Miracle-dz/UniFAR-FTUs huggingface dataset:
Expandability differences in learning transfer between computerized and non-computerized games

Computerized and non-computerized games are used in training designed to improve cognitive function. However, it is unclear which properties of the games influence the transfer of cognitive performance. This study aimed to examine the expandability of this transfer according to the properties of training tools. We introduced two training tools (virtual and standard Rubik’s Cubes) and examined bidirectional transfer between the two cube types and transfer to other cognitive tasks. The results showed that transfer from the virtual cube to the standard cube was greater relative to that observed from the standard cube to the virtual cube. Regarding transfer to other tasks, cognitive transfer did not differ significantly between the virtual and standard cubes, but the training exerted beneficial effects. These results suggest that transfer expandability differed between computerized and non-computerized games. The findings of the study could contribute to the provision of an effective cognitive training programme.
Functional redundancy in natural pico-phytoplankton communities depends on temperature and biogeography

Biodiversity affects ecosystem function, but how this relationship will pan out in a changing world is still a major question in ecology. It remains especially understudied for pico-phytoplankton communities, which contribute to carbon cycles and aquatic food webs year-round. Observational studies show a link between phytoplankton community diversity and ecosystem stability, but there is only scarce causal or empirical evidence. Here, we sampled phytoplankton communities from two biogeographically distinct (but close enough to not be confounded by differences in day length and precipitation) regions in the Southern Baltic Sea, and carried out a series of dilution/regrowth experiments across three assay temperatures. This allowed us to investigate the effects of loss of rare taxa and establish causal links in natural communities between species richness and several ecologically relevant traits (e.g. size, biomass production, and oxygen production), depending on sampling location and assay temperature. We found that the samples’ bio-geographical origin determined whether and how functional redundancy changed as a function of temperature for all traits under investigation. Samples obtained from the slightly warmer and more thermally variable regions showed overall high functional redundancy. Samples from the slightly cooler, less variable, stations showed little functional redundancy, i.e. function decreased the more species were lost from the community. The differences between regions were more pronounced at elevated assay temperatures. Our results imply that the importance of rare species and the amount of species required to maintain ecosystem function even under short-term warming (e.g. during heat waves) may differ drastically even within geographically closely related regions of the same ecosystem.
Cadherin-11 is required for neural crest determination and survival

Neural crest (NC) cells are multipotent embryonic cells that form melanocytes, craniofacial bone and cartilage, and the peripheral nervous system in vertebrates. NC cells express many cadherin proteins, which control their specification, epithelial to mesenchymal transition (EMT), migration, and mesenchymal to epithelial transition. Abnormal NC development leads to congenital defects including craniofacial clefts as well as NC-derived cancers. Here, we identify the role of the type II cadherin protein, Cadherin-11 (CDH11), in early chicken NC development. CDH11 is crucial for NC cell migration in amphibian embryos and is linked to cell survival, proliferation, and migration in cancer cells. It has been linked to the complex neurocristopathy disorder, Elsahy‐Waters Syndrome, in humans. Using immunohistochemistry (IHC), we determined that CDH11 protein has dynamic expression that is first co-localized with neural progenitors in early embryos and subsequently upregulated specifically in NC cells as they are specified in the dorsal neural tube prior to migration. We identified that loss of CDH11 led to a reduction of bonafide NC cells in the dorsal neural tube combined with defects in cell migration and survival. Loss of CDH11 increased p53-mediated programmed-cell death, and blocking the p53 pathway rescued the NC phenotype. Our findings demonstrate an early requirement for CDH11 in NC development, and may increase our understanding of early cadherin-related NC developmental defects. Summary Chicken Cadherin-11 (CDH11), which is expressed in neural crest (NC) cells prior to NC cell migration, is necessary for the determination and survival of the premigratory NC population.
Post-settlement movement of coral reef fishes and bias in survival estimates

Most coral reef fish have a bipartite life-history characterized by a pelaglc larval phase followed by transformation and settlr~rlent into a benthic existence There is inci-eas~ng Interest anlong marine ecologists in determining thc importance of post-settlement processes to reef f ~ s h demography. This study distinguishes movement as an important post-settlement phenomenon affecting estimates of early survivorship of juvenile coral reef fishes. Individuals settling onto artificial patch habitats were collected, marked, released and monitored by visual census over 2 systems of ~sola ted artificial patch habitats. Some recently settled juvenile fish moved as much as 100 m over open sand. Probability of movement was dependent on species; size was a significant factor among species, but not among conspecifics. Survlvorship calculated from observations of uniquely marked indiv~duals was contrasted with survivorsh~p estimated by comparing the initial number of newly settled indiv~duals at a site with the number of indiv~duals there after a given time interval. The comparison revealed that new settlers and immigrants can mask the loss of individuals included in the original census and thereby ~nf la te stimates of survivorship. Coinparing survival estimates with and without accounting for movement demonstrated that survivorship can be underestimated when new settlers subsequently emigrate and survive at another site, but are unwittingly recorded as lost due to mortal~ty. Significant differences were observed in survival experiences for different species and size classes. Where significant differences were found in sur\iival times of mob~le individuals versus sedentary, those that moved survived longer.
Resolution of subcomponents of synaptic release from post-synaptic currents in rat hair-cell/auditory-nerve fiber synapses

The synapse between inner hair cells and auditory nerve fiber dendrites shows large EPSCs, which are either monophasic or multiphasic. Multiquantal or uniquantal flickering release have been proposed to underlie the unusual multiphasic waveforms. Here the nature of multiphasic waveforms is analyzed using EPSCs recorded in vitro in rat afferent dendrites. Spontaneous EPSCs were deconvolved into a sum of presumed release events with monophasic EPSC waveforms. Results include: first, the charge of EPSCs is about the same for multiphasic versus monophasic EPSCs. Second, EPSC amplitudes decline with the number of release events per EPSC. Third, there is no evidence of a mini-EPSC. Most results can be accounted for by versions of either uniquantal or multiquantal release. However, serial neurotransmitter release in multiphasic EPSCs shows properties that are not fully explained by either model, especially that the amplitudes of individual release events is established at the beginning of a multiphasic EPSC, constraining possible models of vesicle release.
Acoustically driven cortical delta oscillations underpin perceptual chunking

Oscillation-based models of speech perception postulate a cortical computational principle by which decoding is performed within a window structure derived by a segmentation process. In the syllable level segmentation is realized by a theta oscillator. We provide evidence for an analogous role of a delta oscillator at the phrasal level. We recorded MEG while participants performed a target identification task. Random-digit strings, with phrasal chunks of two digits, were presented at chunk rates inside or outside of the delta range. Strong periodicities were elicited by acoustic-driven chunk rates inside of delta, in superior and middle temporal areas and speech-motor integration areas. Periodicities were diminished or absent for chunk rates outside of the delta range, closely in line with behavioral performance. No periodicities were observed for top-down driven chunking conditions. Our findings show that phrasal chunking is correlated with acoustic-driven delta oscillations, expressing anatomically specific patterns of neuronal periodicities.
Complexity of intrinsic brain dynamics

7 The brain is a complex, nonlinear system, exhibiting ever-evolving patterns 8 of activities even without external inputs or tasks. Such intrinsic dynamics play 9 a key role in cognitive functions and psychiatric disorders. A challenge is to link 10 the intrinsic dynamics to the underlying structure, given the nonlinearity. Here 11 we use a biophysically constrained, nonlinear-dynamical model to show how 12 the complexity of intrinsic brain dynamics, manifested as its multistability and 13 temporal diversity, can be sculpted by structural properties across scales. At a 14 local level, multistability and temporal diversity can be induced by sufficient 15 recurrent excitatory connectivity and its heterogeneity. At a global level, such 16 functional complexity can also be created by the synergistic interaction between 17 monostable, locally identical regions. Coordination between model brain 18 regions across attractors in the multistable landscape predicts human functional 19 connectivity. Compared to dynamics near a single attractor, cross-attractor 20 coordination better accounts for functional links uncorrelated with structural 21 connectivity. Energy costs of cross-attractor coordination are modulated by 22 both local and global connectivity, and higher in the Default Mode Network. 23 These findings hint that functional connectivity underscores transitions between 24 alternative patterns of activity in the brain—even more than the patterns 25 themselves. This work provides a systematic framework for characterizing 26 intrinsic brain dynamics as a web of cross-attractor transitions and their energy 27 costs. The framework may be used to predict transitions and energy costs 28 associated with experimental or clinical interventions. 29 Significance Statement 30 The brain is a multifunctional system: different brain regions can coordinate flexibly 31 to perform different tasks. Understanding the regional and global structural con32 straints on brain function is critical to understand cognition. Here, using a unified 33 biophysical network model, we show how structural constraints across scales jointly 34 shape the brain’s intrinsic functional repertoire – the set of all possible patterns that 35 a brain could generate. The modeled functional repertoire is enriched by both the 36 flexibility of individual brain regions and their synergistic interaction in a global 37 network. By carefully examining the modeled repertoire, we found that human 38 resting-state functional connectivity was better predicted by transitions between 39 brain activity patterns rather than any specific pattern per se. 40
Large domain movements through lipid bilayer mediate substrate release and inhibition of glutamate transporters

Glutamate transporters are essential players in glutamatergic neurotransmission in the brain, where they maintain extracellular glutamate below cytotoxic levels and allow for rounds of transmission. The structural bases of their function are well established, particularly within a model archaeal homologue, sodium and aspartate symporter GltPh. However, the mechanism of gating on the cytoplasmic side of the membrane remains ambiguous. We report Cryo-EM structures of GltPh reconstituted into nanodiscs, including those structurally constrained in the cytoplasm-facing state and either apo, bound to sodium ions only, substrate, or blockers. The structures show that both substrate translocation and release involve movements of the bulky transport domain through the lipid bilayer. They further reveal a novel mode of inhibitor binding and show how solutes release is coupled to protein conformational changes. Finally, we describe how domain movements are associated with the displacement of bound lipids and significant membrane deformations, highlighting the potential regulatory role of the bilayer.
Expression of tyrosine hydroxylase gene from rat leads to oxidative stress in potato plants

Catecholamines are biogenic aromatic amines common among both animals and plants. In animals they are synthesized via tyrosine hydroxylation, while in plants, both hydroxylation or decarboxylation of tyrosine are possible, depending on the species, though no tyrosine hydroxylase – a counterpart of animal enzyme has been identified yet. It is known that in potato plants it is the decarboxylation of tyrosine that leads to catecholamine production. In this paper we present the effects of induction of an alternative route of catecholamine production by introducing tyrosine hydroxylase gene from rat. We demonstrate that an animal system can be used by the plant, however, it does not function to synthesize catecholamines. Instead it leads to elevated reactive oxygen species content and constant stress condition to the plant which responds with elevated antioxidant level and further with improved resistance to infection. One sentence summary Introduction of rat tyrosine hydroxylase gene to potato disturbs catecholamine synthesis, causes oxidative stress and activates antioxidant response.
Epitope-Based Peptide Vaccine Against Severe Acute Respiratory Syndrome-Coronavirus-2 Nucleocapsid Protein: An in silico Approach

With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.
Workstation benchmark of Spark Capable Genome Analysis ToolKit 4 Variant Calling

Background Rapid and practical DNA-sequencing processing has become essential for modern biomedical laboratories, especially in the field of cancer, pathology and genetics. While sequencing turn-over time has been, and still is, a bottleneck in research and diagnostics, the field of bioinformatics is moving at a rapid pace – both in terms of hardware and software development. Here, we benchmarked the local performance of three of the most important Spark-enabled Genome analysis toolkit 4 (GATK4) tools in a targeted sequencing workflow: Duplicate marking, base quality score recalibration (BQSR) and variant calling on targeted DNA sequencing using a modest hyperthreading 12-core single CPU and a high-speed PCI express solid-state drive. Results Compared to the previous GATK version the performance of Spark-enabled BQSR and HaplotypeCaller is shifted towards a more efficient usage of the available cores on CPU and outperforms the earlier GATK3.8 version with an order of magnitude reduction in processing time to analysis ready variants, whereas MarkDuplicateSpark was found to be thrice as fast. Furthermore, HaploTypeCallerSpark and BQSRPipelineSpark were significantly faster than the equivalent GATK4 standard tools with a combined ∼86% reduction in execution time, reaching a median rate of ten million processed bases per second, and duplicate marking was reduced ∼42%. The called variants were found to be in close agreement between the Spark and non-Spark versions, with an overall concordance of 98%. In this setup, the tools were also highly efficient when compared execution on a small 72 virtual CPU/18-node Google Cloud cluster. Conclusion In conclusion, GATK4 offers practical parallelization possibilities for DNA sequence processing, and the Spark-enabled tools optimize performance and utilization of local CPUs. Spark utilizing GATK variant calling is several times faster than previous GATK3.8 multithreading with the same multi-core, single CPU, configuration. The improved opportunities for parallel computations not only hold implications for high-performance cluster, but also for modest laboratory or research workstations for targeted sequencing analysis, such as exome, panel or amplicon sequencing.
Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting

The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation.
Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders

Noncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment disorders is poorly understood. In this study, we identified 908 brain-enriched noncoding RNAs comprising at least one nervous system-related eQTL polymorphism that is associated with protein coding genes and also overlap with chromatin states characterised as enhancers. We referred to such noncoding RNAs with putative enhancer activity as brain ‘enhancer-ncRNAs’. By integrating GWAS SNPs and Copy Number Variation (CNV) data from neurodevelopment disorders, we found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTL-associated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. Taken together, we identified 49 novel NDD-associated ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders.
Multifocal tDCS modulates resting-state functional connectivity in older adults depending on induced electric field and baseline connectivity

Background Advancing age affects the brain’s resting-state functional networks. Combining non-invasive brain stimulation (NIBS) with neuroimaging is a promising approach to modulate activity across resting-state functional systems and explore their true contribution to cognitive function in aging. However, substantial individual variability in the response to NIBS has been reported and, hence, identifying the individual predictors of NIBS-induced modulatory effects is crucial if we are to harness their potential. Methods Thirty-one cognitively healthy older adults (71.68 ± 2.5 years; 19 females) underwent two different multifocal real tDCS conditions (C1 and C2) and a sham condition in a crossover design during a resting-state functional magnetic resonance imaging (rs-fMRI) acquisition. The real tDCS conditions were designed to induce two distinct electric field distribution patterns either targeting generalized cortical overactivity or a dissociation between the frontal areas and the posteromedial cortex. Stimulation was delivered through an MRI-compatible device using 8 small circular electrodes. Each individuals’ anatomical T1-weighted MRI was used to generate a finite element model to define the individual electric field generated by each tDCS condition. Results The two tDCS conditions modulated resting-state connectivity differently. C1 increased the coactivation of numerous functional couplings as compared to sham, however, a smaller amount of connections increased in C1 as compared to C2, while no differences between C2 and sham were appreciated. At the group level, C1-induced modulations primarily included temporo-occipital areas and distinct cerebellar regions. This functional pattern was anatomically consistent with the estimated distribution of the induced electric field in the C1 condition. Finally, at the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was predicted by baseline resting-state connectivity and simulation-based electric field magnitude. Discussion Our results highlighted that multifocal tDCS procedures can effectively change neural dynamics in the elderly consistently with the spatial distribution of the estimated electric fields on the brain. Furthermore, we showed that specific brain factors that have been revealed to explain part of the individual variability to NIBS in young samples are also relevant in older adults. In accordance, designing multifocal tDCS configurations based on specific fMRI patterns appears to be a valuable approach to precisely adjust those complex neural dynamics sustaining cognition that are affected as a function of age. Furthermore, these innovative NIBS-based interventions should be individually-tailored based on subject-specific structural and functional data to ultimately boost their potential in aged populations.