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See detailCompte-rendu de l'ouvrage: Fake News & viralité avant Internet. Les lapins du Père- Lachaise et autres légendes médiatiques
Schafer, Valerie UL

in Le Temps des Médias (2022), 38

Recension de l'ouvrage : Roy Pinker, Fake News & viralité avant Internet. Les lapins du Père- Lachaise et autres légendes média- tiques, Paris, CNRS Éditions, 2020, 231 pages.

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See detailAggregating and Consolidating two High Performant Network Topologies: The ULHPC Experience
Varrette, Sébastien UL; Cartiaux, Hyacinthe UL; Valette, Teddy UL et al

in ACM Practice and Experience in Advanced Research Computing (PEARC'22) (2022, July)

High Performance Computing (HPC) encompasses advanced computation over parallel processing. The execution time of a given simulation depends upon many factors, such as the number of CPU/GPU cores, their ... [more ▼]

High Performance Computing (HPC) encompasses advanced computation over parallel processing. The execution time of a given simulation depends upon many factors, such as the number of CPU/GPU cores, their utilisation factor and, of course, the inter- connect performance, efficiency, and scalability. In practice, this last component and the associated topology remains the most significant differentiators between HPC systems and lesser perfor- mant systems. The University of Luxembourg operates since 2007 a large academic HPC facility which remains one of the reference implementation within the country and offers a cutting-edge re- search infrastructure to Luxembourg public research. The main high-bandwidth low-latency network of the operated facility relies on the dominant interconnect technology in the HPC market i.e., Infiniband (IB) over a Fat-tree topology. It is complemented by an Ethernet-based network defined for management tasks, external access and interactions with user’s applications that do not support Infiniband natively. The recent acquisition of a new cutting-edge supercomputer Aion which was federated with the previous flag- ship cluster Iris was the occasion to aggregate and consolidate the two types of networks. This article depicts the architecture and the solutions designed to expand and consolidate the existing networks beyond their seminal capacity limits while keeping at best their Bisection bandwidth. At the IB level, and despite moving from a non-blocking configuration, the proposed approach defines a blocking topology maintaining the previous Fat-Tree height. The leaf connection capacity is more than tripled (moving from 216 to 672 end-points) while exhibiting very marginal penalties, i.e. less than 3% (resp. 0.3%) Read (resp. Write) bandwidth degradation against reference parallel I/O benchmarks, or a stable and sustain- able point-to-point bandwidth efficiency among all possible pairs of nodes (measured above 95.45% for bi-directional streams). With regards the Ethernet network, a novel 2-layer topology aiming for improving the availability, maintainability and scalability of the interconnect is described. It was deployed together with consistent network VLANs and subnets enforcing strict security policies via ACLs defined on the layer 3, offering isolated and secure net- work environments. The implemented approaches are applicable to a broad range of HPC infrastructures and thus may help other HPC centres to consolidate their own interconnect stacks when designing or expanding their network infrastructures. [less ▲]

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See detailManagement of an Academic HPC Research Computing Facility: The ULHPC Experience 2.0
Varrette, Sébastien UL; Cartiaux, Hyacinthe UL; Peter, Sarah UL et al

in 6th High Performance Computing and Cluster Technologies Conference (HPCCT 2022) (2022, July)

With the advent of the technological revolution and the digital transformation that made all scientific disciplines becoming computational, the need for High Performance Computing (HPC) has become and a ... [more ▼]

With the advent of the technological revolution and the digital transformation that made all scientific disciplines becoming computational, the need for High Performance Computing (HPC) has become and a strategic and critical asset to leverage new research and business in all domains requiring computing and storage performance. Since 2007, the University of Luxembourg operates a large academic HPC facility which remains the reference implementation within the country. This paper provides a general description of the current platform implementation as well as its operational management choices which have been adapted to the integration of a new liquid-cooled supercomputer, named Aion, released in 2021. The administration of a HPC facility to provide state-of-art computing systems, storage and software is indeed a complex and dynamic enterprise with the soul purpose to offer an enhanced user experience for intensive research computing and large-scale analytic workflows. Most design choices and feedback described in this work have been motivated by several years of experience in addressing in a flexible and convenient way the heterogeneous needs inherent to an academic environment towards research excellence. The different layers and stacks used within the operated facilities are reviewed, in particular with regards the user software management, or the adaptation of the Slurm Resource and Job Management System (RJMS) configuration with novel incentives mechanisms. In practice, the described and implemented environment brought concrete and measurable improvements with regards the platform utilization (+12,64%), jobs efficiency (average Wall-time Request Accuracy improved by 110,81%), the management and funding (increased by 10%). Thorough performance evaluation of the facility is also presented in this paper through reference benchmarks such as HPL, HPCG, Graph500, IOR or IO500. It reveals sustainable and scalable performance comparable to the most powerful supercomputers in the world, including for energy-efficient metrics (for instance, 5,19 GFlops/W (resp. 6,14 MTEPS/W) were demonstrated for full HPL (resp. Graph500) runs across all Aion nodes). [less ▲]

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See detailDigital Twin for Human–Robot Interactions by Means of Industry 4.0 Enabling Technologies
Gallala, Abir; Kumar, Atal Anil UL; Hichri, Bassem UL et al

in Sensors (2022), 22(13), 1-17

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See detailmmWave Cognitive Radar: Adaptive Waveform Design and Implementation
Raei, Ehsan UL

Doctoral thesis (2022)

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See detailAssessing the need for power system flexibility on a global level: A multi-criteria assessment index
Bhuiyan, Rajon UL

Presentation (2022, June 21)

To effectively cope with the intermittency of VRE, power systems will need different flexibility options. The future portfolio of flexibility options will differ among countries, as it will be determined ... [more ▼]

To effectively cope with the intermittency of VRE, power systems will need different flexibility options. The future portfolio of flexibility options will differ among countries, as it will be determined by the political, economic, social, technological, legal, and environmental factors of a country. Thus, some countries might have a greater need for flexibility options than others. Generation and expansion planning for renewable power systems on a national level are complex and require large long-term investments. Therefore, it is crucial to estimate the "need for flexibility" in energy systems from a macro-level. By assessing relevant indicators (e.g., economic) and different boundary conditions (e.g., VRE capacity), power system planners, policymakers, operators, and regulators can evaluate the need for flexibility in power systems and prioritize the needed actions. Published research and international reports do not refer to the countries with the highest need for flexibility options in respective power systems. In this regard, the aim of this paper is to answer the following question: "Which countries in the world have the highest need for flexibility options from a macro-energy systems point of view?" To answer our question, first, we have identified relevant indicators from the literature that can help us to estimate the "need for flexibility" in national power systems. Second, we weighed the different indicators according to their importance by using the analytical hierarchy process (AHP) of the multi- criteria decision analysis (MCDA) process. Finally, this paper proposes a “global index for flexibility need” using these indicators. As for the results, countries were ranked in this index based on indicators and already show us the promising countries with the top 10 dominated by European countries. This index works as a macro-level assessment framework that provides the comparative position of countries with regard to the need for flexibility. This index will help technology providers and increase investor confidence to choose countries with the highest "flexibility need" for technology implementation. This will help relevant stakeholders to focus on key countries first to accelerate the integration of VRE and thus help the global energy transition. [less ▲]

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See detailLight Control over Chirality Selective Functionalization of Substrate Supported Carbon Nanotubes
Gordeev, Georgy UL; Rosenkranz, Thomas; Hennrich, Frank et al

in The journal of physical chemistry C (2022), 126(23), 9803-9812

Diazonium reactions with carbon nanotubes form optical sp3 defects that can be used in optical and electrical circuits. We investigate a direct on-device reaction supported by confined laser irradiation ... [more ▼]

Diazonium reactions with carbon nanotubes form optical sp3 defects that can be used in optical and electrical circuits. We investigate a direct on-device reaction supported by confined laser irradiation and present a technique where an arbitrary carbon nanotube can be preferentially functionalized within a device by matching the light frequency with its transition energy. An exemplary reaction was carried out between (9,7) nanotube and 4-bromobenzenediazonium tetrafluoroborate. The substrate supported nanotubes of multiple semiconducting chiralities were locally exposed to laser light while monitoring the reaction kinetics in situ via Raman spectroscopy. The chiral selectivity of the reaction was confirmed by resonant Raman spectroscopy, reporting a 10 meV E22 transition energy red-shift only of the targeted species. We further demonstrated this method on a single tube (9,7) electroluminescent device and show a 25 meV red-shifted emission of the ground state E11 compared to the emission from the pristine tubes. [less ▲]

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See detailLuxemBERT: Simple and Practical Data Augmentation in Language Model Pre-Training for Luxembourgish
Lothritz, Cedric UL; Lebichot, Bertrand UL; Allix, Kevin UL et al

in Proceedings of the Language Resources and Evaluation Conference, 2022 (2022, June)

Pre-trained Language Models such as BERT have become ubiquitous in NLP where they have achieved state-of-the-art performance in most NLP tasks. While these models are readily available for English and ... [more ▼]

Pre-trained Language Models such as BERT have become ubiquitous in NLP where they have achieved state-of-the-art performance in most NLP tasks. While these models are readily available for English and other widely spoken languages, they remain scarce for low-resource languages such as Luxembourgish. In this paper, we present LuxemBERT, a BERT model for the Luxembourgish language that we create using the following approach: we augment the pre-training dataset by considering text data from a closely related language that we partially translate using a simple and straightforward method. We are then able to produce the LuxemBERT model, which we show to be effective for various NLP tasks: it outperforms a simple baseline built with the available Luxembourgish text data as well the multilingual mBERT model, which is currently the only option for transformer-based language models in Luxembourgish. Furthermore, we present datasets for various downstream NLP tasks that we created for this study and will make available to researchers on request. [less ▲]

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See detailPolygenic Resilience Modulates the Penetrance of Parkinson Disease Genetic Risk Factors
Liu, Hui; Dehestani, Mohammad; Blauwendraat, Cornelis et al

in Annals of Neurology (2022)

Objective: The aim of the current study is to understand why some individuals avoid developing Parkinson disease (PD) despite being at relatively high genetic risk, using the largest datasets of ... [more ▼]

Objective: The aim of the current study is to understand why some individuals avoid developing Parkinson disease (PD) despite being at relatively high genetic risk, using the largest datasets of individual-level genetic data available. Methods: We calculated polygenic risk score to identify controls and matched PD cases with the highest burden of genetic risk for PD in the discovery cohort (International Parkinson's Disease Genomics Consortium, 7,204 PD cases and 9,412 controls) and validation cohorts (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease, 8,968 cases and 7,598 controls; UK Biobank, 2,639 PD cases and 14,301 controls; Accelerating Medicines Partnership–Parkinson's Disease Initiative, 2,248 cases and 2,817 controls). A genome-wide association study meta-analysis was performed on these individuals to understand genetic variation associated with resistance to disease. We further constructed a polygenic resilience score, and performed multimarker analysis of genomic annotation (MAGMA) gene-based analyses and functional enrichment analyses. Results: A higher polygenic resilience score was associated with a lower risk for PD (β = −0.054, standard error [SE] = 0.022, p = 0.013). Although no single locus reached genome-wide significance, MAGMA gene-based analyses nominated TBCA as a putative gene. Furthermore, we estimated the narrow-sense heritability associated with resilience to PD (h2 = 0.081, SE = 0.035, p = 0.0003). Subsequent functional enrichment analysis highlighted histone methylation as a potential pathway harboring resilience alleles that could mitigate the effects of PD risk loci. Interpretation: The present study represents a novel and comprehensive assessment of heritable genetic variation contributing to PD resistance. We show that a genetic resilience score can modify the penetrance of PD genetic risk factors and therefore protect individuals carrying a high-risk genetic burden from developing PD. ANN NEUROL 2022 [less ▲]

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See detailInvestigation in reusable composite flooring systems in steel and concrete based on composite behaviour by friction
Fodor, Jovan UL

Doctoral thesis (2022)

The steel-concrete composite systems proved to be very efficient structural solution in terms of material consumption and mechanical response regarding the construction of the structural floor systems ... [more ▼]

The steel-concrete composite systems proved to be very efficient structural solution in terms of material consumption and mechanical response regarding the construction of the structural floor systems whether in the case of industrial and residential buildings or especially in the case of car parks. However, their contemporary application that relies on the utilization of the welded headed studs as a mean to provide the shear connection between the steel section and the concrete chord renders the system unable to be disassembled (in the best case its steel and concrete parts are recycled). Considering the ongoing push from the linear to circular economical models and the application of 3R principle (Reduce, Reuse & Recycle) such systems are unable to furtherly improve their environmental and economic efficiency through reuse schemes. The profound task in this research is development and the verification of the new demountable shear connector solutions that could allow modularity and demountability (hence reusability) of the steel-concrete composite floor systems while retaining their inherent structural advantages. Based on the previous investigations of the demountable shear connector systems (at the first-place bolted solutions) and investigations of mechanical components that were not strictly related to the shear connectors, four demountable shear connector devices were developed. Having in mind the drawbacks of the earlier solutions, adequate detailing and structural measures were applied and the ease of assembly and disassembly was proved on the constructed prototypes. Afterwards, the mechanical properties of devised demountable connector systems were investigated thoroughly through experimental campaign (push tests) and numerical investigation. Based on the experimental and numerical results of the shear connector behaviour it is concluded that the proposed shear connector device Type B possess adequate strength and stiffness and might be considered ductile in accordance with the EN 1994-1-1 allowing for the application of existent design strategies in accordance with the same design code. The force-slip behaviour of the proposed shear connector is explained and adequate analytic model is proposed. Based on the force-slip behaviour model the applicability of the shear connector is verified on a range of composite beams that represent the demountable floor. [less ▲]

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See detailThe positional value of education in the Americas: dynamics of inequality in labour market returns for highly unequal countries, 2000-2019
Ceron, Francisco UL; Chauvel, Louis UL

Scientific Conference (2022, April 22)

The article examines how the labour market value of education has changed in the context of the expansion of higher education. However, one drawback is understanding how it generates differences between ... [more ▼]

The article examines how the labour market value of education has changed in the context of the expansion of higher education. However, one drawback is understanding how it generates differences between high and low-skilled labour markets, particularly in contexts of high inequality and informality. This could be linked to specific mechanisms by which employers value educational credentials as signalled skills. Using the Luxembourg Income Study (LIS), we analyse trends over two decades in 11 American countries. Our results confirm the previous results for the claim that education has become increasingly positional, compared with the absolute model of education. However, we find that the relative gains in wages for workers with higher levels of education, as the pool of higher education graduates expand over time, increased only slightly in high-skilled occupations, while their relative gains decreased for lower-skilled occupations. This trend is present in both absolute and positional models of education. Moreover, when looking at the structure of labour markets in terms of the linkage between educational credentials and occupational groups, we higher the tertiary education specificity of occupations, the higher the earnings for workers with advantaged positions. These findings are consistent with processes of displacement of low-skilled workers due to increasing competition among highly educated workers, from the positional model of education. [less ▲]

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See detailOn Trustworthy AI and Localized Complex Network Analytics
Esmaeilzadeh Dilmaghani, Saharnaz UL

Doctoral thesis (2022)

We live in a world where the interaction of many different entities results in the formation of complex systems. The communication between billions of smart devices, interactions of millions of people in ... [more ▼]

We live in a world where the interaction of many different entities results in the formation of complex systems. The communication between billions of smart devices, interactions of millions of people in social networks, and the existence of our biological life, which is based on seamless interactions between hundreds of genes and proteins within our cells, all are just a few examples of the complex systems surrounding us. At the core of these complex systems, there is clear evidence of a complex network, which symbolizes the interaction between the system’s components. Analytical metrics and algorithms derived from graph theory are used in network analysis to understand the functionality of complex systems, anticipate system behavior, and control changes. Many of these global patterns in complex networks are generally influenced by decisions made by communities. Communities are a tightly connected group of nodes with sparse connections to the rest of the network. These modular structures are crucial to understanding the complex network due to being closely tied to the system’s functional and topological features. They can, for example, represent modules of proteins with similar functionality in a protein interaction network or influence dynamic network activities such as opinion and epidemic propagation. Local community detection methods have gained popularity among other strategies to dis- cover communities in a complex network. The traditional methods are based on a top-down approach acquiring global information about the entire network; however, due to the growing size and complexity of existing networks, they often result in tangled communities, hence not providing functional information of the network. The primary goal of this thesis is to provide methods and solutions for local network analysis. The following components comprise the thesis contribution: 1) Introduce a transformation approach to construct networks from relational data and describe how network structure affects community detection, 2) Provide a comprehensive evaluation of current local community detection techniques and suggest a locality exploration scheme (LES) for community detection algorithms, 3) Develop a local community detection Algorithm (LCDA) and employ it on real-world data, 4) Extend LCDA to LCDA-GO, which integrates biological functional information and detects protein communities in the cell on the PPI network. Thereby, this thesis proposes a novel community detection algorithm that addresses the shortcomings of prior algorithms by presenting a local method. The applicability of the suggested algorithm is investigated by running it on real-world PPI networks. 7 Furthermore, this thesis contributes to industrial technical reports and whitepapers on the standardization and regulation of big data and Artificial Intelligence (AI). The thesis addresses the critical issues of digital trust in big data and AI by incorporating technical standardization and cutting-edge research solutions. The key contributions include, but are not limited to: 1) A comprehensive review of the state-of-the-art in numerous scientific and standard materials regarding privacy and trustworthiness concerns, including the introduction of privacy leaks and mitigation measures in big data and AI, 2) Investigating the societal implications of artificial intelligence standards in light of the recently initiated worldwide and European standardized processes, 3) Design and implementation of a scheme that connects scientific contributions and stan- dardization efforts in the direction of AI conformity assessment. The contribution of the thesis to standards demonstrates an impact on both scientific and standardization communities by contributing to both and offering recent outcomes from each. [less ▲]

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See detailVerifiable Decryption in the Head
Gjosteen, Kristian; Haines, Thomas; Mueller, Johannes UL et al

in ACISP 2022 (2022)

In this work we present a new approach to verifiable decryption which converts a 2-party passively secure distributed decryption protocol into a 1-party proof of correct decryption. This leads to an ... [more ▼]

In this work we present a new approach to verifiable decryption which converts a 2-party passively secure distributed decryption protocol into a 1-party proof of correct decryption. This leads to an efficient and simple verifiable decryption scheme for lattice-based cryptography, especially for large sets of ciphertexts; it has small size and lightweight computations as we reduce the need of zero-knowledge proofs for each ciphertext. We believe the flexibility of the general technique is interesting and provides attractive trade-offs between complexity and security, in particular for the interactive variant with smaller soundness. Finally, the protocol requires only very simple operations, making it easy to correctly and securely implement in practice. We suggest concrete parameters for our protocol and give a proof of concept implementation, showing that it is highly practical. [less ▲]

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See detailStress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1
Capelle, Christophe M.; Chen, Anna; Zeng, Ni et al

in Immunology (2022), 165(4), 428--444

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that ... [more ▼]

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 naïve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in naïve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene, period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1, which inhibited mTORC1 signalling, thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene, namely PER1. [less ▲]

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See detailCombinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients
Capelle, Christophe M.; Ciré, Séverine; Domingues, Olivia et al

in Cell Reports Medicine (2022), 3(4), 100600

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral ... [more ▼]

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis. The frequency of key innate immune cells and their functional marker expression are impaired in hospitalized patients at day 1 of inclusion. T cell and dendritic cell responses at day 1 are highly predictive for SARS-CoV-2-specific antibody responses after 3 weeks in mild but not hospitalized patients. Our systematic analysis reveals a combinatorial picture and trajectory of various arms of the highly coordinated early-stage immune responses in mild COVID-19 patients. [less ▲]

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See detailMorphological principles of neuronal mitochondria
Mendelsohn, Rachel; Garcia, Guadalupe C.; Bartol, Thomas M. et al

in Journal of Comparative Neurology (2022), 530(6), 886--902

In the highly dynamic metabolic landscape of a neuron, mitochondrial membrane architectures can provide critical insight into the unique energy balance of the cell. Current theoretical calculations of ... [more ▼]

In the highly dynamic metabolic landscape of a neuron, mitochondrial membrane architectures can provide critical insight into the unique energy balance of the cell. Current theoretical calculations of functional outputs like adenosine triphosphate and heat often represent mitochondria as idealized geometries, and therefore, can miscalculate the metabolic fluxes. To analyze mitochondrial morphology in neurons of mouse cerebellum neuropil, 3D tracings of complete synaptic and axonal mitochondria were constructed using a database of serial transmission electron microscopy (TEM) tomography images and converted to watertight meshes with minimal distortion of the original microscopy volumes with a granularity of 1.64 nanometer isotropic voxels. The resulting in-silico representations were subsequently quantified by differential geometry methods in terms of the mean and Gaussian curvatures, surface areas, volumes, and membrane motifs, all of which can alter the metabolic output of the organelle. Finally, we identify structural motifs present across this population of mitochondria, which may contribute to future modeling studies of mitochondrial physiology and metabolism in neurons. [less ▲]

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See detailMicroglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Fixemer, Sonja UL; Ameli, Corrado UL; Hammer, Gaël et al

in Acta Neuropathologica Communications (2022), 10(1), 36

The cellular alterations of the hippocampus lead to memory decline, a shared symptom between Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB) patients. However, the subregional deterioration ... [more ▼]

The cellular alterations of the hippocampus lead to memory decline, a shared symptom between Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB) patients. However, the subregional deterioration pattern of the hippocampus differs between AD and DLB with the CA1 subfield being more severely affected in AD. The activation of microglia, the brain immune cells, could play a role in its selective volume loss. How subregional microglia populations vary within AD or DLB and across these conditions remains poorly understood. Furthermore, how the nature of the hippocampal local pathological imprint is associated with microglia responses needs to be elucidated. To this purpose, we employed an automated pipeline for analysis of 3D confocal microscopy images to assess CA1, CA3 and DG/CA4 subfields microglia responses in post-mortem hippocampal samples from late-onset AD (n = 10), DLB (n = 8) and age-matched control (CTL) (n = 11) individuals. In parallel, we performed volumetric analyses of hyperphosphorylated tau (pTau), amyloid-β (Aβ) and phosphorylated α-synuclein (pSyn) loads. For each of the 32,447 extracted microglia, 16 morphological features were measured to classify them into seven distinct morphological clusters. Our results show similar alterations of microglial morphological features and clusters in AD and DLB, but with more prominent changes in AD. We identified two distinct microglia clusters enriched in disease conditions and particularly increased in CA1 and DG/CA4 of AD and CA3 of DLB. Our study confirms frequent concomitance of pTau, Aβ and pSyn loads across AD and DLB but reveals a specific subregional pattern for each type of pathology, along with a generally increased severity in AD. Furthermore, pTau and pSyn loads were highly correlated across subregions and conditions. We uncovered tight associations between microglial changes and the subfield pathological imprint. Our findings suggest that combinations and severity of subregional pTau, Aβ and pSyn pathologies transform local microglia phenotypic composition in the hippocampus. The high burdens of pTau and pSyn associated with increased microglial alterations could be a factor in CA1 vulnerability in AD. [less ▲]

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See detailSingle-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease
Novak, Gabriela; Kyriakis, Dimitrios UL; Grzyb, Kamil UL et al

in Communication Biology (2022), 5(1), 1--19

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly ... [more ▼]

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson’s disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD. [less ▲]

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See detailGeneration of two human induced pluripotent stem cell lines from fibroblasts of Parkinson’s disease patients carrying the ILE368ASN mutation in PINK1 (LCSBi002) and the R275W mutation in Parkin (LCSBI004)
Novak, Gabriela; Finkbeiner, Steven; Skibinski, Gaia et al

in Stem Cell Resource (2022), 61

Mutations in PINK1 and Parkin are two of the main causes of recessive early-onset Parkinson’s disease (PD). We generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of a 64-year-old ... [more ▼]

Mutations in PINK1 and Parkin are two of the main causes of recessive early-onset Parkinson’s disease (PD). We generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of a 64-year-old male patient with a homozygous ILE368ASN mutation in PINK1, who experienced disease onset at 33 years, and from fibroblasts of a 61-year-old female patient heterozygous for the R275W mutation in Parkin, who experienced disease onset at 44 years. Array comparative genomic hybridization (aCGH) determined genotypic variation in each line. The cell lines were successfully used to generate midbrain dopaminergic neurons, the neuron type primarily affected in PD. [less ▲]

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