Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteome Profiling of Cerebrospinal Fluid Reveals Novel Biomarker Candidates for Parkinson’s Disease

Parkinson’s disease (PD) is a growing burden worldwide, and despite ongoing efforts to find reliable biomarkers for early and differential diagnosis, prognosis and disease monitoring, there is no biofluid biomarker used in clinical routine to date. Cerebrospinal fluid (CSF) is collected often and should closely reflect structural and functional alterations in PD patients’ brains. Here we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling to find specific biomarkers and identify disease-related changes in CSF protein levels in PD. From two independent cohorts consisting of more than 200 individuals, our workflow reproducibly quantified over 1,700 proteins from minimal sample amounts. Combined with machine learning, this identified a group of several proteins, including OMD, CD44, VGF, PRL, and MAN2B1 that were altered in PD patients or significantly correlate with clinical scores, indicative of disease progression. Interestingly, we uncovered signatures of enhanced neuroinflammation in patients with familial PD (LRRK2 G2019S carriers) as indicated by increased levels of CTSS, PLD4, HLA-DRA, HLA-DRB1, and HLA-DPA1. A comparison with urinary proteome changes in PD patients revealed a large overlap in protein composition PD-associated changes in these body fluids, including lysosomal factors like CTSS. Our results validate MS-based proteomics of CSF as a valuable strategy for biomarker discovery and patient stratification in a neurodegenerative disease like PD. Consistent proteomic signatures across two independent CSF cohorts and previously acquired urinary proteome profiles open up new avenues to improve our understanding of PD pathogenesis.
Faces of men with high serum testosterone are less attractive for women during the fertility phase of the menstrual cycle

The attractiveness of the human face plays an essential role in mating as it may signal the genetic suitability of a mate. The controversial ‘ovulatory shift hypothesis’ postulates that women in the fertile phase of the menstrual cycle would prefer faces of masculine men with high testosterone that signals ‘good genes’, whereas in the non-fertile phase they prefer traits signaling the willingness to provide parental care. To examine relationships between men’s testosterone and women’s preferences for men’s faces on day 13 of the menstrual cycle, 19 young women rated the attractiveness of images of the natural faces of 77 young men. Using advanced Bayesian multilevel modeling we showed that the attractiveness of men’s faces is significantly lower in men with a high concentration of serum total testosterone, even taking into account the concentration of serum estrogen in the raters. The average men’s face composited from images of 39 faces rated above pool median attractiveness rate, was slightly narrower than the average face composited from 38 less attractive faces. Our results challenge the ‘ovulatory shift hypothesis’ as faces of males with high circulating testosterone were rated as less attractive than faces of males with lower testosterone by women on the fertile phase of the cycle.
TMPRSS2 promotes SARS-CoV-2 evasion from NCOA7-mediated restriction

Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with the vacuolar ATPase, and promotes endo-lysosomal vesicle acidification and lysosomal protease activity. Here, we used ectopic expression and gene knockout to demonstrate that NCOA7 inhibits infection by SARS-CoV-2 as well as by lentivirus particles pseudotyped with SARS-CoV-2 Spike in lung epithelial cells. Infection with the highly pathogenic, SARS-CoV-1 and MERS-CoV, or seasonal, HCoV-229E and HCoV-NL63, coronavirus Spike-pseudotyped viruses was also inhibited by NCOA7. Importantly, either overexpression of TMPRSS2, which promotes plasma membrane fusion versus endosomal fusion of SARS-CoV-2, or removal of Spike’s polybasic furin cleavage site rendered SARS-CoV-2 less sensitive to NCOA7 restriction. Collectively, our data indicate that furin cleavage sensitizes SARS-CoV-2 Spike to the antiviral consequences of endosomal acidification by NCOA7, and suggest that the acquisition of furin cleavage may have favoured the co-option of cell surface TMPRSS proteases as a strategy to evade the suppressive effects of IFN-induced endo-lysosomal dysregulation on virus infection.
AD Informer Set: Chemical tools to facilitate Alzheimer's disease drug discovery

Introduction The portfolio of novel targets to treat Alzheimer’s disease (AD) has been enriched by the AMP-AD program. Methods A cheminformatics-driven effort enabled identification of existing small molecule modulators for many protein targets nominated by AMP-AD and suitable positive control compounds to be included in the set. Results We have built an annotated set of 171 small molecule modulators, including mostly inhibitors, targeting 98 unique proteins that have been nominated by AMP-AD consortium members as novel targets for AD treatment. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which would require further optimization. A physical copy of the AD Informer Set can be ordered via the AD Knowledge Portal. Discussion Small molecule tools that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD.
Forest tree species composition and abiotic site conditions drive soil fungal communities and functional groups

Soil fungi, especially the functional guilds of saprotrophic and mycorrhizal fungi, play a central role in ecosystem processes by degrading litter, mining for mineral nutrients and linking above- and belowground nutrient fluxes. Fungal community structures are influenced by abiotic habitat filters and management decisions such as tree species selection. Yet, the implications of the enrichment of temperate forests consisting of tree species in their natural range with non-native tree species on soil fungal diversity and their functional groups are unknown. Here, we studied fungal communities in 40 plots located in two regions differing in site conditions (nutrient content and soil moisture) in forests composed of European beech, Norway spruce and Douglas-fir (non-native) and mixtures of beech with either spruce or Douglas-fir. We hypothesized that fungal community structures are driven by soil resources and tree species composition, generally resulting in higher fungal diversity in mixed than in mono-specific forests. We further hypothesized that Douglas-fir has a negative effect on ectomycorrhizal fungal species richness compared to native species, whereas saprotrophic fungal richness is unaffected. We found strong separation of fungal communities between nutrient-rich and nutrient-poor sites and taxonomic divergence between beech and conifer fungal communities and an intermediate pattern in mixed forests. Mycorrhizal species richness did not vary with forest type, but the relative abundance of mycorrhizal species was lower in Douglas-fir and in mixed beech-Douglas-fir forests than in spruce or beech- spruce mixture. Conifer forests contained higher relative abundances of saprotrophic fungi than mono-specific beech forests. Among 16 abundant fungal orders in soil, two containing saprotrophic fungi (Tremellales, Hymenochaetales) were enriched in conifer forests, regardless of site conditions and tree species mixture. The other fungal orders, including those dominated by mycorrhizal fungi (Russulales, Boletales, Atheliales, Cantharellales) showed variable patterns depending on site conditions and tree species. In conclusion, Douglas-fir mono-specific or mixed forests show no loss of fungal species richness, but a shift in functional composition towards saprotrophic fungi.
Fast unconscious processing of emotional stimuli in early stages of the visual cortex

Several cortical and subcortical brain areas have been reported to be sensitive to the emotional content of subliminal stimuli. However, the timing of these activations remains unclear. Our scope was to detect the earliest cortical traces of visual unconscious processing by recording event-related potentials (ERPs) from 43 participants. Subliminal spiders (emotional) and wheels (neutral), sharing similar low-level visual parameters, were presented at two different locations (fixation and periphery). The differential (peak to peak) amplitude from CP1 (77 milliseconds from stimulus onset) to C2 (100 milliseconds), two early visual ERP components originated in V1/V2 according to source localization analyses, was analyzed via Bayesian and traditional analyses. Spiders elicited greater CP1-C2 amplitudes than wheels when presented at fixation. This fast effect of subliminal stimulation -not reported previously to the best of our knowledge-has implications in several debates: i) the amygdala cannot be mediating these effects, ii) latency of other evaluative structures recently proposed, such as the visual thalamus, is compatible with these results, iii) the absence of peripheral stimuli effects points to a relevant role of the parvocellular visual system in unconscious processing.
Phosphorus and Nitrogen Fertilization Effect on Phosphorus Uptake and Phosphatase Activity in Ryegrass and Tall Fescue Grown in a Chilean Andisol

A series of short-term experiments were carried out to assess the effect of phosphorus (P) and nitrogen (ammonium [NH4+-N] or nitrate [NO3−-N]) fertilization on P uptake and phosphatase activity in ryegrass and tall fescue cultivated under greenhouse conditions. Ryegrass or tall fescue plants were grown in an acidic Andisol in the presence or absence of P and increasing doses of NO3−-N or NH4+-N fertilizers. At the end of the experiment, soil phosphatase activity (P-aseRhiz), pH, and Olsen-P were determined in the rhizosphere soil. Plant biomass, P uptake, and root surface phosphatase (P-aseRoot) were also assayed for both plant species. Furthermore, soil incubation experiments at increasing doses of P, NO3−-N, or NH4+-N were performed to evaluate the fertilizer effect on soil phosphatase activity (P-aseBulk) and microbial biomass carbon in the bulk soil. In the absence of plants, P-aseBulk was inhibited and microbial biomass carbon was raised at increasing P supply levels. In the greenhouse experiments, P uptake by tall fescue was about 67% higher than that of ryegrass at low soil P availability, which suggests that tall fescue was less sensitive to P deficiency than ryegrass. For both plant species, P-aseRhiz did not vary as a consequence of P addition. On the other hand, fertilization with the highest NH4+-N dose strongly decreased soil pH and shoot P content, as well as it increased P-aseRoot activity. This fact denotes that P-aseRoot behaved as a strategic response parameter to P stress with insufficient impact on plant P nutrition in both plant species.
Probiotic consortia improve anti-viral immunity to SARS-CoV-2 in Ferrets

Probiotics have been suggested as one solution to counter detrimental health effects by SARS-CoV-2, however, data so far is scarce. We tested the effect of two probiotic consortia, OL-1 and OL-2, against SARS-CoV-2 in ferrets and assessed their effect on cytokine production and transcriptome in a human monocyte-derived macrophage (Mf) and dendritic cell (DC) model. The results showed that the consortia significantly reduced the viral load, modulated immune response, and regulated viral receptor expression in ferrets compared to placebo. In human Mf and DC model, OL-1 and OL-2 induced cytokine production and genes related to SARS-CoV-2 anti-viral immunity. The study results indicate that probiotic stimulation of the ferret immune system leads to improved anti-viral immunity against SARS-COV-2 and that critical genes and cytokines for anti-SARS-CoV-2 immunity are stimulated in human immune cells in vitro. The effect of the consortia against SARS-CoV-2 warrants further investigations in human clinical trials.
Drop, Swap, and Generate: A Self-Supervised Approach for Generating Neural Activity

Meaningful and simplified representations of neural activity can yield insights into how and what information is being processed within a neural circuit. However, without labels, finding representations that reveal the link between the brain and behavior can be challenging. Here, we introduce a novel unsupervised approach for learning disentangled representations of neural activity called Swap-VAE. Our approach combines a generative modeling framework with an instance-specific alignment loss that tries to maximize the representational similarity between transformed views of the input (brain state). These transformed (or augmented) views are created by dropping out neurons and jittering samples in time, which intuitively should lead the network to a representation that maintains both temporal consistency and invariance to the specific neurons used to represent the neural state. Through evaluations on both synthetic data and neural recordings from hundreds of neurons in different primate brains, we show that it is possible to build representations that disentangle neural datasets along relevant latent dimensions linked tso behavior.
Nucleotide degradation of pearl spot during medified atmosphere storage

The effect of modified atmosphere packaging (MAP) at different gas concentration on chill stored pearl spot ( Etroplus suratensis Bloch) was examined by means of nucleotide degradation and sensory evaluation. K value, a quality index for fish, the ratio of the sum of inosine and hypoxanthine to the sum of ATP and related catabolites expressed as a percentage, was determined until sensory rejection during storage up to 23 days at 0 - 20C. The C02 concentration did not affect the K values of pearl spot. K value increased linearly in samples stored under air and four different modified atmospheres. Identical K values were obtained for Pearl spot packed in either aerobic or carbon dioxide modified atmosphere. K values were independent of sensory spoilage and correlate only with the length of storage of pearl spot packed under MAP.
The desmin mutation R349P increases contractility and fragility of stem cell-generated muscle micro-tissues

Desminopathies comprise hereditary myopathies and cardiomyopathies caused by mutations in the intermediate filament protein desmin that lead to severe and often lethal degeneration of striated muscle tissue. Animal and single cell studies hinted that this degeneration process is associated with massive ultrastructural defects correlating with increased susceptibility of the muscle to acute mechanical stress. The underlying mechanism of mechanical susceptibility, and how muscle degeneration develops over time, however, has remained elusive. Here, we investigated the effect of a desmin mutation on the formation, differentiation, and contractile function of in vitro-engineered three-dimensional micro-tissues grown from muscle stem cells (satellite cells) isolated from heterozygous R349P desmin knock-in mice. Micro-tissues grown from desmin-mutated cells exhibited spontaneous unsynchronized contractions, higher contractile forces in response to electrical stimulation, and faster force recovery compared to tissues grown from wild-type cells. Within one week of culture, the majority of R349P desmin-mutated tissues disintegrated, whereas wild-type tissues remained intact over at least three weeks. Moreover, under tetanic stimulation lasting less than five seconds, desmin-mutated tissues partially or completely ruptured, whereas wild-type tissues did not display signs of damage. Our results demonstrate that the progressive degeneration of desmin-mutated micro-tissues is closely linked to extracellular matrix fiber breakage associated with increased contractile forces and unevenly distributed tensile stress. This suggests that the age-related degeneration of skeletal and cardiac muscle in patients suffering from desminopathies may be similarly exacerbated by mechanical damage from high-intensity muscle contractions. We conclude that micro-tissues may provide a valuable tool for studying the organization of myocytes and the pathogenic mechanisms of myopathies.
IFITM3 regulates virus-induced inflammatory cytokine production by titrating Nogo-B orchestration of TLR responses

Interferon induced transmembrane protein 3 (IFITM3) is an important viral restriction factor in viral pathogenesis that also exhibits poorly understood immune regulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 regulates MyD88-dependent TLR-mediated cytokine production following dendritic cell exposure to cytomegalovirus (CMV), and this process limits viral pathogenesis in vivo. IFITM3 also restricted pro-inflammatory (IL-6) cytokine production in response to influenza. IFITM3 bound to and promoted ubiquitination and proteasomal degradation of the reticulon 4 isoform Nogo-B. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and this process involved alteration of TLR dynamics. The anti-inflammatory function of IFITM3 was intrinsically linked to its ability to regulate Nogo-B. Thus, we uncover Nogo-B as an unappreciated driver of viral pathogenesis and highlight a novel immune regulatory pathway where IFITM3 fine-tunes TLR responsiveness of myeloid cells to viral stimulation.
Neural and computational processes of accelerated perceptual awareness and decisions: A 7T fMRI study

Rapidly detecting salient information in our environments is critical for survival. Visual processing in subcortical areas like the pulvinar and amygdala have been shown to facilitate unconscious processing of salient stimuli. It is unknown, however, if and how these areas might interact with cortical networks to facilitate faster conscious perception of salient stimuli. Here we investigated these neural processes using 7T functional Magnetic Resonance Imaging (fMRI) in concert with computational modelling while participants (n = 32) engaged in a breaking continuous flash suppression paradigm (bCFS) in which fearful and neutral faces are initially suppressed from conscious perception but then eventually “breakthrough” into awareness. We found that participants reported faster breakthrough times for fearful faces compared to neutral faces. Drift-diffusion modelling suggested that perceptual evidence was accumulated at a faster rate for fearful faces compared to neutral faces. For both neutral and fearful faces, faster response times coincided with greater activity in the amygdala (specifically within its subregions, including superficial, basolateral and amygdalo-striatal transition area) and the insula. Faster rates of evidence accumulation coincided with greater activity in frontoparietal regions and the occipital lobe, as well as the amygdala. Overall, our findings suggest that hastened perceptual awareness of salient stimuli recruits the amygdala and, more specifically, is driven by accelerated evidence accumulation in fronto-parietal and visual areas. In sum, we have uncovered and mapped distinct neural computations that accelerate perceptual awareness of visually suppressed faces.
Decoding the neural signatures of valence and arousal from portable EEG headset

Emotion classification using electroencephalography (EEG) data and machine learning techniques has been on the rise in the recent past. However, past studies uses data from medical-grade EEG setup with long set-up time and environment constraints. This paper focuses on classifying emotions on the valence-arousal plane using various feature extraction, feature selection and machine learning techniques. We evaluate different feature extraction and selection techniques and propose the optimal set of features and electrodes for emotion recognition. The images from the OASIS image dataset were used to elicit valence and arousal emotions, and the EEG data was recorded using the Emotiv Epoc X mobile EEG headset. The analysis is carried out on publicly available datasets: DEAP and DREAMER for benchmarking. We propose a novel feature ranking technique and incremental learning approach to analyze performance dependence on the number of participants. Leave-one-subject-out cross-validation was carried out to identify subject bias in emotion elicitation patterns. The importance of different electrode locations was calculated, which could be used for designing a headset for emotion recognition. The collected dataset and pipeline are also published. Our study achieved a root mean square score (RMSE) of 0.905 on DREAMER, 1.902 on DEAP, and 2.728 on our dataset for valence label and a score of 0.749 on DREAMER, 1.769 on DEAP and 2.3 on our proposed dataset for arousal label respectively.
Semantic verbal fluency: network analysis in Alzheimer’s and Parkinson’s disease

ABSTRACT Semantic verbal fluency (SVF) help to evaluate lexical retrieval and the semantic organisation. SVF scores are considered a good predictor of cognitive impairment. This study examines the structure and organisation of semantic networks through a network graph analysis of an SVF task performed by persons with typical aging (TA), Parkinson’s disease (PD), or Alzheimer’s disease (AD). Typically aging participants behave differently than those with PD and AD. Those in the AD group produced fewer words than those in the other two groups, controlling for cognitive impairment based on the Mini-Mental State Exam. The AD group presented a smaller number of nodes and edges than those with PD and TA. The small-worldness index of the PD and AD groups, but not of the TA group, was similar to that of the permuted distribution. We interpret this outcome as the consequence of problems in information transmission between concepts in the semantic network.
Quotas in South African cricket – what the players say

Abstract Since 1994, quotas have been a part of the national discourse, as a means of increasing the representation of ‘Black’ players in South African sports teams. This qualitative study investigated players’ and key informants’ perceptions of the effectiveness of a quota intervention in South African cricket. Semi-structured interviews were conducted with elite players from all ethnic groups (n = 43), and with key informants (n = 16). Data were thematically analysed relative to barriers and enablers of talent development. Findings indicate that despite providing opportunities to an increasing number of Black African players at the representative levels, and inspiring young players to play cricket, the quotas have had a limited effect on other barriers and enablers to talent development. Holistic player development was identified as a more effective process of achieving sustainable transformation. Furthermore, quotas have had a negative impact on individual players of all ethnicities and exacerbated the limited inclusivity in team environments.
Relational and health correlates of excessive affection

ABSTRACT The current study examined excessive affection, the perception that someone is receiving more affection than they would prefer. The study posed several hypotheses over three studies that all dealt with various psychosocial correlates of excessive affection. Specifically, the first two studies examined correlates of a more general perception of excessive affection (which were largely unsupported except for both anxious and avoidant attachment), while the third study examined correlates of a more specific perception of excessive affection within romantic relationships. Nearly all of the hypotheses were supported in the third study, including relationships with stress, loneliness, and relational satisfaction.