Miracle-dz/UniFAR-FTUs huggingface dataset:
Polarities of P and S waves, and shear wave splitting observed from the Bucaramanga Nest, Colombia

The Bucaramanga nest, Colombia, is an intense seismic source centered at 6°48′N, 73°10′W and 161-km depth beneath the eastern Andes. During a 3-week period, 161 microearthquakes (mb ≤ 4.3) were recorded by a 260-by-140-km array of 12 three-component University of Wisconsin (UW) seismographs centered above the nest. Eighty-eight percent of the events recorded were from the nest, providing a unique opportunity to study natural events that have different source parameters but nearly the same ray paths. Shear wave splitting analysis shows that the average polarization direction of the first-arriving shear waves from the nest events at nine of the seismographs is N12°E±18°. After corrections based on the amount of discrepancy between the observed average P wave azimuth and the expected event-to-station azimuth, average S wave polarization is N6°E ±15°. Variation in time delays with azimuth and epicentral distance appears to be due to the varying angles between the ray path and the principal axes of the anisotropic system. Shear wave splitting observed from 17 events along the Wadati-Benioff zone outside the nest shows that the time delays increase with increasing depth, and defines a wedge-shaped anisotropic volume above the subducting plate. The anisotropic layer has a maximum thickness of approximately 60 km at the depth of the nest and is thinning updip. The anisotropy most likely results from aligned anisotropic minerals such as olivine and orthopyroxene in a localized mantle flow in the lithosphere above the Wadati-Benioff zone, a region weakened by active fluid migration and mobilized by the heating and shearing along the suducting slab.
Best practices for perturbation MPRA–a computational evaluation framework of sequence design strategies

The advent of the perturbation-based massively parallel reporter assays (MPRAs) technique has enabled delineating of the roles of non-coding regulatory elements in orchestrating gene expression. However, computational efforts remain scant to evaluate and establish guidelines for sequence design strategies for perturbation MPRAs. Here, we propose a framework for evaluating and comparing various perturbation strategies for MPRA experiments. Under this framework, we benchmark three different perturbation approaches from the perspectives of alteration in motif-based profiles, consistency of MPRA outputs, and robustness of models that predict the activities of putative regulatory motifs. Although our analyses show similar while significant results in multiple metrics, the method of randomly shuffling nucleotides outperform the other two methods. Thus, we still recommend designing sequences by randomly shuffling the nucleotides of the perturbed site in perturbation-MPRA. The evaluation framework, together with the benchmarking findings in our work, creates a resource of computational pipelines and illustrates the promise of perturbation-MPRA for predicting non-coding regulatory activities.
The Relationship between Users’ Behavior and Their Flow Experience in Gamified Systems

Modeling users' experience in gameful systems is one of the main contemporary challenges in the field of human-computer interaction. One of the most desired and complex experiences to be identified is the flow experience (i.e., challenge-skill balance, action-awareness merging, clear goals, unambiguous feedback, concentration, sense of control, loss of self-consciousness, transformation of time, and autotelic experience). Facing this challenge, we conducted a quantitative study (N = 313) based on structural equation modeling, aiming to model and predict the users' flow experience through their behavior (represented by performance-related, interaction with gamification, as well as the time they take in different actions) in the system. The main results indicate that i) gamification (i.e., doing well in points, badges, and leader-board) was positively related to users' experience of good challenge-skill balance, ii) whereas it was negatively related to users' concentration. Thirdly iii) user performance was positively related to users' concentration. However, overall, the results indicate that while associations between user behavior and flow experience could be established, there remains future work to be done to fully explain user flow experience while using a system. Our study contributes to the fields of human-computer interaction, gamification, and educational technologies, especially through insights related to modeling and predicting flow experiences in gameful systems through behavior data.
"A feeling of déjà vu": The Effects of Avatar Appearance-Similarity on Persuasiveness in Social Virtual Reality

The similarity effect refers to the tendency for people to be more easily influenced by others who resemble them in appearance. This phenomenon has been found to have positive impacts, including on the building of trust, that enrich the quality of communication (e.g., fluency or collaboration performance). While research has shown that the similarity effect occurs in screen-based communication platforms, it remains unclear how this phenomenon impacts user perceptions, especially of others' persuasiveness, in immersive environments such as virtual reality (VR). In this study, we adopted a mixed-methods approach to exploring how interaction with avatars of similar appearance to one's own self-representation influences conversations. Such similarity was operationalized as having three levels: identicality, moderate similarity, and dissimilarity. The study found that avatars of moderate similarity have the greatest persuasiveness; however, in both identicality and moderate similarity conditions, participants felt it was easier to communicate with and lower eeriness rating to avatars than in the dissimilarity condition. Multiple linear regression further revealed that users who had relatively low self-esteem and/or were relatively conscientious were more susceptible to the positive effect of appearance similarity on persuasiveness. We conclude that the similarity effect, especially when the similarity in question is moderate, could be leveraged to support persuasiveness in VR-based communication.
Toxin-Triggered Liposomes for the Controlled Release of Antibiotics to Treat Infections Associated with Gram-Negative Bacteria

Antibiotic resistance has become an urgent threat to health care in recent years. The use of drug delivery systems provides advantages over conventional administration of antibiotics and can slow the development of antibiotic resistance. In the current study, we developed a toxin- triggered liposomal antibiotic delivery system, in which the drug release is enabled by the leukotoxin (LtxA) produced by the Gram-negative pathogen, Aggregatibacter actinomycetemcomitans. LtxA has previously been shown to mediate membrane disruption by promoting a lipid phase change in nonlamellar lipids, such as 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine-N-methyl (N-methyl-DOPE). In addition, LtxA has been observed to bind strongly and nearly irreversibly to membranes containing large amounts of cholesterol. Here, we designed a liposomal delivery system composed of N-methyl-DOPE and cholesterol to take advantage of these interactions. Specifically, we hypothesized that liposomes composed of N- methyl-DOPE and cholesterol, encapsulating antibiotics, would be sensitive to LtxA, enabling controlled antibiotic release. We observed that liposomes composed of N-methyl-DOPE were sensitive to the presence of low concentrations of LtxA, and cholesterol increased the extent and kinetics of content release. The liposomes were stable under various storage conditions for at least 7 days. Finally, we showed that antibiotic release occurs selectively in the presence of an LtxA-producing strain of A. actinomycetemcomitans but not in the presence of a non-LtxA- expressing strain. Together, these results demonstrate that the designed liposomal vehicle enables toxin-triggered delivery of antibiotics to LtxA-producing strains of A. actinomycetemcomitans.
The FW2.2/CNR protein regulates cell-to-cell communication in tomato by modulating callose deposition at plasmodesmata

The FW2.2 gene is the founding member of the CELL NUMBER REGULATOR (CNR) gene family. More than 20 years ago, FW2.2 was the first cloned gene underlying a Quantitative Trait Locus (QTL) governing fruit size/weight in tomato. However, despite this discovery, the molecular mechanisms by which FW2.2 acts as a negative regulator of cell divisions during fruit growth remain undeciphered. In the present study, we confirm that FW2.2 is a transmembrane spanning protein, whose both N- and C-terminal ends are facing the apoplast. We unexpectedly found that FW2.2 is located at plasmodesmata (PD). FW2.2 participates in the spatiotemporal regulation of callose deposition at PD via an interaction with Callose Synthases, which suggests a regulatory role in cell-to-cell communication by modulating PD transport capacity and trafficking of signaling molecules during fruit development.
A Comparative Analysis of Transformer-based Protein Language Models for Remote Homology Prediction

Protein language models based on the transformer architecture are increasingly shown to learn rich representations from protein sequences that improve performance on a variety of downstream protein prediction tasks. These tasks encompass a wide range of predictions, including prediction of secondary structure, subcellular localization, evolutionary relationships within protein families, as well as superfamily and family membership. There is recent evidence that such models also implicitly learn structural information. In this paper we put this to the test on a hallmark problem in computational biology, remote homology prediction. We employ a rigorous setting, where, by lowering sequence identity, we clarify whether the problem of remote homology prediction has been solved. Among various interesting findings, we report that current state-of-the-art, large models are still underperforming in the "twilight zone" of very low sequence identity.
Brain oscillatory processes related to sequence memory in healthy older adults

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60-80 years) and 26 young participants (20-30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4-8 Hz) and synchronization in gamma (30-45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging.
Formal concept analysis and information systems modeling

In this paper, we present the methodology based on formal concept analysis (FCA) for the information system model verification. We show that FCA can be useful for understanding conceptual model topology and it can be used to improve conceptual model hierarchal structure. IBM's Information Framework (IFW) Financial Services Data Model (FSDM) has been used for the present research. By using FSDM we demonstrate that the IS model can be recreated with formal concept analysis.
Mitochondrial regulator PGC-1a in neuronal metabolism and brain aging

The brain is a high energy tissue, and the cell types of which it is comprised are distinct in function and in metabolic requirements. The transcriptional co-activator PGC-1a is a master regulator of mitochondrial function and is highly expressed in the brain; however, its cell-type specific role in regulating metabolism has not been well established. Here, we show that PGC-1a is responsive to aging and that expression of the neuron specific PGC-1a isoform allows for specialization in metabolic adaptation. Transcriptional profiles of the cortex from male mice show an impact of age on immune, inflammatory, and neuronal functional pathways and a highly integrated metabolic response that is associated with decreased expression of PGC-1a. Proteomic analysis confirms age-related changes in metabolism and further shows changes in ribosomal and RNA splicing pathways. We show that neurons express a specialized PGC-1a isoform that becomes active during differentiation from stem cells and is further induced during the maturation of isolated neurons. Neuronal but not astrocyte PGC-1a responds robustly to inhibition of the growth sensitive kinase GSK3b, where the brain specific promoter driven dominant isoform is repressed. The GSK3b inhibitor lithium broadly reprograms metabolism and growth signaling, including significantly lower expression of mitochondrial and ribosomal pathway genes and suppression of growth signaling, which are linked to changes in mitochondrial function and neuronal outgrowth. In vivo, lithium treatment significantly changes the expression of genes involved in cortical growth, endocrine, and circadian pathways. These data place the GSK3b/PGC-1a axis centrally in a growth and metabolism network that is directly relevant to brain aging.
Functional opsin patterning for Drosophila color vision is established through signaling pathways in adjacent object-detection neurons

Vision is mainly based on two different tasks, object detection and color discrimination through activities of photoreceptor (PR) cells. Drosophila compound eye consists of ∼800 ommatidia. Every ommatidium contains eight PR cells; six outer cells (R1-R6) and two inner cells (R7 and R8) by which object detection and color vision are achieved, respectively. Expression of opsin genes in R7 and R8 is highly coordinated through the instructive signal from R7 to R8, and two major ommatidial subtypes are distributed stochastically; pale type expresses Rh3/Rh5, while yellow type expresses Rh4/Rh6 in R7/R8. The homeodomain protein Defective proventriculus (Dve) is expressed in yellow-type R7 and in six outer PRs, and it is involved in Rh3 repression to specify the yellow-type R7. dve mutant eyes exhibited atypical coupling, Rh3/Rh6 and Rh4/Rh5, indicating that the Dve activity is required for proper opsin coupling. Surprisingly, Dve activity in R1 is required for instructive signal, whereas those in R6 and R7 block the signal. Our results indicate that functional coupling of two different neurons is established through signaling pathways from adjacent neurons that are functionally different. Summary Statement Dve activity is required for proper opsin coupling of two neurons that is established through signaling pathways from adjacent neurons that are functionally different.
The stratigraphical potential of blattodean insects from the late Carboniferous of southern Britain

The Blattodea (cockroaches sensu lato or roachoids) from the southern coalfields of the UK are reviewed or examined, especially species occurring in more than one coal basin including Mylacris abrupta (Bolton, 1930) comb. nov., and undescribed material from Writhlington (Somerset). It is proposed that a derived mylacrid Mylacris–Sooblatta assemblage is used to extend the latest Westphalian and earliest Stephanian insect zonation from the continent to southern Britain, thus augmenting the European Pennsylvanian scheme.
A molecular switch in RCK2 triggers sodium-dependent activation of KNa1.1 (KCNT1) potassium channels

The Na+-activated K+ channel KNa1.1, encoded by the KCNT1 gene, is an important regulator of neuronal excitability. How intracellular Na+ ions bind and increase channel activity is not well understood. Analysis of KNa1.1 channel structures indicate that there is a large twisting of the βN-αQ loop in the intracellular RCK2 domain between the inactive and Na+-activated conformations, with a lysine (K885, human subunit numbering) close enough to form a salt bridge with aspartate (D839) in the Na+-activated state. Concurrently, an aspartate (D884) adjacent in the same loop adopts a position within 4 Å of several acidic or polar residues. In carrying out mutagenesis and electrophysiology with human KNa1.1, we found alanine substitution of each of these residues resulted in almost negligible currents in the presence of up to 40 mM intracellular Na+. The exception was D884A, which resulted in constitutively active channels in both the presence and absence of intracellular Na+. Further mutagenesis of this site revealed an amino acid size-dependent effect. Substitutions at this site by an amino acid smaller than aspartate (D884V) also yielded constitutively active KNa1.1, D884I had Na+- dependence similar to wild-type KNa1.1, whilst increasing the side chain size larger than aspartate (D884E or D884F) yielded channels that could not be activated by up to 40 mM intracellular Na+. We conclude that Na+ binding results in a conformational change that accommodates D884 in the acid-rich pocket, which triggers further conformational changes in the RCK domains and channel activation. Statement of Significance Sodium-activated potassium channels regulate neuronal excitability, and their dysfunction causes severe childhood disorders. Here, we identify a structural determinant in the intracellular domains that is responsible for triggering channel activation in response to sodium ion binding. An increase in the size of a particular amino acid renders the channel sodium-insensitive, whilst a decrease in size enables the channel to activate in the absence of sodium. This enhances our understanding of how this subclass of potassium channels respond to changes in the intracellular ionic environment. Furthermore, this may also further our understanding of the basis of human neurological disorders and their treatment.
Short N-terminal disordered regions and the proline-rich domain are major regulators of phase transitions for full-length UBQLN1, UBQLN2 and UBQLN4

Highly homologous ubiquitin-binding shuttle proteins UBQLN1, UBQLN2 and UBQLN4 differ in both their specific protein quality control functions and their propensities to localize to stress-induced condensates, cellular aggregates and aggresomes. We previously showed that UBQLN2 phase separates in vitro, and that the phase separation propensities of UBQLN2 deletion constructs correlate with their ability to form condensates in cells. Here, we demonstrated that full-length UBQLN1, UBQLN2 and UBQLN4 exhibit distinct phase behaviors in vitro. Strikingly, UBQLN4 phase separates at a much lower saturation concentration than UBQLN1. However, neither UBQLN1 nor UBQLN4 phase separates with a strong temperature dependence, unlike UBQLN2. We determined that the temperature-dependent phase behavior of UBQLN2 stems from its unique proline-rich (Pxx) region, which is absent in the other UBQLNs. We found that the short N-terminal disordered regions of UBQLN1, UBQLN2 and UBQLN4 inhibit UBQLN phase separation via electrostatics interactions. Charge variants of the N-terminal regions exhibit altered phase behaviors. Consistent with the sensitivity of UBQLN phase separation to the composition of the N-terminal regions, epitope tags placed on the N-termini of the UBQLNs tune phase separation. Overall, our in vitro results have important implications for studies of UBQLNs in cells, including the identification of phase separation as a potential mechanism to distinguish the cellular roles of UBQLNs, and the need to apply caution when using epitope tags to prevent experimental artifacts. Highlights 1) Full-length UBQLN1, UBQLN2 and UBQLN4 all exhibit LCST phase transitions but to different degrees. 2) The N-terminal region (N-terminal to the UBL) substantially regulates UBQLN phase separation. 3) Removal of the disease-associated proline-rich (Pxx) region in UBQLN2 removes the strong temperature dependence of UBQLN2 phase separation.
Discovery of essential kinetoplastid-insect adhesion proteins and their function in Leishmania-sand fly interactions

Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide1. Leishmania has a complex life cycle with multiple developmental forms, as it cycles between a sand fly vector and a mammalian host; understanding their life cycle is critical to understanding disease spread2. One of the key life cycle stages is the haptomonad form, which is attached to the insect through its flagellum. This adhesion, which is conserved across kinetoplastid parasites, is implicated to have an important function within their life cycles and hence on disease transmission3–5. Here, we discovered kinetoplastid-insect adhesion proteins (KIAPs), which are localised in the attached haptomonad flagellum. Deletion of these KIAPs impaired cell adhesion in vitro and prevented Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. This result will provide important insights for a comprehensive understanding of the Leishmania life cycle.
Stomata, a vulnerability in the plant defence against phytophagous mites that ABA can overcome

Arthropod herbivory possess a significant threat to crop yield, prompting plants to employ intricate defense mechanisms against pest feeding. The generalist pest, Tetranychus urticae, inflicts rapid damage and remains a challenge due to its broad target range. In this study, we explored Arabidopsis thaliana’s response to T. urticae infestation, revealing the induction of abscisic acid (ABA), a hormone typically associated with abiotic stress adaptation, including stomatal closure during water stress. Leveraging a FRET-based ABA biosensor (nlsABACUS2-400n), we observed elevated ABA levels in various leaf cell types post-mite feeding. While ABA’s role in pest resistance or susceptibility has been debated, an ABA-deficient mutant exhibited increased mite infestation, alongside intact canonical biotic stress signalling, indicating an independent function of ABA in mite defense. Through genetic and pharmacological interventions targeting ABA levels, ABA signalling, stomatal aperture, and density, we established that ABA-triggered stomatal closure effectively hinders mite feeding and minimizes leaf cell damage. This study underscores the critical interplay between biotic and abiotic stresses in plants, highlighting how the vulnerability to mite infestation arising from open stomata, crucial for transpiration and photosynthesis, underscores the intricate relationship between these two stress types.
Electrical Dynamics of the Dendritic Space

1. Definition of the neuron 2. 3D geometry of dendritic arborizations 3. Basics in bioelectricity 4. The cable theory and the dendrites 5. Voltage transfer over the dendrites 6. Current transfer over dendrites 7. Electrical structure of an artificial dendritic path 8. Electrical structure of a bifurcation 9. Geography of the dendritic space 10. Electrical structures of biological dendrites 11. Electrical structure of the whole arborization 12. Electrical structures in the 3D dendritic space 13. Dendritic space as coder of the temporal output patterns 14. Concluding remarks.