Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenomics and Biogeography of North American Trechine Cave Beetles (Coleoptera: Carabidae)

Cave trechines beetles (Coleoptera: Carabidae: Trechini) are members of cave communities globally and important models for understanding the colonization of caves, adaptation to cave life, and the diversification of cave-adapted lineages. In eastern North America, cave trechines are the most species-rich group of terrestrial troglobionts, comprised of over 150 taxa in six genera with no extant surface members. Previous studies have hypothesized the climate change during the Pleistocene was a major driver of cave colonization and diversification in this and other temperate terrestrial cave fauna. However, our time-calibrated molecular phylogeny resulting from the analysis of 16,794 base pairs (bp) from 68 UCE loci for 45 species of the clade supports an alternative hypothesis whereby cave colonization of the surface ancestor of eastern North American cave trechines likely began in the middle Miocene in the Appalachians Ridge and Valley (APP) and dispersed into the Interior Low Plateau (ILP) in an east to west manner around 11.5 Mya. The APP served as a cradle for diversification and also as a bridge linking the southern Appalachians and Interior Low Plateau enabling the dispersal and subsequent diversification of these cave beetles. Major clades in our time-calibrated phylogeny attained their present-day geographic distributions by the early Miocene followed by multiple additional episodes of cave colonization and diversification occurring throughout the Pliocene and Pleistocene. The genera Neaphanops, Darlingtonea, Nelsonites, and Ameroduvalius were nested within specious genus Pseudanopthalmus supporting the hypothesis that these genera are derived Pseudanophtlamus. Moreover, while several morphologically-derived species groups of Pseudanopthalmus were recovered as monophyletic, others were not warranting future taxonomic and systematic research. The molecular systematics and biogeography of these unique cave beetles offer a model for other comparative evolutionary and ecological studies of troglobionts to further our understanding of factors driving speciation and biogeographic patterns.
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size

The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer’s disease. We demonstrate that in response to neutral lipid synthesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the ER lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts. APOE knockdown promotes fewer, larger LDs containing more unsaturated triglyceride. This LD size distribution phenotype was rescued by chimeric APOE that targets only LDs. APOE4-expressing astrocytes also form a small number of large LDs enriched in unsaturated triglyceride. Additionally, the larger LDs in APOE4 cells exhibit impaired turnover and increased sensitivity to lipid peroxidation. Our data indicate that APOE plays a previously unrecognized role as an LD surface protein that regulates LD size and composition. APOE4 is a toxic gain of function variant that causes aberrant LD composition and morphology. We propose that APOE4 astrocytes with large, unsaturated LDs are sensitized to lipid peroxidation or lipotoxicity, which could contribute to Alzheimer’s disease risk. Summary Windham et al. discover that APOE in astrocytes can traffic to lipid droplets (LDs), where it modulates LD composition and size. Astrocytes expressing the Alzheimer’s risk variant APOE4 form large LDs with impaired turnover and increased peroxidation sensitivity.
Improved gene annotation of the fungal wheat pathogen Zymoseptoria tritici based on combined Iso-Seq and RNA-Seq evidence

Despite large omics datasets, the establishment of a reliable gene annotation is still challenging for eukaryotic genomes. Here, we used the reference genome of the major fungal wheat pathogen Zymoseptoria tritici (isolate IPO323) as a case study to develop methods to improve eukaryotic gene prediction. Four previous IPO323 annotations identified 10,933 to 13,260 gene models, but only one third of these coding sequences (CDS) have identical structures. To resolve these discrepancies and improve gene models, we generated full-length transcripts using long-read sequencing. This dataset was used together with other evidence (RNA-Seq transcripts and protein sequences) to generate novel ab initio gene models. The selection of the best structure among novel and existing gene models was performed according to transcript and protein evidence using InGenAnnot, a novel bioinformatics suite. Overall, 13,414 re-annotated gene models (RGMs) were predicted, including 671 new genes among which 53 encoded effector candidates. This process corrected many of the errors (15%) observed in previous gene models (coding sequence fusions, false introns, missing exons). While fungal genomes have poor annotations of untranslated regions (UTRs), our Iso-Seq long-read sequences outlined 5’ and 3’UTRs for 73% of the RGMs. Alternative transcripts were identified for 13% of RGMs, mostly due to intron retention (75%), likely corresponding to unprocessed pre-mRNAs. A total of 353 genes displayed alternative transcripts with combinations of previously predicted or novel exons. Long non-coding transcripts (lncRNAs) and double-stranded RNAs from two fungal viruses were also identified. Most lncRNAs corresponded to antisense transcripts of genes (52%). lncRNAs that were up or down regulated during infection were enriched in antisense transcripts (70%), suggesting their involvement in the control of gene expression. Our results showed that combining different ab initio gene predictions and evidence-driven curation using InGenAnnot improved the quality of gene annotations of a compact eukaryotic genome. Our analysis also provided new insights into the transcriptional landscape of Z. tritici, helping develop an increasingly complex picture of its biology.
Variability and Bias in Microbiome Metagenomic Sequencing: an Interlaboratory Study Comparing Experimental Protocols

Background Several studies have documented the significant impact of methodological choices in microbiome analyses. The myriad of methodological options available complicate the replication of results and generally limit the comparability of findings between independent studies that use differing techniques and measurement pipelines. Here we describe the Mosaic Standards Challenge (MSC), an international interlaboratory study designed to assess the impact of methodological variables on the results. The MSC did not prescribe methods but rather asked participating labs to analyze 7 shared reference samples (5x human stool samples and 2x mock communities) using their standard laboratory methods. To capture the array of methodological variables, each participating lab completed a metadata reporting sheet that included 100 different questions regarding the details of their protocol. The goal of this study was to survey the methodological landscape for microbiome metagenomic sequencing (MGS) analyses and the impact of methodological decisions on metagenomic sequencing results. Results A total of 44 labs participated in the MSC by submitting results (16S or WGS) along with accompanying metadata; thirty 16S rRNA gene amplicon datasets and 14 WGS datasets were collected. The inclusion of two types of reference materials (human stool and mock communities) enabled analysis of both MGS measurement variability between different protocols using the biologically-relevant stool samples, and MGS bias with respect to ground truth values using the DNA mixtures. Owing to the compositional nature of MGS measurements, analyses were conducted on the ratio of Firmicutes: Bacteroidetes allowing us to directly apply common statistical methods. The resulting analysis demonstrated that protocol choices have significant effects, including both bias of the MGS measurement associated with a particular methodological choices, as well as effects on measurement robustness as observed through the spread of results between labs making similar methodological choices. In the analysis of the DNA mock communities, MGS measurement bias was observed even when there was general consensus among the participating laboratories. Conclusion This study was the result of a collaborative effort that included academic, commercial, and government labs. In addition to highlighting the impact of different methodological decisions on MGS result comparability, this work also provides insights for consideration in future microbiome measurement study design.
Not one, but multiple radiations underlie the biodiversity of Madagascar’s endangered lemurs

Lemurs are a well-known example of adaptive radiation. Since colonizing Madagascar, more than 100 extant lemur species have evolved to fill the variety of ecological niches on the island. However, recent work suggests that lemurs do not exhibit one of the hallmarks of adaptive radiations: explosive speciation rates that decline over time. We test this idea using a phylogenomic dataset with broad taxonomic sampling of lemurs and their sister group, the lorisiforms of Asia and continental Africa. We find higher rates of speciation in Madagascar’s lemurs compared to lorisiforms and we confirm that lemurs did not experience an “early burst” of speciation after colonizing Madagascar. Instead, we identify three independent bursts of speciation approximately 15 million years ago that underly much of today’s lemur diversity. We demonstrate that the lemur clades with exceptionally high diversification rates have higher rates of introgression. This suggests that hybridization in these primates is not an evolutionary dead- end, but a driving force for diversification. Considering the conservation crisis affecting strepsirrhine primates, with approximately 95% of species being threatened with extinction, this phylogenomic study offers a new perspective for explaining Madagascar’s exceptional primate diversity and reveals patterns of speciation, extinction, and gene flow that will help inform future conservation decisions.
Surfaces: a software to quantify and visualize interactions within and between proteins and ligands

Computational methods for the quantification and visualization of the relative contribution of molecular interactions to the stability of biomolecular structures and complexes are fundamental to understand, modulate and engineer biological processes. Here we present Surfaces, an easy to use, fast and customizable software for quantification and visualization of molecular interactions based on the calculation of surface areas in contact. Surfaces calculations shows equivalent levels of correlations with experimental data as computationally expensive methods based on molecular dynamics. All scripts are available at https://github.com/nataliateruel/Surfaces Documentation is available at https://surfaces-tutorial.readthedocs. io/en/latest/index.html
Cell based dATP delivery as a therapy for chronic heart failure

Transplanted human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) improve ventricular performance when delivered acutely post-myocardial infarction but are ineffective in chronic myocardial infarction/heart failure. 2’-deoxy-ATP (dATP) activates cardiac myosin and potently increases contractility. Here we engineered hPSC-CMs to overexpress ribonucleotide reductase, the enzyme controlling dATP production. In vivo, dATP-producing CMs formed new myocardium that transferred dATP to host cardiomyocytes via gap junctions, increasing their dATP levels. Strikingly, when transplanted into chronically infarcted hearts, dATP-producing grafts increased left ventricular function, whereas heart failure worsened with wild-type grafts or vehicle injections. dATP-donor cells recipients had greater voluntary exercise, improved cardiac metabolism, reduced pulmonary congestion and pathological cardiac hypertrophy, and improved survival. This combination of remuscularization plus enhanced host contractility offers a novel approach to treating the chronically failing heart. One Sentence Summary Transplanting gene-edited dATP-donor cardiomyocytes in chronically infarcted heart restores their cardiac function, improving both exercise tolerance and survival.
Hippocampal neural fluctuation between memory encoding and retrieval states during a working memory task in humans

Background Working memory (WM) is essential for everyday life, yet its neural mechanism remains unclear. Although the hippocampus plays a critical role in memory consolidation and retrieval, its role in WM tasks has yet to be fully elucidated. We hypothesized that multiunit activities in the hippocampus alter their representations depending on the memory load and phase of a WM task, particularly in relation to sharp-wave ripple complexes (SWRs), which are known as various cognitive biomarkers. Methods We used an open dataset of intracranial electroencephalogram (iEEG) data and multiunit activity recorded from the medial temporal lobe (MTL) of nine patients with epilepsy. The MTL includes the hippocampus, entorhinal cortex, and amygdala. During the recording, all subjects performed an eight-second Sternberg test, in which they memorized sets of four, six, or eight letters (encoding phase), waited for three seconds (maintenance phase), and recalled whether a probe letter was included (Match IN task) or not (Mismatch OUT task) (retrieval phase). We used Gaussian-process factor analysis to visualize the neural trajectories of multiunit activity in MTL regions during the task. We also detected SWRs from the iEEG data in the hippocampus. Findings We found that the trajectory distance between phases of the Sternberg task was larger in the hippocampus compared to the entorhinal cortex and amygdala. Additionally, the trajectory distance between the encoding and retrieval phases was memory load dependent. Moreover, a transient trajectory increase was detected during SWRs. Finally, the trajectory direction of the hippocampus fluctuated between the encoding and retrieval states, and the balance of the fluctuation was shifted to the retrieval state during SWR periods. Interpretation Our results demonstrate the involvement of the hippocampus during a WM task. Furthermore, it is suggested that SWR in the retrieval phase plays a role in memory retrieval for a WM task. Our results provide new insight into the two-stage model of memory formation.
African rice (Oryza glaberrima) genomic introgressions impacting upon panicle architecture in Asian rice (O. sativa) lead to the identification of key QTLs

Background Developing high yielding varieties is a major challenge for breeders tackling the challenges of climate change in agriculture. The panicle (inflorescence) architecture of rice is one of the key components of yield potential and displays high inter- and intra-specific variability. The genus Oryza features two different crop species: Asian rice (Oryza sativa L.) and the African rice (O. glaberrima Steud). One of the main morphological differences between the two independently domesticated species is the structure (or complexity) of the panicle, with O. sativa displaying a highly branched panicle, which in turn produces a larger number of grains than that of O. glaberrima. The genetic interactions that govern the diversity of panicle complexity within and between the two species are still poorly understood. Results To identify genetic factors linked to panicle architecture diversity in the two species, we used a set of 60 Chromosome Segment Substitution Lines (CSSLs) issued from third generation backcross (BC3DH) and carrying genomic segments from O. glaberrima cv. MG12 in the genetic background of O. sativa Tropical Japonica cv. Caiapó. Phenotypic data were collected for rachis and primary branch length, primary, secondary and tertiary branch number and spikelet number. A total of 15 QTLs were localized on chromosomes 1, 2, 3, 7, 11 and 12 and QTLs associated with enhanced secondary and tertiary branch numbers were detected in two CSSLs. Furthermore, BC4F3:5 lines carrying different combinations of substituted segments were produced to decipher the effects of the identified QTL regions on variations in panicle architecture. A detailed analysis of phenotypes versus genotypes was carried out between the two parental genomes within these regions in order to understand how O. glaberrima introgression events may lead to alterations in panicle traits. Conclusion Our analysis led to the detection of genomic variations between O. sativa cv. Caiapó and O. glaberrima cv. MG12 in regions associated with enhanced panicle traits in specific CSSLs. These regions contain a number of key genes that regulate panicle development in O. sativa and their interspecific genomic variations may explain the phenotypic effects observed.
On the Vector Sum of Two Convex Sets in Space

In the paper [KIS2], C. Kiselman studied the boundary smoothness of the vector sum of two smoothly bounded convex sets A and B in . He discovered the startling fact that even when A and B have real analytic boundary the set A + B need not have boundary smoothness exceeding C 20/3 (this result is sharp). When A and B have C ∞ boundaries, then the smoothness of the sum set breaks down at the level C 5 (see [KIS2] for the various pathologies that arise).
Spectral Level Set Methodology in MDO

A desirable feature in multidisciplinary design optimization (MDO) is to achieve an acceptable preliminary or initial design in an expeditiously fashion. One way to pursue this goal is to describe the structural boundary using a small number of design variables. We propose an approach to structural optimization that enhances the performance of multidisciplinary design tools because it greatly decreases the number of design variables assigned to structural definition. This approach is based on the Level Set Methods and uses the coefficients of the Fourier series expansion of the level set function as design variables. The global character of these coefficients and the fact that the level set function is realvalued provide the means to reduce the design space dimension. Within the level set framework, the structure is confined to the region in which the level set function is negative. In this way, the zero level set of this function implicitly describes the structural boundary, which can undergo topological changes during the optimization process as the function evolves. The proposed methodology also averts successive mesh generation. We show that an interface can be described to any desirable accuracy using finitely many Fourier modes of the signed distance to the interface. The total error is inversely proportional to the number of Fourier modes. We present and discuss two application examples in topology optimization, namely the design of short and long cantilevers subject to a pontual load. In these cases, we analyze the results obtained with the Spectral Level Set formulation for different parameter values.
PROJECTIVE REPRESENTATIONS OF A QUIVER WITH THREE VERTICES AND TWO EDGES AS R(x)-MODULES

In this paper we show that the projective properties of representations of a quiver Q = • → • → • as left R(x)-modules. We show that if P is a projective left R-module then 0 / 0 / P(x) is a projective representation of a quiver Q as R(x)-modules, but P(x) / 0 / 0 is not a projective representation of a quiver Q as R(x)-modules, if P 0. And we show a representation 0 / P(x) id / P(x) of a quiver Q is a projective representation, if P is a projective left R-module, but P(x) id / P(x) / 0 is not a projective representation of a quiver Q as R(x)-modules, if P 0. Then we show a representation P(x) id / P(x) id / P(x) of a quiver Q is a projective representation, if P is a projective left R- module.
Deep Reinforcement Learning for 5 × 5 Multiplayer Go

In recent years, much progress has been made in computer Go and most of the results have been obtained thanks to search algorithms (Monte Carlo Tree Search) and Deep Reinforcement Learning (DRL). In this paper, we propose to use and analyze the latest algorithms that use search and DRL (AlphaZero and Descent algorithms) to automatically learn to play an extended version of the game of Go with more than two players. We show that using search and DRL we were able to improve the level of play, even though there are more than two players.
Three-level equivalent-estimation split-plot designs based on subset and supplementary difference set designs

In many industrial experiments, complete randomization of the runs is impossible as, often, they involve factors whose levels are hard or costly to change. In such cases, the split-plot design is a cost-efficient alternative that reduces the number of independent settings of the hard-to-change factors. In general, the use of generalized least squares is required for model estimation based on data from split-plot designs. However, the ordinary least squares estimator is equivalent to the generalized least squares estimator for some split-plot designs, including some second-order split-plot response surface designs. These designs are called equivalent-estimation designs. An important consequence of the equivalence is that basic experimental design software can be used for model estimation. This article introduces two new families of equivalent-estimation split-plot designs, one based on subset designs and another based on supplementary difference set designs. The resulting designs complement existing catalogs of equivalent-estimation designs and allow for a more flexible choice of the number of hard-to-change factors, the number of easy-to-change factors, the number and size of whole plots, and the total sample size. It is shown that many of the newly proposed designs possess good predictive properties when compared to D-optimal split-plot designs.
Scoping out noisy galvanic vestibular stimulation: a review of the parameters used to improve postural control

Objective Noisy galvanic vestibular stimulation (nGVS) has been used to facilitate vestibular function and improve gait and balance in people with poor postural control. The aim of this scoping review is to collate, summarize and report on the nGVS parameters that have been used to augment postural control. Method A systematic scoping review was conducted up to December 2022. Data were extracted and synthesized from 31 eligible studies. Key nGVS parameters were identified, and the importance of these parameters and their influence on postural control evaluated. Results A range of nGVS parameters have been used to augment postural control, including; noise waveform, amplitude, frequency band, duration of stimulation, method of amplitude optimization, size and composition of electrodes and the electrode skin interface. Conclusion Systematic evaluation of the individual parameters that can be manipulated in the nGVS waveform identified that a broad array of settings have been utilized in each parameter across the studies. Choices made around the electrode and electrode-skin interface, as well as the amplitude, frequency band, duration and timing of the waveform are likely to influence the efficacy of nGVS. The ability to draw robust conclusions about the selection of optimal nGVS parameters to improve postural control, is hindered by a lack of studies that directly compare parameter settings or consider the variability in individuals’ response to nGVS. We propose a guideline for the accurate reporting of nGVS parameters, as a first step toward establishing standardized stimulation protocols.