2444402 research outputs found
Sort by
Exploring and learning structure : active inference approach in navigational agents
No full textDrawing inspiration from animal navigation strategies, we introduce a novel computational model for navigation and mapping, rooted in biologically inspired principles. Animals exhibit remarkable navigation abilities by efficiently using memory, imagination, and strategic decision-making to navigate complex and aliased environments. Building on these insights, we integrate traditional cognitive mapping approaches with an Active Inference Framework (AIF) to learn an environment structure in a few steps. Through the incorporation of topological mapping for long-term memory and AIF for navigation planning and structure learning, our model can dynamically apprehend environmental structures and expand its internal map with predicted beliefs during exploration. Comparative experiments with the Clone-Structured Graph (CSCG) model highlight our model’s ability to rapidly learn environmental structures in a single episode, with minimal navigation overlap. This is achieved without prior knowledge of the dimensions of the environment or the type of observations, showcasing its robustness and effectiveness in navigating ambiguous environments.Drawing inspiration from animal navigation strategies, we introduce a novel computational model for navigation and mapping, rooted in biologically inspired principles. Animals exhibit remarkable navigation abilities by efficiently using memory, imagination, and strategic decision-making to navigate complex and aliased environments. Building on these insights, we integrate traditional cognitive mapping approaches with an Active Inference Framework (AIF) to learn an environment structure in a few steps. Through the incorporation of topological mapping for long-term memory and AIF for navigation planning and structure learning, our model can dynamically apprehend environmental structures and expand its internal map with predicted beliefs during exploration. Comparative experiments with the Clone-Structured Graph (CSCG) model highlight our model’s ability to rapidly learn environmental structures in a single episode, with minimal navigation overlap. This is achieved without prior knowledge of the dimensions of the environment or the type of observations, showcasing its robustness and effectiveness in navigating ambiguous environments.C
Fluorescence Lifetime Imaging Microscopy (FLIM) visualizes internalization and biological impact of nanoplastics in live intestinal organoids
No full textThe increasing micro- and nanoplastic (MNP) pollution poses significant risks to human and animal health, yet the mechanisms of their accumulation and effects on absorptive tissues such as the gastrointestinal tract remain poorly understood. Addressing these knowledge gaps requires tractable models coupled to dynamic live cell imaging methods, to enable multi-parameter analysis at single cell resolution. Here we report a new method combining adult stem cell-derived small intestinal organoid cultures with multi-parameter live Fluorescence Lifetime Imaging Microscopy (FLIM) to study MNP interactions with gut epithelium. To facilitate this, we optimized live imaging of porcine and mouse small intestinal organoids with an apical-out topology. Subsequently, we produced a set of pristine MNPs based on PMMA and PS (<200 nm, doped with deep-red fluorescent dye) exhibiting different surface charges, and evaluated their interaction with organoids displaying controlled epithelial polarity. We found that nanoparticles differently interacted with apical and basal membranes of the organoids and even showed a species-specific pattern of cellular uptake. Using a phasor-FLIM approach, we demonstrate better sensitivity of FLIM over conventional intensity-based microscopy. The fluorescence lifetime barcoding enabled distinguishing different types of MNP and their interaction sites within organoids. Finally, we studied short (1 day)- and long (3 days)-term exposure effects of PMMA and PS-based MNPs on mitochondrial function, total energy budget and epithelial inflammation and found that even pristine MNPs could disrupt chemokine production and mitochondrial membrane potential in intestinal epithelial cells. The presented FLIM approach will advance the study of MNP toxicity, their biological impacts on gastrointestinal tissue and help tracing other types of fluorescent nanoparticles in live organoid and 3D ex vivo systems.The increasing micro- and nanoplastic (MNP) pollution poses significant risks to human and animal health, yet the mechanisms of their accumulation and effects on absorptive tissues such as the gastrointestinal tract remain poorly understood. Addressing these knowledge gaps requires tractable models coupled to dynamic live cell imaging methods, to enable multi-parameter analysis at single cell resolution. Here we report a new method combining adult stem cell-derived small intestinal organoid cultures with multi-parameter live Fluorescence Lifetime Imaging Microscopy (FLIM) to study MNP interactions with gut epithelium. To facilitate this, we optimized live imaging of porcine and mouse small intestinal organoids with an apical-out topology. Subsequently, we produced a set of pristine MNPs based on PMMA and PS (<200 nm, doped with deep-red fluorescent dye) exhibiting different surface charges, and evaluated their interaction with organoids displaying controlled epithelial polarity. We found that nanoparticles differently interacted with apical and basal membranes of the organoids and even showed a species-specific pattern of cellular uptake. Using a phasor-FLIM approach, we demonstrate better sensitivity of FLIM over conventional intensity-based microscopy. The fluorescence lifetime barcoding enabled distinguishing different types of MNP and their interaction sites within organoids. Finally, we studied short (1 day)- and long (3 days)-term exposure effects of PMMA and PS-based MNPs on mitochondrial function, total energy budget and epithelial inflammation and found that even pristine MNPs could disrupt chemokine production and mitochondrial membrane potential in intestinal epithelial cells. The presented FLIM approach will advance the study of MNP toxicity, their biological impacts on gastrointestinal tissue and help tracing other types of fluorescent nanoparticles in live organoid and 3D ex vivo systems.
Savickis v. Latvia : the role of immutability and choice in the discrimination analysis of the ECtHR
No full textOn June 9, 2022, the Grand Chamber of the European Court of Human Rights (ECtHR) ruled on Savickis and Others v. Latvia, addressing Latvia’s pension system, which offers preferential benefits to citizens over “permanently resident non-citizens” who chose not to naturalize. This decision marks a departure from the 2009 Andrejeva v. Latvia judgment, which deemed such treatment discriminatory. The Savickis ruling accepted the differential treatment by emphasizing personal choice in naturalization, a stance criticized as victim-blaming and raising fundamental questions about the Court’s criteria for distinguishing between mutable and immutable traits in discrimination cases. This analysis explores the implications of the Savickis judgment on the Court’s approach to justifying discrimination. It argues that the Court’s reasoning may allow states to frame discrimination on mutable grounds, thereby weakening protections under Article 14 ECHR. By extrapolating the Court’s logic to other areas such as religion, gender, disability, and language, the study highlights the potential for absurd outcomes where victims might be expected to alter intrinsic aspects of their identity to avoid discrimination. This challenges the foundational principle of non-discrimination as protected by the Convention and questions the responsibilities placed on individuals to mitigate discrimination.On June 9, 2022, the Grand Chamber of the European Court of Human Rights (ECtHR) ruled on Savickis and Others v. Latvia, addressing Latvia’s pension system, which offers preferential benefits to citizens over “permanently resident non-citizens” who chose not to naturalize. This decision marks a departure from the 2009 Andrejeva v. Latvia judgment, which deemed such treatment discriminatory. The Savickis ruling accepted the differential treatment by emphasizing personal choice in naturalization, a stance criticized as victim-blaming and raising fundamental questions about the Court’s criteria for distinguishing between mutable and immutable traits in discrimination cases. This analysis explores the implications of the Savickis judgment on the Court’s approach to justifying discrimination. It argues that the Court’s reasoning may allow states to frame discrimination on mutable grounds, thereby weakening protections under Article 14 ECHR. By extrapolating the Court’s logic to other areas such as religion, gender, disability, and language, the study highlights the potential for absurd outcomes where victims might be expected to alter intrinsic aspects of their identity to avoid discrimination. This challenges the foundational principle of non-discrimination as protected by the Convention and questions the responsibilities placed on individuals to mitigate discrimination.A
Atypical spindle cell lipomatous tumor in the pelvis causing sciatic nerve compression: A case report
No full textA frameshift variant in the SLC6A5 gene is associated with startle disease in a family of Old English Sheepdogs
No full textA 2-week-old litter of three Old English Sheepdog puppies presented with episodic generalised muscle hypertonia and cyanosis triggered by touch and noise. Owing to poor response to therapy and progression of symptoms, the puppies were euthanised. Post-mortem histology revealed perineuronal incrustations in the spinal cord, suggestive of ischemia or neuronal necrosis. Clinical symptoms, combined with necropsy and histopathology findings, led to a suspicion of startle disease, prompting a referral to a specialised clinical genetics centre. Whole exome sequencing (WES) of the nuclear family identified a homozygous truncating variant in the SLC6A5 gene in affected individuals, with both unaffected parents being heterozygous. Additional population screening found three phenotypically unaffected carriers, indicating that the variant segregates within the Old English Sheepdog breed. This raises concerns about the management of carriers and their breeding contributions if not properly guided by DNA testing. This study addresses a frameshift variant SLC6A5:c.1322del found in Old English Sheepdogs. Next to this, the value of genetic counselling and clinical genetics services in breeding programmes is highlighted to identify carriers and guide informed breeding decisions. Finally, the findings demonstrate the utility of WES in veterinary diagnostics and provide practical insights for breeders, veterinarians and geneticists to improve the health and welfare of Old English Sheepdogs.A 2-week-old litter of three Old English Sheepdog puppies presented with episodic generalised muscle hypertonia and cyanosis triggered by touch and noise. Owing to poor response to therapy and progression of symptoms, the puppies were euthanised. Post-mortem histology revealed perineuronal incrustations in the spinal cord, suggestive of ischemia or neuronal necrosis. Clinical symptoms, combined with necropsy and histopathology findings, led to a suspicion of startle disease, prompting a referral to a specialised clinical genetics centre. Whole exome sequencing (WES) of the nuclear family identified a homozygous truncating variant in the SLC6A5 gene in affected individuals, with both unaffected parents being heterozygous. Additional population screening found three phenotypically unaffected carriers, indicating that the variant segregates within the Old English Sheepdog breed. This raises concerns about the management of carriers and their breeding contributions if not properly guided by DNA testing. This study addresses a frameshift variant SLC6A5:c.1322del found in Old English Sheepdogs. Next to this, the value of genetic counselling and clinical genetics services in breeding programmes is highlighted to identify carriers and guide informed breeding decisions. Finally, the findings demonstrate the utility of WES in veterinary diagnostics and provide practical insights for breeders, veterinarians and geneticists to improve the health and welfare of Old English Sheepdogs.A
How nitrogen deposition hampers common juniper regeneration in heathlands
No full textAims Common Juniper (Juniper communis) populations in western Europe are rapidly declining due to a lack of regeneration, which has been linked to nitrogen (N) deposition. However, the mechanisms by which N deposition affects juniper are not clear. Nitrogen deposition can lead to N eutrophication and soil acidification, which cause nutrient leaching and metal mobilisation with potential negative impacts on juniper regeneration. We investigated associations among soil element concentration (soil [E]), needle element concentration (needle [E]) and plant performance in terms of height growth and viable seed production. Methods We sampled adult females and juveniles across 6 natural heathland areas in the Netherlands and Belgium, and applied linear mixed models for eleven elements to test associations among plant performance, soil [E], and needle [E]. Results Soil [E] was reflected in needle [E], which subsequently was associated with juniper growth. However, direct associations between soil [E] and growth were absent. Seed viability was positively associated with soil Mg concentration, marginally with Ca and needle Ca and K concentrations, and negatively with soil NO3 and needle N, S and Zn concentrations. Generally seed viability, needle Ca and K concentrations were low. Soil Al/P ratio was a better predictor for needle P than soil P concentration indicating that Al inhibits P uptake. Conclusion We conclude that 1) N eutrophication reduces seed viability, but increases growth, 2) nutrient leaching reduces nutrient uptake, seed viability and subsequently growth, and 3) Al mobilisation reduces P uptake and indirectly growth. N deposition amplifies these mechanisms and therefore inhibits regeneration and survival of juniper populations in western Europe.Aims Common Juniper (Juniper communis) populations in western Europe are rapidly declining due to a lack of regeneration, which has been linked to nitrogen (N) deposition. However, the mechanisms by which N deposition affects juniper are not clear. Nitrogen deposition can lead to N eutrophication and soil acidification, which cause nutrient leaching and metal mobilisation with potential negative impacts on juniper regeneration. We investigated associations among soil element concentration (soil [E]), needle element concentration (needle [E]) and plant performance in terms of height growth and viable seed production. Methods We sampled adult females and juveniles across 6 natural heathland areas in the Netherlands and Belgium, and applied linear mixed models for eleven elements to test associations among plant performance, soil [E], and needle [E]. Results Soil [E] was reflected in needle [E], which subsequently was associated with juniper growth. However, direct associations between soil [E] and growth were absent. Seed viability was positively associated with soil Mg concentration, marginally with Ca and needle Ca and K concentrations, and negatively with soil NO3 and needle N, S and Zn concentrations. Generally seed viability, needle Ca and K concentrations were low. Soil Al/P ratio was a better predictor for needle P than soil P concentration indicating that Al inhibits P uptake. Conclusion We conclude that 1) N eutrophication reduces seed viability, but increases growth, 2) nutrient leaching reduces nutrient uptake, seed viability and subsequently growth, and 3) Al mobilisation reduces P uptake and indirectly growth. N deposition amplifies these mechanisms and therefore inhibits regeneration and survival of juniper populations in western Europe.A
