Miracle-dz/UniFAR-FTUs huggingface dataset:
Ataxin-7 promotes Drosophila posterior follicle cell maturation by suppressing yorkie function

Ataxin-7 is a key component of the Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex that anchors Non-stop/USP22, a deubiquitinase, to the complex, thereby helping to coordinate SAGA’s different activities. Recently, we found that non-stop is required in the Drosophila ovary for expression of Hippo signalling pathway components ex and mer, and polarisation of the actin cytoskeleton during collective epithelial cell migration. Here we show that in addition to being required for collective migration, Ataxin-7 plays an essential role in posterior follicle cells (PFCs) to control epithelial maturation and architecture, as well as body axis specification which depends on correct PFC differentiation. Loss of both the deubiquitinase and acetyltransferase modules of SAGA phenocopy loss of Ataxin-7 in PFCs, demonstrating a redundant requirement for SAGA’s enzymatic modules. Strikingly, loss of yorkie completely suppressed effects of Ataxin-7 loss-of-function in PFCs, indicating that the only essential function of Ataxin-7 in PFCs is to suppress yorkie function. This may have broad relevance to the roles of SAGA and Ataxin-7 in development and disease.
I. Yu. Sergeyev ANALYSIS OF THE GENERALIZED STRUCTURAL SCHEME OF THE ITERATIVELY INTEGRATING MEASUREMENT CONVERTER

A significant place among structural methods to increase the accuracy of measuring converters occupy iterative methods of error correction based on a well-developed in mathematics the theory of iterative methods. At the same time, the measurement technique is very widely used various integrating converters, due to their advantages such as high accuracy, noise immunity and sensitivity, simplicity, reliability, low cost, etc. Combining methods of integrating conversion and additive iterative correction of errors has generated a method called by the author iteratively integrating conversion method and devices using this method – iteratively integrating converters. Many of iteratively integrating converters possess high metrological parameters. Generalized structural scheme of the measurement converter which uses iteratively integrating conversion method is described. Analysis of its conversion equation and errors for two cases: first one – where the output value Y = Y (t) is not a constant, while the input values X, Z1, Z2 are constant and second one – where the input value X = X(t) and output value Y=Y(t) are not constant, while the input values Z1, Z2 are constant, were produced. Basic expressions for the calculation are listed.
CIARA: a cluster-independent algorithm for the identification of markers of rare cell types from single-cell RNA seq data

A powerful feature of single-cell RNA-sequencing data analysis is the possibility to identify novel rare cell types. However, rare cell types are often missed by standard clustering approaches. We have developed CIARA (Cluster Independent Algorithm for the identification of markers of RAre cell types), a computational tool available in R and Python that outperforms existing methods for rare cell type detection. With CIARA, we found a small group of precursor cells among mouse embryonic stem cells and previously uncharacterized rare populations of cells in a human gastrula.
Controller of Power Supplies for Corrector Magnets of European XFEL

The European XFEL is under construction now in Hamburg [1]. It is a big international project. Budker Institute of Nuclear Physics (BINP) developed, produced and delivered power supplies for corrector magnets of XFEL. A controller for these power supplies was developed. It provides an 18 bits resolution of digital-toanalog converter and 6 channels of precise analog-todigital converter with high accuracy and resolution. A combination of the general-purpose functions with the specific function for power supplies allowed using the same controller for different equipment of corrector magnet subsystem. Here is described the controller, its properties and main applications.
Prosperity of the commons: Generalist mycorrhizal species dominate a mixed forest and may promote forest diversity by mediating resource sharing among trees

Mechanisms of host–microbe interactions and their direct impact on both parties have been extensively researched, however, much less is known on the effect of these interactions on the ecology of the host-community. Here we investigate tree-fungi mycorrhizal interactions, focusing on mycorrhizal-meditated resource sharing among trees, while examining the dynamics between specialist and generalist fungi and their implications on the forest ecology. Using genetic meta- barcoding, we identified the fungal community colonizing different trees in a mixed forest, and generated an extensive mapping connecting fungal sequences to their tree hosts. The mycorrhizal fungal community diverged between ectomycorrhizal and arbuscular host trees, but, unexpectedly, multiple ectomycorrhizal species colonized roots of non-ectomycorrhizal host trees. We complemented these findings by a novel computational framework, modeling competition between generalist and specialist mycorrhizal fungi, accounting for fungal-mediated resource sharing among neighboring trees. The analysis of the model revealed that generalist mycorrhizal networks may affect the entire tree community, and contribute to the maintenance of forest diversity in the long run. Furthermore, higher initial spatial mixing of trees can promote the evolution of generalist mycorrhizal species. These novel belowground interactions among trees and fungi may significantly impact forest biodiversity.
Change the direction: 3D optimal control simulation by directly tracking marker and ground reaction force data

Optimal control simulations of musculoskeletal models can be used to reconstruct motions measured with optical motion capture to estimate joint and muscle kinematics and kinetics. These simulations are mutually and dynamically consistent, in contrast to traditional inverse methods. Commonly, optimal control simulations are generated by tracking generalized coordinates in combination with ground reaction forces. The generalized coordinates are estimated from marker positions using, for example, inverse kinematics. Hence, inaccuracies in the estimated coordinates are tracked in the simulation. We developed an approach to reconstruct arbitrary motions, such as change of direction motions, using optimal control simulations of 3D full-body musculoskeletal models by directly tracking marker and ground reaction force data. For evaluation, we recorded three trials each of straight running, curved running, and a v-cut for 10 participants. We reconstructed the recordings with marker tracking simulations, coordinate tracking simulations, and inverse kinematics and dynamics. First, we analyzed the convergence of the simulations and found that the wall time increased three to four times when using marker tracking compared to coordinate tracking. Then, we compared the marker trajectories, ground reaction forces, pelvis translations, joint angles, and joint moments between the three reconstruction methods. Root mean squared deviations between measured and estimated marker positions were smallest for inverse kinematics (e.g., 7.6 ± 5.1 mm for v-cut). However, measurement noise and soft tissue artifacts are likely also tracked in inverse kinematics, meaning that this approach does not reflect a gold standard. Marker tracking simulations resulted in slightly higher root mean squared marker deviations (e.g., 9.5 ± 6.2 mm for v-cut) than inverse kinematics. In contrast, coordinate tracking resulted in deviations that were nearly twice as high (e.g., 16.8 ± 10.5 mm for v-cut). Joint angles from coordinate tracking followed the estimated joint angles from inverse kinematics more closely than marker tracking (e.g., root mean squared deviation of 1.4 ± 1.8 deg vs. 3.5 ± 4.0 deg for v-cut). However, we did not have a gold standard measurement of the joint angles, so it is unknown if this larger deviation means the solution is less accurate. In conclusion, we showed that optimal control simulations of change of direction running motions can be created by tracking marker and ground reaction force data. Marker tracking considerably improved marker accuracy compared to coordinate tracking. Therefore, we recommend reconstructing movements by directly tracking marker data in the optimal control simulation when precise marker tracking is required.
Canonical Wnt signaling regulates soft palate development through mediating ciliary homeostasis

Craniofacial morphogenesis requires complex interactions among tissues, signaling pathways, secreted factors, and organelles. The details of these interactions remain elusive. In this study, we analyzed the molecular mechanisms and homeostatic cellular activities governing soft palate development to improve regenerative strategies for cleft palate patients. We have identified canonical Wnt signaling as a key signaling pathway primarily active in cranial neural crest (CNC)-derived mesenchymal cells surrounding soft palatal myogenic cells. Using Osr2-Cre;β-cateninfl/fl mice, we further discovered that Wnt signaling is indispensable for mesenchymal cell proliferation and subsequently myogenesis through mediating ciliogenesis. Specifically, we identified that Wnt signaling directly regulates expression of the ciliary gene Ttll3 through β-catenin/Tcf7l2 complex. Impaired ciliary disassembly leads to differentiation defects of mesenchymal cells and indirectly disrupts myogenesis through decreased expression of Dlk1, a mesenchymal cell-derived pro-myogenesis factor. Moreover, we found that restoring ciliary homeostasis rescues mesenchymal cell proliferation in Osr2-Cre;β-cateninfl/fl samples. This study highlights the role of Wnt signaling in palatogenesis through controlling ciliary homeostasis, which establishes a new mechanism for Wnt-regulated craniofacial morphogenesis.
Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells

Background SARS-CoV-2 vaccination with BNT162b2 (Pfizer BioNTech) has been shown to be 95% effective.1 Double-dose vaccination generates high levels of spike-specific antibodies, memory B cells (Bmem) and T cells. However, variants of concern (VoC) with mutations in the spike Receptor Binding Domain (RBD) can evade antibody responses. Booster vaccinations improve antibody recognition of VoC, but it is unclear if this is due to higher total antibodies or their capacity to bind VoC. We here addressed the capacity of surface Ig on single Wuhan-specific Bmem after first and second dose BNT162b2 vaccination to recognize variant RBD. Methods Samples were collected from 30 healthy COVID-19 naive individuals pre-BNT162b2 vaccination, 3 weeks post-dose 1 and 4-weeks post-dose 2. Plasma antibodies and Bmem were evaluated using recombinant RBD proteins of the Wuhan, Gamma and Delta strains. Results All individuals generated a robust antibody response to BNT162b2 vaccination with all participants producing neutralizing antibodies following dose 2. IgM+ and IgG+ RBD-specific Bmem were generated after one vaccine dose, and those expressing IgG1 increased in absolute number after dose 2. The majority of RBD-specific Bmem bound the Gamma and/or Delta variants, and this proportion significantly increased after the second dose. Conclusion The second dose of BNT162b2 increases the number of circulating Ig-class switched RBD-specific Bmem. Importantly, the second dose of vaccination is required for a high frequency of RBD-specific Bmem to recognize Gamma and Delta variants. This suggests that dose 2 not only increases the number of RBD-specific Bmem but also the affinity of the Bmem to overcome the point mutations in VoC.
Depletion of Plasma Membrane PI4P by ORP5 Requires Hydrolysis by SAC1 in Acceptor Membranes

The authors have withdrawn their manuscript because the central conclusion is incorrect. We discovered this while revising the paper after peer review. In the original submission, we described ectopic targeting of the PI4P transfer protein, ORP5. We reported that when combined with orthogonal targeting of SAC1 to the mitochondrial outer membrane, ORP5 facilitates depletion of PM PI4P when targeted to PM-mitochondria contact sites. New experiments revealed that orthogonal targeting of SAC1 to the mitochondria alone is sufficient to deplete PM PI4P; ORP5 is not required. Thus, although the data reported in the manuscript are valid and reproducible, the conclusion was incorrect. We are currently performing additional experiments to better characterize and understand the effects of mitochondrially-targeted SAC1 on PM pools of PI4P. We will post a new manuscript detailing these findings on bioRXiv, which will be submitted for peer review at the original journal as a revision. In the meantime, we are withdrawing the preprint so as not to mislead the field with the erroneous conclusion. We sincerely apologize to anyone whose work was misdirected by our honest mistake. Therefore, the authors do not wish this work to be cited as reference for the project in its present form. If you have any questions, please contact the corresponding author.
Competitive HIV budding suggests that a self-packaging gRNA:Gag-Pol complex directs HIV assembly and enforces infectivity

To resolve the assembly mechanism of infectious HIV virions, we tested the ability of HIV to assemble infectious virions in the presence of a titrated mix of infectious/ non-infectious proviral genomes. The analysis of our assembly competitions shows that during translation, 15 ± 5 Gag-Pols bind back to their parental gRNA creating a gRNA1: Gag-Pol15 complex. This complex initiates the infectious virion assembly through interactions mediated by cis packaged Gag/Gag-pols and the plasma membrane. Our analysis also shows the number of Gag-Pol and Env proteins packaged in an infectious HIV virion and the minimum functional units of these proteins required for viral infectivity. We suggest that aside from orchestrating the infectious virion assembly the gRNA1: Gag-Pol15 complex plays a major role in HIV evolution and likely hampers effectiveness of antiviral therapies. One-Sentence Summary Competitive HIV budding reveals gRNA1: Gag-Pol15 complex orchestrating viral assembly.
α-Arrestins maintain phospholipid balance and Atg18 distribution to permit efficient autophagy

Cells selectively reorganize their membrane proteome in response to stressors via selective protein trafficking. The α-arrestins, a family of conserved protein trafficking adaptors, bind to select membrane proteins and interact with the ubiquitin ligase Rsp5. The α-arrestins recruit Rsp5 to its membrane protein substrates, permitting their ubiquitination and endocytosis. To identify new α-arrestin functions, we performed a genetic screen to isolate mutants that alter α-arrestin-mediated resistance to rapamycin, a drug that inhibits TORC1. Interestingly, loss of many of the ATG genes, which encode the machinery needed for the self-degradative process of autophagy, disrupted α-arrestins’ ability to promote growth on rapamycin. Herein we define a genetic network linking α-arrestins to autophagy. We show autophagy impairment in the absence of select α-arrestins, with increased autophagosome lifetimes and delayed/reduced delivery of autophagosomes to the vacuole. The α-arrestin mutants that impeded autophagy had vacuole morphology defects and increased vacuolar retention of Atg18, a member of the PROPPIN family that is needed to maintain vacuole shape and facilitate lipid transfer to expanding autophagosomes. Atg18 binds phosphatidylinositol 3 phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), and we observed increased PI3P on the vacuole membrane in α-arrestin mutants. The levels of Vps34 and Fab1, the kinases responsible for the generation of PI3P and PI(3,5)P2, respectively, were also elevated at vacuole membranes in cells lacking α-arrestins. We posit that altered phospholipids in the vacuolar membrane form the basis for the Atg18-Atg2 mislocalization and autophagy defect. These data demonstrate a previously unappreciated link between the α-arrestins and autophagy, expanding the functional impact of these trafficking adaptors in responding to nutrient stress. Author Summary Cells survive nutrient starvation by degrading parts of themselves through the process of autophagy. During autophagy, cells make a double membrane, known as an autophagosome (AP), around bits of cytoplasm or organelles. The AP and its engulfed material are delivered to the vacuole, an organelle that helps break down proteins and lipids. These materials can then be used as building blocks to generate the essential components needed for the cell to survive starvation. For cells to undergo efficient autophagy, they need α-arrestins, a group of proteins important for deciding where membrane proteins localize. In cells lacking α-arrestins, the AP forms slowly, likely due to a problem in growing the AP membrane. This results in less material being delivered to the vacuole via APs when cells do not have α-arrestins. This study defines a new role for α-arrestins in promoting AP formation and starvation survival.
Spastin is an essential regulator of male meiosis, acrosome formation, manchette structure and nuclear integrity

The development and function of male gametes is critically dependent on a dynamic microtubule network, yet how this is regulated remains poorly understood. We have recently shown that microtubule severing, via the action of the meiotic AAA ATPase protein clade, plays a critical role in this process. Here, we sought to elucidate the roles of spastin, an as yet unexplored member of this clade in spermatogenesis. Using a SpastKO/KO mouse model, we reveal that spastin loss resulted in a complete loss of functional germ cells. Spastin plays a critical role in the assembly and function of the male meiotic spindle, and in its absence, apoptosis is significantly increased. Consistent with meiotic failure, round spermatid nuclei were enlarged, indicating aneuploidy, but were still able to enter spermiogenesis. During spermiogenesis, we observed extreme abnormalities in manchette structure, supernumerary acrosome formation, and commonly, a loss of nuclear integrity. This work defines a novel and essential role for spastin in regulating microtubule dynamics during spermatogenesis and is of potential relevance to patients carrying Spastin variants and to the medically assisted reproductive technology industry. Summary statement We identify an essential role for the microtubule severing enzyme spastin in the regulation of microtubule dynamics during spermatogenesis.
Temporal regulation of cold transcriptional response in switchgrass

Switchgrass low-land ecotypes have significantly higher biomass but lower cold tolerance compared to up-land ecotypes. Understanding the molecular mechanisms underlying cold response, including the ones at transcriptional level, can contribute to improving tolerance of high-yield switchgrass under chilling and freezing environmental conditions. Here, by analyzing an existing switchgrass transcriptome dataset, the temporal cis-regulatory basis of switchgrass transcriptional response to cold is dissected computationally. We found that the number of cold-responsive genes and enriched Gene Ontology terms increased as duration of cold treatment increased from 30 min to 24 hours, suggesting an amplified response/cascading effect in cold-responsive gene expression. To identify genomic sequences likely important for regulating cold response, machine learning models predictive of cold response were established using k-mer sequences enriched in the genic and flanking regions of cold-responsive genes but not non-responsive genes. These k-mers, referred to as putative cis-regulatory elements (pCREs) are likely regulatory sequences of cold response in switchgrass. There are in total 655 pCREs where 54 are important in all cold treatment time points. Consistent with this, eight of 35 known cold-responsive CREs were similar to top-ranked pCREs in the models and only these eight were important for predicting temporal cold response. More importantly, most of the top-ranked pCREs were novel sequences in cold regulation. Our findings suggest additional sequence elements important for cold-responsive regulation previously not known that warrant further studies.
Milkweed plants bought at nurseries may expose monarch caterpillars to harmful pesticide residues

The decline of monarch butterflies in both the eastern and western United States has garnered widespread public interest. Planting milkweeds, their larval host plants, has been promoted as one action individuals can take, but little is known with respect to potential pesticide contamination of store-bought milkweeds. In this study, we collected leaf samples from 235 milkweed plants purchased at 33 retail nurseries across the US to screen for pesticides. Across all samples, we detected 61 different pesticides with an average of 12.2 (±5.0) compounds per plant. While only 9 of these compounds have been experimentally tested on monarch caterpillars, 38% of samples contained a pesticide above a concentration shown to have a sub-lethal effect for monarchs. We detected only a modest predictive ability of retailer size and milkweed species; and plants with labels advertising their value for wildlife did not have fewer pesticides at concentrations known to have a negative effect on monarchs. These results demonstrate the extensiveness of pesticide exposure within nursery milkweeds and the potential impacts on monarchs and other insects exposed to store-bought plants. Highlights Milkweeds were collected from stores in the United States and screened for pesticides. We detected multiple pesticides in every milkweed plant sampled. Over one third of samples contained a pesticide at a known harmful concentration for monarchs. Plants labeled as wildlife-friendly did not have fewer potentially harmful compounds.
Plant defense synergies and antagonisms affect performance of specialist herbivores of common milkweed

As a general rule, plants defend against herbivores with multiple traits. The defense synergy hypothesis posits that some traits are more effective when co-expressed with others compared to their independent efficacy. However, this hypothesis has rarely been tested outside of phytochemical mixtures, and seldom under field conditions. We tested for synergies between multiple defense traits of common milkweed (Asclepias syriaca) by assaying the performance of two specialist chewing herbivores on plants in natural populations. We employed regression and a novel application of Random Forests to identify synergies and antagonisms between defense traits. We found the first direct empirical evidence for two previously hypothesized defense synergies in milkweed (latex by secondary metabolites, latex by trichomes), and identified numerous other potential synergies and antagonisms. Our strongest evidence for a defense synergy was between leaf mass per area and low nitrogen content; given that these “leaf economic” traits typically covary in milkweed, a defense synergy could reinforce their co-expression. We report that each of the plant defense traits showed context-dependent effects on herbivores, and increased trait expression could well be beneficial to herbivores for some ranges of observed expression. The novel methods and findings presented here complement more mechanistic approaches to the study of plant defense diversity, and provide some of the best evidence to date that multiple classes of plant defense synergize in their impact on insects. Plant defense synergies against highly specialized herbivores, as shown here, are consistent with ongoing reciprocal evolution between these antagonists.