Miracle-dz/UniFAR-FTUs huggingface dataset:
Common computations in automatic cue combination and metacognitive confidence reports

Appropriate perceptual decision making necessitates the accurate estimation and use of sensory uncertainty. Such estimation has been studied in the context of both low-level multisensory cue combination and metacognitive estimation of confidence, but it remains unclear whether the same computations underlie both sets of uncertainty estimation. We created visual stimuli with low vs. high overall motion energy, such that the high-energy stimuli led to higher confidence but lower accuracy in a visual-only task. Importantly, we tested the impact of the low- and high-energy visual stimuli on auditory motion perception in a separate task. Despite being irrelevant to the auditory task, both visual stimuli impacted auditory judgments presumably via automatic low-level mechanisms. Critically, we found that the high-energy visual stimuli influenced the auditory judgments more strongly than the low-energy visual stimuli. This effect was in line with the confidence but contrary to the accuracy differences between the high- and low-energy stimuli in the visual-only task. These effects were captured by a simple computational model that assumes common computational principles underlying both confidence reports and multisensory cue combination. Our results reveal a deep link between automatic sensory processing and metacognitive confidence reports, and suggest that vastly different stages of perceptual decision making rely on common computational principles.
A Simulation Study on High Spatio-Temporal Resolution Acousto-Electrophysiological Neuroimaging

Acousto-electrophysiological neuroimaging is a technique hypothesized to record electrophysiological activity of the brain with millimeter spatial and sub-millisecond temporal resolution. This improvement is obtained by tagging areas with focused ultrasound (fUS). Due to mechanical vibration with respect to the measuring electrodes, the electrical activity of the marked region will be modulated onto the ultrasonic frequency. The region’s electrical activity can subsequently be retrieved via demodulation of the measured signal. In this study, the feasibility of this hypothesized technique is tested. This is done by calculating the forward electroencephalography (EEG) response under quasi-static assumptions. The head is simplified as a set of concentric spheres. Two sizes are evaluated representing human and mouse brains. Moreover, feasibility is assessed for wet and dry transcranial, and for cortically placed electrodes. The activity sources are modeled by dipoles, with their current intensity profile drawn from a power-law power spectral density. It is shown that mechanical vibration modulates the endogenous activity onto the ultrasonic frequency. The signal strength depends non-linearly on the alignment between dipole orientation, vibration direction and recording point. The strongest signal is measured when these three dependencies are perfectly aligned. The signal strengths are in the pV-range for a dipole moment of 5 nAm and ultrasonic pressures within FDA-limits. The endogenous activity can then be accurately reconstructed via demodulation. Two interference types are investigated: vibrational and static. Depending on the vibrational interference, it is shown that millimeter resolution signal detection is possible also for deep brain regions. Subsequently, successful demodulation depends on the static interference, that at MHz-range has to be sub-picovolt.
Decreased inter-hemispheric connectivity predicts a coherent retrieval of auditory symbolic material in a laboratory model of cultural transmission

Investigating the transmission of information between individuals is essential to understand how human culture evolved. Coherent information transmission (i.e., transmission without significant modifications or loss of fidelity) helps preserving cultural traits and traditions over time, while innovation may lead to new cultural variants. Although much research has focused on the cognitive mechanisms underlying cultural transmission, little is known on the brain underpinnings of coherent transmission of information. To address this gap, we combined a laboratory model of cultural transmission, the signalling games, with structural (from high-resolution diffusion imaging) and functional connectivity (from resting-state functional magnetic resonance imaging [fMRI]). We found that individuals who exhibited more coherence in the transmission of the information were characterized by lower levels of both structural and functional inter-hemispheric connectivity. Specifically, higher coherence negatively correlated with the strength of bilateral structural connections between frontal and subcortical, insular and temporal brain regions. Similarly, we observed increased inter-hemispheric functional connectivity between inferior frontal brain regions derived from structural connectivity analysis in individuals who exhibited lower transmission coherence. Our results suggest that inter-hemispheric connections may bwe detrimental for preserving coherence in information transmission, while a certain degree of lateralization in the brain may be required.
AutoMacq: an automatic pipeline to analyse macaque structural MRI data

MRI scanning of rhesus macaques is a growing field due to their evolutionary proximity and similar neuroanatomy to humans. As such, there is a need for automatic macaque MRI processing pipelines. AutoMacq is a pipeline capable of processing rhesus macaque MRI data to produce both voxel-based and surface-based metrics. It involves minimal manual intervention and can be carried out without expert knowledge of macaque neuroanatomy. To test the quality of the pipeline, scans from 74 subjects across 8 different sites were processed. Results indicate that over 87% of tissue segmentations and surfaces were of satisfactory quality to not require additional manual correction. Hemispheric comparisons and analyses of scan-rescan data showed strong reliability of the volumetric and surface-based outputs. Finally, to illustrate potential applications of AutoMacq, the change in grey matter volume with ageing was investigated cross-sectionally using subjects aged 3-15 years (corresponding to adolescence until mid-adulthood). The analysis revealed a linear decrease in grey matter volume with age similar to what has been found in humans, reinforcing the value of rhesus macaques as a model of healthy human ageing.
Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis

During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC- fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.
Importin α as a molecular marker for investigating the microenvironment of micronuclei

Micronuclei (MN) are nuclear membrane-enclosed cellular structures that contain DNA/chromatin fibers that can lead to genomic instability. Here, we report that importin α, known as the nuclear transport factor, is highly concentrated in some of the MN in cultured human cancer cells. We observed that importin α1 accumulated in the MN together with other subtypes, indicating that this represented a conserved feature of the importin α family. Indirect immunofluorescence analysis revealed that the MN localization of importin α1 was regulated independently of canonical nuclear transport-related factors such as importin β1, CAS/CSE1L, nucleoporins, and lamins. In contrast, importin α1 signals merged with histone H3 modified by trimethylation at lysine 4 in MN, indicating that importin α1 was associated with euchromatin in MN. Furthermore, we found a mutually exclusive relationship between importin α1 and RAD51, a homologous recombination repair protein, in relation to MN accumulation in cells exposed to etoposide, a DNA damaging reagent. Our findings suggest that importin α is a previously overlooked molecular marker for assessing the microenvironment and quality control of MN in human cancer cells. Summary statement Accumulation of importin α in micronuclei, followed by alteration of their microenvironment, suggests the non-canonical function of importin α in genome instability and cancer development.
Multiple sex chromosomes of Yponomeuta ermine moths suggest a role of sexual antagonism in sex chromosome turnover in Lepidoptera

Sex chromosome-autosome fusions give rise to neo-sex chromosomes, which provide an insight into early evolution of sex chromosomes and drivers of chromosomal fusions. While sex chromosome-autosome fusions are scarce in vertebrates with female heterogamety (♀ZW/♂ZZ), they are common in moths and butterflies (Lepidoptera), the most species rich group with heterogametic females. This contradicts theoretical model that assumes chromosome fusions to be random and predicts them to be rare in taxa with high chromosome number such as Lepidoptera. In the present study we analyzed sex chromosomes in nine ermine moths of the genus Yponomeuta (Yponomeutidae) and their two outgroups, Teinoptila gutella (Yponomeutidae) and Plutella xylostella (Plutellidae). We employed genomic in situ hybridization to identify sex chromosomes and used a custom designed microarray to identify Z-linked genes. Our results confirmed a multiple sex chromosome system Z1Z2W to be present in T. gutella and all Yponomeuta spp. except for Y. tokyonella. The multiple sex chromosome system resulted from a fusion between the W chromosome and autosome homeologous to the Bombyx mori chromosome 2 (BmChr2). The BmChr2 bears a cluster of genes with ovary-specific expression which suggests that sexually antagonistic selection could have driven fixation of the fusion in a common ancestor of Yponomeuta and Teinoptila genera. We hypothesize that sex chromosome turnover in Lepidoptera could be driven by sexual antagonism.
Imaging the pharmacokinetics and therapeutic availability of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models

Background CD3 bispecific antibodies (CD3-bsAbs) require binding of both a tumor-associated surface antigen and CD3 for their immunotherapeutic effect. Their efficacy is, therefore, influenced by the absolute tumor uptake and the extracellular dose. To optimize their currently limited efficacy in solid tumors, increased understanding of their pharmacokinetics and in vivo internalization is needed. Methods Here were studied the pharmacokinetics and in vivo internalization of CD3xTRP1, a fully murine Fc-inert bsAb, in endogenous TRP1-expressing immunocompetent male C57BL/6J mice bearing TRP1-positive and negative tumors over time. Matching bsAbs lacking TRP1- or CD3-binding capacity served as controls. BsAbs were radiolabeled with 111In to investigate their pharmacokinetics, target binding, and biodistribution through SPECT/CT imaging and ex vivo biodistribution analyses. Co-injection of 111In- and 125I-labeled bsAb was performed to investigate the in vivo internalization by comparing tissue concentrations of cellular residing 111In versus effluxing 125I. Anti-tumor therapy effects were evaluated by monitoring tumor growth and immunohistochemistry. Results SPECT/CT and biodistribution analyses showed that CD3xTRP1 specifically targeted TRP1-positive tumors and CD3-rich lymphoid organ and uptake peaked 24 hours pi (KPC3-TRP1: 37.7±5.3 %ID/g, spleen: 29.0±3.9 %ID/g). Studies with control bsAbs demonstrated that uptake of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues was primarily receptor-mediated. Together with CD3xTRP1 in the circulation being mainly unattached, this indicates that CD3+ T cells are generally not traffickers of CD3-bsAbs to the tumor. Additionally, “antigen-sink” effects by TRP1-expressing melanocytes were not observed. We further demonstrated rapid internalization of CD3xTRP1 in KPC3-TRP1 tumors (24h pi: 54.9±2.3% internalized) and CD3-rich tissues (spleen, 24h pi: 79.7±0.9% internalized). Therapeutic effects by CD3xTRP1 were observed for TRP1-positive tumors and consisted of high tumor influx of CD8+ T cells and neutrophils, which corresponded with increased necrosis and growth delay. Conclusions We show that CD3xTRP1 efficiently targets TRP1-positive tumors and CD3-rich tissues primarily through receptor-mediated targeting. We further demonstrate rapid receptor-mediated internalization of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues. Even though this significantly decreases the therapeutical available dose, CD3xTRP1 still induced effective anti-tumor T-cell responses and inhibited tumor growth. Together, our data on the pharmacokinetics and mechanism of action of CD3xTRP1 pave the way for further optimization of CD3-bsAb therapies. Graphical abstract Imaging the pharmacokinetics and therapeutic availability of the bispecific CD3xTRPl antibody in syngeneic mouse tumor models
Neuronal Activation of the Gαq Protein EGL-30/GNAQ Late in Life Rejuvenates Cognition Across Species

Cognitive decline is perhaps the most devastating aging loss. EGL-30/GNAQ and Gαq signaling pathways are highly conserved between C. elegans and mammals. We find that activation of EGL-30 in aged worms at least triples memory span, and we wondered if this highly conserved pathway could also improve memory in very old mice. Murine Gnaq is enriched in hippocampal excitatory neurons and declines with age. Furthermore, GNAQ gain-of-function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice rescued age-related impairments in health metrics and long-term memory. Single-nucleus RNAseq revealed gene expression changes related to synaptic function, axon guidance, and learning and memory pathways. Several worm orthologs of mouse genes upregulated by GNAQ(gf) overexpression are required for EGL-30(gf)-dependent memory improvement. These results demonstrate that the molecular and genetic pathways between C. elegans and mammals are highly conserved, as activation of EGL-30/GNAQ, a pathway first identified in worms, rejuvenates cognitive function in two-year old mice (the equivalent of 70-80 yo humans). To our knowledge, this is the oldest age an intervention has successfully improved age-related cognitive decline. One-Sentence Summary Neuronal activation of the Gαq protein EGL-30/GNAQ restores long-term memory at old age in worms and mice.
A region‐resolved proteomic map of the human brain enabled by high‐throughput proteomics

Substantial efforts are underway that aim to deepen our understanding of human brain morphology, structure and function using high-resolution imaging as well has high-content molecular profiling technologies. The current work adds to these efforts by providing a comprehensive and quantitative protein expression map of 13 anatomically distinct brain regions covering more than 10,000 proteins. This was enabled by the optimization, characterization and implementation of a high-sensitivity and high-throughput micro-flow liquid chromatography timsTOF tandem mass spectrometry system (LC-MS/MS) capable of analyzing >2,000 consecutive samples prepared from formalin fixed paraffin embedded (FFPE) material. Analysis of this proteomic resource highlighted e.g. brain region-enriched protein expression patterns and functional protein classes, protein localization differences between brain regions and individual protein markers for specific brain regions. To facilitate access to and ease further mining of the data by the scientific community, all data can be explored online in a purpose-built Shiny App (https://brain-region-atlas.proteomics.ls.tum.de).
A Constraint-based Approach to Dynamic Colour Management for Windowing Interfaces

Selecting harmonious colours for traditional window systems can be a difficult and frustrating endeavor. At the root of this problem is the fact that typical window systems do not allow abstract properties of colours to be specified. Instead, they insist that users specify individual colour values exactly. When many colours are used, the value of each colour must be chosen to satisfy any relationships that exist between it and previously chosen colours. Unfortunately, the difficulty of colour selection often prevents users from taking full advantage of the functional benefits of colour, particularly that of resolving context. A more desirable approach is to allow the aesthetic and functional properties of colours to be specified and to allow users to select values for the colours they wish. The window system can choose the remaining colours using these properties. Another failing of typical window systems is that once a colour value has been determined it will not change without explicit direction from the user. When windows open or close the factors which motivated a choice of colour value may change. Unfortunately, if the user wishes the chosen colour value to change as the environment changes, he or she must typically perform the modifications. A dynamic window system assists the user in making these choices. By specifying colour properties as constraints, a dynamic window system can adjust colour values as the environment changes, to satisfy these constraints. The potential problems with dynamic window systems incorporating colour constraints are investigated in this thesis. An implementation that uses a distributed, jostling, constraint-solver based on a simple dynamical system shows that this approach is possible.
The Multifaceted Effects of Short-Term Acute Hypoxia Stress: Insights into the Tolerance Mechanism of Propsilocerus akamusi (Diptera: Chironomidae)

Plenty of freshwater species, especially macroinvertebrates that are essential to the provision of numerous ecosystem functions, encountered higher mortality due to acute hypoxia. However, within the family Chironomidae, a wide range of tolerance to hypoxia/anoxia is displayed and Propsilocerus akamusi depends on this great endurance to become a dominant species in eutrophic lakes. To further understand how P. akamusi responds to acute hypoxic stress, we used multi-omics analysis in combination with histomorphological characteristics and physiological indicators. To evaluate enzyme activity, the transcriptome and metabolome, and histomorphological characteristics, we set up two groups: a control group (DO 8.4mg/L) and a hypoxic group (DO 0.39mg/L). With blue-black chromatin, cell tightness, cell membrane invagination, and the production of apoptotic vesicles, tissue cells displayed typical apoptotic features. While lactate dehydrogenase (LDH), (Alcohol dehydrogenase) ADH, catalase (CAT), and Na+/K+ -ATPase (NKA) activities were dramatically enhanced under hypoxic stress, glycogen content, and superoxide dismutase (SOD) activities were significantly reduced compared to the control group. The above results were further supported by the joint analysis of the transcriptome and metabolome, which further revealed that in addition to carbohydrates, including glycogen, the energy metabolism of the fatty acid, trehalose, and glyoxylate cycles is also included. Furthermore, we also revealed the ethanol tested in hypoxic stress should derive from symbiodinium of P akamusi. Understanding the processes which enable P. akamusi to survive lengthy periods of hypoxia in eutrophic lakes might help to design sensitive biomonitoring procedures, and this species has the potential to be used as an effective eutrophication indicator.
Developing a Multidimensional Financial Inclusion Index: A Comparison Based on Income Groups

The aim of our paper is to construct a multidimensional financial inclusion (FI) index to measure the level of FI in 91 countries across different income groups. In order to address our research problem, we use the principal component analysis method. This approach addresses the criticism of the arbitrary selection of weights and reflects the degree of financial inclusion in depth. The data are drawn from the International Monetary Fund (IMF) Financial Access Survey (FAS), the World Development Indicators (World Bank) and the Global Findex Database during the period of 2004–2020. This paper is the first to consider so many indicators of financial inclusion (13 indicators), belonging to three different dimensions of FI, in order to take into account the maximum number of aspects related to this concept. In addition, unlike previous work, this paper considers both developing and developed countries, which makes it possible to identify differences between them. The proposed index has some advantages. First, it is robust, comparable across countries and has good predictive power in tracking household microeconomic indicators (accounts and savings). It is also well correlated with macroeconomic variables such as literacy rate, poverty, GINI index, real interest rate and employers. Second, our results clearly show that, as a country’s income level grows higher, its level of financial inclusion also grows higher.
Exploring Inclusive MedTech Innovations for Resource-Constrained Healthcare in India

The potential of inclusive medical technological innovations to create access to a ﬀ ordable and appropriate products and services for local healthcare systems in developing countries has emerged as a critical area of academic and policy debates. This research contributes to these debates by studying the key factors, actors and their interactions in ﬂ uencing the development and adoption of three innovative diagnostic devices to resolve the healthcare needs of the local population in the Indian healthcare systems. It highlights the critical role of the state in in ﬂ uencing the development and adoption of inclusive MedTech innovations in resource-constraint settings. It further reveals that the availability of ﬁ nance facilitated the early-stage development of innovations. At the same time, collaborative arrangements with a diverse set of stakeholders contributed to late-stage development and adoption of innovations in the local healthcare systems. This research also expands on the conceptualization of inclusivity in the MedTech sector by providing a holistic interpretation of a ﬀ ordability as reducing healthcare costs over a longer period through access to early diagnostics rather than the purchase cost of a product. These research ﬁ ndings have signi ﬁ cant implications for innovation and healthcare policies that can help to resolve the challenges of accessible healthcare in developing countries.