Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells

The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal “starburst” amacrine cells is proposed to underlie their direction selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ∼ 3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Together, these results provide direct support for the ‘space-time wiring’ model for direction selectivity.
Phylogenomics suggests that larvae are ancestral in polyclads, but not homologous to the trochophore

Platyhelminthes (flatworms) are a diverse invertebrate phylum that are useful for exploring life history evolution. Within Platyhelminthes, only two clades develop through a larval stage: free-living polyclads and parasitic neodermatans. Neodermatan larvae are considered evolutionarily derived, whereas polyclad larvae are hypothesized to be retained from the last common ancestor of Platyhelminthes – and Spiralia – due to ciliary band similarities among polyclad and other spiralian larvae. However, larval evolution has been challenging to investigate within polyclads due to low support for deeper phylogenetic relationships. To investigate polyclad life history evolution, we generated transcriptomic data for 21 species of polyclads to build a well-supported phylogeny for the group. We then used ancestral state reconstruction to investigate ancestral modes of development (direct vs indirect) within Polycladida, and flatworms in general. The resulting tree provides strong support for deeper nodes and we recover a new monophyletic clade of early branching cotyleans. Early branching clades of acotyleans and cotyleans possess diverse modes of development, suggesting a complex history of larval evolution in polyclads that likely includes multiple losses and/or multiple gains. Our ancestral state reconstructions in previous platyhelminth phylogenies also suggest that larval similarities between flatworms and other phyla are most likely convergently evolved.
High-throughput Identification of Novel Heat Tolerance Genes via Genome-wide Pooled Mutant Screens in the Model Green Alga Chlamydomonas reinhardtii

Different high temperatures adversely affect crop and algal yields with various responses in photosynthetic cells. The list of genes required for thermotolerance remains elusive. Additionally, it is unclear how carbon source availability affects heat responses in plants and algae. We utilized the insertional, indexed, genome-saturating mutant library of the unicellular, eukaryotic green alga Chlamydomonas reinhardtii to perform genome-wide, quantitative, pooled screens under moderate (35°C) or acute (40°C) high temperatures with or without organic carbon sources. We identified heat-sensitive mutants based on quantitative growth rates and identified putative heat tolerance genes (HTGs). By triangulating HTGs with heat-induced transcripts or proteins in wildtype cultures and MapMan functional annotations, we present a high/medium-confidence list of 933 Chlamydomonas genes with putative roles in heat tolerance. Triangulated HTGs include those with known thermotolerance roles and novel genes with little or no functional annotation. About 50% of these high-confidence HTGs in Chlamydomonas have orthologs in green lineage organisms, including crop species. Arabidopsis thaliana mutants deficient in the ortholog of a high-confidence Chlamydomonas HTG were also heat sensitive. This work expands our knowledge of heat responses in photosynthetic cells and provides engineering targets to improve thermotolerance in algae and crops.
AMASES, Trento, 1-4 Settembre 2008

Stochastic programming approaches are increasingly adopted to address different types of financial planning problems: from the classical asset-liability management problem [14] and large enterprise-wide risk management problems [13], to financial engineering applications [3] and complex portfolio management problems [2]. We discuss in this article a credit portfolio problem characterised by a complex underlying model of uncertainty [10, 1]. Increasing computational power, the ability to reach a very accurate, still manageable, representation of the decision problem and the growing evidence that for practical purposes a possibly large yet finite number of scenarios is sufficient to identify an optimal strategy are all pushing in favour of stochastic programming formulations. Financial applications, to a large extent independently from the specific financial problem, rely on a common information structure linking the optimal problem formulation to an accurate description of risk factors dynamics, expected to be consistent with general theoretical assumptions and typically specified in analytic form [7]. The solution of the stochastic optimization problem will strongly depend on the adopted description of the underlying financial risk. Modern risk management approaches integrate in an accurate mathematical and statistical framework the evaluation of the portfolio risk exposure and the derivation of the optimal hedging strategy [12]. It is natural to regard the stochastic programming approach as an efficient combination of the two steps, in which a peculiar role is played by the required scenario-based problem discretization. This view will result in a relevant sequence of methodological steps supporting an efficient decision process: i. the mathematical representation of the financial planning problem and the specification of the decision space (the universe of possible investment instruments in a dynamic portfolio problem for instance); ii. the definition of the risk sources of the portfolio (the risk factors) and the introduction of an associated stochastic model (the risk model); iii. the derivation of a possibly extended set of pricing functions mapping the risk factors dynamics into the evolution of financial prices for the given security universe; iv. the derivation, through an appropriate statistical procedure, of portfolio risk exposure; v. the introduction of an approximation scheme leading to the specification of a scenario tree over the problem horizon; vi. the generation of a stochastic programming instance of the problem and its solution.
Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories as well as complex trait architectures remain hidden due to the lack of Big Data. To fill this gap, the Mexican Biobank project genotyped 1.8 million markers in 6,057 individuals from 32 states and 898 sampling localities across Mexico with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Through a suite of state-of-the-art methods for ancestry deconvolution and inference of identity-by-descent (IBD) segments, we inferred detailed ancestral histories for the last 200 generations in different Mesoamerican regions, unraveling native and colonial/post-colonial demographic dynamics. We observed large variations in runs of homozygosity (ROH) among genomic regions with different ancestral origins reflecting their demographic histories, which also affect the distribution of rare deleterious variants across Mexico. We analyzed a range of biomedical complex traits and identified significant genetic and environmental factors explaining their variation, such as ROH found to be significant predictors for trait variation in BMI and triglycerides.
Low-Cost Platform for Multianimal Chronic Local Field Potential Video Monitoring with Graphical User Interface (GUI) for Seizure Detection and Behavioral Scoring

Abstract Experiments employing chronic monitoring of neurophysiological signals and video are commonly used in studies of epilepsy to characterize behavioral correlates of seizures. Our objective was to design a low-cost platform that enables chronic monitoring of several animals simultaneously, synchronizes bilateral local field potential (LFP) and video streams in real time, and parses recorded data into manageable file sizes. We present a hardware solution leveraging Intan and Open Ephys acquisition systems and a software solution implemented in Bonsai. The platform was tested in 48-h continuous recordings simultaneously from multiple mice (male and female) with chronic epilepsy. To enable seizure detection and scoring, we developed a graphical user interface (GUI) that reads the data produced by our workflow and allows a user with no coding expertise to analyze events. Our Bonsai workflow was designed to maximize flexibility for a wide variety of experimental applications, and our use of the Open Ephys acquisition board would allow for scaling recordings up to 128 channels per animal.
Localized heterochrony integrates overgrowth potential of oncogenic clones

Somatic oncogenic mutations are frequent and can occur early during development. The result is the formation of a patchwork of mutant clones. Such mosaicism has been implicated in a broad range of developmental anomalies however their etiology is poorly understood. Patients carrying a common somatic oncogenic mutation in either PIK3CA or AKT1, can present with disproportionally large digits or limbs. How mutant clones, carrying an oncogenic mutation that often drives unchecked proliferation leads to controlled and coordinated overgrowth is unknown. We use the zebrafish to explore growth dynamics of oncogenic clones during development. In subset of clones, we observe a local increase in proportion of the fin skeleton closely resembling patient overgrowth phenotypes. We unravel the cellular and developmental mechanisms of these overgrowths and pinpoint the cell type and timing of clonal expansion. Coordinated overgrowth is associated with rapid clone expansion during early pre-chondrogenic phase of bone development inducing a heterochronic shift that drives the change in bone size. Our study details how development integrates and translates growth potential of oncogenic clones, thereby shaping the phenotypic consequences of somatic mutations.
Whole exome sequencing study identifies candidate loss of function variants and locus heterogeneity in familial cholesteatoma

Cholesteatoma is a rare progressive disease of the middle ear. Most cases are sporadic, but some patients report a positive family history. Identifying functionally important gene variants associated with this disease has the potential to uncover the molecular basis of cholesteatoma pathology with implications for disease prevention, surveillance, or management. We performed an observational WES study of 21 individuals treated for cholesteatoma who were recruited from ten multiply affected families. These family studies were complemented with gene-level mutational burden analysis. We also applied functional enrichment analyses to identify shared properties and pathways for candidate genes and their products. Filtered data collected from pairs and trios of participants within the ten families revealed 398 rare, loss of function (LOF) variants co-segregating with cholesteatoma in 389 genes. We identified six genes DENND2C, DNAH7, NBEAL1, NEB, PRRC2C, and SHC2, for which we found LOF variants in two or more families. The parallel gene-level of mutation-burden identified a significant mutation burden for the genes in the DNAH gene family, which encode products involved in ciliary structure. Functional enrichment analyses identified common pathways for the candidate genes which included GTPase regulator activity, calcium ion binding, and degradation of the extracellular matrix. The number of candidate genes identified and the locus heterogeneity that we describe within and between multiply affected families suggest that the genetic architecture for familial cholesteatoma is complex.
Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers

Background Controllability is a measure of the brain’s ability to orchestrate neural activity which can be quantified in terms of properties of the brain’s network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging. Methods In a sample of 814 healthy individuals (aged 33.9±12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability). Results and conclusion In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers.
Canalization of genome-wide transcriptional activity in Arabidopsis thaliana accessions by MET1-dependent CG methylation

Background Despite its conserved role on gene expression and transposable element (TE) silencing, genome-wide CG methylation differs substantially between wild Arabidopsis thaliana accessions. Results To test our hypothesis that global reduction of CG methylation would reduce epigenomic, transcriptomic, and phenotypic diversity in A. thaliana accessions, we knock out MET1 , which is required for CG methylation, in 18 early-flowering accessions. Homozygous met1 mutants in all accessions suffer from common developmental defects such as dwarfism and delayed flowering, in addition to accession-specific abnormalities in rosette leaf architecture, silique morphology, and fertility. Integrated analysis of genome-wide methylation, chromatin accessibility, and transcriptomes confirms that MET1 inactivation greatly reduces CG methylation and alters chromatin accessibility at thousands of loci. While the effects on TE activation are similarly drastic in all accessions, the quantitative effects on non-TE genes vary greatly. The global expression profiles of accessions become considerably more divergent from each other after genome-wide removal of CG methylation, although a few genes with diverse expression profiles across wild-type accessions tend to become more similar in mutants. Most differentially expressed genes do not exhibit altered chromatin accessibility or CG methylation in cis , suggesting that absence of MET1 can have profound indirect effects on gene expression and that these effects vary substantially between accessions. Conclusions Systematic analysis of MET1 requirement in different A. thaliana accessions reveals a dual role for CG methylation: for many genes, CG methylation appears to canalize expression levels, with methylation masking regulatory divergence. However, for a smaller subset of genes, CG methylation increases expression diversity beyond genetically encoded differences.
mergem: merging and comparing genome-scale metabolic models using universal identifiers

Numerous methods exist to produce and refine genome-scale metabolic models. However, due to the use of incompatible identifier systems for metabolites and reactions, computing and visualizing the metabolic differences and similarities of such models is a current challenge. Furthermore, there is a lack of automated tools that can combine the strengths of multiple reconstruction pipelines into a curated single comprehensive model by merging different drafts, which possibly use incompatible namespaces. Here we present mergem, a novel method to compare and merge two or more metabolic models. Using a universal metabolic identifier mapping system constructed from multiple metabolic databases, mergem robustly can compare models from different pipelines and merge their common elements. mergem is implemented as a command line tool, a Python package, and on the web-application Fluxer, which allows simulating and visually comparing multiple models with different interactive flux graphs. The ability to merge and compare diverse genome scale metabolic models can facilitate the curation of comprehensive reconstructions and the discovery of unique and common metabolic features among different organisms.
Dual-Microring Resonator Based 8×8 Silicon Photonic Switch

First demonstration of a dual-microring 8×8 silicon-photonic switch in a compact 4 mm2 footprint shows 4.4–8.4 dB end-to-end on-chip loss, −16.75 dB first-order switching crosstalk, and 40 GHz switching bandwidth capable of high-data-rate datacenter transmissions.
MukBEF-dependent chromosomal organization in widened Escherichia coli

The bacterial chromosome is spatially organized through protein-mediated compaction, supercoiling, and cell-boundary confinement. Structural Maintenance of Chromosomes (SMC) complexes are a major class of chromosome-organizing proteins present throughout all domains of life. Here, we study the role of the Escherichia coli SMC complex MukBEF in chromosome architecture and segregation. Using quantitative live-cell imaging of shape-manipulated cells, we show that MukBEF is crucial to preserve the toroidal topology of the E. coli chromosome and that it is non-uniformly distributed along the chromosome: it prefers locations towards the origin and away from the terminus of replication, and it is unevenly distributed over the origin of replication along the two chromosome arms. Using an ATP hydrolysis-deficient MukB mutant, we find that MukBEF translocation along the chromosome is ATP-dependent, in contrast to its loading onto DNA. MukBEF and MatP are furthermore found to be essential for sister chromosome decatenation. We propose a model that explains how MukBEF, MatP, and their interacting partners organize the chromosome and contribute to sister segregation and recombination. The combination of bacterial cell-shape modification and quantitative fluorescence microscopy paves way to investigating chromosome-organization factors in vivo.
Restoring morphology of light sheet microscopy data based on magnetic resonance histology

The combination of cellular-resolution whole brain light sheet microscopy (LSM) images with an annotated atlas enables quantitation of cellular features in specific brain regions. However, most existing methods register LSM data with existing canonical atlases, e.g. The Allen Brain Atlas (ABA), which limits the precision of measuring regional volumes and eliminates the individual difference in brain partitions for different strains, ages, and environmental exposures. Thus, these approaches obscure valuable anatomical information. Here, we present a method to combine LSM data with magnetic resonance histology (MRH) of the same brain restoring the morphology of the LSM images to the in-skull morphology. Our pipeline which maps 3D LSM data (terabyte level per dataset) to magnetic resonance histology of the same mouse brain provides accurate registration with low displacement error in 10 hours with limited manual input. Optimization and validation, from initialization of the data, designing the quantitative loss function, optimizing the 20+ image processing variables on multiple resolution scales, and finalizing the application on full resolution data has been integrated through a structured workflow. Excellent agreement has been seen between registered data and reference data both locally and globally. This workflow has been applied to a collection of datasets with varied MRH and LSM contrast providing a routine method for streamlined registration of LSM images to MRH.
Shared and host-specific transcriptomic response of Pseudomonas donghuensis P482 to the exudates of tomato (Dicot) and maize (Monocot) shed light on the host-adaptive traits in the promiscuous root colonizing bacteria

Plants of different genotypes and physiological states recruit different populations of root microbiota. The selection is driven by the immune response of the plant and the composition of root exudates. Some bacteria, including Pseudomonas spp. , are promiscuous root colonizers. It is yet unclear what particular changes in lifestyle enable them to thrive in the company of different plant hosts. In this study, we used RNAseq to identify genes of the differential (host-specific) and shared (host-independent) transcriptomic responses of a biocontrol strain Pseudomonas donghuensis P482 to the root exudates of two phylogenetically distinct plant species, tomato (Dicot) and maize (Monocot), both of which can be colonized by the bacterium. The host-independent response of P482 to exudates involved upregulated expression of arsenic resistance genes and bacterioferritin synthesis. Contrary, we observed downregulation of pathways related to sulfur assimilation, sensing of ferric citrate and/or other iron carriers, the acquisition of heme, the assembly of the type VI secretion system, and amino acid transport. Pathways upregulated in P482 specifically by tomato exudates included nitric oxide detoxification, repair of iron-sulfur clusters, respiration through the cyanide-insensitive cytochrome bd, and catabolism of amino acids and/or fatty acids. The maize-specific response included upregulation of genes associated with motility, the activity of MexE and two other RND efflux pumps, and copper tolerance. To provide more context to the study, we determined the chemical composition of exudates by GC-MS, NMR, and LC-SRM. Our results bring new insight into the host-driven metabolic adaptations of promiscuous root colonizing bacteria. Significance statement Understanding factors determining the composition and the activity of plant-associated microbiota is crucial to harnessing their potential to benefit plant health. Traits that enable microorganisms to colonize plants have long been the subject of study, with many important factors identified for particular host-microbe systems. However, studies involving more than a single plant host are rare. This results in many unanswered questions on the host-specific and universal aspects of metabolism that enable more promiscuous root colonizers to interact with different plant hosts. The presented study begins to fill this knowledge gap by providing data on the metabolic pathways involved in the differential and shared response of Pseudomonas donghuensis strain P482 to the exudates of phylogenetically distant plant species: tomato and maize.