Miracle-dz/UniFAR-FTUs huggingface dataset:
Obsidian source classification and defining “local” in early Holocene Southeast Alaska

Despite the ubiquity of obsidian in early Holocene archaeological assemblages across Southeast Alaska, artifact sourcing using bi‐plots and Principal Component Analysis has been hampered by the highly correlated geochemistry of two major sources: local Aguada Cove on Suemez Island, and distant Mount Edziza, in the Coast Mountain range. Partial Least Squares Discriminant Analysis (PLS‐DA) models constructed with device‐specific portable X‐ray fluorescence (pXRF) source catalogs benefit from the precision of individual pXRF machines and the ability of PLS‐DA to handle highly correlated data sets to provide a source classification system that complements existing methods. Of the known obsidian sources in or near Southeast Alaska, four are identified in early Holocene archaeological assemblages: Obsidian Cove and Aguada Cove on Suemez Island, Mount Edziza in the Coast Mountain Range, and a newly identified source on Zim Creek, Kupreanof Island. A comprehensive reanalysis of early Holocene microblade cores (101 cores from 13 archaeological sites) across Southeast Alaska confirms the presence of exotic obsidian from Mount Edziza in one of the oldest sites, alongside possible evidence of landscape learning: testing of the obsidian source on Kupreanof Island. The dominance of the Obsidian Cove source for microblade core production supports hypotheses framing Northwest Coast microblade core morphology as an adaptation to the small nodules of raw material available at the source. A simple distance‐decay model indicates no relationship between core reduction intensity and distance from the source, suggesting high forager mobility characterized by regular trips to Suemez Island (a voyage of up to 380 km) throughout the early Holocene.
High resolution species distribution and abundance models cannot predict separate shrub datasets in adjacent Arctic fjords

Improving species distribution models (SDMs) and species abundance models (SAMs) of woody shrubs is critical for predicting biodiversity changes in the Arctic, which is experiencing especially high warming rates. Yet, it remains relatively unexplored if SDMs and SAMs can explain local scale patterns. We aim to identify predictor differences for the distribution versus abundance of two widespread Arctic shrub species with high resolution models and to compare validation approaches to assess the models’ predictive abilities.
HETEROTYPIC ENDOSOMAL INTERACTIONS DRIVE EMERGENT EARLY ENDOSOMAL MATURATIONS

Endosomal trafficking in single cells entails the generation of membrane vesicles; their motor protein-mediated transport; morphological alterations such as tubulation, fusion and fission; as well as dynamic maintenance of various identities, defined by the lipid composition and localisation of specific proteins on their membranes. Endosomal maturation is a major feature of this process. It is classically described as endosomes shedding one specific protein and acquiring another, resulting in an identity change. This step governs the flux and the number of distinct endosomal populations. Many of the molecular players that characterise different compartments have been identified — for example, APPL1 on very early endosomes, and EEA1 on early endosomes. However, how an ensemble population of endosomes matures at a whole cell level has remained unstudied. Here, we describe a novel inter-endosomal interaction-based feed-forward mechanism that drives endosomal conversions and controls ensemble conversion rates at the whole cell level. Furthermore, using live-cell Förster Resonance Energy Transfer, we demonstrate that this process is underpinned by co-ordinated precedence in EEA1 binding via its N- and C-terminal domains, ensuring the biochemical maturation of these vesicles. Using simulations, we provide a quantitative framework to recapture the experimentally observed characteristics in the reaction scheme and the activity of EEA1. We demonstrate that the model of APPL1 to EEA1 endosomal maturation needs to be extended to include heterotypic interactions between endosomes that result in conversions, which form a significant fraction of events, in addition to the previously reported single endosome-centric maturation models. Based on these results, we motivate how temporal specificity emerges in an inherently stochastic system — namely, through a timekeeping mechanism via an N-terminal EEA1 trigger that enables deterministic outcomes in ensemble endosomal conversions.
A bug’s tale: revealing the history, biogeography and ecological patterns of 500 years of insect introductions

The arrival of Europeans to the Americas triggered a massive exchange of organisms on a continental scale. This exchange was accelerated by the amazing increase in the movement of people and goods during the 20th century. In Chile, scientific and technical literature contains hundreds of records of exotic insect species in different parts of the territory, from the hyperarid Atacama Desert to the Magallanes Region. Here, we analyze the biological patterns obtained from the database of introductions of exotic insects to Chile from the European arrival to the present. Our task includes a review of old records in museums, libraries, collections, expedition records and catalogs. Almost 600 species of exotic insects have been reported in Chile. Introductions started at the very arrival of Europeans to the central valley of Chile and underwent a huge acceleration in the second half of the 20th century. The order Hemiptera was the most prevalent among introduced insects. Most species are linked to agriculture and forestry. Species are of Palearctic origin in more than 50% of the records. In terms of temporal trends, the rate of introduced species shows an abrupt increase at the beginning of the 1950s. This change may be associated with the strong development in agriculture and forestry in Chile after World War II and the increase in intercontinental air traffic. We believe that the understanding of past patterns of introductions is an important component in the design of current policies to minimize the impact of invasive insects.
Optimal gap-affine alignment in O(s) space

Motivation Pairwise sequence alignment remains a fundamental problem in computational biology and bioinformatics. Recent advances in genomics and sequencing technologies demand faster and scalable algorithms that can cope with the ever-increasing sequence lengths. Classical pairwise alignment algorithms based on dynamic programming are strongly limited by quadratic requirements in time and memory. The recently proposed wavefront alignment algorithm (WFA) introduced an efficient algorithm to perform exact gap-affine alignment in O(ns) time, where s is the optimal score and n is the sequence length. Notwithstanding these bounds, WFA’s O(s2) memory requirements become computationally impractical for genome-scale alignments, leading to a need for further improvement. Results In this paper, we present the bidirectional WFA algorithm (BiWFA), the first gap-affine algorithm capable of computing optimal alignments in O(s) memory while retaining WFA’s time complexity of O(ns). As a result, this work improves the lowest known memory bound O(n) to compute gap-affine alignments. In practice, our implementation never requires more than a few hundred MBs aligning noisy Oxford Nanopore Technologies reads up to 1 Mbp long while maintaining competitive execution times. Availability All code is publicly available at https://github.com/smarco/BiWFA-paper Contact santiagomsola@gmail.com
Compendium-wide analysis of P. aeruginosa core and accessory genes reveal more nuanced transcriptional patterns

Strains of Pseudomonas aeruginosa, an opportunistic pathogen that causes difficult to treat infections, have significant genomic heterogeneity including the presence of diverse accessory genes that are only present in some strains or clades. Both core genes, which are conserved across strains, and accessory genes have been associated with traits such as biofilm formation and virulence. Much of what we know about core and accessory gene content comes from genome analyses. Here, we use a newly assembled transcriptome compendium to analyze the transcriptional patterns of core and accessory gene expression in PAO1 and PA14 strains across thousands of samples from hundreds of distinct experiments. We found that a subset of core genes were stable, having consistent correlated expression patterns across samples regardless of strain background, with a focus on strains PAO1 and PA14. These stable core genes had fewer co-expressed neighbors that were accessory genes. Significance Pseudomonas aeruginosa is a ubiquitous pathogen. There is a lot of diversity amongst P. aeruginosa strains, some which are clinically relevant. Understanding how these different strain-level traits manifest is important for identifying targets that regulate different traits of interest. With the availability of a PAO1-mapped and PA14-mapped RNA-seq compendium, which contain hundreds of strains, it is now possible to examine the effect of different strains on expression, which can mediate different traits. In this study we developed an approach to compare expression profiles across different P. aeruginosa gene groups – core and accessory genes. This approach revealed a subset of core genes with different transcriptional patterns across strains, which could contribute to trait differences.
ScisorWiz: visualizing differential isoform expression in single-cell long-read data

RNA isoforms contribute to the diverse functionality of the proteins they encode within the cell. Visualizing how isoform expression differs across cell types and brain regions can inform our understanding of disease and gain or loss of functionality caused by alternative splicing with potential negative impacts. However, the extent to which this occurs in specific cell types and brain regions is largely unknown. This is the kind of information that ScisorWiz plots can provide in an informative and easily communicable manner. ScisorWiz affords its user the opportunity to visualize specific genes across any number of cell types, and provides various sorting options for the user to gain different ways to understand their data. ScisorWiz provides a clear picture of differential isoform expression through various clustering methods and highlights features such as alternative exons and Single Nucleotide Variants (SNVs). Tools like Scisor-Wiz are key for interpreting single-cell isoform sequencing data. This tool applies to any single-cell long-read RNA sequencing data in any cell type, tissue, or species.
A Fijivirus Major Viroplasm Protein Shows RNA-Stimulated ATPase Activity by Adopting Pentameric and Hexameric Assemblies of Dimers

The mal de Río Cuarto virus (MRCV) causes an important maize disease in Argentina. MRCV replicates in several species of Gramineae plants and planthopper vectors. ABSTRACT Fijiviruses replicate and package their genomes within viroplasms in a process involving RNA-RNA and RNA-protein interactions. Here, we demonstrate that the 24 C-terminal residues (C-arm) of the P9-1 major viroplasm protein of the mal de Río Cuarto virus (MRCV) are required for its multimerization and the formation of viroplasm-like structures. Using an integrative structural approach, the C-arm was found to be dispensable for P9-1 dimer assembly but essential for the formation of pentamers and hexamers of dimers (decamers and dodecamers), which favored RNA binding. Although both P9-1 and P9-1ΔC-arm catalyzed ATP with similar activities, an RNA-stimulated ATPase activity was only detected in the full-length protein, indicating a C-arm-mediated interaction between the ATP catalytic site and the allosteric RNA binding sites in the (do)decameric assemblies. A stronger preference to bind phosphate moieties in the decamer was predicted, suggesting that the allosteric modulation of ATPase activity by RNA is favored in this structural conformation. Our work reveals the structural versatility of a fijivirus major viroplasm protein and provides clues to its mechanism of action. IMPORTANCE The mal de Río Cuarto virus (MRCV) causes an important maize disease in Argentina. MRCV replicates in several species of Gramineae plants and planthopper vectors. The viral factories, also called viroplasms, have been studied in detail in animal reovirids. This work reveals that a major viroplasm protein of MRCV forms previously unidentified structural arrangements and provides evidence that it may simultaneously adopt two distinct quaternary assemblies. Furthermore, our work uncovers an allosteric communication between the ATP and RNA binding sites that is favored in the multimeric arrangements. Our results contribute to the understanding of plant reovirids viroplasm structure and function and pave the way for the design of antiviral strategies for disease control.
Impact of sequencing technologies on long non-coding RNA computational identification

The correct annotation of non-coding RNAs, especially long non-coding RNAs (lncRNAs), is still an important critial challenge in genome analyses. One crucial issue in lncRNA transcript annotation is the transcriptome resource that supports lncRNA loci. Long-read technologies now bring the potential to improve the quality of transcriptome annotation. Consequently, long non-coding RNAs (lncRNA) are probably the most benefited class of transcripts that would have improved annotation using this novel technology. However, there is a gap regarding benchmarking studies that highlighted if the direct use of lncRNA predictors in long-reads makes more precise identification of these transcripts. Considering that these lncRNA tools were not trained with these reads, we want to address: how is the performance of these tools? Are they also able to efficiently identify lncRNAs? We could provide evidence of where and how to make potential better approaches for the lncRNA annotation by understanding these issues. Keywords: Non-coding RNAs, high-throughput sequencing technologies, coding, methods, benchmarking, tools, NGS, transcripts
Sustained morphine delivery suppresses bone formation and alters metabolic and circulating miRNA profiles in male C57BL/6J mice

Opioid use is detrimental to bone health, causing both indirect and direct effects on bone turnover. While the mechanisms of these effects are not entirely clear, recent studies have linked chronic opioid use to alterations in circulating miRNAs. Our aim was to develop a model of opioid-induced bone loss to understand bone turnover and identify candidate miRNA-mediated regulatory mechanisms. We evaluated the effects of sustained morphine treatment on the skeleton, metabolism, and body composition of male and female C57BL/6J mice by treating with vehicle (0.9% saline) or morphine (18 mg/kg) using subcutaneous osmotic minipumps for 25 days. Morphine-treated mice had higher energy expenditure and respiratory quotient, indicating a shift toward carbohydrate metabolism. Microcomputed tomography (µCT) analysis indicated that male mice treated with morphine had reduced trabecular bone volume fraction (Tb.BV/TV) (15%) and Tb. bone mineral density (BMD) (14%) in the distal femur compared to vehicle. Conversely, bone microarchitecture was not changed in females after morphine treatment. Histomorphometric analysis demonstrated that in males, morphine reduced bone formation rate compared to vehicle, but osteoclast parameters were not different. Furthermore, morphine reduced bone formation marker gene expression in the tibia of males (Bglap and Dmp1). Circulating miRNA profile changes were evident in males, with 14 differentially expressed miRNAs associated with morphine treatment. Target analysis indicated hypoxia inducible factor (HIF) signaling pathway was targeted by miR-223-3p and fatty acid metabolism by miR-484, - 223-3p, and -328-3p. In summary, we have established a model where morphine leads to a lower trabecular bone formation in males. Further, understanding the mechanisms of bone loss from opioid treatment will be important for improving management of the adverse effects of opioids on the skeleton.
Rapid microglial phenotype changes modulate neuronal networks and sharp wave-ripple activity in acute slice preparations

Microglia, the main immune cells of the central nervous system (CNS) have long been 1 known for their remarkable sensitivity to tissue disturbance or injury, but its implications to 2 the interpretation of results from ex vivo models of the CNS have remained largely unclear to 3 date. To this end, we have followed the course of microglial phenotype changes and 4 contribution to neuronal network organisation and functioning in acute brain slices prepared 5 from mice, widely used to study the physiology of the brain from nanoscale events to complex 6 circuits. We found that upon acute slice preparation, microglial cell bodies dislocate and 7 migrate towards the surface of slices, alongside with rapidly progressing morphological 8 changes and altered interactions with neurons. This is accompanied by gradual depolarization 9 and downregulation of P2Y12 receptors, which are instrumental for microglia-neuron 10 communication. Quantitative post-embedding immunofluorescent labelling reveals time- 11 dependent increase in the number of excitatory and inhibitory synapses upon slice preparation 12 in the cerebral cortex, which are markedly influenced by microglia. In line with this, the 13 absence of microglia diminishes the incidence, amplitude and frequency of sharp wave-ripple 14 activity in hippocampal slices. Collectively, our data suggest that microglia are not only 15 inherent modulators of complex neuronal networks, but their specific actions on network 16 reorganisation and functioning must be taken into account when learning lessons from ex vivo 17 models of the CNS. 18 their time-dependent we set microglia and the neuronal network simultaneously in slice preparations using an experimentally relevant timeframe. Our results that microglia for basic features of networks in acute slice We suggest that these of both and studies applying the slice technique.
A nanobody toolbox to investigate localisation and dynamics of Drosophila titins and other key sarcomeric proteins

Measuring the positions and dynamics of proteins in intact tissues or whole animals is key to understand protein function. However, to date this is still a challenging task, as accessibility of large antibodies to dense tissues is often limited and fluorescent proteins inserted close to a domain of interest may affect function of the tagged protein. These complications are particularly present in the muscle sarcomere, arguably one of the most protein dense structures in nature, which makes studying morphogenesis at molecular resolution challenging. Here, we have employed an efficient pipeline to generate a nanobody toolbox specifically recognising various domains of two large Drosophila titin homologs, Sallimus and Projectin. We demonstrate the superior labelling qualities of our nanobodies compared to conventional antibodies in intact muscle tissue. Applying our nanobody toolbox to larval muscles revealed a gigantic Sallimus isoform stretched more than 2 µm to bridge the sarcomeric I-band. Furthermore, N- and C-terminal nanobodies against Projectin identified an unexpected polar orientation of Projectin covering the myosin filaments in larval muscles. Finally, expression of a Sallimus nanobody in living larval muscles confirmed the high affinity binding of nanobodies to target epitopes in living tissue and hence demonstrated their power to reveal the in vivo dynamics of sarcomeric protein domains. Together, our toolbox substantiates the multiple advantages of nanobodies to study sarcomere biology. It may inspire the generation of similar toolboxes for other large protein complexes in Drosophila or mammals.
Evidence for a Single Rather than a Triple Dissociation in the Medial Temporal Lobe: an fMRI Recognition Memory Replication Study

Common research practices in neuroimaging studies using functional magnetic resonance imaging may produce outcomes that are difficult to replicate. Results that cannot be replicated have contributed to a replication crisis in psychology, neuroscience, and other disciplines over the years. Here we replicate two previous papers in which the authors present two analysis paths for a dataset in which participants underwent fMRI while performing a recognition memory test for old and new words. Both studies found activation in the medial temporal lobe including the hippocampus, with the first demonstrating a distinction in activation corresponding to true and perceived oldness of stimuli and the second demonstrating that activation reflects the subjective experience of the participant. We replicated the behavioral and MRI acquisition parameters reported in the two target articles (Daselaar, Fleck, & Cabeza, 2006; Daselaar, Fleck, Prince, et al., 2006) with N=53 participants. We focused fMRI analyses on regions of interest reported in the target articles examining fMRI activation for differences corresponding with true and perceived oldness and those associated with the subjective memory experiences of recollection, familiarity, and novelty. Comparisons between true and perceived oldness revealed main effects not only for true, but also perceived oldness along with significant interaction effects. We replicate the findings of recollection and familiarity signals in the hippocampus and medial temporal lobe cortex, respectively, but failed to replicate a novelty signal in the anterior medial temporal lobe. These results remained when we analyzed only correct trials, indicating that the effects were not due to selectively averaging correct and incorrect trials. Taken together, our findings demonstrate that activation in the hippocampus corresponds to the subjective experience associated with correct recognition memory retrieval. Highlights We replicated the methods of two influential papers using fMRI to examine recognition memory. The hippocampus consistently signals the subjective experience of remembering but not the objective old/new status of stimuli. Hippocampal response was consistent with recollection while the medial temporal lobe (MTL) cortex response was consistent with familiarity. We did not observe any regions in the MTL that signaled novelty, indicating recognition memory does not involve a triple dissociation of recollection, familiarity, and novelty in the MTL.
Cooperative ectodomain interaction among TCRαβ, CD3γε, and CD3δε enhances TCR mechanotransduction

The T-cell receptor (TCR) complex comprises TCRαβ, CD3γε, CD3δε, and CD3ζζ. TCRαβ engagement with peptide-bound major histocompatibility complex (pMHC) triggers CD3 phosphorylation, which is regulated by mechanical force. However, the inner workings of the TCR mechanotransduction machinery remains unclear. TCR ectodomain (ECD) interactions have been inferred from structural and mutagenesis studies. Due to their extreme weakness, however, direct measurements of affinity had failed and of force regulation have never been attempted. Here we measured two-dimensional affinities and force-dependent lifetimes of interactions among TCRαβ, CD3γε, and CD3δε ECDs, showing a cooperative CD3δε–TCRαβ–CD3γε catch bond with longer- lasting lifetime that exceeds the TCR–pMHC bond lifetime. Molecular dynamics stimulations revealed a central interacting region surrounded by TCR ECDs and identified critical interacting residues at their interfaces. Interfering TCR ECD interactions by antibodies impaired TCR–pMHC interaction and T cell function. Mutating residues that mediate TCR ECD cis-interactions with CD3s altered the catch bond of TCR–pMHC trans-interaction, which correlates with changed T cell cytokine production. Thus, TCR mechanotransduction is supported by cooperative TCR ECD interactions, which regulates T cell function. Our results provide a missing link between pMHC ligation and CD3 signaling and may guide future TCR engineering design for immunotherapies.