam defi nir e caracterizar os factores condicionantes que maior infl uência exercem sobre os processos de instabilidade. Neste trabalho apresentam-se os resultados obtidos para o fl uxo de detritos de Frades (Arcos de Valdevez), discutindo-se a importância do contexto morfo-estrutural, das formações superfi ciais e do seu comportamento hidrológico, analisados através de ensaios laboratoriais e in situ, designadamente, granulometria, composição mineralógica, condutividade hidráulica, resistência à penetração e refracção sísmica. O estudo desenvolvido, para além de demonstrar a existência de caminhos preferenciais da circulação interna da água, em associação com condicionamentos ligados às características das formações superfi ciais, revela que a rede de drenagem subsuperfi cial tem uma ligação evidente com o escoamento que se processa à superfície, embora possa sofrer alterações motivadas por estruturas subjacentes.The occurrence of landslides in northern Portugal has motivated the development of several case studies, rehearsing different methodologies that seek to defi ne and characterize the conditioning factors with the greatest infl uence over the geomorphologic instability processes. This paper presents the results obtained for Frades (Arcos de Valdevez) debris fl ow, discussing the importance of morphostructural context, surfi cial formations and their hydrological behavior, analyzed by in situ and laboratory tests, namely, grain size, mineralogy, hydraulic conductivity, penetration resistance and seismic refraction. The developed study shows the existence of preferential paths of internal water circulation, in combination with constraints linked to the characteristics of the surfi cial formations, revealing also that the subsurface drainage network has an obvious link with the fl ow that takes place at the surface, although it may present changes motivated by underlying structures.info:eu-repo/semantics/publishedVersio

Local modulation of the natriuretic peptide system in the rat remnant kidney

Background. The natriuretic peptide (NP) system plays a central role in the renal adaptations to acute volume expansion. However, the modulation of the NP system in chronic renal insufficiency (CRI) remains to be elucidated. In the present study, we evaluated cardiac haemodynamics, plasma type-B natriuretic peptide (BNP) levels and the expression of natriuretic peptide receptor A (NPR-A) and NPR-C in the renal cortex (RC) and medulla (RM) of Sham and 3/4 nephrectomized (3/4nx) rats, up to 26 weeks after surgery. Methods. Male Wistar-Han rats (190-220 g; n = 49) were randomly assigned to 3/4nx or Sham surgery. Two, 10 and 26 weeks after surgery, non-invasive blood pressure (BP) and left ventricular (LV) haemodynamics were performed, and urine and blood were collected for metabolic studies and plasma BNP determination. In addition, tissue samples from RC and RM were obtained for NPR-A and NPR-C quantification (RT-PCR and western blotting) as well as NPR-A immunodetection. Results. In 3/4nx rats, the progressive interstitial fibrosis and tubular atrophy were accompanied by a time-dependent increase of BP and impaired natriuretic response to volume expansion (VE). This was accompanied in 3/4nx rats by an early and time-dependent elevation of BNP circulating levels that was not associated with cardiac dysfunction or increased myocardial BNP gene expression. In 3/4nx rats, NPR-A expression in the remnant RM was consistently reduced at 2, 10 and 26 weeks, and this was accompanied by an increase in NPR-C expression in the remnant RC from 3/4nx rats. Conclusions. BP elevation and compromised natriuretic response to VE in 3/4nx rats is associated with increased circulating BNP levels in the absence of cardiac dysfunction. This is accompanied in 3/4nx rats by both impaired NPR-A expression in the RM and upregulation of NPR-C in the RC suggesting a novel mechanism for NP resistance in CRI

NeuroAIreh@b: an artificial intelligence-based methodology for personalized and adaptive neurorehabilitation

Cognitive impairments are a prevalent consequence of acquired brain injury, dementia, and age-related cognitive decline, hampering individuals' daily functioning and independence, with significant societal and economic implications. While neurorehabilitation represents a promising avenue for addressing these deficits, traditional rehabilitation approaches face notable limitations. First, they lack adaptability, offering one-size-fits-all solutions that may not effectively meet each patient's unique needs. Furthermore, the resource-intensive nature of these interventions, often confined to clinical settings, poses barriers to widespread, cost-effective, and sustained implementation, resulting in suboptimal outcomes in terms of intervention adaptability, intensity, and duration. In response to these challenges, this paper introduces NeuroAIreh@b, an innovative cognitive profiling and training methodology that uses an AI-driven framework to optimize neurorehabilitation prescription. NeuroAIreh@b effectively bridges the gap between neuropsychological assessment and computational modeling, thereby affording highly personalized and adaptive neurorehabilitation sessions. This approach also leverages virtual reality-based simulations of daily living activities to enhance ecological validity and efficacy. The feasibility of NeuroAIreh@b has already been demonstrated through a clinical study with stroke patients employing a tablet-based intervention. The NeuroAIreh@b methodology holds the potential for efficacy studies in large randomized controlled trials in the future

Dinâmicas de (investig)ação em contextos de promoção da língua portuguesa: a presença do CIDTFF na rede Camões, I.P.

Sem resumo disponível.publishe