Miracle-dz/UniFAR-FTUs huggingface dataset:
DGRPool: A web tool leveraging harmonized Drosophila Genetic Reference Panel phenotyping data for the study of complex traits

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Drosophila Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool.epfl.ch), which aggregates phenotyping data of 935 phenotypes across 125 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide association analyses (GWAS) and Phenome-WAS analyses. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, sleep duration, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community.
Proteostatic tuning underpins the evolution of novel multicellular traits

The evolution of multicellularity paved the way for the origin of complex life on Earth, but little is known about the mechanistic basis of early multicellular evolution. Here, we examine the molecular basis of multicellular adaptation in the Multicellularity Long Term Evolution Experiment (MuLTEE). We demonstrate that cellular elongation, a key adaptation underpinning increased biophysical toughness and organismal size, is convergently driven by downregulation of the chaperone Hsp90. Mechanistically, Hsp90-mediated morphogenesis operates by destabilizing the cyclin-dependent kinase Cdc28, resulting in delayed mitosis and prolonged polarized growth. Reinstatement of Hsp90 or Cdc28 expression resulted in shortened cells that formed smaller groups with reduced multicellular fitness. Together, our results show how ancient protein folding systems can be tuned to drive rapid evolution at a new level of biological individuality by revealing novel developmental phenotypes. Teaser Downregulation of Hsp90 decouples cell cycle progression and growth to drive the evolution of macroscopic multicellularity.
Difference in determinants and changing patterns of plant community composition with and without grazing across semi-arid and arid regions in Mongolian steppe

Aridity, edaphic variables related to aridity, and livestock grazing are major drivers of plant community composition across dryland grasslands. With accounting these factors, little is known about differences in determinants and changing patterns along aridity gradients with different average of aridity. Thus, the comparative investigations of communities without and with grazing in semi-arid and arid regions are suitable to clarify the difference in compositional responses along aridity gradients between potential vegetations and degraded ones with grazing. We investigated compositional changes of communities without/with grazing in semi-arid (north) /arid (south) regions across Mongolia. The compositional changes based on Bray-Curtis dissimilarity were investigated by generalized dissimilarity modeling, including geographic distance, aridity, soil pH, and sand and clay contents as independent variables. The determinants and changing patterns of community composition were compared among the four groups. Aridity had significant impacts on community composition regardless of the regions and the absence/presence of grazing. However, without the dependency on grazing, the difference in response patterns was observed between the regions. The compositional change was steeper especially at the upper edge of aridity rather than the lower edge in the arid region. This indicates the vulnerability of plant communities to aridity shifts due to future climate change in desert steppe of Mongolia. In addition, regardless of the regions, the effects of soil pH on community composition were eliminated by grazing. Because soil pH indirectly affected by aridity shifts can have impacts on community composition of potential vegetations without grazing, the long-term monitoring of vegetation dynamics needs observations of both of communities without and with grazing.
Tracking a Moving Target by a Fixed-wing UAV Based on Sliding Mode Control

This paper presents a target tracking algorithm that enables a fixed-wing unmanned aerial vehicle (UAV) to keep tracking an uncooperative, moving target. The proposed tracking algorithm is based on sliding mode control, and it ensures that the UAV can maintain a persistent circular motion with respect to the moving target as long as the target is not faster than the UAV. Special attention is taken to eliminate the inherent chattering phenomenon involved in sliding mode control, and asymptotic stability is achieved for the tracking algorithm. Simulation results are presented to demonstrate the performance of the proposed algorithm.
Attention Modulates Human Visual Responses to Objects by Tuning Sharpening

Visual stimuli compete with each other for cortical processing and attention biases this competition in favor of the attended stimulus. How does the relationship between the stimuli affect the strength of this attentional bias? Here, we used functional MRI to explore the effect of target-distractor similarity in neural representation on attentional modulation in the human visual cortex using univariate and multivariate pattern analyses. Using stimuli from four object categories (human bodies, cats, cars and houses), we investigated attentional effects in the primary visual area V1, the object-selective regions LO and pFs, the body-selective region EBA, and the scene-selective region PPA. We demonstrated that the strength of the attentional bias towards the target is not fixed but decreases with increasing distractor-target similarity. Simulations provided evidence that this result pattern is explained by tuning sharpening rather than an increase in gain. Our findings provide a mechanistic explanation for behavioral effects of target-distractor similarity on attentional biases and suggest tuning sharpening as the underlying mechanism in object-based attention.
Graph Laplacian Spectrum of Structural Brain Networks is Subject-Specific, Repeatable but Highly Dependent on Graph Construction Scheme

The human brain is a complex network that can be summarized as a graph where nodes refer to anatomical brain regions while edges encode the neuronal interactions or structural connections between them at both the micro and macroscopic levels, allowing the application of graph theory to investigate the network brain architecture. Various network metrics have been proposed and adopted so far describing both local and global properties of the relevant brain network. It has been proposed that connectomic harmonic patterns that emerged from the brain’s structural network underlie the human brain’s resting-state activity. Connectome harmonics refer to Laplacian eigenfunctions of the structural connectivity matrices (2D) and is an extension of the well-known Fourier basis of a signal (1D). The estimation of the normalized graph Laplacian over a brain network’s spectral decomposition can reveal the connectome harmonics (eigenvectors) corresponding to certain frequencies (eigenvalues). Here, we used test-retest dMRI data from the Human Connectome Project to explore the repeatability of connectome harmonics and eigenvalues across five graph construction schemes. Normalized Laplacian eigenvalues were found to be subject-specific and repeatable across the five graph construction schemes, but their range is highly dependent on the graph construction scheme. The repeatability of connectome harmonics is lower than that of the Laplacian eigenvalues and shows a heavy dependency on the graph construction scheme. In parallel, we investigated the properties of the structural networks and their relationship with the Laplacian spectrum. Our results provide a proof of concept for repeatable identification of the graph Laplacian spectrum of structural brain networks based on the selected graph construction scheme.
Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While we know how color information is processed in visual brain areas of primates, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. This type of color-opponency in the receptive field center of V1 neurons was not present in the receptive field center of retinal ganglion cells and, therefore, is likely computed by integrating center and surround information down-stream of the retina. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of “predatory”-like dark UV-objects in noisy day-light scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species. More broadly, they support the hypothesis that the visual cortex combines upstream information towards computing neuronal selectivity to behaviorally-relevant sensory features.
"On Exposing Strategic and Structural Mismatches Between Business and Information Systems: Misalignment Symptom Detection Based on Enterprise Architecture Model Analysis"

One of the most important issues on information systems (IS) research is the need to align business with information systems and information technology (IT). Since information systems facilitate the success of business strategies, the importance of business-IT (or strategic) alignment is unquestionable. While organisations address alignment achievement, they are continually suffering from misalignments. These difficulties (the misalignments) encumber the achievement of alignment, and lead us to the phenomenon of misalignment. This Ph.D. dissertation deals with the concept of misalignment, with special attention on enterprise architecture (EA)-based analytical potential. The main purpose of the proposed research is to analyse strategic misalignment between the business dimension and the information systems dimension. The problem of business-IT alignment is translated into the aspects of enterprise architecture. The study aims to accomplish an EA-based, systematic analysis of mismatches between business and information systems.
Sodium content in processed food items in Sweden compared to other countries: a cross-sectional multinational study

Background Dietary sodium has a dose-response relationship with cardiovascular disease, and sodium intake in Sweden exceeds national and international recommendations. Two thirds of dietary sodium intake comes from processed foods, and adults in Sweden eat more processed foods than any other European country. We hypothesized that sodium content in processed foods is higher in Sweden than in other countries. The aim of this study was to investigate sodium content in processed food items in Sweden, and how it differs from Australia, France, Hong Kong, South Africa, the United Kingdom and the United States. Methods Data were collected from retailers by trained research staff using standardized methods. Data were categorized into 10 food categories and compared using Kruskal-Wallis test of ranks. Sodium content in the food items was compared in mg sodium per 100 g of product, based on the nutritional content labels on the packages. Results Compared to other countries, Sweden had among the highest sodium content in the “dairy” and “convenience foods” categories, but among the lowest in “cereal and grain products,” “seafood and seafood products” and “snack foods” categories. Australia had the overall lowest sodium content, and the US the overall highest. The highest sodium content in most analyzed countries was found in the “meat and meat products” category. The highest median sodium content in any category was found among “sauces, dips, spreads and dressings” in Hong Kong. Conclusion The sodium content differed substantially between countries in all food categories, although contrary to our hypothesis, processed foods overall had lower sodium content in Sweden than in most other included countries. Sodium content in processed food was nonetheless high also in Sweden, and especially so in increasingly consumed food categories, such as “convenience foods”.
Effects of chronic core training on serum and erythrocyte oxidative stress parameters in amputee football players

Objective: The positive impact of aerobic exercise on blood oxidative stress parameters is well documented. However, the effect of core exercises on these parameters in amputee football players (AF) remains unclear. Therefore, this study aims to investigate the impact of core exercises on blood oxidative stress parameters in this population. Methods: Experimental method was adopted in the study. Eleven elite AF players participated in the study. The participants were divided randomly into two groups a core exercise group (CEG) and a control group (CG). Blood measurements were taken before and after the 8-week core exercise program. Blood measurements included erythrocyte Total Oxidant Status (eTOS), erythrocyte Total Antioxidant Status (eTAS), erythrocyte oxidative stress index (eOSI), serum nitric oxide (sNO), serum Total Oxidant Status (sTOS), serum Total Antioxidant Status (sTAS), serum oxidative stress index (sOSI), serum total thiol (sTT), serum native thiol (sNT), and serum disulfide (sDS) parameters were studied. Results: According to the results of the study, a significant difference was found between the 0th and eighth week pre-aerobic training load (ATL) sTOS (p = .028) values of CEG values. A significant difference was found in sTOS (p = .028) and sOSI (p = .028) values after the 0th and eighth-week pre-ATL. A significant difference was found in the sTOS (p = .043) and sOSI values (p = .043) of CG at week 0th and eighth-week pre-ATL. Conclusion: Overall, the results suggest that core exercises had a positive effect on blood oxidative stress parameters in AF players by reducing blood total oxidant levels.
Long-term improvements in executive functions after frontal-midline theta neurofeedback in a (sub)clinical group

Impairments in executive functions (EFs) are common across disorders and can greatly affect daily functioning. Frontal-midline (FM) theta neurofeedback (NF) has been shown effective in enhancing EFs in healthy adults, prompting interest in exploring its potential as an alternative treatment for EFs in (sub)clinical samples. This study aims to determine the effects of FM theta NF on EFs in a sample of 58 adults (aged 20–60 years) with pronounced subjective EF complaints in daily life. Using a pre/post/follow-up design with a sham NF group, the present study assessed upregulation of FM theta in an eight-session individualized FM theta NF training and its immediate and long-term transfer effects on objective and subjective measures of EFs. These included behavioral performance on EF tasks assessing working memory updating (N-back task), set-shifting (Switching task), conflict monitoring (Stroop task), and response inhibition (Stop-signal task), as well as FM theta power during these tasks, and subjective EFs in daily life (BRIEF-A). The results indicate that there are only differences in FM theta self-upregulation between the NF group and sham group when non-responders are excluded from the analysis. Regarding behavioral transfer effects, NF-specific improvements are found in working memory updating reaction time (RT) and conflict monitoring RT variability at 6-month follow-up, but not immediately after the NF training. The effects on FM theta power during the EF tasks and subjective changes in EFs in daily life were not specific to the NF training. As a next step, research should identify the best predictors to stratify NF training, as well as explore ways to improve NF responsiveness, for instance by increasing neuroplasticity.
Differences in fall-related characteristics across cognitive disorders

Approximately 40–60% of falls in the elderly lead to injuries, resulting in disability and loss of independence. Despite the higher prevalence of falls and morbidity rates in cognitively impaired individuals, most fall risk assessments fail to account for mental status. In addition, successful fall prevention programmes in cognitively normal adults have generally failed in patients with cognitive impairment. Identifying the role of pathological aging on fall characteristics can improve the sensitivity and specificity of fall prevention approaches. This literature review provides a thorough investigation into fall prevalence and fall risk factors, the accuracy of fall risk assessments, and the efficacy of fall prevention strategies in individuals with diverse cognitive profiles. We show that fall-related characteristics differ between cognitive disorders and fall risk assessment tools as well as fall prevention strategies should critically consider each patient’s cognitive status to facilitate the identification of fallers at an earlier stage and support clinical decision-making.
Editorial: Highlights in medical and surgical rehabilitation 2021/22

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Revisiting the neuroinflammation hypothesis in Alzheimer’s disease: a focus on the druggability of current targets

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease and disability in the elderly; it is estimated to account for 60%–70% of all cases of dementia worldwide. The most relevant mechanistic hypothesis to explain AD symptoms is neurotoxicity induced by aggregated amyloid-β peptide (Aβ) and misfolded tau protein. These molecular entities are seemingly insufficient to explain AD as a multifactorial disease characterized by synaptic dysfunction, cognitive decline, psychotic symptoms, chronic inflammatory environment within the central nervous system (CNS), activated microglial cells, and dysfunctional gut microbiota. The discovery that AD is a neuroinflammatory disease linked to innate immunity phenomena started in the early nineties by several authors, including the ICC´s group that described, in 2004, the role IL-6 in AD-type phosphorylation of tau protein in deregulating the cdk5/p35 pathway. The “Theory of Neuroimmunomodulation”, published in 2008, proposed the onset and progression of degenerative diseases as a multi-component “damage signals” phenomena, suggesting the feasibility of “multitarget” therapies in AD. This theory explains in detail the cascade of molecular events stemming from microglial disorder through the overactivation of the Cdk5/p35 pathway. All these knowledge have led to the rational search for inflammatory druggable targets against AD. The accumulated evidence on increased levels of inflammatory markers in the cerebrospinal fluid (CSF) of AD patients, along with reports describing CNS alterations caused by senescent immune cells in neuro-degenerative diseases, set out a conceptual framework in which the neuroinflammation hypothesis is being challenged from different angles towards developing new therapies against AD. The current evidence points to controversial findings in the search for therapeutic candidates to treat neuroinflammation in AD. In this article, we discuss a neuroimmune-modulatory perspective for pharmacological exploration of molecular targets against AD, as well as potential deleterious effects of modifying neuroinflammation in the brain parenchyma. We specifically focus on the role of B and T cells, immuno-senescence, the brain lymphatic system (BLS), gut-brain axis alterations, and dysfunctional interactions between neurons, microglia and astrocytes. We also outline a rational framework for identifying “druggable” targets for multi-mechanistic small molecules with therapeutic potential against AD. Graphical Abstract Main immuno-target for treat Alzheimer´s disease from a neuro-immunomodulatory perspective.
Inequity in care delivery in cardio-oncology: dissecting disparities in underrepresented populations

It is well known that patients with cancer have a significantly higher cardiovascular mortality risk than the general population. Cardio-oncology has emerged to focus on these issues including risk reduction, detection, monitoring, and treatment of cardiovascular disease or complications in patients with cancer. The rapid advances in early detection and drug development in oncology, along with socioeconomic differences, racial inequities, lack of support, and barriers to accessing quality medical care, have created disparities in various marginalized populations. In this review, we will discuss the factors contributing to disparities in cardio-oncologic care in distinct populations, including Hispanic/Latinx, Black, Asian and Pacific Islander, indigenous populations, sex and gender minorities, and immigrants. Some factors that contribute to differences in outcomes in cardio-oncology include the prevalence of cancer screening rates, genetic cardiac/oncologic risk factors, cultural stressors, tobacco exposure rates, and physical inactivity. We will also discuss the barriers to cardio-oncologic care in these communities from the racial and socioeconomic context. Appropriate and timely cardiovascular and cancer care in minority groups is a critical component in addressing these disparities, and there need to be urgent efforts to address this widening gap.