bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of MYB34 transcription factor that controls feedback loop in indole glucosinolate biosynthesis supports backward evolution of this pathway within Camelineae tribe
Authors: Czerniawski Paweł , Piślewska-Bednarek Mariola , Piasecka Anna , Kułak Karolina , Bednarek Paweł 
Published: July 2022

SummaryGlucosinolates are specialized defensive metabolites characteristic for the Brassicales order. Among them aliphatic and indolic glucosinolates (IGs) are usually highly abundant in the species from Brassicaceae family. The exception from this trend is constituted by species representing a subclade of Camelineae tribe, including Capsella and Camelina genera, which have reduced capacity to produce and metabolize IGs. Our study addresses contribution of specific glucosinolate-related MYB transcription factors to this unprecedented backward evolution of IG biosynthesis. To this end we performed phylogenomic and functional studies of respective MYB proteins. Obtained results revealed weakened conservation of glucosinolate-related MYB transcription factors, including loss of functional MYB34 protein, in the investigated species. We showed that introduction of functional MYB34 from Arabidopsis thaliana partially restores IG biosynthesis in Capsella rubella indicating that loss of this transcription factor contributes to the backward evolution of this metabolic pathway. Finally, we performed analysis of the impact of particular myb mutations on the feedback loop in IG biosynthesis, which drives auxin overproduction, metabolic dysregulation and strong growth retardation caused by mutations in IG biosynthetic genes. This uncovered unique function of MYB34 among IG-related MYBs in this feedback regulation and consequently in IG conservation in Brassicaceae plants.
Comparing the speed of action initiation and action inhibition
Authors: Du Yue , Forrence Alexander D. , Metcalf Delaney M. , Haith Adrian M. 
Published: July 2022

AbstractMuch work has examined the process of canceling or inhibiting an impending action. However, the converse process of initiating a movement has, comparatively, been much less studied. Action initiation and action inhibition are generally considered to be independent and qualitatively distinct processes, while the exact relationship between these processes remains unclear. One respect in which action initiation and action inhibition are often thought to differ is in their speed; action inhibition is typically considered to be faster than action initiation, which allows for impending actions to be inhibited before they are initiated. This apparent contrast is, however, largely observed in tasks in which there is much greater urgency to inhibit an action that there is to initiate an action. This asymmetry in the urgency between action initiation and action inhibition, as well as other asymmetries in how action initiation and inhibition are cued, make it impossible to compare their relative time courses. Here, we demonstrate that, when action initiation and action inhibition are measured under conditions that are matched as closely as possible, their speed is the same. In light of this, we suggest that action initiation and action inhibition may not necessarily be qualitatively distinct processes, but may instead reflect two opposing states of a single process supporting a decision about whether to act or not. This perspective carries significant implications for computational models and presumed neural mechanisms of action control.
The impact of ants and vertebrate predators on arthropods and plants: a meta-analysis
Authors: Sam Katerina , Tahadlova Marketa , Freiberga Inga , Mrazova Anna , Toszogyova Anna , Sreekar Rachakonda 
Published: July 2022

AbstractThe trophic interactions between plants, insect herbivores and their predators are complex and prone to trophic cascades. Theory predicts that predators increase plant biomass by feeding on herbivores. However, it remains unclear whether different types of predators regulate herbivores to the same degree, and how intraguild predation impacts these trophic interactions. Specifically, we lack a more comprehensive look at the effects of various groups of predators on a global scale. Here we report a meta-analysis of 486 experiments gathered from 157 publications reporting the effect of insectivorous vertebrates (birds and bats) and ants on abundances of predatory (spiders, ants, others) and herbivorous (chewers and others) arthropods; on arthropod richness and plant damage. Generally, the absence of vertebrate predators led to the increase of predatory arthropods by 18%, herbivorous arthropods by 75%, and plant damage by 47%. In contrast, after the removal of ants, the increase in the abundances of other predatory arthropods did not compensate for missing ants, herbivore arthropods increased their abundances by 53%, and plant damage increased by 146%. The effects of ant exclosures were stronger in communities at lower elevations and latitudes, while we did not detect any clear geographical patterns in the effect of vertebrate exclosures. Neither precipitation nor NDVI had a significant impact on most of the measured effects, and the effect of exclosures was robust for both plant growth forms and different habitat types. We found vertebrate insectivores to be the more dominant predators of arthropods, but we detected that the strength of their trophic cascades was weakened by intraguild predation. On the other hand, we found that although ants were relatively less dominant as predators, and their influence was detectable only in the most productive sites, the effect of trophic cascades on plants they caused was stronger than that of vertebrate insectivores.
OSCAR: Optimal subset cardinality regression using the L0-pseudonorm with applications to prognostic modelling of prostate cancer
Authors: Halkola Anni S. , Joki Kaisa , Mirtti Tuomas , Mäkelä Marko M. , Aittokallio Tero , Laajala Teemu D. 
Published: July 2022

AbstractIn many real-world applications, such as those based on patient electronic health records, prognostic prediction of patient survival is based on heterogeneous sets of clinical laboratory measurements. To address the trade-off between the predictive accuracy of a prognostic model and the costs related to its clinical implementation, we propose an optimized L0-pseudonorm approach to learn sparse solutions in multivariable regression. The model sparsity is maintained by restricting the number of nonzero coefficients in the model with a cardinality constraint, which makes the optimization problem NP-hard. In addition, we generalize the cardinality constraint for grouped feature selection, hence making it possible to identify key sets of predictors that may be measured together in a kit in clinical practice. We demonstrate the operation of our cardinality constraint-based feature subset selection method, named OSCAR, in the context of prognostic modelling of prostate cancer, where it enabled one to determine the key explanatory predictors at different levels of model sparsity, and to explore how the model sparsity affects the model accuracy and implementation cost.Author summaryFeature selection has become a crucial part in building biomedical models, due to the abundance of available predictors in many applications, yet there remains an uncertainty of their importance and generalization ability. Regularized regression methods have become popular approaches to tackle this challenge by balancing the model goodness-of-fit against the increasing complexity of the model in terms of coefficients that deviate from zero. Regularization norms are pivotal in formulating the model complexity, and currently L1 (LASSO), L2 (Ridge Regression) and their hybrid (Elastic Net) norms dominate the field. In this paper, we present a novel methodology using the L0-pseudonorm, also known as the best subset selection, which has largely gone overlooked due to its challenging discrete nature. Our methodology makes use of a continuous transformation of the discrete optimization problem, and provides effective solvers implemented in a user friendly R software package. We exemplify the use of oscar-package in the context of prostate cancer prognostic prediction using both real-world hospital registry and clinical cohort data. By benchmarking the methodology against related regularization methods, we illustrate the advantages of the L0-pseudonorm for better clinical applicability and selection of grouped features.
Epigenetic feedback on noisy expression boosts evolvability
Authors: Daalman Werner Karl-Gustav , Laan Liedewij 
Published: July 2022

AbstractAdapting organisms often face fitness valleys, i.e. barriers imposed by ubiquitous genetic interactions, while optimizing functions. Elucidating mechanisms that facilitate fitness valley traversals is integral to understanding evolution. Therefore, we investigated how protein expression noise, mechanistically decomposed into instant variation and epigenetic inheritance of optimal protein dosage (‘transgenerational feedback’), shapes the fitness landscape. For this purpose, we combined a minimal model for expression noise with diverse data of Saccharomyces cerevisiae from literature on e.g. expression and fitness to representatively simulate mutational fitness effects. For our proxy of point mutations, which are very often near-neutral, instant dosage variation by expression noise typically incurs a 8.7% fitness loss (17% in essential genes) for non-neutral point mutations. However, dosage feedback mitigates most of this deleterious effect, and additionally extends the time until extinction when essential gene products are underexpressed. Taken together, we consider dosage feedback as a relevant example of Waddington’s canalization: a mechanism which temporarily drives phenotypes towards the optimum upon a genetic mismatch, thereby promoting fitness valley traversal and evolvability.Author summaryGene products frequently interact to generate unexpected phenotypes. This universal phenomenon is known as epistasis, and complicates step-wise evolution to an optimum. Attempts to understand and/or predict how the optimum is found are further compromised by the countless combinations of mutations that are considered by nature, and necessitate the formulation of general rules on how the obstacles that epistasis presents are bridged. To make such a rule as insightful as possible, we reduced cell division to a generation-based model focusing on one protein at a time for reproductive success. Importantly, protein production between divisions is stochastic and we show how the resulting expression noise affects epistasis. After validating the model on experimental fitness landscapes, we combine high-throughput data of budding yeast from multiple sources to make our model predictions on mutational effects on fitness as representative as possible. We find different effects per mutation type: gene duplications have little effect, as genes in our simulated pool are rarely toxic, loss-of-function mutations decrease mutational gains as adaptation progresses, and point mutations permit expression noise to unlock its roles in adaptation. For non-neutral point mutations, noise imposes a sizeable fitness penalty or even induces extinction, which is alleviated by an epigenetic, transgenerational feedback on protein dosage which is never deleterious. Particularly for essential genes, we predict that this effect reduces the obstacles of epistasis and hence significantly increases evolvability, adding to the general rules of evolution.
A scaling law relating the rate of destruction of a solid tumor and the fractal dimension of its boundary
Authors: López Álvaro G. , Sanjuán Lorena R. 
Published: July 2022

AbstractWe investigate the scaling law relating the size of the boundary of a solid tumor and the rate at which it is lysed by a cell population of non-infiltrating cytotoxic lymphocytes. We do it in the context of enzyme kinetics through geometrical, analytical and numerical arguments. Following the Koch island fractal model, a scale-dependent function that describes the constant rate of the decay process and the fractal dimension is obtained in the first place. Then,in silicoexperiments are accomplished by means of a stochastic hybrid cellular automaton model. This model is used to grow several tumors with varying morphology and to test the power decay law when the cell-mediated immune response is effective, confirming its validity.
Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation
Authors: Hu Jing , Zhou Bingna , Lin Xiaoyun , Zhang Qian , Guan Feifei , Sun Lei , Liu Jiayi , Wang Ou , Jiang Yan , Xia Weibo , Xing Xiaoping , Li Mei 
Published: July 2022

AbstractOsteoporosis is a highly prevalent disorder with a strong genetic component. Recent studies identify PLS3 as a novel bone regulator of bone metabolism and PLS3 mutations lead to a rare monogenic early-onset osteoporosis. However, the mechanism of PLS3 mutation leading to osteoporosis is unknown with no animal models carrying patient-derived PLS3 mutations generated. The effective treatment strategies for PLS3-related have not been established. Here we have constructed a novel rat model with clinically relevant hemizygous E10-16del mutation of PLS3 (PLS3E10-16del/0) that recapitulate the osteoporotic phenotypes with obviously thinner cortical thickness, significant decreases in yield load, maximum load, and breaking load of femora at 3, 6, 9 months compared to WT rats. Histomorphometric analysis indicates a significantly lower mineral apposition rate in PLS3E10-16del/0rats. Treatment with alendronate (ALN, 1.0 ug/kg per day) or teriparatide (TPTD, 40ug/kg five times weekly) for 8 weeks significantly improved bone mass and bone microarchitecture, and bone strength was significantly increased after TPTD treatment (P < 0.05). Thus, our results indicate the roles of PLS3 in the regulation of bone microstructure and bone strength, providing a novel animal model for the study of early-onset osteoporosis. Alendronate and teriparatide treatment could be a potential treatment for early-onset osteoporosis induced by PLS3 mutation.
Dimensionality reduction and statistical modeling of scGET-seq data
Authors: de Pretis Stefano , Cittaro Davide 
Published: July 2022

AbstractSingle cell multiomics approaches are innovative techniques with the ability to profile orthogonal features in the same single cell, giving the opportunity to dig more deeply into the stochastic nature of individual cells. We recently developed scGET-seq, a technique that exploits a Hybrid Transposase (tnH) along with the canonical enzyme (tn5), which is able to profile altogether closed and open chromatin in a single experiment. This technique adds an important feature to the classic scATAC-seq assays. In fact, the lack of a closed chromatin signal in scATAC: (i) restricts sampling of DNA sequence to a very small portion of the chromosomal landscapes, substantially reducing the ability to investigate copy number alteration and sequence variations, and (ii) hampers the opportunity to identify regions of closed chromatin, that cannot be distinguished between non-sampled open regions and truly closed. scGET-seq overcomes these issues in the context of single cells. In this work, we describe the latest advances in the statistical analysis and modeling of scGET-seq data, touching several aspects of the computational framework: from dimensionality reduction, to statistical modeling, and trajectory analysis.
Brain-wide connectivity map of mouse thermosensory cortices
Authors: Bokiniec Phillip , Whitmire Clarissa J. , Leva Tobias M. , Poulet James F.A. 
Published: July 2022

ABSTRACTIn the thermal system, skin cooling is represented in the primary somatosensory cortex (S1) and the posterior insular cortex (pIC). Whether S1 and pIC are nodes in anatomically separated or overlapping thermal sensorimotor pathways is unclear, as the brain-wide connectivity of the thermal system has not been mapped. We address this using functionally targeted, dual injections of anterograde viruses or retrograde tracers into S1 and pIC. Our data show that inputs to S1 and pIC originate from two non-overlapping populations, supporting the existence of parallel input pathways. While outputs from S1 and pIC were more widespread and share a number of cortical and subcortical regions, within target structures axonal projections were often separable. We observed a high degree of reciprocal connectivity with thalamic and cortical regions from both S1 and pIC, but output to the mid- and hind-brain was unidirectional. Notably, pIC showed exclusive connectivity with regions associated with thermal processing. Together, these data indicate that cutaneous thermal information is routed to the cortex via multiple, parallel streams of information which are forwarded to overlapping downstream regions for the binding of complex somatosensory percepts and integration with ongoing behavior.
Gene drive designs for efficient and localisable population suppression using Y-linked editors
Authors: Geci René , Willis Katie , Burt Austin 
Published: July 2022

AbstractThe sterile insect technique (SIT) has been successful in controlling some pest species but is not practicable for many others due to the large numbers of individuals that need to be reared and released. Previous computer modelling has demonstrated that the release of males carrying a Y-linked editor that kills or sterilises female descendants could be orders of magnitude more efficient than SIT while still remaining spatially restricted, particularly if combined with an autosomal sex distorter. In principle, further gains in efficiency could be achieved by using a self-propagating double drive design, in which each of the two components (the Y-linked editor and the sex ratio distorter) boosted the transmission of the other. To better understand the expected dynamics and impact of releasing constructs of this new design, we have analysed a deterministic population genetic and population dynamic model. Our modelling demonstrates that this design can suppress a population from very low release rates, with no invasion threshold. Importantly, the design can work even if homing rates are low and sex chromosomes are silenced at meiosis, potentially expanding the range of species amenable to such control. Moreover, the predicted dynamics and impacts can be exquisitely sensitive to relatively small (e.g., 25%) changes in allele frequencies in the target population, which could be exploited for sequence-based population targeting. Analysis of published Anopheles gambiae genome sequences indicates that even for weakly differentiated populations with an FST of 0.02 there may be thousands of suitably differentiated genomic sites that could be used to restrict the spread and impact of a release. Our proposed design, which extends an already promising development pathway based on Y-linked editors, is therefore a potentially useful addition to the menu of options for genetic biocontrol.
Enabling spectrally resolved single-molecule localization microscopy at high emitter densities
Authors: Martens Koen J.A. , Gobes Martijn , Archontakis Emmanouil , Brillas Roger R. , Zijlstra Niels , Albertazzi Lorenzo , Hohlbein Johannes 
Published: July 2022

AbstractSingle-molecule localization microscopy (SMLM) is a powerful technique for elucidating structure and dynamics in the life- and material sciences with sub-50 nm spatial resolution. The simultaneous acquisition of spectral information (spectrally resolved SMLM, sSMLM) enables multiplexing using spectrally distinct fluorophores or enable the probing of local chemical environments by using solvachromatic fluorophores such as Nile Red. Until now, the widespread utilisation of sSMLM was hampered by several challenges: an increased complexity of the optical detection pathway, limited software solutions for data analysis, lower accessible emitter densities or smaller field-of-views, and overall compromised spatio-spectral resolution. Here, we present a low-cost implementation of sSMLM that addresses these challenges. Using a blazed, low-dispersion transmission grating positioned close to the image plane here represented by the camera sensor, the +1st diffraction order is minimally elongated compared to the point spread function of the 0th order and can therefore be analysed using common subpixel single-molecule localization algorithms. The distance between both PSFs provides accurate information on the spectral properties of the emitter. The minimal excess width of 1st order PSFs enables a fivefold higher emitter density compared to other sSMLM approaches whilst achieving a spatio-spectral localization accuracy sufficient to discriminate between fluorophores whose peak emission are less than 15 nm apart as demonstrated using dSTORM, DNA-PAINT and smFRET. We provide an ImageJ/Fiji plugin (sSMLMAnalyzer) and suitable Matlab scripts for data analysis. We envision that our approach will find widespread use in super-resolution applications that rely on distinguishing spectrally different fluorophores under low photon conditions.
A bifunctional CPD/(6-4)- photolyase from the cyanobacteria Synechococcus sp. PCC 7335 constitutes an UV-B inducible operon: new insights into photolyases phylogenetic evolution
Authors: Belén Fernández María , Lucas Latorre , Natalia Correa-Aragunde , Cassia Raúl 
Published: July 2022

AbstractPhotosynthetic organisms are continuously exposed to solar ultraviolet radiation-B (UV-B) because of their autotrophic lifestyle. UV-B provokes DNA damages, as cyclobutane pyrimidine dimers (CPD) or pyrimidine (6-4) pyrimidone photoproducts (6-4 PPs). The cryptochrome/ photolyase family (CPF) comprises flavoproteins that are able to bind damaged or undamaged DNA. Photolyases (PHRs) are enzymes that repair either CPDs or 6-4 PPs. A natural bifunctional CPD/(6-4)- PHR (PhrSph98) was recently isolated from the UV-resistant bacteria Sphingomonas UV9. In this work, phylogenetic studies of bifunctional CPD/(6-4)- photolyases and its evolutionary relationship with other CPF members were performed. Amino acids involved in electron transfer and binding to FAD cofactor and DNA lesions were conserved in proteins from proteobacteria, planctomycete, bacteroidete, acidobacteria and cyanobacteria clades. Genome analysis revealed that the cyanobacteria Synechococcus sp. PCC 7335 encodes a two-gene assembly operon coding for a PHR and a bifunctional CPD/(6-4)- PHR. Operon structure was validated by RT-qPCR analysis and the polycistronic transcript accumulated after 15 minutes of UV-B irradiation. Conservation of structure and evolution is discussed. This is the first report of an UV-B inducible PHRs operon which encodes a CPD/(6-4)- photolyase with putative bifunctional role in the repair of CPDs and 6-4 PPs damages in oxygenic photosynthetic organisms.