Miracle-dz/UniFAR-FTUs huggingface dataset:
Signal Diversification Is Associated with Corollary Discharge Evolution in Weakly Electric Fish

Communication signal diversification is a driving force in the evolution of sensory and motor systems. However, little is known about the evolution of sensorimotor integration. Mormyrid fishes generate stereotyped electric pulses (electric organ discharge [EOD]) for communication and active sensing. The EOD has diversified extensively, especially in duration, which varies across species from 0.1 to >10 ms. In the electrosensory hindbrain, a corollary discharge that signals the timing of EOD production provides brief, precisely timed inhibition that effectively blocks responses to self-generated EODs. However, corollary discharge inhibition has only been studied in a few species, all with short-duration EODs. Here, we asked how corollary discharge inhibition has coevolved with the diversification of EOD duration. We addressed this question by comparing 7 mormyrid species (both sexes) having varied EOD duration. For each individual fish, we measured EOD duration and then measured corollary discharge inhibition by recording evoked potentials from midbrain electrosensory nuclei. We found that delays in corollary discharge inhibition onset were strongly correlated with EOD duration as well as delay to the first peak of the EOD. In addition, we showed that electrosensory receptors respond to self-generated EODs with spikes occurring in a narrow time window immediately following the first peak of the EOD. Direct comparison of time courses between the EOD and corollary discharge inhibition revealed that the inhibition overlaps the first peak of the EOD. Our results suggest that internal delays have shifted the timing of corollary discharge inhibition to optimally block responses to self-generated signals. SIGNIFICANCE STATEMENT Corollary discharges are internal copies of motor commands that are essential for brain function. For example, corollary discharge allows an animal to distinguish self-generated from external stimuli. Despite widespread diversity in behavior and its motor control, we know little about the evolution of corollary discharges. Mormyrid fishes generate stereotyped electric pulses used for communication and active sensing. In the electrosensory pathway that processes communication signals, a corollary discharge inhibits sensory responses to self-generated signals. We found that fish with long-duration pulses have delayed corollary discharge inhibition, and that this time-shifted corollary discharge optimally blocks electrosensory responses to the fish's own signal. Our study provides the first evidence for evolutionary change in sensorimotor integration related to diversification of communication signals.
Visuomotor Transformation for the Lead Leg Affects Trail Leg Trajectories During Visually Guided Crossing Over a Virtual Obstacle in Humans

When walking around a room or outside, we often need to negotiate external physical objects, such as walking up stairs or stepping over an obstacle. In previous studies on obstacle avoidance, lead and trail legs in humans have been considered to be controlled independently on the basis of visual input regarding obstacle properties. However, this perspective has not been sufficient because the influence of visuomotor transformation in the lead leg on the trail leg has not been fully elucidated due to technical limitations in the experimental tasks of stepping over physical obstacles. In this study, we investigated how visuomotor transformation in the lead leg affected movement trajectories in the trail leg using a visually guided task of crossing over a virtual obstacle. Trials for stepping over a physical obstacle were established followed by visually guided tasks in which cursors corresponding to the subject’s lead and trail limb toe positions were displayed on a head-mounted display apparatus. Subjects were instructed to manipulate the cursors so that they precisely crossover a virtual obstacle. In the middle of the trials, the vertical displacement of the cursor only in the lead leg was reduced relative to the actual toe movement during one or two consecutive trials. This visuomotor perturbation resulted in higher elevation not only in the lead limb toe position but also in the trail limb toe trajectories, and then the toe heights returned to the baseline in washout trials, indicating that the visuomotor transformation for obstacle avoidance in the lead leg affects the trail leg trajectory. Taken together, neural resources of limb-specific motor memories for obstacle crossing movements in the lead and trail legs can be shared based on visual input regarding obstacle properties.
Leigh Syndrome-inducing Mutations Affect LRPPRC / SLIRP Complex Formation

Mitochondria are essential organelles carrying their own genetic information which require specific gene expression processes. The leucine rich pentatricopeptide protein (LRPPRC) and its partner the SRA stem-loop interacting RNA binding protein (SLIRP) form a stable complex implicated in mRNA stability and polyadenylation. LRPPRC/SLIRP complex formation is still poorly characterized. We demonstrate that SLIRP interacts with the N-terminal region of LRPPRC in a RNA independent manner. We further show that the complex is stable in presence of high salt concentration. Point mutation and deletions found in the LRPPRC protein and responsible for the French-Canadian Leigh Syndrome (LSFC) are shown to affect complex formation in vitro. Our data are identifying the key region of LRPPRC involved in SLIRP association and showing the direct consequence of various LSFC mutations on the complex formation. Further experiments aiming at deciphering LRPPRC/SLIRP function(s) in vivo will benefit from our functional domain characterization.
Benefits of Collisional Cross Section Assisted Precursor Selection (caps-PASEF) for Cross-linking Mass Spectrometry

Ion mobility separates molecules in the gas-phase on their physico-chemical properties, providing information about their size as collisional cross-sections. The timsTOF Pro combines trapped ion mobility with a quadrupole, collision cell and a time-of-flight mass analyzer, to probe ions at high speeds with on-the-fly fragmentation. Here, we show that on this platform ion mobility is beneficial for cross-linking mass spectrometry (XL-MS). Cross-linking reagents covalently link amino acids in close proximity, resulting in peptide pairs after proteolytic digestion. These cross-linked peptides are typically present at low abundance in the background of normal peptides, which can partially be resolved by using enrichable cross-linking reagents. Even with a very efficient enrichable cross-linking reagent, like PhoX, the analysis of cross-linked peptides is still hampered by the co-enrichment of peptides connected to a partially hydrolyzed reagent – termed mono-linked peptides. For experiments aiming to uncover protein-protein interactions these are unwanted byproducts. Here, we demonstrate that gas-phase separation by ion mobility enables the separation of mono-linked peptides from cross-linked peptide pairs. A clear partition between these two classes is observed at a CCS of 500 Å2 and a monoisotopic mass of 2 kDa, which can be used for targeted precursor selection. A total of 50 - 70% of the mono-linked peptides are prevented from sequencing, allowing the analysis to focus on sequencing the relevant cross-linked peptide pairs. In applications to both simple proteins and protein mixtures and a complete highly complex lysate this approach provides a substantial increase in detected cross-linked peptides.
Complex dynamics induced by delayed adaptive behavior during epidemics

The behavioral response of individuals to an epidemic, and the timing of their behavior change, can have important consequences for epidemic dynamics. While the importance of behavior-change for epidemic dynamics is broadly recognized, the approaches to modeling the coupled dynamics of epidemics and behavior change have been limited. An important mode of behavior change in epidemics is a reduction in potentially infectious contacts. We develop a model for endogenous change of the effective contact rate of Susceptible-Infectious-Susceptible (SIS) epidemic model by positing a dynamic utility function associated with the expected number of contacts people have in the population. This utility function trades off the ideal number of social contacts with the expected cost of becoming infected. Our analysis of this simple, deterministic model reveals the existence of a non-zero endemic equilibrium, oscillatory dynamics under some parametric conditions, and complex dynamic regimes that shift under small parameter perturbations. Time-lag between current epidemic conditions and behavioral response is essential for the more exotic dynamics. These results suggest that reducing this lag may reduce both the final-size of the epidemic and the uncertainty associated with epidemic projections.
Origin, conservation, and loss of alternative splicing events that diversify the proteome in Saccharomycotina budding yeasts

Many eukaryotes use alternative splicing to express multiple proteins from the same gene. However, while the majority of mammalian genes are alternatively spliced, other eukaryotes use this process less frequently. The budding yeast Saccharomyces cerevisiae has been successfully used to study the mechanism of splicing and the splicing machinery, but alternative splicing in yeast is relatively rare and has not been extensively studied. We have recently shown that the alternative splicing of SKI7/HBS1 is widely conserved, but that yeast and a few other eukaryotes have replaced this one alternatively spliced gene with a pair of duplicated unspliced genes as part of a whole genome doubling (WGD). Here we show that other examples of alternative splicing that were previously found to have functional consequences are widely conserved within the Saccharomycotina. We also show that the most common mechanism by which alternative splicing has disappeared is by the replacement of an alternatively spliced gene with duplicate genes. Saccharomycetaceae that diverged before WGD use alternative splicing more frequently than S. cerevisiae. This suggests that the WGD is a major reason for the low frequency of alternative splicing in yeast. We anticipate that whole genome doublings in other lineages may have had the same effect.
Transient Expression of IL-17A in Foxp3 Fate-Tracked Cells in Porphyromonas gingivalis-Mediated Oral Dysbiosis

In periodontitis Porphyromonas gingivalis contributes to the development of a dysbiotic oral microbiome. This altered ecosystem elicits a diverse innate and adaptive immune response that simultaneously involves Th1, Th17, and Treg cells. It has been shown that Th17 cells can alter their gene expression to produce interferon-gamma (IFN-γ). Forkhead box P3 (Foxp3) is considered the master regulator of Treg cells that produce inhibitory cytokines like IL-10. Differentiation pathways that lead to Th17 and Treg cells from naïve progenitors are considered antagonistic. However, it has been reported that Treg cells expressing IL-17A as well as IFN-γ producing Th17 cells have been observed in several inflammatory conditions. Each scenario appears plausible with T cell transdifferentiation resulting from persistent microbial challenge and consequent inflammation. We established that oral colonization with P. gingivalis drives an initial IL-17A dominated Th17 response in the oral mucosa that is dependent on intraepithelial Langerhans cells (LCs). We hypothesized that Treg cells contribute to this initial IL-17A response through transient expression of IL-17A and that persistent mucosal colonization with P. gingivalis drives Th17 cells toward an IFN-γ phenotype at later stages of infection. We utilized fate-tracking mice where IL-17A- or Foxp3-promoter activity drives the permanent expression of red fluorescent protein tdTomato to test our hypothesis. At day 28 of infection timeline, Th17 cells dominated in the oral mucosa, outnumbering Th1 cells by 3:1. By day 48 this dominance was inverted with Th1 cells outnumbering Th17 cells by nearly 2:1. Tracking tdTomato+ Th17 cells revealed only sporadic transdifferentiation to an IFN-γ-producing phenotype by day 48; the appearance of Th1 cells at day 48 was due to a late de novo Th1 response. tdTomato+ Foxp3+ T cells were 35% of the total live CD4+T cells in the oral mucosa and 3.9% of them developed a transient IL-17A-producing phenotype by day 28. Interestingly, by day 48 these IL-17A-producing Foxp3+ T cells had disappeared. Therefore, persistent oral P. gingivalis infection stimulates an initial IL-17A-biased response led by Th17 cells and a small but significant number of IL-17A-expressing Treg cells that changes into a late de novo Th1 response with only sporadic transdifferentiation of Th17 cells.
Mixing and matching methylotrophic enzymes to design a novel methanol utilization pathway in E. coli

One-carbon (C1) compounds, such as methanol, have recently gained attention as alternative low-cost and non-food feedstocks for microbial bioprocesses. Considerable research efforts are thus currently focused on the generation of synthetic methylotrophs by transferring methanol assimilation pathways into established bacterial production hosts. In this study, we used an iterative combination of dry and wet approaches to design, implement and optimize this metabolic trait in the most common chassis, E. coli. Through in silico modeling, we designed a new route that “mixed and matched” two methylotrophic enzymes: a bacterial methanol dehydrogenase (Mdh) and a dihydroxyacetone synthase (Das) from yeast. To identify the best combination of enzymes to introduce into E. coli, we built a library of 266 pathway variants containing different combinations of Mdh and Das homologues and screened it using high-throughput 13C-labeling experiments. The highest level of incorporation, 22% of labeled methanol carbon into the multi-carbon compound PEP, was obtained using a variant composed of a Mdh from A. gerneri and a codon-optimized version of P. angusta Das. Finally, the activity of this new synthetic pathway was further improved by engineering strategic metabolic targets identified using omics and modelling approaches. The final synthetic strain had 1.5 to 5.9 times higher methanol assimilation in intracellular metabolites and proteinogenic amino acids than the starting strain did. Broadening the repertoire of methanol assimilation pathways is one step further toward synthetic methylotrophy in E. coli.
Fungi of the Fortuna Forest Reserve: Taxonomy and ecology with emphasis on ectomycorrhizal communities

Panamanian montane forests harbor a high diversity of fungi, particularly of ectomycorrhizal (ECM) fungi, however their taxonomy and diversity patterns remain for the most part unexplored. Here we present state of the art fungal taxonomy and diversity patterns at Fortuna Forest Reserve based on morphological and molecular identification of over 1,000 fruiting body collections of macromycetes made over a period of five years. We compare these new results with previously published work based on environmental sampling of Oreomunnea mexicana root tips. We compiled a preliminary list of species and report 22 new genera and 29 new fungal species for Panama. Based on fruiting body collection data we compare the species composition of ECM fungal communities associated with Oreomunnea stands across sites differing in soil fertility and amount of rainfall. We also examine the effect of a long-term nitrogen addition treatment on the fruiting body production of ECM fungi. Finally, we discuss the biogeographic importance of Panama collections which fill in the knowledge gap of ECM fungal records between Costa Rica and Colombia. Given that the isthmus of Panama was an important migration route of ECM tree and fungal species from northern temperate areas to South America, the ECM fungal communities of Panama might show a high degree of isolation and therefore a high level of endemism. We expect that the forests at Fortuna will continue to yield new ECM macromycete data as we continue to study the collected specimens and describe new species.
The macroecology and evolution of avian competence for Borrelia burgdorferi

Aim Predicting novel reservoirs of zoonotic pathogens would be improved by identifying inter-specific drivers of host competence, the ability to transmit pathogens to new hosts or vectors. Tick-borne pathogens can provide a useful model system, as larvae become infected only when feeding on a competent host during their first bloodmeal. For tick-borne diseases, competence has been best studied for Borrelia burgdorferi sensu lato (Bbsl), which causes Lyme borreliosis. Major reservoirs include several small mammal species, but birds may play an underrecognized role in human risk given their ability to disperse infected ticks across large spatial scales. Here, we provide a global synthesis of the ecological and evolutionary factors that determine the ability of bird species to infect larval ticks with Bbsl. Location Global Time period 1983 to 2019 Major taxa studied Birds Methods We compiled a dataset of Bbsl competence across 183 bird species and applied meta-analysis, phylogenetic factorization, and boosted regression trees to describe spatial and temporal patterns in competence, characterize its phylogenetic distribution across birds, reconstruct its evolution, and evaluate the trait profiles associated with competent avian species. Results Half of sampled bird species show evidence of competence for Bbsl. Competence displays moderate phylogenetic signal, has evolved multiple times across bird species, and is pronounced in the genus Turdus. Trait-based analyses distinguished competent birds with 80% accuracy and show that such species have low baseline corticosterone, exist on both ends of the pace-of-life continuum, breed and winter at high latitudes, and have broad migratory movements into their breeding range. We use these trait profiles to predict various likely but unsampled competent species, including novel concentrations of avian reservoirs within the Neotropics. Main conclusion Our results can generate new hypotheses for how birds contribute to the dynamics of tick-borne pathogens and help prioritize surveillance of likely but unsampled competent birds. Our findings further emphasize that birds display underrecognized variation in their contributions to enzootic cycles of Bbsl and the broader need to better consider competence in ecological and predictive studies of multi-host pathogens.
3D Carbon Networks Constructed NaVPO4F/C/rGO as a Cathode Material for High-Performance Sodium-Ion Batteries

The fluorophosphate NaVPO4F (NVPF) is a good candidate of cathode material for sodium-ion batteries (SIBs) due to its high theoretical specific capacity, high working voltage and stable structure. However, due to the low electronic conductivity of NVPF, its electrochemical properties are difficult to demonstrate. In order to address the insufficient and then enhance its electrochemical performance, a 3D carbon networks constructed NaVPO4F/C/rGO (NVPF/C/rGO) nanocomposite is prepared by freeze-drying assisted high-temperature solid-state method. When used as a cathode material for SIBs, the prepared NVPF/C/rGO can deliver a capacity of about 108.7 mA h g−1 at 0.05 C. Moreover, NVPF/C/rGO nanocomposite also exhibits the excellent electrochemical performance, including superior rate capacities (about 65.8 mA h g−1 specific capacity at 10 C) and outstanding cycling performance (~95.1% capacity retention after 200 cycles at 0.05 C), which can be attribute to the 3D carbon networks and the nanoparticles in NVPF/C/rGO nanocomposite. The preliminary results illustrate that the 3D carbon networks constructed NVPF/C/rGO could be a promising cathode material for SIBs.
Infection of Monocytes From Tuberculosis Patients With Two Virulent Clinical Isolates of Mycobacterium tuberculosis Induces Alterations in Myeloid Effector Functions

Monocytes play a critical role during infection with Mycobacterium tuberculosis (Mtb). They are recruited to the lung, where they participate in the control of infection during active tuberculosis (TB). Alternatively, inflammatory monocytes may participate in inflammation or serve as niches for Mtb infection. Monocytes response to infection may vary depending on the particularities of the clinical isolate of Mtb from which they are infected. In this pilot study, we have examined the baseline mRNA profiles of circulating human monocytes from patients with active TB (MoTB) compared with monocytes from healthy individuals (MoCT). Circulating MoTB displayed a pro-inflammatory transcriptome characterized by increased gene expression of genes associated with cytokines, monocytopoiesis, and down-regulation of MHC class II gene expression. In response to in vitro infection with two clinical isolates of the LAM family of Mtb (UT127 and UT205), MoTB displayed an attenuated inflammatory mRNA profile associated with down-regulation the TREM1 signaling pathway. Furthermore, the gene expression signature induced by Mtb UT205 clinical strain was characterized by the enrichment of genes in pathways and biological processes mainly associated with a signature of IFN-inducible genes and the inhibition of cell death mechanisms compared to MoTB-127, which could favor the establishment and survival of Mtb within the monocytes. These results suggest that circulating MoTB have an altered transcriptome that upon infection with Mtb may help to maintain chronic inflammation and infection. Moreover, this functional abnormality of monocytes may also depend on potential differences in virulence of circulating clinical strains of Mtb.
Predicting the viability of beta-lactamase: How folding and binding free energies correlate with beta-lactamase fitness

One of the long-standing holy grails of molecular evolution has been the ability to predict an organism’s fitness directly from its genotype. With such predictive abilities in hand, researchers would be able to more accurately forecast how organisms will evolve and how proteins with novel functions could be engineered, leading to revolutionary advances in medicine and biotechnology. In this work, we assemble the largest reported set of experimental TEM-1 β-lactamase folding free energies and use this data in conjunction with previously acquired fitness data and computational free energy predictions to determine how much of the fitness of β-lactamase can be directly predicted by thermodynamic folding and binding free energies. We focus upon β-lactamase because of its long history as a model enzyme and its central role in antibiotic resistance. Based upon a set of 21 β-lactamase single and double mutants expressly designed to influence protein folding, we first demonstrate that modeling software such as FoldX and PyRosetta designed to compute folding free energies can meaningfully, although not perfectly, predict the experimental folding free energies of single mutants. Interestingly, while these techniques also yield sensible double mutant free energies, we show that they do so for the wrong physical reasons. We then go on to assess how well both experimental and computational folding free energies explain single mutant fitness. We find that folding free energies account for, at most, 24% of the variance in β-lactamase fitness values according to linear models and, somewhat surprisingly, complementing folding free energies with computationally-predicted binding free energies of residues near the active site only increases the folding-only figure by a few percent. This strongly suggests that the majority of β-lactamase’s fitness is controlled by factors other than free energies. Overall, our results shed a bright light on to what extent the community is justified in using thermodynamic measures to infer protein fitness as well as how applicable modern computational techniques for predicting free energies will be to the large data sets of multiply-mutated proteins forthcoming.