Miracle-dz/UniFAR-FTUs huggingface dataset:
Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS

Slit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers SVZ-NPC migration to ectopic locations and their recruitment by the lesion, suggesting a possible role for Slit1 in SVZ-NPCs ectopic dispersal regulation in pathological conditions. Here, we have investigated the function of Slit1 protein in the recruitment of SVZ-NPCs after CNS demyelination. We find that the dynamics of oligodendrogenesis and temporal profile of developmental myelination in Slit1–/– mice are similar to Slit1+/− controls. SVZ micro-dissection and RT-PCR from wild-type mice, show that Slits and Robos are physiologically regulated at the transcriptional level in response to corpus callosum demyelination suggesting their role in the process of SVZ-NPC ectopic migration in demyelinating conditions. Moreover, we find that the number of SVZ-NPCs recruited by the lesion increases in Sli1–/– mice compared to Slit1+/− mice, leading to higher numbers of Olig2+ cells within the lesion. Time-lapse video-microscopy of immuno-purified NPCs shows that Slit1-deficient cells migrate faster and make more frequent directional changes than control NPCs, supporting a cell-autonomous mechanism of action of Slit1 in NPC migration. In conclusion, while Slit1 does not affect the normal developmental process of oligodendrogenesis and myelination, it regulates adult SVZ-NPC ectopic migration in response to demyelination, and consequently oligodendrocyte renewal within the lesion.
Systematic Review of Plant Ribosome Heterogeneity and Specialization

Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static protein synthesis machines that are not subject to extensive regulation but only read mRNA and produce polypeptides accordingly. New and increasing evidence across various model organisms demonstrated the heterogeneous nature of ribosomes. This heterogeneity can constitute specialized ribosomes that regulate mRNA translation and control protein synthesis. A prominent example of ribosome heterogeneity is seen in the model plant, Arabidopsis thaliana, which, due to genome duplications, has multiple paralogs of each ribosomal protein (RP) gene. We support the notion of plant evolution directing high RP paralog divergence toward functional heterogeneity, underpinned in part by a vast resource of ribosome mutants that suggest specialization extends beyond the pleiotropic effects of single structural RPs or RP paralogs. Thus, Arabidopsis is a highly suitable model to study this phenomenon. Arabidopsis enables reverse genetics approaches that could provide evidence of ribosome specialization. In this review, we critically assess evidence of plant ribosome specialization and highlight steps along ribosome biogenesis in which heterogeneity may arise, filling the knowledge gaps in plant science by providing advanced insights from the human or yeast fields. We propose a data analysis pipeline that infers the heterogeneity of ribosome complexes and deviations from canonical structural compositions linked to stress events. This analysis pipeline can be extrapolated and enhanced by combination with other high-throughput methodologies, such as proteomics. Technologies, such as kinetic mass spectrometry and ribosome profiling, will be necessary to resolve the temporal and spatial aspects of translational regulation while the functional features of ribosomal subpopulations will become clear with the combination of reverse genetics and systems biology approaches.
Acute Cellular and Functional Changes With a Combinatorial Treatment of Ion Channel Inhibitors Following Spinal Cord Injury

Reducing the extent of secondary degeneration following spinal cord injury (SCI) is necessary to preserve function, but treatment options have thus far been limited. A combination of the ion channel inhibitors Lomerizine (Lom), YM872 and oxATP, to inhibit voltage-gated Ca2+ channels, Ca2+ permeable AMPA receptors, and purinergic P2X7 receptors respectively, effectively limits secondary consequences of injury in in vitro and in vivo models of CNS injury. Here, we investigated the efficacy of these inhibitors in a clinically relevant model of SCI. Fischer (F344) rats were subjected to a moderate (150 kD) contusive SCI at thoracic level T10 and assessed at 2 weeks or 10 weeks post-injury. Lom was delivered orally twice daily and YM872 and oxATP were delivered via osmotic mini-pump implanted at the time of SCI until 2 weeks following injury. Open field locomotion analysis revealed that treatment with the three inhibitors in combination improved the rate of functional recovery of the hind limb (compared to controls) as early as 1-day post-injury, with beneficial effects persisting to 14 days post-injury, while all three inhibitors were present. At 2 weeks following combinatorial treatment, the functional improvement was associated with significantly decreased cyst size, increased immunoreactivity of β-III tubulin+ve axons, myelin basic protein, and reduced lipid peroxidation by-products, and increased CC1+ve oligodendrocytes and NG2+ve/PDGFα+ve oligodendrocyte progenitor cell densities, compared to vehicle-treated SCI animals. The combination of Lom, oxATP, and YM872 shows preclinical promise for control of secondary degeneration following SCI, and further investigation of long-term sustained treatment is warranted.
Phylogenetic analysis of peat bog methanogen populations

Peat bog samples from two upland sites in the UK were analysed for the diversity of methanogens using DNA sequence analysis of approximately 300 bp of the MCR I operon contained in 42 cloned amplimers. The clones could be represented as up to five clusters, the largest of which (designated A) contained DNA sequences from a site in the Upper Pennine Hills, UK (called the Moorhouse site), whilst clones from two of the other clusters were from the other site in Galway, South West Scotland (called the Ellergower Moss site). 10 clones were selected as representatives of each cluster and a phylogenetic analysis was performed using 628-bp fragments of the MCR I operon. This phylogenetic analysis supported the phylogenies generated from the shorter sequence analysis, suggested that they represented hitherto uncharacterised mcr genes and that the closest relative of these clones was Methanosarcina barkeri.
Prognostic Nutritional Index for Predicting 3-Month Outcomes in Ischemic Stroke Patients Undergoing Thrombolysis

Objective: Malnutrition has been reported to be related to adverse prognosis in acute ischemic stroke (AIS) patients. Unfortunately, traditional nutritional assessment tools usually increase the workload of neurologists, which makes them unfeasible in the daily clinic work. We aimed to elucidate the association between the prognostic nutritional index (PNI), an easily obtainable baseline nutritional marker, and 3-month outcomes in AIS patients receiving intravenous thrombolysis (IVT). Research methods and procedures: The present study retrospectively included 405 patients. PNI was calculated as 5*lymphocyte count (109 /L) + serum albumin concentration (g/L), and the good prognosis was defined as modified Rankin Scale score of 0–3. The relationship between PNI and clinical parameters was evaluated. The multiple logistic regression model was performed to find out independent predictors of the 3-month outcomes. Results: We found that the patients in the low PNI group had a higher frequency of anemia (12.9 vs. 2.3%, P < 0.001) and a higher level of the Controlling nutritional status (CONUT) score (P < 0.001). The relationship between PNI and nutrition-related factors, such as body mass index (r = 0.208, P = 0.001), age (r = −0.329, P < 0.001), total cholesterol (r = 0.268, P < 0.001) and hemoglobin concentration (r = 0.328, P < 0.001), was significant. Low PNI value (adjusted odds ratio: 2.250, confidence interval: 1.192–4.249, p = 0.012) stayed as an independent predictor for the poor outcome at three months, after adjustment for potential confounders. Conclusions: The PNI was independently associated with 3-month outcomes in AIS patients undergoing IVT. As an easily obtainable nutritional marker, PNI may be a useful nutritional assessment tool in the clinic work.
How do species barriers decay? Concordance and local introgression in mosaic hybrid zones of mussels

The Mytilus complex of marine mussel species forms a mosaic of hybrid zones, found across temperate regions of the globe. This allows us to study ‘replicated’ instances of secondary contact between closely related species. Previous work on this complex has shown that local introgression is both widespread and highly heterogeneous, and has identified SNPs that are outliers of differentiation between lineages. Here, we developed an ancestry‐informative panel of such SNPs. We then compared their frequencies in newly sampled populations, including samples from within the hybrid zones, and parental populations at different distances from the contact. Results show that close to the hybrid zones, some outlier loci are near to fixation for the heterospecific allele, suggesting enhanced local introgression, or the local sweep of a shared ancestral allele. Conversely, genomic cline analyses, treating local parental populations as the reference, reveal a globally high concordance among loci, albeit with a few signals of asymmetric introgression. Enhanced local introgression at specific loci is consistent with the early transfer of adaptive variants after contact, possibly including asymmetric bi‐stable variants (Dobzhansky‐Muller incompatibilities), or haplotypes loaded with fewer deleterious mutations. Having escaped one barrier, however, these variants can be trapped or delayed at the next barrier, confining the introgression locally. These results shed light on the decay of species barriers during phases of contact.
Evolution of nuptial gifts and its coevolutionary dynamics with “masculine” female traits for multiple mating

Many male animals donate nutritive materials during courtship or mating to their female mates. Donation of large-sized gifts, though costly to prepare, can result in increased sperm transfer during mating and delayed remating of the females, resulting in a higher paternity Nuptial gifting sometimes causes severe female-female competition for obtaining gifts (i.e., sex-role reversal in mate competition) and female polyandry, changing the intensity of sperm competition and the resultant paternity gains. We built a theoretical model to analyze such coevolutionary feedbacks between nuptial gift size (male trait) and propensity for multiple mating (female trait). Our genetically explicit, individual-based computer simulations demonstrate that a positive correlation between donated gift size and the resultant paternity gain is a requisite for the co-occurrence of large-sized gifts and females’ competitive multiple mating for the gifts. When donation of gifts imposes monandry, exaggeration in nuptial gift size also occurs under the assumption that the last male monopolizes paternity. We also analyzed the causes and consequences of the evolution of a female persistence trait in trading of nuptial gifts, that is, double receptacles for nuptial gifts known to occur in an insect group with a “female penis” (Neotrogla spp.).
Tissue-specific dynamic codon redefinition in Drosophila

Significance Here we describe efficient, developmentally regulated stop codon readthrough of the Drosophila kelch gene. Stop codon readthrough is a form of translational recoding in which a UGA, UAG, or UAA codon is redefined as a sense codon, allowing translation to continue. We show that readthrough of the kelch stop codon occurs at highest efficiency specifically in neurons of the central nervous system (CNS), and we define a short sequence near the kelch ORF1 UGA codon that stimulates efficient readthrough. We also show that stop codon readthrough for three additional genes occurs with high efficiency in the CNS, suggesting that stop codon readthrough may contribute significantly to the neuronal proteome. Translational stop codon readthrough occurs in organisms ranging from viruses to mammals and is especially prevalent in decoding Drosophila and viral mRNAs. Recoding of UGA, UAG, or UAA to specify an amino acid allows a proportion of the protein encoded by a single gene to be C-terminally extended. The extended product from Drosophila kelch mRNA is 160 kDa, whereas unextended Kelch protein, a subunit of a Cullin3-RING ubiquitin ligase, is 76 kDa. Previously we reported tissue-specific regulation of readthrough of the first kelch stop codon. Here, we characterize major efficiency differences in a variety of cell types. Immunoblotting revealed low levels of readthrough in malpighian tubules, ovary, and testis but abundant readthrough product in lysates of larval and adult central nervous system (CNS) tissue. Reporters of readthrough demonstrated greater than 30% readthrough in adult brains, and imaging in larval and adult brains showed that readthrough occurred in neurons but not glia. The extent of readthrough stimulatory sequences flanking the readthrough stop codon was assessed in transgenic Drosophila and in human tissue culture cells where inefficient readthrough occurs. A 99-nucleotide sequence with potential to form an mRNA stem-loop 3′ of the readthrough stop codon stimulated readthrough efficiency. However, even with just six nucleotides of kelch mRNA sequence 3′ of the stop codon, readthrough efficiency only dropped to 6% in adult neurons. Finally, we show that high-efficiency readthrough in the Drosophila CNS is common; for many neuronal proteins, C-terminal extended forms of individual proteins are likely relatively abundant.
Near-Automatic Routine Field Calibration/Correction of Glider Salinity Data Using Whitespace Maximization Image Analysis of Theta/S Data

Glider vehicles are now perhaps some of the most prolific providers of real-time and near-real-time operational oceanographic data. However, the data from these vehicles can and should be considered to have a long-term legacy value capable of playing a critical role in understanding and separating inter-annual, inter-decadal, and long-term global change. To achieve this, we have to go further than simply assuming the manufacturer’s calibrations, and field correct glider data in a more traditional way, for example, by careful comparison to water bottle calibrated lowered CTD datasets and/or “gold” standard recent climatologies. In this manuscript, we bring into the 21st century a historical technique that has been used manually by oceanographers for many years/decades for field correction/inter-calibration, thermal lag correction, and adjustment for biological fouling. The technique has now been made semi-automatic for machine processing of oceanographic glider data, although its future and indeed its origins have far wider scope. The subject of this manuscript is drawn from the original Description of Work (DoW) for a key task in the recently completed JERICO-NEXT (Joint European Research Infrastructure network for Coastal Observatories) EU-funded program, but goes on to consider future application and the suitability for integration with machine learning.
EFFECTS OF FOOD DEPRIVATION AND HANDLING STRESS ON FAULT-BAR FORMATION IN NESTLING AMERICAN KESTRELS Falco sparverius

We document the extent of fault-bar formation in the wing and tail feathers of 45 hand-reared and 18 parentally reared American Kes­ trels Falco sparverius raised in captivity on temporarily interrupted (30 birds) and uninterrupted (15 birds) ad libitum diets. Hand-reared birds were handled extensively throughout the experiment, parentally reared birds were not. Hand-reared nestlings developed an average of 2.8, 8.0 and 4.3 and parentally reared nestlings an average of 0.6, 1.4 and 0.4 fault bars on their rectrices, primaries and secondaries, respectively. All hand-reared birds, including the group whose diet was not interrupted, had significantly more fault bars on their rectrices, primaries and secondaries, than did pa­ rentally reared birds. Fault-bar formation in birds whose ad libitum diets were interrupted did not increase at times of food deprivation and hand­ reared birds from which ad libitum food had been withheld for 24 to 48 hours did not have more fault bars than hand-reared birds whose diets had not been interrupted. Our results suggest that excessive fault-bar formation in captive birds is most likely due to handling stress, rather than to food deprivation.
Differential Developmental Regulation and Functional Effects on Pre-TCR Surface Expression of Human pTαa and pTαb Spliced Isoforms1

Functional rearrangement at the TCRβ locus leads to surface expression on developing pre-T cells of a pre-TCR complex composed of the TCRβ-chain paired with the invariant pre-TCRα (pTα) chain and associated with CD3 components. Pre-TCR signaling triggers the expansion and further differentiation of pre-T cells into TCRαβ mature T cells, a process known as β selection. Besides the conventional pTα transcript (termed pTαa), a second, alternative spliced, isoform of the pTα gene (pTαb) has been described, whose developmental relevance remains unknown. In this study, phenotypic, biochemical, and functional evidence is provided that only pTαa is capable of inducing surface expression of a CD3-associated pre-TCR complex, which seems spontaneously recruited into lipid rafts, while pTαb pairs with and retains TCRβ intracellularly. In addition, by using real-time quantitative RT-PCR approaches, we show that expression of pTαa and pTαb mRNA spliced products is differentially regulated along human intrathymic development, so that pTαb transcriptional onset is developmentally delayed, but β selection results in simultaneous shutdown of both isoforms, with a relative increase of pTαb transcripts in β-selected vs nonselected pre-T cells in vivo. Relative increase of pTαb is also shown to occur upon pre-T cell activation in vitro. Taken together, our data illustrate that transcriptional regulation of pTα limits developmental expression of human pre-TCR to intrathymic stages surrounding β selection, and are compatible with a role for pTαb in forming an intracellular TCRβ-pTαb complex that may be responsible for limiting surface expression of a pTαa-containing pre-TCR and/or may be competent to signal from a subcellular compartment.
Cyberbullying and Adolescent Neurobiology

Whilst it is well documented that cyberbullying is linked to poor mental health outcomes, limited research has examined how cyberbullying may influence brain development adolescents, and the influence of each of these factors. The article’s primary objective was to develop an understanding of research to date that addresses any relationship between adolescent brain development and cyberbullying. The current article reviews any existing literature regarding the impact of cyberbullying on adolescent brain development, paying particular attention to research using magnetic resonance imaging (MRI) techniques. Whilst brain studies have examined neural mechanisms associated with conduct disorders, antisocial behavior, and aggression in young people; there is a paucity of research examining these factors specifically in relation to cyberbullying. In particular, little research has examined how MRI research could help understand how the brain is affected by cyberbullying, not only in bullies and victims but also bystanders. This article highlights the gaps in the cyberbullying field in relation to neuroscience research, and the need for further, longitudinal research examining cyberbullying and how it may affect brain development in young people. This article concludes by suggesting a framework for future research, and highlights the importance of future findings for developing interventions and understanding short and long term effects.
Toward Engineering Biosystems With Emergent Collective Functions

Many complex behaviors in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans many length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modeling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modeling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviors offers a means to take synthetic biology beyond single molecules or cells and toward the creation of systems with functions that can only emerge from collectives at multiple scales.
CNN-Based Estimation of Sagittal Plane Walking and Running Biomechanics From Measured and Simulated Inertial Sensor Data

Machine learning is a promising approach to evaluate human movement based on wearable sensor data. A representative dataset for training data-driven models is crucial to ensure that the model generalizes well to unseen data. However, the acquisition of sufficient data is time-consuming and often infeasible. We present a method to create realistic inertial sensor data with corresponding biomechanical variables by 2D walking and running simulations. We augmented a measured inertial sensor dataset with simulated data for the training of convolutional neural networks to estimate sagittal plane joint angles, joint moments, and ground reaction forces (GRFs) of walking and running. When adding simulated data, the root mean square error (RMSE) of the test set of hip, knee, and ankle joint angles decreased up to 17%, 27% and 23%, the RMSE of knee and ankle joint moments up to 6% and the RMSE of anterior-posterior and vertical GRF up to 2 and 6%. Simulation-aided estimation of joint moments and GRFs was limited by inaccuracies of the biomechanical model. Improving the physics-based model and domain adaptation learning may further increase the benefit of simulated data. Future work can exploit biomechanical simulations to connect different data sources in order to create representative datasets of human movement. In conclusion, machine learning can benefit from available domain knowledge on biomechanical simulations to supplement cumbersome data collections.