bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tailoring and optimizing fatty acid production by oleaginous yeasts through the systematic exploration of their physiological fitness
Authors: Duman-Özdamar Zeynep Efsun , Martins dos Santos Vitor A.P. , Hugenholtz Jeroen , Suarez-Diez Maria 
Published: June 2022

BackgroundThe use of palm oil for our current needs is unsustainable. Replacing palm oil with oils produced by microbes through the conversion of sustainable feedstocks is a promising alternative. However, there are major technical challenges that must be overcome to enable this transition. Foremost among these challenges is the stark increase in lipid accumulation and production of higher content of specific fatty acids. Therefore, there is a need for more in-depth knowledge and systematic exploration of the oil productivity of the oleaginous yeasts. In this study, we cultivated Cutaneotrichosporon oleaginosus and Yarrowia lipolytica at various C/N ratios and temperatures in a defined medium with glycerol as carbon source and urea as nitrogen source. We ascertained the synergistic effect between various C/N ratios of a defined medium at different temperatures with Response Surface Methodology (RSM) and explored the variation in fatty acid composition through Principal Component Analysis.ResultsBy applying RSM, we determined a temperature of 30 °C and a C/N ratio of 175 g/g to enable maximal oil production by C. oleaginosus and a temperature of 21 °C and a C/N ratio of 140 g/g for Y. lipolytica. We increased production by 71 % and 66 % respectively for each yeast compared to the average lipid accumulation in all tested conditions. Modulating temperature enabled us to steer the fatty acid compositions. Accordingly, switching from higher temperature to lower cultivation temperature shifted the production of oils from more saturated to unsaturated by 14 % in C. oleaginosus and 31 % in Y. lipolytica. Higher cultivation temperatures resulted in production of even longer saturated fatty acids, 3 % in C. oleaginosus and 1.5 % in Y. lipolytica.ConclusionsIn this study, we provided the optimum C/N ratio and temperature for C. oleaginosus and Y. lipolytica by RSM. Additionally, we demonstrated that lipid accumulation of both oleaginous yeasts was significantly affected by the C/N ratio and temperature. Furthermore, we systematically analyzed the variation in fatty acids composition and proved that changing the C/N ratio and temperature steer the composition. We have further established these oleaginous yeasts as platforms for production of tailored fatty acids.
Differences in neurotoxic outcomes of organophosphorus pesticides revealed via multi-dimensional screening in adult and regenerating planarians
Authors: Ireland Danielle , Zhang Siqi , Bochenek Veronica , Hsieh Jui-Hua , Rabeler Christina , Meyer Zane , Collins Eva-Maria S. 
Published: June 2022

AbstractOrganophosphorus pesticides (OPs) are a chemically diverse class of commonly used insecticides. Epidemiological studies suggest that low dose chronic prenatal and infant exposures can lead to life-long neurological damage and behavioral disorders. While inhibition of acetylcholinesterase (AChE) is the shared mechanism of acute OP neurotoxicity, OP-induced developmental neurotoxicity (DNT) can occur independently and/or in the absence of significant AChE inhibition, implying that OPs affect alternative targets. Moreover, different OPs can cause different adverse outcomes, suggesting that different OPs act through different mechanisms. These findings emphasize the importance of comparative studies of OP toxicity. Freshwater planarians are an invertebrate system that uniquely allows for automated, rapid and inexpensive testing of adult and developing organisms in parallel to differentiate neurotoxicity from DNT. Effects found only in regenerating planarians would be indicative of DNT, whereas shared effects may represent neurotoxicity. We leverage this unique feature of planarians to investigate potential differential effects of OPs on the adult and developing brain by performing a comparative screen to test 7 OPs (acephate, chlorpyrifos, dichlorvos, diazinon, malathion, parathion and profenofos) across 10 concentrations in quarter-log steps. Neurotoxicity was evaluated using a wide range of quantitative morphological and behavioral readouts. AChE activity was measured using an Ellman assay. The toxicological profiles of the 7 OPs differed across the OPs and between adult and regenerating planarians. Toxicological profiles were not correlated with levels of AChE inhibition. Twenty-two “mechanistic control compounds” known to target pathways suggested in the literature to be affected by OPs (cholinergic neurotransmission, serotonin neurotransmission, endocannabinoid system, cytoskeleton, adenyl cyclase and oxidative stress) and 2 negative controls were also screened. When compared with the mechanistic control compounds, the phenotypic profiles of the different OPs separated into distinct clusters. The phenotypic profiles of adult vs regenerating planarians exposed to the OPs clustered differently, suggesting some developmental-specific mechanisms. These results further support findings in other systems that OPs cause different adverse outcomes in the (developing) brain and build the foundation for future comparative studies focused on delineating the mechanisms of OP neurotoxicity in planarians.
Chrna5 and lynx prototoxins identify acetylcholine super-responder subplate neurons
Authors: Venkatesan Sridevi , Chen Tianhui , Liu Yupeng , Turner Eric E , Tripathy Shreejoy , Lambe Evelyn K 
Published: June 2022

SummaryAttention depends on cholinergic excitation of prefrontal neurons but is sensitive to perturbation of α5-containing nicotinic receptors encoded byChrna5. However,Chrna5-expressing (Chrna5+) neurons remain enigmatic, despite their potential as a target to improve attention. Here, we generate complex transgenic mice to probe Chrna5+ neurons and their sensitivity to endogenous acetylcholine. Through opto-physiological experiments, we discover that Chrna5+ neurons contain a distinct population of acetylcholine super-responders. Leveraging single-cell transcriptomics, we discover molecular markers conferring subplate identity on this subset. We determine that Chrna5+ super-responders express a unique complement of GPI-anchored lynx prototoxin genes (Lypd1, Ly6g6e, andLypd6b), predicting distinct nicotinic receptor regulation. To manipulate lynx regulation of endogenous nicotinic responses, we developed a pharmacological strategy guided by transcriptomic predictions. Overall, we revealChrna5-Cre mice as a transgenic tool to target the diversity of subplate neurons in adulthood, yielding new molecular strategies to manipulate their cholinergic activation relevant to attention disorders.
From Easy to Hopeless - Predicting the Difficulty of Phylogenetic Analyses
Authors: Haag Julia , Höhler Dimitri , Bettisworth Ben , Stamatakis Alexandros 
Published: June 2022

AbstractPhylogenetic analyses under the Maximum Likelihood model are time and resource intensive. To adequately capture the vastness of tree space, one needs to infer multiple independent trees. On some datasets, multiple tree inferences converge to similar tree topologies, on others to multiple, topologically highly distinct yet statistically indistinguishable topologies. At present, no method exists to quantify and predict this behavior. We introduce a method to quantify the degree of difficulty for analyzing a dataset and present Pythia, a Random Forest Regressor that accurately predicts this difficulty. Pythia predicts the degree of difficulty of analyzing a datasetpriorto initiating Maximum Likelihood based tree inferences. Pythia can be used to increase user awareness with respect to the amount of signal and uncertainty to be expected in phylogenetic analyses, and hence inform an appropriate (post-)analysis setup. Further, it can be used to select appropriate search algorithms for easy-, intermediate-, and hard-to-analyze datasets.
(-)-Gossypol inhibition of musashi-mediated forgetting improves memory and age-dependent memory decline in Caenorhabditis elegans
Authors: Mastrandreas Pavlina , Arnold Andreas , Boglari Csaba , de Quervain Dominique J.-F. , Stetak Attila , Papassotiropoulos Andreas 
Published: June 2022

AbstractMusashi RNA-binding proteins retain a pivotal role in stem cell maintenance, tumorigenesis, and nervous system development. Recently, we showed in C. elegans that MSI1 actively promotes forgetting upon associative learning via a 3’UTR-dependent translational expression of the Arp2/3 actin branching complex. Here, we investigated the evolutionary conserved role of MSI proteins and the effect of their pharmacological inhibition on memory. Expression of human MSI1 and MSI2 under the endogenous musashi promoter fully rescued the phenotype of msi-1(lf) worms. Furthermore, pharmacological inhibition of MSI1 and MSI2 activity using (−)-gossypol resulted in improved memory retention, without causing locomotor, chemotactic, or learning deficits. No drug effect was observed in msi-1(lf) treated worms. Using Western blotting and confocal microscopy we found no changes in MSI-1 protein abundance following (−)-gossypol treatment, suggesting that musashi gene expression remains unaltered and that the compound exerts its inhibitory effect post-translationally. Additionally, (−)-gossypol suppressed the previously seen rescue of the msi-1(lf) phenotype in worms expressing human MSI1 specifically in the AVA neuron, indicating that (−)-gossypol can regulate the musashi pathway in a memory-related neuronal circuit in worms. Finally, treating aged worms with (−)-gossypol reversed physiological age-dependent memory decline. Taken together, our findings indicate that pharmacological inhibition of musashi might represent a promising approach for memory modulation.
Bcmap: fast alignment-free barcode mapping for linked-read sequencing data
Authors: Lüpken Richard , Krannich Thomas , Kehr Birte 
Published: June 2022

AbstractThe bottleneck for genome analysis will soon shift from sequencing cost to computationally expensive read alignment. Here, we propose to circumvent full read alignment computation on linked-read sequencing data when only portions of the genome are of interest. Our novel barcode mapping approach ‘bcmap’ indexes and places barcoded read sets on the reference genome, thereafter allowing the extraction of reads originating from genomic regions of interest directly from FASTQ files. We demonstrate that bcmap is accurate and an order of magnitude faster than full read alignment. As example application, we use bcmap to locally assemble a known variant region.
Flower patterns improve foraging efficiency in bumblebees independent of nectary guidance
Authors: Richter Robin , Dietz Alexander , Foster James , Spaethe Johannes , Stöckl Anna 
Published: June 2022

AbstractColourful patterns on flowers are thought to benefit both pollinators and the plants they visit, by increasing the plants’ pollination success via an improved foraging efficiency of its pollinators. This increased efficiency is thought to result from a guidance effect of the flower patterns, correspondingly termed ‘nectar guides’, which indicate the position of the nectary to visiting pollinators. While it is well established that flower patterns play an important role in flower choice, the mechanisms underlying their function for flower-visiting insects remain poorly understood. In this study, we quantified the contributions of patterns to all phases of flower interaction in the buff-tailed bumblebee (Bombus terrestris). We analysed their flight paths, as well as landing positions and walking tracks on artificial flowers with different pattern types. We reveal that flower patterns improved the overall foraging efficiency of the bees by up to 30%, by guiding their approach flight, landing positions, and departure decisions. Surprisingly, these effects were not related to nectary guidance. Since we conducted the experiments with experienced foragers, which represent the majority of insect pollinators active in nature, the newly described nectary-independent guidance effects of flower patterns are of fundamental importance to plant-pollinator interactions under natural conditions.
Variability of functional and biodiversity responses to perturbations is predictable and informative
Authors: Orr James A. , Piggott Jeremy J. , Jackson Andrew L. , Jackson Michelle C. , Arnoldi Jean-François 
Published: June 2022

AbstractPerturbations such as climate change, invasive species and pollution, impact the functioning and diversity of ecosystems. But because there is no unique way to measure functioning and diversity, this leads to a ubiquitous and overwhelming variability in community-level responses, that is often seen as a barrier to prediction in ecology. Here, we show that this variability can instead provide insights into hidden features of a community’s functions and responses to perturbations. By first analysing a dataset of global change experiments in microbial soil systems we show that variability of functional and diversity responses to a given perturbation is not random: aggregate properties that are thought to be mechanistically similar tend to respond similarly. We then formalise this intuitive observation to demonstrate that the variability of community-level responses to perturbations is not only predictable, but that it can also be used to access hidden and useful information about population-level responses to perturbations (i.e., response diversity and scaling by species biomass). Our theory offers a baseline expectation for the variability of community-level responses to perturbations and helps to explain the complexity of ecological responses to global change.Significance StatementMeasures of biodiversity and ecosystem functioning show highly variable responses to a given perturbation. This variability is traditionally thought of as reflecting our inability to predict ecological responses to global change. Our work, however, finds that variability of community-level responses is itself predictable and can even be used to gain insights about how species respond to perturbations and collectively contribute to ecosystem functions.
A minimal-complexity light-sheet microscope maps network activity in 3D neuronal systems
Authors: Wysmolek Paulina M , Kiessler Filippo D , Salbaum Katja A , Shelton Elijah R , Sonntag Selina M , Serwane Friedhelm 
Published: June 2022

AbstractIn vitrosystems mimicking brain regions, brain organoids, are revolutionizing the neuroscience field. However, characterization of their electrical activity has remained a challenge as this requires readout at millisecond timescale in 3D at single-neuron resolution. While custom-built microscopes used with genetically encoded sensors are now opening this door, a full 3D characterization of organoid neural activity has not been performed yet, limited by the combined complexity of the optical and the biological system. Here, we introduce an accessible minimalistic light-sheet microscope to the neuroscience community. Designed as an add-on to a standard inverted microscope it can be assembled within one day. In contrast to existing simplistic setups, our platform is suited to record volumetric calcium traces. We successfully extracted 4D calcium traces at high temporal resolution by using a lightweight piezo stage to allow for 5Hz volumetric scanning combined with a processing pipeline for true 3D neuronal trace segmentation. As a proof of principle, we created a 3D connectivity map of a stem cell derived neuron spheroid by imaging its activity. Our fast, low complexity setup empowers researchers to study the formation of neuronal networksin vitrofor fundamental and neurodegeneration research.
E-Cigarette Synthetic Cooling Agent WS-23 and Nicotine Aerosols Differentially Modulate Airway Epithelial Cell Responses
Authors: Manevski Marko , Devadoss Dinesh , Yogeswaran Shaiesh , Rahman Irfan , Chand Hitendra S. 
Published: June 2022

ABSTRACTElectronic cigarette (e-cig) aerosol/vape exposures are strongly associated with pulmonary dysfunctions, and the airway epithelial cells (AECs) of respiratory passages play a pivotal role in understanding this association. However, not much is known about the effect of synthetic cooling agents such as WS-23 on AECs. WS-23 is a synthetic menthol-like cooling agent widely used to enhance the appeal of e-cigs and to suppress the harshness and bitterness of other e-cig constituents. Using primary human AECs, we compared the effects of aerosolized WS-23 with propylene glycol/vegetable glycerin (PG/VG) vehicle control and nicotine aerosol exposures. AECs treated with 3% WS-23 aerosols showed a significant increase in viable cell numbers compared to PG/VG-vehicle aerosol exposed cells and cell growth was comparable following 2.5% nicotine aerosol exposure. AEC inflammatory factors, IL-6 and ICAM-1 levels were significantly suppressed by WS-23 aerosols compared to PG/VG-controls. When differentiated AECs were challenged with WS-23 aerosols, there was a significant increase in MUC5AC+ goblet cells with no discernible change in SCGB1A1+ secretory cells. Compared to PG/VG-controls, WS-23 or nicotine aerosols presented with increased goblet cell numbers, but there was no synergistic effect of WS-23+nicotine combination exposure. Thus, WS-23 and nicotine aerosols modulate the AEC responses and induce goblet cell hyperplasia, which could impact the airway physiology and susceptibility to respiratory diseases.
The interaction between coping styles with relationship breakdowns, loss, and conflict and the frequency of self-harm thoughts and behaviours: a longitudinal analysis of 21,581 UK adults
Authors: Paul Elise , Fancourt Daisy 
Published: June 2022

AbstractBackgroundRelationship breakdowns or conflict are frequent precipitants for self-harm thoughts and behaviours, but the majority who experience these stressful life events do not think about or engage in self-harm. Understanding factors that attenuate or exacerbate this risk is therefore needed. The aim of this paper is to investigate whether relationship breakdowns, loss, and conflict lead to more frequent self-harm thoughts and behaviours. We also examine whether coping styles and neuroticism, posited by diathesis-stress models of suicide risk to interact with these events, attenuate or exacerbate the risk for self-harm thoughts and behaviours from these events.MethodsThis study utilised data collected during the COVID-19 pandemic, which acted as a natural experiment by leading to a greater prevalence of relationship breakdowns than usual. Data from 21,581 adults who participated in the UCL COVID-19 Social Study between 28 February 2021 and 4 April 2022 were utilised. Poisson regression models which controlled for socio-demographics and a diagnosed mental health condition were used to examine the impact of four predictor variables (separation or divorce, family problem, an ‘other’ relationship breakdown [e.g., friend or colleague], and the death of a close relative or friend) with the number of times self-harm thoughts and behaviours were reported over the study period. Interactions between these events and coping styles (problem-focused, emotion-focused, socially supported, and avoidant coping) were also examined.ResultsVariables representing relationship breakdowns, loss, and conflict were associated with an increased frequency of self-harm thoughts (incidence rate ratio [RRR] range: 1.04 to 1.77) and behaviours (RRR range: 1.48 to 1.96). The use of more avoidant coping strategies (e.g., substance use, denial) increased the risk for both outcomes but unexpectedly attenuated associations between predictor variables and self-harm thoughts. Socially supported coping increased the likelihood of both outcomes, but not in sensitivity analyses which excluding ‘venting’ from the scale. Problem-focused coping strategies (e.g., active planning) attenuated the impact of separation or divorce and having had a family problem on the frequency of self-harm behaviours.ConclusionsFindings underscore the importance of interpersonal loss and conflict for the frequency of thinking about and engaging in self-harm and suggest that the magnitude of these associations may depend on different coping styles.
VirPool: Model-Based Estimation of SARS-CoV-2 Variant Proportions in Wastewater Samples
Authors: Gafurov Askar , Baláž Andrej , Amman Fabian , Boršová Kristína , Čabanová Viktória , Klempa Boris , Bergthaler Andreas , Vinař Tomáš , Brejová Broňa 
Published: June 2022

AbstractBackgroundThe genomes of SARS-CoV-2 are classified into variants, some of which are monitored as variants of concern (e.g. the delta variant B.1.617.2 or omicron variant B.1.1.529). Proportions of these variants in a population are typically estimated by large-scale sequencing of individual patient samples. Sequencing a mixture of SARS-CoV-2 RNA molecules from wastewater provides a cost-effective alternative, but requires methods for estimating variant proportions in a mixed sample.ResultsWe propose a new method based on a probabilistic model of sequencing reads, capturing sequence diversity present within individual variants, as well as sequencing errors. The algorithm is implemented in an open source Python program called VirPool. We evaluated the accuracy of VirPool on several simulated and real sequencing data sets from both Illumina and nanopore sequencing platforms, including wastewater samples from Austria and France monitoring the onset of alpha and delta variants.ConclusionsVirPool is a versatile tool for wastewater and other mixed-sample analysis that can handle both short- and long-read sequencing data. Our approach does not require pre-selection of characteristic mutations for variant profiles, it is able to use the entire length of reads instead of just the most informative positions, and can also capture haplotype dependencies within a single read.AvailabilityVirPool is an open source software available at https://github.com/fmfi-compbio/virpool.