Miracle-dz/UniFAR-FTUs huggingface dataset:
LncRNA PAINT is Associated with Aggressive Prostate Cancer and Dysregulation of Slug and Related Genes

Long non-coding RNAs (lncRNAs) play regulatory roles in cellular processes and their aberrant expression may drive cancer progression. Here we report the function of a lncRNA PAINT (Prostate Cancer Associated Intergenic Non-Coding Transcript) in promoting prostate cancer (PCa) progression. Upregulation of PAINT was noted in advanced stage and metastatic PCa. Inhibition of PAINT decreased cell proliferation, S-phase progression, increased expression of apoptotic markers, and improved sensitivity to docetaxel and Aurora kinase inhibitor VX-680. Inhibition of PAINT decreased cell migration and reduced expression of Slug and Vimentin. Ectopic expression of PAINT suppressed E-cadherin, increased S-phase progression and cell migration. PAINT expression in PCa cells induced larger colony formation and higher expression of mesenchymal markers. Transcriptome analysis followed by qRT-PCR validation showed differentially expressed genes involved in epithelial mesenchymal transition (EMT), apoptosis and drug resistance in PAINT-expressing cells. Our study establishes an oncogenic function of PAINT in PCa.
Assortative Mating, Autistic Traits, Empathizing, and Systemizing

It has been suggested that the children of parents with particular interests and aptitude for understanding systems via input-operation-output rules (i.e. systemizing) are at increased likelihood of developing autism. Furthermore, assortative mating (i.e. a non-random pattern in which individuals are more likely to pair with others who are similar to themselves) is hypothesised to occur in relation to systemizing, and so romantic couples may be more similar on this variable than chance would dictate. However, no published study has yet tested this hypothesis. We therefore examined intra-couple correlations for a measure of autistic traits (Autism Spectrum Quotient [AQ]), self-report measures of empathizing (Empathy Quotient [EQ]), and systemizing (Systemizing Quotient-Revised [SQ-R]), as well as the Reading the Mind in the Eyes Test (RMET) and Embedded Figures Task (EFT). We observed positive intra-couple correlations of small-to-medium magnitude for all measures except EQ. Further analyses suggest that these effects are attributable to people pairing with those who are more similar to themselves than chance (initial assortment) rather than becoming more alike over the course of a relationship (convergence), and to seeking out self-resembling partners (active assortment) rather than pairing in this manner due to social stratification increasing the likelihood of similar people meeting in the first place (social homogamy). Additionally, we found that the difference in scores for the AQ, SQ-R, RMET and EFT of actual couples were smaller (i.e. more similar) than the average difference scores calculated from all other possible male-female pairings within the dataset. The current findings therefore provide clear evidence in support of the assortative mating theory of autism.
The Big Five personality traits and CNS arousal in the resting state

Based on Eysenck’s pioneering work, CNS arousal has long been considered an encouraging biological candidate that may explain individual differences in human personality. Yet, results from empirical studies remained inconclusive. Notably, the vast majority of published results have been derived from small samples, and EEG alpha power has usually served as exclusive indicator for CNS arousal. In this study, we selected N = 468 individuals of the LIFE-Adult cohort and investigated the associations between the Big Five personality traits and CNS arousal by using the low-resolution electromagnetic tomography-based analysis tool VIGALL. Our analyses revealed that subjects who reported higher levels of extraversion and openness to experience, respectively, exhibited lower levels of CNS arousal in the resting state. Bayesian and frequentist analysis results were especially convincing for openness to experience. Among the lower-order personality traits, we obtained strongest evidence for neuroticism facet ‘impulsivity’ and reduced CNS arousal. We regard these findings as well in line with the postulations of Eysenck and Zuckerman and consistent with the assumptions of the ‘arousal regulation model’. Our results also agree with meta-analytically derived effect sizes in the field of individual differences research, highlighting the need for large studies with at least several hundreds of subjects.
Convergent evolution of Streptomyces protease inhibitors involving a tRNA-mediated condensation-minus NRPS

Small peptide aldehydes (SPAs) with protease inhibitory activity are natural products typically synthesized by nonribosomal peptide synthetases (NRPS). SPAs are widely used in biotechnology, as therapeutic agents, they are physiologically relevant and regulate development of the natural hosts. During genome evolutionary analysis of Streptomyces lividans 66 we identified an NRPS-like biosynthetic gene cluster (BGC) that lacked a condensation (C) domain but included a tRNA-Utilizing Enzyme (tRUE) belonging to the leucyl/phenylalanyl (L/F) transferase family. This system was predicted to direct the synthesis of a novel SPA with protease inhibitory activity, called livipeptin. Following genome mining and phylogenomic analyses we confirmed the presence of tRUEs within diverse Streptomyces genomes, including fusions with a C-minus NRPS-like protein. We further demonstrate functional cooperation between these enzymes and provide the biosynthetic rules for the synthesis of livipeptin, expanding the known universe of acetyl-leu/phe-arginal SPAs. The L/F-transferase C-minus NRPS productive interaction was shown to be tRNA-dependent after semisynthetic assays in the presence of RNAse, which contrasts with leupeptin, an acetyl-leu-arginal SPA that we show to be produced by Streptomyces roseous ATCC 31245 via a tRUE-minus BGC with multiple complete NRPSs. Thus, livipeptin and leupeptin are the result of convergent evolution, which has driven the appearance of unprecedented biosynthetic logics directing the synthesis of protease inhibitors thought to be at the core of Streptomyces colony biology. Our results pave the way for understanding this Streptomyces trait, as well as for the discovery of novel natural products following evolutionary genome mining approaches. Abstract importance Convergent evolution in microbiology is believed to be highly recurrent yet examples that have been comprehensively characterized are scarce. Proteases inhibition by small peptide aldehydes is at the core of many microbiological processes, both within the cell and during colony development, and in microbial ecology. Here we report the biosynthetic foundations of leupeptin, the main Streptomyces protease inhibitor, and of livipeptin, a protease inhibitor produced by Streptomyces lividans. Although these peptides belong to the same chemical class, here we show that their biosynthetic routes result from convergent evolution, as they involve unrelated biosynthetic mechanisms, including the recruitment of a tRNA-utilizing enzyme that functionally replaces the condensation domain of a nonribosomal peptide synthetase during livipeptin biosynthesis. Thus, these results pave the way for understanding Streptomyces protease inhibitors as a trait and provide unprecedented knowledge for genome mining of natural products and synthetic biology where proteases inhibition is desirable.
Species level resolution of female bladder microbiota from marker gene surveys

The human bladder contains bacteria in the absence of infection. Interest in studying these bacteria and their association with bladder conditions is increasing, but the chosen experimental method can limit the resolution of the taxonomy that can be assigned to the bacteria found in the bladder. 16S rRNA gene sequencing is commonly used to identify bacteria, but is typically restricted to genus-level identification. Our primary aim was to determine if accurate species-level identification of bladder bacteria is possible using 16S rRNA gene sequencing. We evaluated the ability of different classification schemes, each consisting of combinations of a 16S rRNA gene variable region, a reference database, and a taxonomic classification algorithm to correctly classify bladder bacteria. We show that species-level identification is possible, and that the reference database chosen is the most important component, followed by the 16S variable region sequenced. Importance Species-level information may deepen our understanding of associations between bladder microbiota and bladder conditions, such as lower urinary tract symptoms and urinary tract infections. The capability to identify bacterial species depends on large databases of sequences, algorithms that leverage statistics and available computer hardware, and knowledge of bacterial genetics and classification. Taken together, this is a daunting body of knowledge to become familiar with before the simple question of bacterial identity can be answered. Our results show the choice of taxonomic database and variable region of the 16S rRNA gene sequence makes species level identification possible. We also show this improvement can be achieved through the more careful application of existing methods and use of existing resources.
Application of clustering algorithm in social network user scenario prediction

In order to improve the ability of social network user behavior analysis and scenario pattern prediction, optimize social network construction, combine data mining and behavior analysis methods to perform social network user characteristic analysis and user scenario pattern optimization mining, and discover social network user behavior characteristics. Design multimedia content recommendation algorithms in multimedia social networks based on user behavior patterns. The current existing recommendation systems do not know how much the user likes the currently viewed content before the user scores the content or performs other operations, and the user’s preference may change at any time according to the user’s environment and the user’s identity, Usually in multimedia social networks, users have their own grading habits, or users’ ratings may be casual. Cluster-based algorithm, as an application of cluster analysis, based on clustering, the algorithm can predict the next position of the user. Because the algorithm has a “cold start”, it is suitable for new users without trajectories. You can also make predictions. In addition, the algorithm also considers the user’s feedback information, and constructs a scoring system, which can optimize the results of location prediction through iteration. The simulation results show that the accuracy of social network user scenario prediction using this method is higher, the accuracy of feature registration of social network user scenario mode is improved, and the real-time performance of algorithm processing is better.
Methods and procedures for reducing soy trypsin inhibitor activity by means of heat treatment combined with chemical methods

Abstract We have developed a new procedure for reducing soy trypsin inhibitor activity by means of heat treatment combined with chemical methods, through which soy trypsin inhibitor activity decreases to the tenth or twentieth part of the original value. We determined the optimal concentration of the applied chemicals (hydrogen-peroxide, ammonium-hydroxide) as well as the optimal temperature and duration of the treatment. The chemical procedure combined with heat treatment results in lower energy consumption as compared to the original heat treatment methods.
Spatio-temporal Memory for Navigation in a Mushroom Body Model

Insects, despite relatively small brains, can perform complex navigation tasks such as memorising a visual route. The exact format of visual memory encoded by neural systems during route learning and following is still unclear. Here we propose that interconnections between Kenyon cells in the Mushroom Body (MB) could encode spatio-temporal memory of visual motion experienced when moving along a route. In our implementation, visual motion is sensed using an event-based camera mounted on a robot, and learned by a biologically constrained spiking neural network model, based on simplified MB architecture and using modified leaky integrate-and-fire neurons. In contrast to previous image-matching models where all memories are stored in parallel, the continuous visual flow is inherently sequential. Our results show that the model can distinguish learned from unlearned route segments, with some tolerance to internal and external noise, including small displacements. The neural response can also explain observed behaviour taken to support sequential memory in ant experiments. However, obtaining comparable robustness to insect navigation might require the addition of biomimetic pre-processing of the input stream, and determination of the appropriate motor strategy to exploit the memory output.
APOEε3/ε4 and APOEε4/ε4 genotypes drive unique gene signatures in the cortex of young mice

Background Restrictions on mouse models have significantly impacted research towards understanding the most common genotype contributing to dementia in the human population – APOEε3/ε4. To address this, as part of MODEL-AD, we created new versions of humanized APOEε4 and APOEε3 mice on a C57BL/6J background that allow for unrestricted distribution and breeding. Methods To determine similarities and differences between APOEε3/ε4 and APOEε4/ε4 risk genotypes, we analyzed peripheral lipid concentrations as well as performed unbiased transcriptional profiling of the cortex at two and four months of age, comparing APOEε3/ε4 and APOEε4/ε4 to the reference APOEε3/ε3. To further compare APOE genotypes, cohorts of APOEε3/ε3, APOEε3/ε4, and APOEε4/ε4 mice were exercised by voluntary running from 1 month to 4 months of age. Results Cholesterol composition was significantly influenced by APOE genotype as early as 2 months, while triglycerides were affected by APOE genotype at 4 months. Importantly, RNA-sequencing of the cortex followed by linear modeling or weighted gene co-expression network analysis (WGCNA) revealed that the APOEε3/ε4 genotype showed unique transcriptomic signatures to that of APOEε4/ε4. Functional enrichment of the APOEε3/ε4, but not APOEε3/ε4 genotype, revealed sulfur and heparin binding as significant terms at 2 months, and extracellular matrix and blood coagulation at 4 months. Further, cell specific contributions of significant genes identified endothelial cells as overrepresented in the APOEε3/ε4 but not APOEε4/ε4 genotype. WGCNA analysis confirmed findings from linear modeling but also predicted that running at a young age affects myelination and gliogenesis across APOE genotypes. Conclusions In summary, APOEε3/ε4 genotype-specific effects were observed in cortical transcriptional profiles, suggesting therapies aimed at modifying APOE biology to treat dementias may need to be targeted to specific APOE genotypes.
Enhanced neural tracking of the fundamental frequency of the voice

Objective ‘F0 tracking’ is a novel method that investigates the neural processing of the fundamental frequency of the voice (f0) in continuous speech. Through linear modelling, a feature that reflects the stimulus f0 is predicted from the EEG data. Then, the neural response strength is evaluated through the correlation between the predicted and actual f0 feature. The aim of this study was to improve upon this ‘f0 tracking’ method by optimizing the f0 feature. Approach Specifically, we aimed to design a feature that approximates the expected EEG responses to the f0. We hypothesized that this would improve neural tracking results, because the more similar the feature and the neural response are, the easier it will be to reconstruct the one from the other. Two techniques were explored: a phenomenological model to simulate neural processing in the auditory periphery and a low-pass filter to approximate the effect of more central processing on the f0 response. Since these optimizations target different aspects of the auditory system, they were also applied in a cumulative fashion. Results Results obtained from EEG evoked by a Flemish story in 34 subjects indicated that both the use of the auditory model and the addition of the low-pass filter significantly improved the correlations between the actual and reconstructed feature. The combination of both strategies almost doubled the mean correlation over subjects, from 0.78 to 0.13. Moreover, canonical correlation analysis with the modelled feature revealed two distinct processes contributing to the f0 response: one driven by the compound activity of auditory nerve fibers with center frequency up to 8 kHz and one driven predominantly by the auditory nerve fibers with center frequency below 1 kHz. Significance The optimized f0 features developed in this study enhance the analysis of f0-tracking responses and facilitate future research and applications.
Corticostriatal Projections of Macaque Area 44

Ventrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. Yet, the corticostriatal circuitry that may contribute to area 44 functions is not clear, as prior investigation of area 44 corticostriatal projections is limited. Here, we used anterograde and retrograde tracing in macaques to map the innervation zone of area 44 corticostriatal projections, quantify their strengths, and evaluate their convergence with corticostriatal projections from non-motor and motor-related frontal regions. First, terminal fields from a rostral area 44 injection site were found primarily in the central caudate nucleus, whereas those from a caudal area 44 injection site were found primarily in the ventrolateral putamen. Second, amongst sampled striatal retrograde injection sites, area 44 input as a percentage of total frontal cortical input was highest in the ventral putamen at the level of the anterior commissure. Third, area 44 projections converged with both orofacial premotor area 6VR and other motor related projections (in the putamen), and with non-motor prefrontal projections (in the caudate nucleus). These findings support the role of area 44 as an interface between motor and non-motor functional domains, possibly facilitated by rostral and caudal area 44 subregions with distinct corticostriatal connectivity profiles.
Annotation Method for Human Activity and Device State Recognition Based on Smartphone Notification Removals

: With the increasing spread of smartphones and wearable devices equipped with various sensors, human activities, biometric information, and surrounding situations can be recognized. The process of human activity recognition must construct a model that has learned annotated sensor data, i.e., ground truth, labels, or answer activity, in advance. Therefore, a large and diverse set of annotated data is required to improve and evaluate model performance. It is di ﬃ cult to judge a user’s situation even after observing acceleration data; thus, it is necessary to annotate the collected acceleration data. In this paper, we propose a method to estimate user and device situations from the user’s response to a notiﬁcation generated by a device, e.g., a smartphone. The user and device situations are estimated from the user’s response time to the notiﬁcation and the device’s acceleration values. An estimation result with high conﬁdence is given to the sensor data as an annotation. Increasing the frequency of notiﬁcations, response to the notiﬁcations can be used as a sensor. We assume that acceleration values are a ﬀ ected by a user and device situation when the device notiﬁcations are taken instantly after its generation. The system pursues a high precision of estimation by selecting input acceleration data based on the interaction to the notiﬁcation so that the estimations can be used as annotations. Through an evaluation experiment, for seven types of annotation classes, an average precision of 0.769 and 0.963 for user-independent experiments and user-dependent experiments were achieved, respectively. We also tested the proposed method in a natural environment, where 25 correct annotations were given for 45 responses to notiﬁcations, no annotations were given for 19 responses, and only one incorrect notiﬁcation was observed.
Label-free composition determination for biomolecular condensates with an arbitrarily large number of components

Biomolecular condensates are membrane-less organelles made of multiple components, often including several distinct proteins and nucleic acids. However, current tools to measure condensate composition are limited and cannot capture this complexity quantitatively, as they either require fluorescent labels, which we show can perturb composition, or can distinguish only 1-2 components. Here, we describe a label-free method based on quantitative phase microscopy to measure the composition of condensates with an arbitrarily large number of components. We first validate the method empirically in binary mixtures, revealing sequence-encoded density variation and complex aging dynamics for condensates composed of full-length proteins. In simplified multi-component protein/RNA condensates, we uncover a regime of constant condensate density and a large range of protein:RNA stoichiometry when varying average composition. The unexpected decoupling of density and composition highlights the need to determine molecular stoichiometry in multi-component condensates. We foresee this approach enabling the study of compositional regulation of condensate properties and function.
A β-catenin-driven switch in TCF/LEF transcription factor binding to DNA targets sites promotes commitment of mammalian nephron progenitor cells

The canonical Wnt pathway transcriptional co-activator β-catenin regulates self-renewal and differentiation of mammalian nephron progenitor cells (NPCs). We modulated β-catenin levels in NPC cultures using the GSK3 inhibitor CHIR9902 (CHIR) to examine opposing developmental actions of β-catenin. Low CHIR-mediated maintenance and expansion of NPCs is independent of direct engagement of TCF/LEF/ β-catenin transcriptional complexes at low-CHIR dependent cell-cycle targets. In contrast, in high CHIR, TCF7/LEF1/β-catenin complexes replaced TCF7L1/TCF7L2 binding on enhancers of differentiation-promoting target genes. Chromosome confirmation studies showed pre-established promoter-enhancer connections to these target genes in NPCs. High CHIR-associated de novo looping was observed in positive transcriptional feedback regulation to the canonical Wnt pathway. Thus, β-catenin’s direct transcriptional role is restricted to the induction of NPCs where rising β-catenin levels switch inhibitory TCF7L1/TCF7L2 complexes to activating LEF1/TCF7 complexes at primed gene targets poised for rapid initiation of a nephrogenic program.
Women show enhanced attractiveness ratings and neural processing of male faces associated with male chemosensory signals

There is growing evidence that humans use olfactory chemosensory signals for social communication, but their role in affective associative learning is largely unknown. To examine this, women implicitly learned face-odor associations by pairing different neutral male faces with either a male chemosignal presumably involved in human mating behavior (dissolved Δ4,16-androstadien-3-one, “AND”), a pleasant smell (dissolved vanillin) or the neutral solvent alone. After learning, women rated faces previously paired with AND or vanillin as more attractive than faces paired with solvent, even though they were unable to identify the contingency of face-odor pairings above chance level. On a neurophysiological level, both AND- and vanillin-associated faces evoked stronger magnetoencephalographic correlates of enhanced emotional attention than solvent-associated faces at early (<120 ms) and mid-latency (140-270 ms) processing stages. This study stresses the role of AND as a human chemosignal in implicit social communication and demonstrates its effectiveness in modulating emotional learning.