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Humans have been altering the Mediterranean landscapes for millennia. To diminish the probability of encounters with domestic animals, humans and their activities, many species adjust their behavior to become more nocturnal. Even habitat-generalist species, such as red fox and stone marten that are somehow tolerant to environmental changes, might be affected by anthropic disturbances. Nevertheless, only a small number of studies were implemented in Iberia targeting these mesocarnivores’ activity patterns, and fewer have assessed the temporal ecology of these species in Eucalyptus plantations, the current main forest cover in Portugal. Based on camera traps, we aimed to analyze: 1) the temporal and spatio-temporal activity patterns of red fox and stone marten; and 2) how they are affected by distinct human disturbances (i.e., humans, livestock, dogs, plantations, and hunting). Foxes presented a higher crepuscular activity, while martens were entirely nocturnal, suggesting some avoidance behavior. Both mesocarnivores showed a higher overlap with dogs’ activity than with humans or livestock. Foxes’ activity patterns vary between seasons and habitats but were not influenced by the hunting period. Results suggest that both mesocarnivores, besides setting apart their activity from humans related disturbances, also show a tendency to temporally avoid each other. While the increase of nocturnality may indicate an anthropic disturbance impact, a reduction of activity overlap between mesocarnivores may be a strategy to reduce competition. These results may help support the sustainable management of landscapes by highlighting critical periods where activity overlaps may occur, and thus the anthropic impacts on wildlife are higher.

The circadian rhythm is essential in order to maintain metabolic homeostasis and insulin sensitivity. Disruption of circadian mechanisms is associated with the development of metabolic diseases, such as diabetes. Lifestyle changes such as an equilibrated diet and physical activity are known to improve glycaemic control in diabetic patients. One of the mechanisms possibly involved in such an improvement is the restoration of insulin circadian rhythms. There are several available dietary schemes based on circadian rhythms. Some of them are associated with better regulation of daily insulin fluctuations and the improvement of Type 2 Diabetes and metabolic syndrome. In the current review, we aim to explore how the different types of diet can impact glucose metabolism and insulin sensitivity in patients with diabetes, highlighting the interactions with the mechanisms of circadian insulin rhythm and the prevention of hyperinsulinemia.

It is now well-accepted that psychostimulants act on glial cells causing neuroinflammation and adding to the neurotoxic effects of such substances. Neuroinflammation can be described as an inflammatory response, within the CNS, mediated through several cytokines, reactive oxygen species, chemokines and other inflammatory markers. These inflammatory players, in particular cytokines, play important roles. Several studies have demonstrated that psychostimulants impact on cytokine production and release, both centrally and at the peripheral level. Nevertheless, the available data is often contradictory. Because understanding how cytokines are modulated by psychoactive substances seems crucial to perspective successful therapeutic interventions, here, we conducted a scoping review of the available literature. We have focused on how different psychostimulants impact on the cytokine profile. Publications were grouped according to the substance addressed (methamphetamine, cocaine, methylphenidate, MDMA or other amphetamines), the type of exposure and period of evaluation (acute, short- or long-term exposure, withdrawal, and reinstatement). Studies were further divided in those addressing central cytokines, circulating (peripheral) levels, or both. Our analysis showed that the classical pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were those more investigated. The majority of studies have reported increased levels of these cytokines in the central nervous system after acute or repeated drug. However, studies investigating cytokine levels during withdrawal or reinstatement have shown higher variability in their findings. Although we have identified fewer studies addressing circulating cytokines in humans, the available data suggest that the results may be more robust in animal models than in patients with problematic drug use. As a major conclusion, an extensive use of arrays for relevant cytokines should be considered to better determine which cytokines, upon the classical ones, may be involved in the progression from episodic use to the development of addiction. A concerted effort is still necessary to address the link between peripheral and central immune players, including from a longitudinal perspective. Until there, the identification of new biomarkers and therapeutic targets to envision personalized immune-based therapeutics will continue to be unlikely.

Early life stress can have significant effects on the developing brain and lead to changes in the structure and function of brain regions involved in stress regulation, emotion and cognitive control. Here, we used the social instability stress (SIS) protocol to understand the impact of social stress during mild (PND30) and late (PND45) adolescence. Our results revealed that SIS can compromise the dominance-subordination coping strategy but does not affect social recognition and motivation in rats. Moreover, SIS can lead to subtle modifications at the molecular level that hamper normal development of the prefrontal cortex in a sex- and age-dependent manner. Understanding the impact of early life stress on brain organization is crucial for developing effective prevention and intervention strategies. By identifying those who are most vulnerable to the effects of stress and providing targeted support and resources, it may be possible to mitigate the negative consequences of early adversity and promote healthy brain development.

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.

Humans have negatively impacted most ecosystems on Earth, altering how species use habitats and resources available to them, but also their circadian rhythms. Among many factors affecting animal activity patterns, conversion of native habitat into production forests and hunting are critical, and their impacts may be exacerbated by seasonal weather conditions. Both these factors are issues in Mediterranean Europe, especially in Portugal. Nevertheless, their impact on native species behavior remains largely unknown, even for generalist species often resilient to human disturbance such as wild boar (Sus scrofa). Therefore, we assessed temporal activity patterns of wild boar in Portugal to explore differences between habitats (native forest versus Eucalyptus plantations), hunting and non-hunting periods, or between seasons. We found that wild boars were primarily nocturnal, with greater nighttime activity more evident during the dry season and within plantations. Furthermore, they appeared to avoid dusk during the hunting season. Together, these patterns indicate that even a species typically resilient to disturbance and environmental change, such as wild boar, tends to avoid adverse weather conditions and disturbance factors, namely high daytime temperatures in summer and probability of encountering forestry workers or hunters. Accordingly, other more sensitive or resource-demanding mammals may also be affected, so evaluating the impacts of the studied anthropic drivers on other mammals should be prioritized to provide information for sustainable plantation management and hunting.

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure. This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT— Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-030647 (PTDC/ SAU-TOX/30647/2017) in TS lab. FEDER Portugal (Norte-01-0145-FEDER000008000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); FCOMP-01-0124-FEDER-021333). CCP and RS hold employment contracts financed by national funds through FCT –in the context of the program-contract described in paragraphs 4, 5, and 6 of art. 23 of Law no. 57/ 2016, of August 29, as amended by Law no. 57/2017 of July 2019. TC, TOA, AFT, JB, AIS and AM were supported by FCT (SFRH/BD/117148/2016, SFRH/BD/147981/2019, 2020.07188.BD, PD/BD/135450/2017, SFRH/BD/144324/2019, and IF/00753/2014). Work in JBR lab was supported by the FCT project PTDC/ MED-NEU/31318/2017. JFO was also supported by FCT projects PTDC/MED-NEU/31417/2017 and POCI-01- 0145-FEDER-016818; Bial Foundation Grants 207/14 and 037/18, by National funds, through FCT - project UIDB/50026/2020; and by the projects NORTE-01-0145-FEDER000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Funding of i3S Scientific Platforms: Advanced Light Microscopy (ALM), a member of the national infrastructure PPBI-Portuguese Platform of BioImaging (POCI-01–0145-FEDER022122); and Genomics through GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by FCT.

Purpose The purpose of this paper is to develop new boundary conditions for simulating the injection molding process of polymer melts. Design/methodology/approach The boundary conditions are derived and implemented to simulate real-life air vents (used to allow the air escape from the mold). The simulations are performed in the computational libraryOpenFOAM (R) by considering two different fluid models, namely, Newtonian and generalized Newtonian (Bird-Carreau model). Findings A detailed study on the accuracy of the solverinterFoamfor simulating the filling stage is presented, by considering simple geometries and adaptive mesh refinement. The verified code is then used to study the three-dimensional filling of a more complex geometry. Originality/value The results obtained showed that the numerical method is stable and allows one to model the filling process, simulating the real injection molding process., This work is funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT (Portuguese Foundation for Science and Technology) under the projects UID-B/05256/2020, UID-P/05256/2020 and MOLDPRO-Aproximacoes multi-escala para moldacao por injecao de materiais plasticos (POCI-01-0145-FEDER-016665).The research of L.L. Ferras was partially financed by the Portuguese Funds through FCT within the Projects UID-B/00013/2020, UID-P/00013/2020 and the scholarship SFRH/BPD/100353/2014.The authors would like to acknowledge the Minho University Cluster (NORTE-07-0162-FEDER-000086) for providing the HPC resources that contributed to the research results reported within this paper.

Analysis of rodents’ behavior/activity is of fundamental importance in many research fields. However, many behavioral experiments still rely on manual scoring, with obvious problems in reproducibility. Despite important advances in video-analysis systems and computational ethology, automated behavior quantification is still a challenge. The need for large training datasets, background stability requirements, and reduction to two-dimensional analysis (impairing full posture characterization), limit their use. Here we present a novel integrated solution for behavioral analysis of individual rats, combining video segmentation, tracking of body parts, and automated classification of behaviors, using machine learning and computer vision methods. Low-cost depth cameras (RGB-D) are used to enable three-dimensional tracking and classification in dark conditions and absence of color contrast. Our solution automatically tracks five anatomical landmarks in dynamic environments and recognizes seven distinct behaviors, within the accuracy range of human annotations. The developed free software was validated in experiments where behavioral differences between Wistar Kyoto and Wistar rats were automatically quantified. The results reveal the capability for effective automated phenotyping. An extended annotated RGB-D dataset is also made publicly available. The proposed solution is an easy-to-use tool, with low-cost setup and powerful 3D segmentation methods (in static/dynamic environments). The ability to work in dark conditions means that natural animal behavior is not affected by recording lights. Furthermore, automated classification is possible with only ~30 minutes of annotated videos. By creating conditions for high-throughput analysis and reproducible quantitative measurements of animal behavior experiments, we believe this contribution can greatly improve behavioral analysis research.

Acute ischemic stroke (AIS) remains a leading cause of mortality, despite significant advances in therapy (endovascular thrombectomy). Failure in developing novel effective therapies is associated with unsuccessful translation from preclinical studies to clinical practice, associated to inconsistent and highly variable infarct areas and lack of relevant post-stroke functional evaluation in preclinical research. To outreach these limitations, we optimized the intraluminal transient middle cerebral occlusion, a widely used mouse stroke model, in two key parameters, selection of appropriate occlusion filaments and time of occlusion, which show a significant variation in the literature. We demonstrate that commercially available filaments with short coating length (1-2 mm), together with 45-min occlusion, results in a consistent affected brain region, similar to what is observed in most patients with AIS. Importantly, a dedicated post-stroke care protocol, based on clinical practice applied to patients who had stroke, resulted in lower mortality and improved mice welfare. Finally, a battery of tests covering relevant fine motor skills, sensory functions, and learning/memory behaviors revealed a significant effect of tMCAO brain infarction, which is parallel to patient symptomatology as measured by relevant clinical scales (NIH Stroke Scale, NIHSS and modified Rankin Scale, mRS). Thus, in order to enhance translation to clinical practice, future preclinical stroke research must consider the methodology described in this study, which includes improved reproducible surgical procedure, postoperative care, and the battery of functional tests. This will be a major step s closing the gap from bench to bedside, rendering the development of novel effective therapeutic approaches.

Helicobacter pylori infects half of the world population, being associated with several gastric disorders, such as chronic gastritis and gastric carcinoma. The Helicobacter genus also includes other gastric helicobacters, such as H. heilmannii¸ H. ailurogastricus, H. suis, H. felis, H. bizzozeronii, and H. salomonis. These gastric helicobacters colonize both the human and animal stomach. The prevalence of gastric non-Helicobacter pylori Helicobacter (NHPH) species in humans has been described as low, and the in vitro binding to the human gastric mucosa was never assessed. Herein, human gastric tissue sections were used for the evaluation of the tissue glycophenotype and for the binding of gastric NHPH strains belonging to different species. Histopathological evaluation showed that 37.5% of the patients enrolled in our cohort presented chronic gastritis, while the presence of neutrophil or eosinophilic activity (chronic active gastritis) was observed in 62.5% of the patients. The secretor phenotype was observed in 68.8% of the individuals, based on the expression of Lewis B antigen and binding of the UleX lectin. The in vitro binding assay showed that all the NHPH strains evaluated were able to bind, albeit in low frequency, to the human gastric mucosa. The H. heilmannii, H. bizzozeronii, and H. salomonis strains displayed the highest binding ability both to the gastric superficial epithelium and to the deep glands. Interestingly, we observed binding of NHPH to the gastric mucosa of individuals with severe chronic inflammation and intestinal metaplasia, suggesting that NHPH binding may not be restricted to the healthy gastric mucosa or slight chronic gastritis. Furthermore, the in vitro binding of NHPH strains was observed both in secretor and non-secretor individuals in a similar frequency. In conclusion, this study is the first report of the in vitro binding ability of gastric NHPH species to the human gastric mucosa. The results suggest that other glycans, besides the Lewis antigens, could be involved in the bacterial adhesion mechanism; however, the molecular intervenients remain unknown.

Heparan Sulfate Proteoglycans (HSPGs) are important cell surface and Extracellular Matrix (ECM) maestros involved in the orchestration of multiple cellular events in physiology and pathology. These glycoconjugates bind to various bioactive proteins via their Heparan Sulfate (HS) chains, but also through the protein backbone, and function as scaffolds for protein-protein interactions, modulating extracellular ligand gradients, cell signalling networks and cell-cell/cell-ECM interactions. The structural features of HS chains, including length and sulfation patterns, are crucial for the biological roles displayed by HSPGs, as these features determine HS chains binding affinities and selectivity. The large HS structural diversity results from a tightly controlled biosynthetic pathway that is differently regulated in different organs, stages of development and pathologies, including cancer. This review addresses the regulatory mechanisms underlying HS biosynthesis, with a particular focus on the catalytic activity of the enzymes responsible for HS glycan sequences and sulfation motifs, namely D-Glucuronyl C5-Epimerase, N- and O-Sulfotransferases. Moreover, we provide insights on the impact of different HS structural epitopes over HSPG-protein interactions and cell signalling, as well as on the effects of deregulated expression of HS modifying enzymes in the development and progression of cancer. Finally, we discuss the clinical potential of HS biosynthetic enzymes as novel targets for therapy, and highlight the importance of developing new HS-based tools for better patients’ stratification and cancer treatment.

Microglial homeostatic functions are fundamental to regulate the central nervous system microenvironment. We use conditional cell-specific gene targeting, RNA-seq profiling, high-throughput proteomics, phosphoproteomics, systems biology, and animal behavior to report a critical role for the RhoGTPase Rac1 in regulating adult microglia physiology. Ablation of Rac1 in adult microglia impaired their ability to sense and interpret the brain microenvironment and affected their capacity to communicate with synapses to drive cognitive performance, both at the steady-state and during experience-dependent plasticity. Overall, our results reveal a novel and central role for Rac1 as a regulator of microglia homeostasis and a molecular driver of the microglia-synapse crosstalk required for context-dependent sociability and learning related to memory.

Heparan sulfate (HS) proteoglycans (HSPGs) are abundant glycoconjugates in cells' glycocalyx and extracellular matrix. By acting as scaffolds for protein-protein interactions, HSPGs modulate extracellular ligand gradients, cell signaling networks, and cell-extracellular matrix crosstalk. Aberrant expression of HSPGs and enzymes involved in HSPG biosynthesis and processing has been reported in tumors, with impact in cancer cell behavior and tumor microenvironment properties. However, the roles of specific glycosyltransferases in the deregulated biosynthesis of HSPGs are not fully understood. In this study, we established glycoengineered gastric cancer cell models lacking either exostosin-like glycosyltransferase 2 (EXTL2) or EXTL3 and revealed their regulatory roles in both HS and chondroitin sulfate (CS) biosynthesis and structural features. We showed that EXTL3 is key for initiating the synthesis of HS chains in detriment of CS biosynthesis, intervening in the fine-tuned balance of the HS/CS ratio in cells, while EXTL2 functions as a negative regulator of HS biosynthesis, with impact over the glycoproteome of gastric cancer cells. We demonstrated that KO of EXTL2 enhanced HS levels along with concomitant upregulation of Syndecan-4, which is a major cell surface carrier of HS. This aberrant HS expression profile promoted a more aggressive phenotype, characterized by higher cellular motility and invasion, and impaired activation of Ephrin type-A 4 cell surface receptor tyrosine kinase. Our findings uncover the biosynthetic roles of EXTL2 and EXTL3 in the regulation of cancer cell GAGosylation and proteoglycans expression and unravel the functional consequences of aberrant HS/CS balance in cellular malignant features.

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n=31,573) has the highest number of records followed by Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496), Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n=12,159], Monachus monachus [n=1,512], and Lynx pardinus [n=197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications.

Prosocial behavior in rats is known to occur in response to a familiar rat's distress, but the motivations underlying prosocial behavior remain elusive. In this study, we adapted the experimental setting of Ben-Ami Bartal, Decety, and Mason (2011) to explore different motivations behind helping behavior in adolescent rats. In the original setting, a free rat is placed in an arena where a cagemate is trapped inside a restrainer that can only be opened from the outside by the free rat. Here we added a dark compartment to the experimental setting that allowed the free rat to escape the arena and the distress evoked by the trapped cagemate, based on rodents' aversion to bright areas. As a control, we tested rats in the same arena but with the door to the dark area closed. Our results showed that all free rats, except one in the escape condition, learned to open the restrainer's door. However, in the escape condition, rats took significantly longer to open the restrainer to the cagemates when compared with rats that could not escape. To further explore the motivations underlying these group differences in door-opening latencies, we measured both rats' behavior. We found that struggling behavior (i.e., distress) in the trapped rat did not affect door-opening, whereas exploratory behavior (i.e., proactive/positive behavior) in both rats contributed to shorter times. Our results highlight that adolescent rats show prosocial behavior even when they can escape without helping and contribute to demonstrate the role of positive emotional states in prosocial behavior., This research project was financed by Fundacao para a Ciencia e Tecnologia (FCT) and Orcamento do Estado in the framework of the project IF/00753/2014/CP1241/CT0005 at Institute for Research and Innovation in Health Sciences and by European Regional Development Fund (FEDER) funds through Programa Operacional Factores de Competitividade-COMPETE and by Portuguese funds through FCT, in the framework of the project PTDC/MHCPAP/5304/2012 awarded to Instituto de Ciencias Biomedias de Abel Salazar at University of Porto. Part of this study was conducted at Psychology Research Centre (PSI/01662), University of Minho, supported by FCT and the Portuguese Ministry of Science, Technology and Higher Education through national funds, and cofinanced by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). Ana Magalhaes was supported by FCT (IF/00753/2014). Joana Carvalheiro holds an FCT fellowship (PD/BD/128467/2017). Ana Seara-Cardoso was supported by FCT (SFRH/BPD/94970/2013). Ana Raquel Mesquita was supported by FCT (IF/00750/2015). Teresa Summavielle was supported by FCT (IF/00875/2012).

Methylphenidate (MPH) is the classic treatment for attention deficit hyperactivity disorder (ADHD) among children and adults. Despite its beneficial effects, non-medical use of MPH is nowadays a problem with high impact on society. Thus, our goal was to uncover the neurovascular and cognitive effects of MPH chronic use during a critical period of development in control conditions. For that, male Wistar Kyoto rats were treated with MPH (1.5 or 5 mg/kg/day at weekdays, per os) from P28 to P55. We concluded that the higher dose of MPH caused hippocampal blood-brain barrier (BBB) hyperpermeability by vesicular transport (transcytosis) concomitantly with the presence of peripheral immune cells in the brain parenchyma. These observations were confirmed by in vitro studies, in which the knockdown of caveolin-1 in human brain endothelial cells prevented the increased permeability and leukocytes transmigration triggered by MPH (100 µM, 24 h). Furthermore, MPH led to astrocytic atrophy and to a decrease in the levels of several synaptic proteins and impairment of AKT/CREB signaling, together with working memory deficit assessed in the Y-maze test. On the contrary, we verified that the lower dose of MPH (1.5 mg/kg/day) increased astrocytic processes and upregulated several neuronal proteins as well as signaling pathways involved in synaptic plasticity culminating in working memory improvement. In conclusion, the present study reveals that a lower dose of MPH in normal rats improves memory performance being associated with the modulation of astrocytic morphology and synaptic machinery. However, a higher dose of MPH leads to BBB dysfunction and memory impairment.

The replacement of natural areas with forestry plantations is a worldwide expanding process with direct consequences for biodiversity and ecosystem functionality. In the Mediterranean region, Eucalyptus spp. plantations are widespread, forming monospecific landscapes that in Portugal dominate most of its forested areas. The reduction in the availability of native habitats induces important challenges to native wildlife, namely changes in habitat use patterns and behavior. In this study, we evaluated the influence of Eucalyptus globulus exotic plantations on the occupancy patterns of the red fox (Vulpes vulpes L.), a mesocarnivore widely distributed in the Palearctic, and we examined potential drivers shaping those patterns. We conducted camera trapping surveys in Central Portugal (Southwestern Europe), in eight 16 km2 grids, and analyzed the resulting occurrence data accounting for imperfect detection. Our analysis revealed a preference of the red fox for native vegetation over non-native plantations and avoidance of areas with higher human disturbance. Our data suggest that the current structure of exotic plantations can have a negative impact on species occurrence, even for generalist and resilient species such as the red fox. By gaining insight into landscape structures that promotes fox occupancy, our research can contribute to the development and implementation of more integrative management measures aiming to promote the presence and conservation of mesocarnivores in Eucalyptus dominated landscapes while ensuring sustainable exploitation of these plantations.

Agnaldo Manoel dos Santos dans son studio (années 1950) Ce dossier examine la relation qui s’est instaurée au Brésil, de 1950 à 1980, entre la culture matérielle – les gravures sur bois de la Literatura de cordel par exemple – et les arts visuels des années 1950-1980 comme la peinture pop. Dans cette introduction, nous utilisons les termes « culture matérielle » et « objets vernaculaires » pour identifier des objets auparavant appelés « populaires », nous attachant à leur forme, à leurs qual...

Helicobacter species infections may be associated with the development of gastric disorders, such as gastritis, peptic ulcers, intestinal metaplasia, dysplasia and gastric carcinoma. Binding of these bacteria to the gastric mucosa occurs through the recognition of specific glycan receptors expressed by the host epithelial cells. This review addresses the state of the art knowledge on these host glycan structures and the bacterial adhesins involved in Helicobacter spp. adhesion to gastric mucosa colonization. Glycans are expressed on every cell surface and they are crucial for several biological processes, including protein folding, cell signaling and recognition, and host-pathogen interactions. Helicobacter pylori is the most predominant gastric Helicobacter species in humans. The adhesion of this bacterium to glycan epitopes present on the gastric epithelial surface is a crucial step for a successful colonization. Major adhesins essential for colonization and infection are the blood-group antigen-binding adhesin (BabA) which mediates the interaction with fucosylated H-type 1 and Lewis B glycans, and the sialic acid-binding adhesin (SabA) which recognizes the sialyl-Lewis A and X glycan antigens. Since not every H. pylori strain expresses functional BabA or SabA adhesins, other bacterial proteins are most probably also involved in this adhesion process, including LabA (LacdiNAc-binding adhesin), which binds to the LacdiNAc motif on MUC5AC mucin. Besides H. pylori, several other gastric non-Helicobacter pylori Helicobacters (NHPH), mainly associated with pigs (H. suis) and pets (H. felis, H. bizzozeronii, H. salomonis, and H. heilmannii), may also colonize the human stomach and cause gastric disease, including gastritis, peptic ulcers and mucosa-associated lymphoid tissue (MALT) lymphoma. These NHPH lack homologous to the major known adhesins involved in colonization of the human stomach. In humans, NHPH infection rate is much lower than in the natural hosts. Differences in the glycosylation profile between gastric human and animal mucins acting as glycan receptors for NHPH-associated adhesins, may be involved. The identification and characterization of the key molecules involved in the adhesion of gastric Helicobacter species to the gastric mucosa is important to understand the colonization and infection strategies displayed by different members of this genus.

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies beta 3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth. Santa Casa da Misericordia de Lisboa MC-39-2019, Wings for Life WFL-PT-21/20, Portuguese Foundation for Science and Technology UID/BIM/04773/2013/CBMR info:eu-repo/semantics/publishedVersion

Depressive mothers often find the mother-child interaction to be challenging. Parental stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depression (Wistar and Kyoto) to investigate the impact of stress (maternal separation-MS) on maternal behaviour and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behaviour after weaning, while worsening their adolescent offspring cognitive behaviour. Whereas MS in Wistar dams elicited higher quality of pup-directed behaviour, increasing Brain-Derived Neurotrophic Factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to impact the salience of the social environment cues (as negative for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behaviour and stress regulatory processes.

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation that contributes to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders linked to cognitive impairment and neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in human Meth abusers), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a manner dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production or suppressing astrocytic calcium mobilization prevented microglia reactivity and abolished the behavioral phenotype elicited by Meth exposure. Overall, our data indicate that glial crosstalk is critical to relay behavioral alterations caused by acute Meth exposure.One Sentence SummaryGlial crosstalk under methamphetamine exposure

Cognitive dysfunction and dementia are presently recognized as major complications in α-synucleinopathies, namely in Dementia with Lewy Bodies (DLB) and Parkinson’s disease with dementia (PDD). In these disorders, α-Synuclein (αSyn) accumulation affects severely the hippocampus by inducing synaptic dysfunction which culminates in cognitive impairment. To characterize the mechanisms underlying αSyn-induced neuronal dysfunction we analysed the effect of overexpression or extracellular administration of αSyn on hippocampal neurons. We observed that αSyn induces the dysregulation of the actin-binding protein cofilin and its assembly into rod structures in a mechanism mediated by the cellular prion protein (PrPC). Moreover, we unraveled cofilin pathology as mediator of αSyn-induced dendritic spine impairment in hippocampal neurons. Importantly, in a synucleinopathy mouse model with cognitive impairment we validated cofilin dysregulation and synaptic dysfunction at the same age when cognitive deficits were observed. Our data supports cofilin as a novel player on hippocampal synaptic dysfunction triggered by αSyn on Lewy Body dementias.

Helicobacter species infections may be associated with the development of gastric disorders, such as gastritis, peptic ulcers, intestinal metaplasia, dysplasia and gastric carcinoma. Binding of these bacteria to the gastric mucosa occurs through the recognition of specific glycan receptors expressed by the host epithelial cells. This review addresses the state of the art knowledge on these host glycan structures and the bacterial adhesins involved in Helicobacter spp. adhesion to gastric mucosa colonization. Glycans are expressed on every cell surface and they are crucial for several biological processes, including protein folding, cell signaling and recognition, and host-pathogen interactions. Helicobacter pylori is the most predominant gastric Helicobacter species in humans. The adhesion of this bacterium to glycan epitopes present on the gastric epithelial surface is a crucial step for a successful colonization. Major adhesins essential for colonization and infection are the blood-group antigen-binding adhesin (BabA) which mediates the interaction with fucosylated H-type 1 and Lewis B glycans, and the sialic acid-binding adhesin (SabA) which recognizes the sialyl-Lewis A and X glycan antigens. Since not every H. pylori strain expresses functional BabA or SabA adhesins, other bacterial proteins are most probably also involved in this adhesion process, including LabA (LacdiNAc-binding adhesin), which binds to the LacdiNAc motif on MUC5AC mucin. Besides H. pylori, several other gastric non-Helicobacter pylori Helicobacters (NHPH), mainly associated with pigs (H. suis) and pets (H. felis, H. bizzozeronii, H. salomonis, and H. heilmannii), may also colonize the human stomach and cause gastric disease, including gastritis, peptic ulcers and mucosa-associated lymphoid tissue (MALT) lymphoma. These NHPH lack homologous to the major known adhesins involved in colonization of the human stomach. In humans, NHPH infection rate is much lower than in the natural hosts. Differences in the glycosylation profile between gastric human and animal mucins acting as glycan receptors for NHPH-associated adhesins, may be involved. The identification and characterization of the key molecules involved in the adhesion of gastric Helicobacter species to the gastric mucosa is important to understand the colonization and infection strategies displayed by different members of this genus.

One of the challenges in fashion recommendations is how to incorporate the concepts of fashion and style to provide a more tailored personalized experience for fashion lovers. Despite that these concepts are subjective, our fashion experts at Farfetch have defined a few key sets of aesthetics which attempt to capture the essence of users’ styles into groups. This categorization will help us to understand the customers’ fashion preferences and hence guide our recommendations through the subjectivity. In this paper, we will demonstrate that such concepts can be predicted from users’ behaviors and the products they have interacted with. We not only compared a popular machine learning algorithm—Random Forest with a more recent deep learning algorithm—Convolutional Neural Network (CNN), but also looked at 3 different sets of features: text, image, and inferred user statistics, together with their various combinations in building such models. Our results show that it is possible to identify a customer’s aesthetic based on this data. Moreover, we found that the use of the textual descriptions of products interacted by the customer led to better classification results.

Recommender systems in the context of luxury fashion need to have expert domain knowledge to offer the informed experience expected by the customers of this sector. Fashion experts have a strong understanding of the intricacies of the fashion scope. The brands and designers are some of the most important features of this landscape and the affinity between them is not always easy to grasp. This paper proposes an application of state-of-the-art NLP techniques to map the knowledge provided by experts in the form of texts. The outcome was a process to extract brand embeddings which mirror the semantic adjacency between all the brands in a catalogue. To test the utility of such an approach, we conducted extensive offline and online tests which have proven the positive reaction of the customers to the new feature. We applied the embeddings as boosting to a base recommender system and we observed an engagement uplift of up to 10%, and applied the embeddings as a content-based recommender to obtain an engagement uplift of up to 3%. Overall, we are confident of the importance of brand affinity information in recommender systems in the luxury fashion domain.

Com a finalidade de auxiliar na atividade de recuperacao de areas no bioma Cerrado, objetivou-se avaliar a restauracao florestal em uma comunidade arbustivo-arborea antropizada. A area de estudo localiza-se na Usina Hidreletrica Luiz Carlos Barreto Carvalho e foi utilizada como canteiro de obras, bota-fora e disposicao de residuos urbanos. Foram coletados dados em tres subareas separadas em baixa (B), media (M) e alta (A) interferencia antropica. Para a caracterizacao da regeneracao, foram coletados dados de altura e diâmetro a altura do solo das especies com altura > 0,50 m. Para as especies plantadas, foram mensuradas todas as especies, inclusive os individuos com altura inferior a 0,5 m. Foram identificados 40 familias, distribuidas em 98 especies, um total de 2.849 individuos. A familia de maior riqueza especifica foi a Fabaceae, e a especie Kielmeyera speciosa apresentou elevado valor de cobertura. Apesar do tempo curto de restauracao (24 meses), foram observadas semelhancas em diversidade quando comparado com areas conservadas de Cerrado strictu sensu. Verificou-se elevado numero de individuos produtores de sementes e de rebrota, como a Curatella americanan e Kielmeyera speciosa respectivamente. Em funcao da area de estudo apresentar predominância de especies com capacidade de rebrota e elevada producao de sementes, a conducao da regeneracao somada ao plantio de mudas para enriquecimento correspondem as tecnicas adequadas para reabilitacao do ambiente em detrimento aos procedimentos frequentes de plantio total da area com especies em diferentes niveis sucessionais.

Pancreatic cancers (PC) are highly metastatic with poor prognosis, mainly due to delayed detection. We previously showed that PC-derived extracellular vesicles (EVs) act on macrophages residing in the liver, eliciting extracellular matrix remodeling in this organ and marked hepatic accumulation of CD11b+ bone marrow (BM) cells, which support PC liver metastasis. We here show that PC-EVs also bind to CD11b+ BM cells and induce the expansion of this cell population. Transcriptomic characterization of these cells shows that PC-EVs upregulate IgG and IgA genes, which have been linked to the presence of monocytes/macrophages in tumor microenvironments. We also report here the transcriptional downregulation of genes linked to monocyte/macrophage activation, trafficking, and expression of inflammatory molecules. Together, these results show for the first time the existence of a PC–BM communication axis mediated by EVs with a potential role in PC tumor microenvironments.

The development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the Project POCI-01-0145-FEDER-032231 (PTDC/SAU-TOX/32231/2017). AM was supported by FCT and Orçamento do Estado in the framework of the Project EXPL-AMAGALHÃES - IF/00753/2014/CP1241/CT0005. RLA was supported by an FCT Grant (PD/BD/114266/2016). CCP hold an employment contract financed by national funds through FCT - Fundação para a Ciência e a Tecnologia, I.P., in the context of the program-contract described in paragraphs 4, 5 and 6 of art. 23 of Law no. 57/2016, of August 29, as amended by Law no. 57/2017 of July 19. AM was supported by FCT (IF/00753/2014).

Analysis of rodents' behavior/activity is of fundamental importance in many research fields. However, many behavioral experiments still rely on manual scoring, with obvious problems in reproducibility. Despite important advances in video-analysis systems and computational ethology, automated behavior quantification is still a challenge. The need for large training datasets, background stability requirements, and reduction to two-dimensional analysis (impairing full posture characterization), limit their use. Here we present a novel integrated solution for behavioral analysis of individual rats, combining video segmentation, tracking of body parts, and automated classification of behaviors, using machine learning and computer vision methods. Low-cost depth cameras (RGB-D) are used to enable three-dimensional tracking and classification in dark conditions and absence of color contrast. Our solution automatically tracks five anatomical landmarks in dynamic environments and recognizes seven distinct behaviors, within the accuracy range of human annotations. The developed free software was validated in experiments where behavioral differences between Wistar Kyoto and Wistar rats were automatically quantified. The results reveal the capability for effective automated phenotyping. An extended annotated RGB-D dataset is also made publicly available. The proposed solution is an easy-to-use tool, with low-cost setup and powerful 3D segmentation methods (in static/dynamic environments). The ability to work in dark conditions means that natural animal behavior is not affected by recording lights. Furthermore, automated classification is possible with only ~30 minutes of annotated videos. By creating conditions for high-throughput analysis and reproducible quantitative measurements of animal behavior experiments, we believe this contribution can greatly improve behavioral analysis research.

In osteoarthritis (OA), pain is the dominant clinical symptom, yet the therapeutic approaches remain inadequate. The knowledge of the nociceptive mechanisms in OA, which will allow to develop effective therapies for OA pain, is of utmost need. In this study, we investigated the nociceptive mechanisms involved in post-traumatic OA pain, using the destabilization of the medial meniscus (DMM) mouse model. Our results revealed the development of peripheral pain sensitization, reflected by augmented mechanical allodynia. Along with the development of pain behaviour, we observed an increase in the expression of calcitonin gene-related peptide (CGRP) in both the sensory nerve fibers of the periosteum and the dorsal root ganglia. Interestingly, we also observed that other nociceptive mechanisms commonly described in non-traumatic OA phenotypes, such as infiltration of the synovium by immune cells, neuropathic mechanisms and also central sensitization were not present. Overall, our results suggest that CGRP in the sensory nervous system is underlying the peripheral sensitization observed after traumatic knee injury in the DMM model, highlighting the CGRP as a putative therapeutic target to treat pain in post-traumatic OA. Moreover, our findings suggest that the nociceptive mechanisms involved in driving pain in post-traumatic OA are considerably different from those in non-traumatic OA. This work was financed by the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). CJA was supported by the project NORTE-01-0145-FEDER-000008 financed by NORTE 2020, under the PORTUGAL 2020 Partnership Agreement, through the ERDF. DMS is recipient of Fundação para a Ciência e a Tecnologia (FCT) Post-Doc fellowship (SFRH/BPD/115341/2016). LL and FC are recipients of FCT Ph.D. fellowships (SFRH/BD/109686/2015 and SFRH/BD/128771/2017, respectively). The authors acknowledge the support of the i3S Scientific Platforms Bioimaging, and Histology and Electron Microscopy (HEMS), members of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122), and Cláudia Machado (Instituto de Investigação e Inovação em Saúde) for helping with histology procedures.

Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in in vitro and in vivo hippocampal neurons. Moreover, these structural and synaptic roles of megalin impact on learning and memory mechanisms, since megalin heterozygous mice show hippocampal-related memory and learning deficits in several behaviour tests. Altogether, we unveil a complete novel role of megalin in the physiological neuronal activity, mainly in synaptic plasticity with impact in learning and memory. Importantly, we contribute to disclose the molecular mechanisms underlying the cognitive and intellectual disabilities related to megalin gene pathologies., Donnai-Barrow syndrome, genetic disorder linked to megalin mutations, shows unexplained intellectual deficits. We describe that megalin, a multifunctional receptor, via its ligand TTR, regulates neuronal activity and survival. Additionally, we unravel a novel role of megalin in synaptic plasticity, with impact on learning and memory, explaining the described intellectual disabilities., Graphical Abstract Graphical Abstract

Citizen science is increasingly contributing to ecology and conservation research, mostly by the extensive collection of field data. Although webcams attract numerous observers, they have been underused in this respect. We used prey delivery records deposited by citizen scientists in an internet forum linked to webcams to explore the diet composition and food provisioning in a forest-dwelling raptor of conservation concern, the Lesser Spotted Eagle (Clanga pomarina). Four pairs were studied throughout the breeding season. Most of the identified prey items were mammals (62.1%), followed by frogs (31.2%), birds (6.6%) and fish (0.1%). Among mammals, voles accounted for 84.6%, moles 12.1%, water voles 2.4% and weasels 0.4%. Frogs were the most frequently detected prey item in the spring, with a slight increase towards the end of the season, the proportion of mammals increased during the breeding season, and birds were hunted mostly in the middle of the breeding season. However, exact temporal patterns differed between nests. The food delivery rate of males increased over time but decreased somewhat before fledging the young. Females started hunting in mid-summer and their rapidly increasing effort compensated for a reduced male hunting intensity. The data collected by citizen scientists via webcams reflected the general patterns detected in earlier studies, supporting the reliability of crowd-sourced web-based data collection in avian foraging ecology.

The migration and dissemination of architectural models, which may be recognized all along the History of Architecture, accelerated throughout the 20th century, particularly after the Second World War. If on the one hand the geopolitical map as then defined led to a new paradigm of globalization, on the other hand the doctrinal, and often dogmatic, consistency of the architectural thought and production right from the origins of the Modern Movement allowed for the construction of models that facilitated their spreading and acceptance. The concept of flow or exchange associated with the mobility of architects between regions and cultures or with the dissemination of ideas and works is one of the main features of the Modern Movement. It is also under the sign of the idea of flow and exchange that we may understand the architectural production in Angola and Mozambique, both former Portuguese colonies, during the period of the second post-war until their independences in 1975. This paper’s intention is, on the one hand, to understand the mechanisms of dissemination of international architectural models and their acceptance in those African countries from a historical point of view, and on the other hand, to analyse the processes of their interpretation in a more orthodox, hybrid or critical meaning. Africa meant for the architects who built there an ideal laboratory for experimenting the modern language, not only by adopting such formal vocabulary, but also by testing building and geography and tropical climate adaptation. At the same time, it is necessary to consider how such idea of modernity and progress was developed within the framework of a colonial society and led to an ideological paradox: how was the assertion of democracy that is present in the genesis of the Modern Movement reconciled with the colonial ideology?

Using a simple experimental layout, some results on the evolution of global heat transfer coefficient for two phase change materials (PCM), during fusion and solidification processes, were determined. To do this, a system using commercially available thermal oil as the heat transfer carrier was used and the phase change material being tested operated in a fusion and solidification cycle. The heat transfer oil transferred heat to the phase change material during the fusion step and carried heat away from the phase change material during the solidification step. The influence of the mass flow rate of the heat transfer fluid, as well as of its temperature, in the evolution of the overall heat transfer coefficient from the thermal oil to the PCM during its fusion and in the opposite direction during the PCM solidification, for a given experimental set-up, was studied. One of the tested phase change materials was a salt while the other was a paraffin.

International audience; Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.

Alcohol use adversely impacts the life of millions of people worldwide. Deficits in synaptic transmission and in microglial function are common findings in human alcohol users and in animal models of alcohol intoxication. Here, we show that alcohol intake over ten consecutive days resulted in substantial loss of excitatory synapse in the prefrontal cortex, a consequence of aberrant synaptic pruning, which led to increased anxiety-like behavior. Mechanistically, these effects of alcohol intake were mediated by a detrimental increase of microglia engulfment capacity via Src-dependent activation of NFkB and consequent TNF production. Accordingly, pharmacological blockade of Src activation or TNF production by microglia, genetic ablation of TNF, or diphtheria toxin-mediated conditional ablation of microglia attenuated aberrant synaptic pruning preventing excitatory synapse loss and anxiety-like behavior. Overall, our data suggest that aberrant pruning of excitatory synapses by microglia might disrupt synaptic transmission during alcohol use.

CD44 isoforms are often upregulated in gastric cancer and have been associated with increased metastatic potential and poor survival. To evaluate the functional impact of O-glycan truncation on CD44 we have analysed glyco-engineered cancer cell models displaying shortened O-glycans. Here, we demonstrate that induction of aberrant O-glycan termination through various molecular mechanisms affects CD44 molecular features. We show that CD44 is a major carrier of truncated O-glycans and that this truncation is accompanied by an increased hyaluronan binding capacity and affects extracellular shedding. In addition, short O-glycans promoted the colocalization of CD44v6 with the receptor tyrosine kinase RON and concomitantly increased activation. Our in vitro findings were validated in gastric cancer clinical samples. We This This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; POCI-01-0145-FEDER-028489) and National Funds through the Foundation for Science and Technology (FCT), under the projects: PTDC/BBB-EBI/0567/2014 (to CAR), PTDC/MED-ONC/28489/2017 (to AM), UID/BIM/04293/2013 and CEECIND/02760/2017 (to SM); and the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We acknowledge the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 748880 (to MB). The authors acknowledge the support by Gastric Glyco Explorer Initial Training Network (European Union Seventh Framework Programme GastricGlycoExplorer project, grant number 316929). The authors declare noconflict of interest.

O-glycosylation is a highly frequent post-translation modification of proteins, with important functional implications in both physiological and disease contexts. The biosynthesis of O-glycans depends on several layers of regulation of the cellular glycosylation machinery, being organ-, tissue- and cell-specific. This review provides insights on the molecular mechanism underlying O-glycan biosynthesis and modification, and highlights illustrative examples of diseases that are triggered or modulated by aberrant cellular O-glycosylation. Particular relevance is given to genetic disorders of glycosylation, infectious diseases and cancer. Finally, we address the potential of O-glycans and their biosynthetic pathways as targets for novel therapeutic strategies.

We conducted a floristic survey of “Cerrado” sensu stricto on Quartzipsamment soils in the northeastern state of Goias, Brazil, in Terra Ronca State Park (PETeR). In addition, we analysed phytogeographical aspects to investigate the floristic relationships between “Cerrado” and the Amazon, Atlantic Forest and “Caatinga” biomes. Furthermore, we assessed the shrub–tree flora similarity with other sites having the same type of physiognomy and soil class. We collected species along three 5 km × 60 m (90 ha) transects and recorded 278 species. Erythroxylum loefgrenii Diogo, Eugenia blanchetiana O.Berg and Martianthus stachydifolius (Epling) Harley & J.F.B.Pastore were listed as new records for the “Cerrado” (Brazilian savanna), and thirteen species were newly recorded for the state of Goias. Approximately, 28% of the species are endemic to the “Cerrado”, and 72% are shared with other Brazilian biomes. The shrub–tree layer of the “Cerrado” shares more species with the “Caatinga”, which shows the transitional aspects and affinities of the local flora with this biome. The high similarity between the woody flora of PETeR and “Cerrado” sensu stricto on Quartzipsamment soil sites in Bahia and northern Minas Gerais state associated with the occurrence of floristic elements that considered typical of the north–northeast portion of the “Cerrado” phytogeographical province reinforces the inclusion of the northeast region of Goias in this floristic province. The protected area in the Vao do Parana region represents only 3.3% of the total area of the region and 6% of the remaining natural vegetation in the area. Considering that the studied region holds an important flora and at the same time presents strong anthropogenic pressure from the occupation of agribusiness, it would be extremely important to prioritize conservation strategies to maintain the remaining natural vegetation in the northeastern portion of the “Cerrado”.