Miracle-dz/UniFAR-FTUs huggingface dataset:
Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates

The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. ABSTRACT The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploid (genomic DNA, 1N-2N), diploid (2N), or hyperdiploid (>2N) form under in vivo or in vitro conditions. Stable diploid cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain existed only in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, United States, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of respects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid forms under both in vitro and in vivo conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. IMPORTANCE The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological respects, including morphology, antifungal susceptibility, virulence, and global gene expression profile. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a strategy for rapid adaptation to environmental changes and could function as an alternative to sexual reproduction.
The Planar Rook Algebra and Pascal's Triangle

Even themultiplicative structure of the binomial coecients arises from the representa-tion theory of the planar rook algebras, as we discover upon decomposition oftensor product representations.The planar rook algebra is an example of a \diagram algebra," which forour purposes is a nite-dimensional algebra with a basis given by a collectionof diagrams and multiplication described combinatorially by diagram concate-nation. When the basis diagrams can be drawn without edge crossings, we geta planar algebra. There is a growing theory of planar algebras initiated by V.Jones (see [Jo]) that uses a more re ned de nition of planarity than what wegive here.The main goal of this paper is to work out the combinatorial representationtheory of the planar rook algebra CP
Universal features of rigidity transitions in vertex models for biological tissues

For confluent or nearly confluent tissues, simulations and analyses of simple vertex models – where the cell shape is defined as a network of edges and vertices – have proven useful for making predictions about mechanics and collective behavior, including rigidity transitions. Scientists have developed many versions of vertex models with different assumptions. Here we investigate a set of vertex models which differ in the functional form that describes how energy depends on the vertex positions. We analyze whether such models have a well-defined shear modulus in the limit of zero applied strain rate, and if so how that modulus depends on model parameters. We identify a class of models with a well-defined shear modulus, and demonstrate that these models do exhibit a cross-over from a soft or floppy regime to a stiff regime as a function of a single control parameter, similar to the standard vertex model. Moreover, and perhaps more surprisingly, the rigidity crossover is associated with a crossover in the observed cell shape index (the ratio of the cell perimeter to the square root of the cell area), just as in the standard vertex model, even though the control parameters are different. This suggests that there may be a broad class of vertex models with these universal features, and helps to explain why vertex models are able to robustly predict these features in experiments.
Developmental evidence for parental conflict in driving Mimulus species barriers

The endosperm, a tissue that nourishes the embryo in the seeds of flowering plants, is often disrupted in inviable hybrid seeds between species presumed to have divergent histories of parental conflict. Despite the potential importance of parental conflict in plant speciation, we lack direct evidence of its action in driving species barriers. Here, we performed reciprocal crosses between pairs of three monkeyflower species (Mimulus caespitosa, M. tilingii, and M. guttatus). The severity of hybrid seed inviability varies among these crosses, which we determined was due to species divergence in effective ploidy. By performing a time series of seed development, we assessed whether regions within the endosperm were potential targets of parental conflict. We found that the chalazal haustorium, a tissue within the endosperm that occurs at the maternal-filial boundary, develops abnormally in hybrid seeds when the paternal parent has the greater effective ploidy. Within these Mimulus species, parental conflict might target the chalazal haustorium to control sucrose movement from the maternal parent into the endosperm. Consequently, conflict may be exposed in crosses between species. Our study suggests that parental conflict in the endosperm may function as a driver of speciation by targeting regions and developmental stages critical for resource allocation.
Force propagation between epithelial cells depends on active coupling and mechano-structural polarization

Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern (“cell doublet”). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells shows an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depends on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue is key to maintain signal strength and leads to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.
Condensin pinches a short negatively supercoiled DNA loop during each round of ATP usage

Condensin extrudes DNA loops using an ATP-dependent mechanism that remains to be elucidated. Here, we show how condensin activity alters the topology of the interacting DNA. High condensin concentrations restrain DNA positive supercoils. However, in experimental conditions that sustain DNA loop extrusion, condensin restrains negative supercoils. Namely, upon ATP-mediated loading onto DNA, each condensin constrains a DNA linking number difference (ΔLk) of -0.4. This ΔLk increases to -0.8 during ATP binding and resets to -0.4 upon ATP hydrolysis. These ΔLk values reflect the transient formation of a short left-handed loop of DNA, which is not the extruding loop. We conclude that, upon condensin ATPase-head engagement, a segment of DNA is pinched to form a short negatively supercoiled loop, which can be subsequently merged with the extruding loop. Such “pinch and merge” mechanism implies that the DNA is transferred between two dynamic DNA-binding sites while anchored at a third site.
Action planning modulates the representation of object features in human fronto‐parietal and occipital cortex

The role of the visual cortex has been extensively studied to determine its role in object recognition but to a lesser degree to determine how action planning influences the representation of objects’ features. We used functional MRI and pattern classification methods to determine if during action planning, object features (orientation and location) could be decoded in an action-dependent way. Sixteen human participants used their right dominant hand to perform movements (Align or Open reach) towards one of two 3D-real oriented objects that were simultaneously presented and placed on either side of a fixation cross. While both movements required aiming toward target location, Align but not Open reach movements required participants to precisely adjust hand orientation. Therefore, we hypothesized that if the representation of object features is modulated by the upcoming action, pre-movement activity pattern would allow more accurate dissociation between object features in Align than Open reach tasks. We found such dissociation in the anterior and posterior parietal cortex, as well as in the dorsal premotor cortex, suggesting that visuomotor processing is modulated by the upcoming task. The early visual cortex showed significant decoding accuracy for the dissociation between object features in the Align but not Open reach task. However, there was no significant difference between the decoding accuracy in the two tasks. These results demonstrate that movement-specific preparatory signals modulate object representation in the frontal and parietal cortex, and to a lesser extent in the early visual cortex, likely through feedback functional connections.
Transcriptional activity is shaped by the chromatin landscapes in Arabidopsis

How histone variants and histone modifications shape nucleosome-mediated transcriptional repression, and how transcriptional activity shapes the enrichment of histone modifications and variants remain unclear. To clarify these relationships, we examined chromatin organization in the Arabidopsis thaliana genome, identifying a limited number of chromatin landscapes that distinguish transposon families and distinct groups of genes based on their transcriptional regulation. Unexpectedly, H2A variants are strong determinants of the landscape architecture. Combinations of H2A.W and four histone modifications define six domains that are occupied by specific transposon families and organized concentrically around the centromere. Moreover, H2A.Z defines transcriptional gene repression in specific domains. Expressed genes occupy four chromatin landscapes with specific RNA Polymerase II profiles. Although the composition of each chromatin landscape is invariant, they cover genes with a wide range of expression levels. Therefore, chromatin landscapes control the range of transcriptional activity, but transcriptional activity has little effect on chromatin composition. One Sentence Summary Histone variants and histone modifications build a limited number of distinct chromatin landscapes that instruct the transcriptional regulation of genes and transposons in Arabidopsis.
Efficient decision-makers evaluate relative reward per effort

Understanding how humans and animals can make effective decisions would have a profound impact on economics, psychology, ecology, and related fields. Neoclassical economics provides a formalism for optimal decisions, but the apparatus requires a large number of evaluations of the decision options as well as representations and computations that are biologically implausible. This article shows that natural constraints distill the economic optimization into an efficient and biologically plausible decision strategy. In this strategy, decision-makers evaluate the relative reward across their options and allocate their effort proportionally, thus equalizing the reward per effort across their options. Using a combination of analytical and simulation approaches, the article shows that this strategy is efficient, providing optimal or near-optimal gain following a single evaluation of decision options. The strategy is also rational; satisficing and indifferent decision-makers are found to perform relatively poorly. Moreover, the relativistic value functions underlying this efficient strategy provide an account of time discounting, effort discounting, and resource discounting in general.
Assortative mixing in micro-architecturally annotated brain connectomes

The wiring of the brain connects micro-architecturally diverse neuronal populations. The conventional graph model encodes macroscale brain connectivity as a network of nodes and edges, but abstracts away the rich biological detail of each regional node. Regions are different in terms of their microscale attributes, many of which are readily available through modern technological advances and data-sharing initiatives. How is macroscale connectivity related to nodal attributes? Here we investigate the systematic arrangement of white-matter connectivity with respect to multiple biological annotations. Namely, we formally study assortative mixing in annotated connectomes by quantifying the tendency for regions to be connected with each other based on the similarity of their micro-architectural attributes. We perform all experiments using four cortico-cortical connectome datasets from three different species (human, macaque and mouse), and consider a range of molecular, cellular and laminar annotations, including gene expression, neurotransmitter receptors, neuron density, laminar thickness and intracortical myelin. Importantly, we disentangle the relationship between neural wiring, regional heterogeneity and spatial embedding using spatial autocorrelation-preserving null models. We show that mixing between micro-architecturally diverse neuronal populations is supported by long-distance connections. Using meta-analytic decoding, we find that the arrangement of connectivity patterns with respect to biological annotations shape patterns of regional functional specialization. Specifically, regions that connect to biologically similar regions are associated with executive function; conversely, regions that connect with biologically dissimilar regions are associated with memory function. By bridging scales of cortical organization, from microscale attributes to macroscale connectivity, this work lays the foundation for next-generation annotated connectomics.
Genome-Wide Large-Scale Multi-Trait Analysis Characterizes Global Patterns of Pleiotropy and Unique Trait-Specific Variants

Genome-wide association studies (GWAS) have found widespread evidence of pleiotropy, but characterization of global patterns of pleiotropy remain highly incomplete due to insufficient power of current approaches. We develop fastASSET, an extension of the method ASSET, to allow computationally efficient detection of variant-level pleiotropic association across a large number of traits. We analyze GWAS summary statistics of 116 complex traits of diverse types collected from the NIH GRASP repository and a number of other large GWAS consortia. We identify a total of 2,293 independent loci at the genome-wide significance level and found that the lead variants in nearly all of these loci (∼99%) to be associated with to two or more (median = 6) traits. Further, the estimated degree of pleiotropy for the detected variants strongly predicted their degree of pleiotropy across a much larger number of traits (K=4,114) in the UK Biobank Study. Follow-up analyses of 21 unique trait-specific variants suggest that they are often linked to the expression in trait-related tissues for a small number of genes, some of which are well known to be involved in relevant biological processes. Our findings provide deeper insight into the nature of complex trait pleiotropy and leads to, for the first time, identification of highly unique trait-specific susceptibility variants.
Diffusion MR imaging in the cortical spinal tract of idiopathic scoliosis

Many studies have shown that idiopathic scoliosis is not only a deformity of the spine. It is often associated with neurological impairment without any macroscopic abnormality in the brain. In our previous diffusion MRI study, we demonstrated that children with right-thoracic idiopathic scoliosis had abnormal white matter microstructure of the crossing premotor fibres in the corpus callosum. Based on this, we hypothesized that similar microstructural changes could affect the main descending white matter tracts, the corticospinal tract. We compared the fractional anisotropy values along the corticospinal tracts in ten patients with right-thoracic and ten patients with left-thoracic idiopathic scoliosis to 49 healthy controls. We found abnormal left-right asymmetry of the fractional anisotropy values in scoliosis patients at the level of the pons. Whereas at upper levels the values were similar across all groups. Our results suggest that abnormal sensorimotor integration at the level of the pons is associated with the development of idiopathic scoliosis.
The Aedes aegypti peritrophic matrix controls arbovirus vector competence through HPx1, a heme–induced peroxidase

Aedes aegypti mosquitoes are the main vectors of arboviruses. The peritrophic matrix (PM) is an extracellular layer that surrounds the blood bolus and acts as an immune barrier that prevents direct contact of bacteria with midgut epithelial cells during blood digestion. Here, we describe a heme-dependent peroxidase, hereafter referred to as heme peroxidase 1 (HPx1). HPx1 promotes PM assembly and antioxidant ability, modulating vector competence. Mechanistically, the heme presence in a blood meal induces HPx1 transcriptional activation mediated by the E75 transcription factor. HPx1 knockdown increases midgut reactive oxygen species (ROS) production by the DUOX NADPH oxidase. Elevated ROS levels reduce microbiota growth while enhancing epithelial mitosis, a response to tissue damage. However, simultaneous HPx1 and DUOX silencing was not able to rescue bacterial population growth, as explained by increased expression of antimicrobial peptides (AMPs), which occurred only after double knockdown. This result revealed hierarchical activation of ROS and AMPs to control microbiota. HPx1 knockdown produced a 100-fold decrease in Zika and Dengue 2 midgut infection, demonstrating the essential role of the mosquito PM in the modulation of arbovirus vector competence. Our data show that the PM connects blood digestion to midgut immunological sensing of the microbiota and viral infections.
Best organic farming expansion scenarios for pest control: a modeling approach

Organic Farming (OF) has been expanding recently in response to growing consumer demand and as a response to environmental concerns. The area under OF is expected to further increase in the future. The effect of OF expansion on pest densities in organic and conventional crops remains difficult to predict because OF expansion impacts Conservation Biological Control (CBC), which depends on the surrounding landscape (i.e. both the crop mosaic and semi-natural habitats). In order to understand and forecast how pests and their biological control may vary during OF expansion, we modeled the effect of spatial changes in farming practices on population dynamics of a pest and its natural enemy. We investigated the impact on pest density and on predator to pest ratio of three contrasted scenarios aiming at 50% organic fields through the progressive conversion of conventional fields. Scenarios were 1) conversion of Isolated conventional fields first (IP), 2) conversion of conventional fields within Groups of conventional fields first (GP), and 3) Random conversion of conventional field (RD). We coupled a neutral spatially explicit landscape model to a predator-prey model to simulate pest dynamics in interaction with natural enemy predators. The three OF expansion scenarios were applied to nine landscape contexts differing in their proportion and fragmentation of semi-natural habitat. We further investigated if the ranking of scenarios was robust to pest control methods in OF fields and pest and predator dispersal abilities. We found that organic farming expansion affected more predator densities than pest densities for most combinations of landscape contexts and OF expansion scenarios. The impact of OF expansion on final pest and predator densities was also stronger in organic than conventional fields and in landscapes with large proportions of highly fragmented semi-natural habitats. Based on pest densities and the predator to pest ratio, our results suggest that a progressive organic conversion with a focus on isolated conventional fields (scenario IP) could help promote CBC. Careful landscape planning of OF expansion appeared most necessary when pest management was substantially less efficient in organic than in conventional crops, and in landscapes with low proportion of semi-natural habitats.
Equidistribution of Fekete points on complex manifolds

We prove the several variable version of a classical equidistribution theorem for Fekete points of a compact subset of the complex plane, which settles a well-known conjecture in pluri-potential theory. The result is obtained as a special case of a general equidistribution theorem for Fekete points in the setting of a given holomorphic line bundle over a compact complex manifold. The proof builds on our recent work “Capacities and weighted volumes for line bundles”.
Managing International Development Projects—Lessons Learned

This article will discuss lessons learned in managing the implementation of international development projects. First we will define the type of projects we are talking about. Then we will discuss the types of problems commonly encountered on international projects and finally we will compare that list of problems with a similar list from the United States. The basic conclusion is that the problems are almost exactly the same and that the solution is to learn the basics lessons of good project management and to apply them in the specific context of each specific project.