Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Price and Breeder’s equations for variable environments

The Breeder’s and Price equations are static models of evolution. Recent work has demonstrated how components of these equations, such as selection differentials and heritabilities, can be calculated for each time-step from dynamic, evolutionarily-explicit, structured population models. These dynamic models consist of functions that describe how environmental factors impact associations of genotypes and phenotypic traits with survival, reproduction, development, and non-genetic inheritance. Because evolutionarily explicit versions of these structured models can include feedbacks and can capture all the routes via which environmental variation can impact evolution, they i) provide a more powerful predictive tool for modelling eco-evolution in natural settings than existing approaches, and ii) reveal how key evolutionary parameters incorporated into static models change with time as evolution, or environmental change, proceeds.
SSRIs modulate asymmetric learning from reward and punishment

Human instrumental learning is driven by a history of outcome success and failure. We demonstrate that week-long treatment with a serotonergic antidepressant modulates a valence-dependent asymmetry in learning from reinforcement. In particular, we show that prolonged boosting of central serotonin reduces reward learning, and enhances punishment learning. This treatment induced learning asymmetry can result in lowered positive and enhanced negative expectations. A consequential effect is more rewarding, and less disappointing, experiences and this may, in part, explain the slow temporal evolution of serotonin’s well-established antidepressant effects.
Active zone compaction in presynaptic homeostatic potentiation

Brain function relies on neurotransmission which is stabilized by presynaptic homeostatic potentiation (PHP). PHP operates on time scales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). At Drosophila melanogaster neuromuscular junctions, earlier work ascribed AZ enlargement by incorporating more Bruchpilot (Brp) scaffold protein a central mechanistic role in PHP. We used localization microscopy (direct stochastic optical reconstruction microscopy, dSTORM) and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) to study AZ plasticity during PHP. We found that both acute, philanthotoxin (PhTx)-induced and chronic, genetically-induced PHP lead to compaction of individual AZs without altering Brp copy numbers per AZ. This compaction even occurs within Brp subclusters of the AZ scaffold which also move towards AZ centers. Furthermore, lowering imaging resolution revealed how AZ compaction in PHP translates into apparent increases in AZ area and Brp protein content as implied earlier. Our results suggest AZ compaction in PHP as an effective mechanism to raise presynaptic protein density and transmitter release. SIGNIFICANCE STATEMENT Homeostatic plasticity stabilizes chemical synaptic transmission in multiple organisms ranging from insects to humans. Changes in active zones (AZs), membrane specializations of the presynapse where synaptic vesicles are discharged, are thought to be crucial in homeostatic adaptations. AZ growth by protein incorporation was proposed as a core mechanism in presynaptic homeostatic potentiation (PHP). Localization microscopy of an abundant AZ scaffold protein uncovered that instead of growing, AZs are compacted in acute and chronic PHP. At lower imaging resolution, however, AZs appear larger and brighter although protein numbers are not increased. In summary, our findings suggest AZ compaction as new and effective mechanism to raise presynaptic protein density and transmitter release in PHP.
Substitutional landscape of a split fluorescent protein fragment using high-density peptide microarrays

Split fluorescent proteins have wide applicability as biosensors for protein-protein interactions, genetically encoded tags for protein detection and localization, as well as fusion partners in super-resolution microscopy. We have established and validated a novel platform for functional analysis of leave-one-out split fluorescent proteins (LOO-FPs) in high throughput and with rapid turnover. We have screened more than 12,000 strand 10 variants using high-density peptide microarrays for binding and functional complementation in Green Fluorescent Protein. We studied the effect of peptide length and the effect of different linkers to the solid support and mapped the effect of all possible amino acid substitutions on each position as well as in the context of some single and double amino acid substitutions. As all peptides were tested in 12 duplicates, the analysis rests on a firm statistical basis allowing determination of robustness and precision of the method. We showed that the microarray fluorescence correlated with the affinity in solution between the LOO-FP and peptides. A double substitution yielded a peptide with 9-fold higher affinity than the starting peptide.
One enzyme many faces: alkaline phosphatase-based phosphorus-nutrient strategies and the regulatory cascade revealed by CRISPR/Cas9 gene knockout

Phosphorus (P) is an essential macronutrient for marine phytoplankton responsible for ∼50% of global carbon fixation. As P availability is variable and likely will decrease in future warming oceans, phytoplankton growth will be constrained by their strategies to scavenge dissolved organophosphate. To enhance our mechanistic understanding of these strategies, here we employ CRISPR/Cas9 to create mutants of alkaline phosphatase (AP) PhoA and PhoD and a putative regulator in the diatom model Phaeodactylum tricornutum, coupled with transcriptomic profiling to interrogate their modes of function and P- regulatory network. Results indicate that these two AP isoforms are differentiated in subcellular localization and substrate specialization, and are mutually compensatory and replaceable. Further analyses reveal a regulatory cascade of P scavenging and potential roles of AP in iron and ammonium uptake as well as diverse metabolic pathways. These findings have important implications in how phytoplankton community will respond to future changing microenvironments of global oceans.
Modeling Human Peripheral Myelin Fully from Pluripotent Stem Cells and Immune-mediated Neuropathy In Vitro using ZIKA Virus

The generation of in vitro model of human peripheral myelin development and associated disease from human pluripotent stem cells (hPSCs) has been a challenge so far. In addition, the underlying mechanism for ZIKA virus (ZIKV) infection incurred Guillain-Barré syndrome (GBS) remains unexplored due to the lack of a suitable model. Here, we report the de novo generation of a human peripheral myelination model with competent Schwann cells (SCs). Those human SCs generated from hPSCs via compound screening were capable of forming compact myelin both in vitro and in vivo. We found ZIKV infection caused GBS-like events in vitro including myelin sheath degeneration, as well as dysregulated transcriptional profile including the activated cell death pathways and cytokine production. These effects could be partially reversed by several pharmacological inhibitors. Our model therefore provides a new and robust tool for studying the pathogenic mechanisms and developing of therapeutic strategies for related neuropathies.
Did We Get Sensorimotor Adaptation Wrong? Implicit Adaptation as Direct Policy Updating Rather than Forward-Model-Based Learning

The human motor system can rapidly adapt its motor output in response to errors. The prevailing theory of this process posits that the motor system adapts an internal forward model that predicts the consequences of outgoing motor commands and uses this forward model to plan future movements. However, despite clear evidence that adaptive forward models exist and are used to help track the state of the body, there is no definitive evidence that such models are used in movement planning. The human motor system can rapidly adapt its motor output in response to errors. The prevailing theory of this process posits that the motor system adapts an internal forward model that predicts the consequences of outgoing motor commands and uses this forward model to plan future movements. However, despite clear evidence that adaptive forward models exist and are used to help track the state of the body, there is no definitive evidence that such models are used in movement planning. An alternative to the forward-model-based theory of adaptation is that movements are generated based on a learned policy that is adjusted over time by movement errors directly (“direct policy learning”). This learning mechanism could act in parallel with, but independent of, any updates to a predictive forward model. Forward-model-based learning and direct policy learning generate very similar predictions about behavior in conventional adaptation paradigms. However, across three experiments with human participants (N = 47, 26 female), we show that these mechanisms can be dissociated based on the properties of implicit adaptation under mirror-reversed visual feedback. Although mirror reversal is an extreme perturbation, it still elicits implicit adaptation; however, this adaptation acts to amplify rather than to reduce errors. We show that the pattern of this adaptation over time and across targets is consistent with direct policy learning but not forward-model-based learning. Our findings suggest that the forward-model-based theory of adaptation needs to be re-examined and that direct policy learning provides a more plausible explanation of implicit adaptation. SIGNIFICANCE STATEMENT The ability of our brain to adapt movements in response to error is one of the most widely studied phenomena in motor learning. Yet, we still do not know the process by which errors eventually result in adaptation. It is known that the brain maintains and updates an internal forward model, which predicts the consequences of motor commands, and the prevailing theory of motor adaptation posits that this updated forward model is responsible for trial-by-trial adaptive changes. Here, we question this view and show instead that adaptation is better explained by a simpler process whereby motor output is directly adjusted by task errors. Our findings cast doubt on long-held beliefs about adaptation.
A large accessory protein interactome is rewired across environments

To characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in yeast across 9 growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a 3-fold increase over PPIs identified in one condition. A few “immutable” PPIs are present across all conditions, while most “mutable” PPIs are rarely observed. Immutable PPIs aggregate into highly connected “core” network modules, with most network remodeling occurring within a loosely connected “accessory” module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.
Multi-Scale 3D Cryo-Correlative Microscopy for Vitrified Cells

Three-dimensional (3D) visualization of vitrified cells can uncover structures of subcellular complexes without chemical fixation or staining. Here, we present a pipeline integrating three imaging modalities to visualize the same specimen at cryogenic temperature at different scales: cryo-fluorescence confocal microscopy, volume cryo-focused ion beam scanning electron microscopy, and transmission cryo-electron tomography. Our proof-of-concept benchmark revealed the 3D distribution of organelles and subcellular structures in whole heat-shocked yeast cells, including the ultrastructure of protein inclusions that recruit fluorescently-labelled chaperone Hsp104. Since our workflow efficiently integrates imaging at three different scales and can be applied to other types of cells, it could be used for large-scale phenotypic studies of frozen-hydrated specimens in a variety of healthy and diseased conditions with and without treatments.
Prediction of regional wildfire activity with a probabilistic Bayesian framework

Modelling wildfire activity is crucial for informing science-based risk management and understanding fire-prone ecosystem functioning worldwide. Models also help to disentangle the relative roles of different factors, to understand wildfire predictability or to provide insights into specific events. Here, we develop a two-component Bayesian hierarchically-structured probabilistic model of daily fire activity, which are modelled as the outcome of a marked point process in which individual fires are the points (occurrence component) and the fire sizes are the marks (size component). The space-time Poisson model for occurrence is adjusted to gridded fire counts using the integrated nested Laplace approximation (INLA) combined with the Stochastic Partial Differential Equation (SPDE) approach. The size model is based on piecewise-estimated Pareto and Generalized-Pareto distributions, also adjusted with INLA. The Fire Weather Index (FWI) and Forest Area are the main explanatory variables. Seasonal and spatial residuals as well as a post-2003 effect are included to improve the consistency of the relationship between climate and fire occurrence, in accordance with parsimonious criteria. A set of 1000 simulations of the posterior model of fire activity is evaluated at various temporal and spatial scales in Mediterranean France. The number of escaped fires (≥1ha) across the region can be coarsely reproduced at the daily scale, and is more accurately predicted on a weekly basis or longer. The regional weekly total number of larger fires (10 to 100 ha) can be predicted as well, but the accuracy decays with size, as the model uncertainty increases with event rareness. Local predictions of fire numbers or burnt areas likewise require a longer aggregation period to maintain model accuracy. Regarding the year 2003 -which was characterized by an extreme burnt area in France associated with a heat wave-, the estimation of the number of escaped fires was consistent with observations, but the model systematically underrepresents larger fires and burnt areas, which suggests that the FWI does not consistently rate the danger of large fire occurrence during heat waves. Our study sheds new light on the stochastic processes underlying fire hazard, and is promising for predicting and projecting future fire hazard in the context of climate change.
Laminin N-terminus α31 protein distribution in adult human tissues

Laminin N terminus α31 (LaNt α31) is a netrin-like protein derived from alternative splicing of the laminin α3 gene. Although LaNt α31 has been demonstrated to influence corneal and skin epithelial cell function, its expression has not been investigated beyond these tissues. In this study, we used immunohistochemistry to characterise the distribution of this protein in a wide-array of human tissue sections in comparison to laminin α3. These data revealed widespread LaNt α31 expression. In epithelial tissue, LaNt α31 was present in the basal layer of the epidermis, throughout the epithelium of the digestive tract, and much of the epithelium of the reproductive system. LaNt α31 was also found throughout the vasculature of most tissues, with enrichment in reticular-like fibres in the extracellular matrix surrounding large vessels. A similar matrix pattern was observed around the terminal ducts in the breast and around the alveolar epithelium in the lung, where basement membrane staining was also evident. Specific enrichment of LaNt α31 was identified in sub-populations of cells of the kidney, liver, pancreas, and spleen, with variations in intensity between different cell types in the collecting ducts and glomeruli of the kidney being of particular note. Intriguingly, LaNt α31 immunoreactivity was also evident in neurons of the central nervous system, in the cerebellum, cerebral cortex, and spinal cord. Together these findings suggest that LaNt α31 may be functionally relevant in a wider range of tissue contexts than previously thought, and provides a valuable basis for investigation into this interesting protein.
Methodological Issues with Search in MEDLINE: A Longitudinal Query Analysis

This study compares the results of data collected from a longitudinal query analysis of the MEDLINE database hosted on multiple platforms that include PubMed, EBSCOHost, Ovid, ProQuest, and Web of Science in order to identify variations among the search results on the platforms after controlling for search query syntax. We devised twenty-nine sets of search queries comprised of five queries per set to search against the five MEDLINE database platforms. We ran our queries monthly for a year and collected search result count data to observe changes. We found that search results vary considerably depending on MEDLINE platform, both within sets and across time. The variation is due to trends in scholarly publication that include publishing online first versus publishing in journal issues, which leads to metadata differences in the bibliographic record; to differences in the level of specificity among search fields provided by the platforms; to database integrity issues that lead to large fluctuations in monthly search results based on the same query; and to database currency issues that arise due to when each platform updates its MEDLINE file. Specific bibliographic databases, like PubMed and MEDLINE, are used to inform clinical decision-making, create systematic reviews, and construct knowledge bases for clinical decision support systems. Since they serve as essential information retrieval and discovery tools that help identify and collect research data and are used in a broad range of fields and as the basis of multiple research designs, this study should help clinicians, researcher, librarians, informationalists, and others understand how these platforms differ and inform future work in their standardization.
Effect of mechanical properties of monofilament twines on the catch efficiency of biodegradable gillnets

Gillnets made of the biodegradable resin polybutylene succinate co-adipate-co-terephthalate (PBSAT) were tested under commercial fishing conditions to compare their fishing performance with that of conventional nylon polyamide (PA) gillnets. Both types of gillnets were made of 0.55 mm Ø monofilaments. However, since the biodegradable nets are weaker than nylon PA nets when using the same monofilament diameter, we also used biodegradable nets made of 0.60 mm Ø monofilament that had a similar tensile strength to the 0.55 mm Ø nylon PA nets. The relative catch efficiency of the different gillnet types was evaluated over the 2018 autumn fishing season for saithe and cod in northern Norway. For cod, both biodegradable gillnets (0.55 and 0.60 mm) had a significantly lower catch efficiency compared to the traditional nylon PA net (0.55 mm) with estimated catch efficiencies of 62.38% (CI: 50.55–74.04) and 54.96% (CI: 35.42–73.52) compared with the nylon PA net, respectively. Similarly for saithe, both biodegradable gillnets (0.55 and 0.60 mm) had a lower estimated catch efficiency compared to the traditional nylon PA net (0.55 mm) with estimated catch efficiencies of 83.40% (71.34–94.86) and 83.87% (66.36–104.92), compared with the nylon PA net, respectively. Tensile strength does not explain the differences in catch efficiency between the two gillnet types, since increasing the twine diameter of the biodegradable gillnets (to match the strength of nylon PA gillnets) did not yield similar catch efficiencies. However, the elasticity and stiffness of the materials may be responsible for the differences in catch efficiency between the nylon PA and biodegradable gillnets.
A Mobile Phone–Based Gait Assessment App for the Elderly: Development and Evaluation

Background Gait disorders are common among older adults. With an increase in the use of technology among older adults, a mobile phone app provides a solution for older adults to self-monitor their gait quality in daily life. Objective This study aimed to develop a gait-monitoring mobile phone app (Pocket Gait) and evaluate its acceptability and usability among potential older users. Methods The app was developed to allow older adults to track their gait quality, including step frequency, acceleration root mean square (RMS), step regularity, step symmetry, and step variability. We recruited a total of 148 community-dwelling older adults aged 60 years and older from two cities in China: Beijing and Chongqing. They walked in three ways (single task, dual task, and fast walking) using a smartphone with the gait-monitoring app installed and completed an acceptability and usability survey after the walk test. User acceptability was measured by a questionnaire including four quantitative measures: perceived ease of use, perceived usefulness, ease of learning, and intention to use. Usability was measured using the System Usability Scale (SUS). Interviews were conducted with participants to collect open-ended feedback questions. Results Task type had a significant effect on all gait parameters, namely, step frequency, RMS, step variability, step regularity, and step symmetry (all P values <.001). Age had a significant effect on step frequency (P=.01), and region had a significant effect on step regularity (P=.04). The acceptability of the gait-monitoring app was positive among older adults. Participants identified the usability of the system with an overall score of 59.7 (SD 10.7) out of 100. Older adults from Beijing scored significantly higher SUS compared with older adults from Chongqing (P<.001). The age of older adults was significantly associated with their SUS score (P=.048). Older adults identified improvements such as a larger font size, inclusion of reference values for gait parameters, and inclusion of heart rate and blood pressure monitoring. Conclusions This mobile phone app is a health management tool for older adults to self-manage their gait quality and prevent adverse outcomes. In the future, it will be important to take factors such as age and region into consideration while designing a mobile phone–based gait assessment app. The feedback of the participants would help to design more elderly-friendly products.
Reproductive biology of a riverine cyprinid, Labeo umbratus (Teleostei: Cyprinidae), in small South African reservoirs

The reproductive and recruitment characteristics of moggel, Labeo umbratus, populations were examined in four small South African reservoirs. Reproduction, characterised by an extended spawning season, high fecundity, short incubation time and rapid larval development, appears to be ideally suited to the highly variable environment of small reservoirs. Evidence suggested that L. umbratus spawns in the reservoirs. In two reservoirs where samples were conducted monthly, GSI (gonado-somatic index) was positively correlated with both water temperature and day length, whilst the CPUE (catch per unit effort) of juveniles was not related to any environmental variable. The success of moggel spawning appeared to increase when there was early spring and consistent summer rainfall.