bluuebunny/crossref_metadata_2025_split huggingface dataset:
The indispensable soma of Cardiocondyla obscurior ants
Authors: Jaimes-Nino LM , Süß A , Heinze J , Schultner E , Oettler J 
Published: October 2022

AbstractThe evolutionary mechanisms that shape aging in social insects are not well understood. It is commonly assumed that queens live long and prosperous, while workers are regarded as a short-lived disposable caste because of their low reproductive potential. Queens of the ant Cardiocondyla obscurior gain high fitness late in life by increasing investment into sexual offspring as they age. This results in strong selection against senescence until shortly before death. Here, we show that workers have the same lifespan and shape of aging as queens, even though workers lack reproductive organs and cannot gain direct fitness. Under consideration of the prevailing aging theories and the biology of the species, we hypothesize that programmed aging has possibly evolved under kin selection.Impact statementMorphologically distinct fertile queen and sterile worker castes in the model ant Cardiocondyla obscurior show the same pace and shape of aging, contradicting the paradigm of queen/worker lifespan divergence in social insects.
Flaver: mining transcription factors in genome-wide transcriptome profiling data using weighted rank correlation statistics
Authors: Huang Tinghua , Huang Xinmiao , Wang Binyu , He Hao , Yao Min , Gao Xuejun 
Published: October 2022

AbstractBackgroundMining key transcription factors (TFs) in genome-wide transcriptome profiling data has been an active research area for many years and it has been partially solved by mathematically modelling the ranking orders of genes in the target gene-set for the TF of interest in the gene-list ranked by expression values, called gene-set enrichment analysis (GSEA). However, in some application scenarios the gene-set itself also has a rank attribute, such as the putative target gene-set predicted by the Grit software and other alternatives like FIMO and Pscan. New algorithms must be developed to analyze these data properly.Methodology/Principal FindingsBy implementing the weighted Kendall’s tau statistic, we proposed a method for genome-wide transcriptome profiling data mining that can identify the key TFs orchestrating a profile. Theoretical properties of the proposed method were established, and its advantages over the GSEA approach were demonstrated when analyzing the RNA-Atlas datasets. The results showed that the top-rated TFs by our method always have experimentally supported evidences in the literatures. Benchmarking using gene ontology (GO) annotations in the AmiGO database indicated that the geometry performance (SQR_P) of our method is higher than GSEA in more than 14% of the cases.SignificanceThe developed method is suitable for analyzing the significance of overrepresentation of ranked gene-sets in a ranked gene-list. A software implementing the method, called “Flaver”, was developed and is publicly available athttp://www.thua45.cn/flaverunder an academic free license.Author SummaryIdentification of the regulation roles of TFs in the transcriptome is fundamental in understanding various biological processes. Improve the performance of the prediction tools is important because accurate TF-mining in transcriptome data can finely improve the efficiency of wet-lab experiments. Also, genome wide TF-mining can provide new target genes for transcriptome regulation analysis in system biology perspective. This study developed a new TF-mining tool based on weighted rank correlation statistical method. The tool has better performance in analyzing ranked gene-set and ranked gene-list than its competitor, the GSEA tool. It can help the researchers in identification of the most important TFs in transcriptional data.
Connectomics of the Octopus vulgaris vertical lobe provides insight into conserved and novel principles of a memory acquisition network
Authors: Bidel Flavie , Meirovitch Yaron , Schalek Richard Lee , Lu Xiaotang , Pavarino Elisa Catherine , Yang Fuming , Peleg Adi , Wu Yuelong , Shomrat Tal , Berger Daniel Raimund , Shaked Adi , Lichtman Jeff William , Hochner Binyamin 
Published: October 2022

SummaryWe present the first analysis of the connectome of the vertical lobe (VL) of Octopus vulgaris, a brain structure mediating acquisition of long-term memory in this behaviorally advanced mollusk. Serial section electron microscopy revealed new types of interneurons, cellular components of extensive modulatory systems and multiple synaptic motifs. The sensory input to the VL is conveyed via ~1,800,000 axons that sparsely innervate two parallel and interconnected feedforward networks formed by the two types of amacrine interneurons (AM), simple AMs (SAMs) and complex AMs (CAMs). SAMs make up 89.3% of the ~25,000,000 VL cells, each receiving a synaptic input from only a single input neuron on its non-bifurcating primary neurite, suggesting that each input neuron is represented in only ~12 SAMs. This synaptic site is likely a “memory site” as it is endowed with LTP. The CAMs, a newly described AM type, comprise 1.6% of the VL cells. Their bifurcating neurites integrate multiple inputs from the input axons and SAMs. While the SAM network appears to feedforward sparse “memorizable” sensory representations into the VL output layer, the CAMs appear to monitor global activity and feedforward a balancing inhibition for “sharpening” the stimulus-specific VL output. While sharing morphological and wiring features with circuits supporting associative learning in other animals, the VL has evolved a unique circuit that enables associative learning based strictly on feedforward information flow.
Targeted editing of GTR1 and GTR2 homologs directs the development of ideal low-seed and high-leaf glucosinolate oilseed mustard
Authors: Kumari Juhi , Mann Avni , Kumar Roshan , Pradhan Akshay K. , Pental Deepak , Bisht Naveen C. 
Published: October 2022

AbstractGlucosinolate content in the Brassica oilseed crops has been reduced to the globally accepted Canola quality levels, making the seed meal useful as a protein-rich animal feed. However, the overall lower glucosinolate content in such plants renders them vulnerable to pests. We report CRISPR/Cas9-based editing of glucosinolate transporter (GTR) family genes to develop ideal oilseed mustard lines with the desired low levels of seed glucosinolates while maintaining high glucosinolate levels in leaves and pod walls, without affecting the seed yield and seed quality traits. The low-seed and high-leaf glucosinolate mustard lines with improved nutritional and defense traits will raise its international trade potential both as oilseed and feed crop.
aMeta: an accurate and memory-efficient ancient Metagenomic profiling workflow
Authors: Pochon Zoé , Bergfeldt Nora , Kırdök Emrah , Vicente Mário , Naidoo Thijessen , van der Valk Tom , Altınışık N. Ezgi , Krzewińska Maja , Dalen Love , Götherström Anders , Mirabello Claudio , Unneberg Per , Oskolkov Nikolay 
Published: October 2022

AbstractAnalysis of microbial data from archaeological samples is a rapidly growing field with a great potential for understanding ancient environments, lifestyles and disease spread in the past. However, high error rates have been a long-standing challenge in ancient metagenomics analysis. This is also complicated by a limited choice of ancient microbiome specific computational frameworks that meet the growing computational demands of the field. Here, we propose aMeta, an accurate ancient Metagenomic profiling workflow designed primarily to minimize the amount of false discoveries and computer memory requirements. Using simulated ancient metagenomic samples, we benchmark aMeta against a current state-of-the-art workflow, and demonstrate its superior sensitivity and specificity in both microbial detection and authentication, as well as substantially lower usage of computer memory. aMeta is implemented as a Snakemake workflow to facilitate use and reproducibility.
Foraging for locally and spatially varying resources: Where exploitation competition, local adaptation and kin selection meet
Authors: Schmid Max , Rueffler Claus , Lehmann Laurent , Mullon Charles 
Published: October 2022

AbstractIn patch- or habitat-structured populations different processes can lead to diversity at different scales. While spatial heterogeneity generates spatially disruptive selection favoring variation between patches, local competition can lead to locally disruptive selection promoting variation within patches. So far, almost all theory has studied these two processes in isolation. Here, we use mathematical modelling to investigate how resource variation within and between habitats influences the evolution of variation in a consumer population where individuals compete in finite patches connected by dispersal. We find that locally and spatially disruptive selection typically act in concert, favoring polymorphism under a significantly wider range of conditions than when in isolation. But when patches are small and dispersal between them is low, kin competition inhibits the emergence of polymorphism, especially when driven by local competition. We further use our model to clarify what comparisons between trait and neutral genetic differentiation (Qst/Fst comparisons) can tell about the nature of selection. Overall, our results help understand the interaction between two major drivers of diversity: locally and spatially disruptive selection; and how this interaction is modulated by the unavoidable effects of kin selection under limited dispersal.
Comprehensive monitoring of tissue composition using in vivo imaging of cell nuclei and deep learning
Authors: Das Gupta Amrita , John Jennifer , Asan Livia , Beretta Carlo , Kuner Thomas , Knabbe Johannes 
Published: October 2022

AbstractComprehensive analysis of tissue composition has so far been limited to ex-vivo approaches. Here, we introduce NuCLear (Nucleus-instructed tissuecomposition using deeplearning), an approach combining in vivo two-photon imaging of histone 2B-eGFP-labeled cell nuclei with subsequent deep learning-based identification of cell types from structural features of the respective cell nuclei. Using NuCLear, we were able to classify almost all cells per imaging volume in the secondary motor cortex of the mouse brain (0.25 mm3containing ∼25000 cells) and to identify their position in 3D space in a non-invasive manner using only a single label throughout multiple imaging sessions. Twelve weeks after baseline, cell numbers did not change yet astrocytic nuclei significantly decreased in size. NuCLear opens a window to study changes in relative abundance and location of different cell types in the brains of individual mice over extended time periods, enabling comprehensive studies of changes in cellular composition in physiological and pathophysiological conditions.
Inclusion Complexation of S-Nitrosoglutathione for Sustained NO Release and Reduced Device Infection
Authors: Li Wuwei , Wang Danyang , Lao Ka Un , Wang Xuewei 
Published: October 2022

AbstractS-nitrosoglutathione (GSNO) is a non-toxic nitric oxide (NO)-donating compound that occurs naturally in the human body. The use of GSNO to deliver exogenous NO for therapeutic and protective applications is limited by the high lability of dissolved GSNO in aqueous formulations. In this paper, we report a host-guest chemistry-based strategy to modulate the GSNO reactivity and the NO release kinetics. Cyclodextrins (CDs) are host molecules that are typically used to encapsulate hydrophobic guest molecules into their hydrophobic cavities. However, we found that CDs form inclusion complexes with GSNO, an extremely hydrophilic molecule with a solubility of over 1 M at physiological pH. More interestingly, the host-guest complexation reduces the decomposition reactivity of GSNO in the order of αCD > γCD > hydroxypropyl βCD. The lifetime of 0.1 M GSNO is increased to up to 15 days in the presence of CDs at 37°C, which is more than twice the lifetime of free GSNO. Quantum chemistry calculations indicate that GSNO in αCD undergoes a conformational change that significantly reduces the S-NO bond distance and increases its stability. The calculated S-NO bond dissociation enthalpies of free and complexed GSNO well agree with the experimentally observed GSNO decomposition kinetics. The NO release from GSNO-CD solutions, compared to GSNO solutions, has suppressed initial bursts and extended durations, enhancing the safety and efficacy of NO-based therapies and device protections. In an example application as an anti-infective lock solution for intravascular catheters, the GSNO-αCD solution exhibits potent antibacterial activities for both planktonic and biofilm bacteria, both intraluminal and extraluminal environments, both prevention and treatment of infections, and against multiple bacterial strains including a multidrug-resistant strain. In addition to solutions, the inclusion complexation also enables the preparation of GSNO hydrogels with enhanced stability and improved antibacterial efficacy. Since methods to suppress and control the GSNO decomposition rate are rare, this supramolecular strategy provides new opportunities for the formulation and application of this natural NO donor.
De novo cholesterol biosynthesis in the bacterial domain
Authors: Lee Alysha K. , Wei Jeremy H. , Welander Paula V. 
Published: October 2022

AbstractSterols are versatile lipids primarily associated with eukaryotes. While bacteria also produce sterols and studies of bacterial biosynthesis proteins have revealed novel biosynthetic pathways and a potential evolutionary role in the origin of sterol biosynthesis, no bacterium has been shown to synthesize highly modified eukaryotic sterols, such as cholesterol. This has led to the notion that bacteria only produce biosynthetically simple sterols and has lessened the consideration of bacterial production in discussions of sterol biosynthesis. In this study, we demonstrate two phylogenetically distinct bacteria, Enhygromyxa salina and Calothrix sp. NIES-4105, are capable of de novo cholesterol production. We also identified 25-hydroxycholesterol released as a product of acid hydrolysis in extracts from both bacteria, suggesting cholesterol exists as a conjugated molecule in these organisms. We coupled our lipid extractions to bioinformatic analyses and heterologous expression experiments to identify genetic pathways driving cholesterol production in each bacterium. E. salina shares much of its cholesterol biosynthesis pathway with the canonical eukaryotic pathway, except for C-4 demethylation where we identified a unique variation on the bacterial C-4 demethylation pathway. Calothrix lacks homologs for several steps in cholesterol biosynthesis, suggesting this bacterium may harbor a novel mechanism for completing cholesterol biosynthesis. Altogether, these results demonstrate the complexity underpinning bacterial sterol biosynthesis and raise further questions about the functional and regulatory roles of sterols in bacteria.
Convergence and molecular evolution of floral fragrance after independent transitions to self–fertilization
Authors: Wozniak Natalia , Sartori Kevin , Kappel Christian , Zhao Lihua , Erban Alexander , Fehrle Ines , Jantzen Friederike , Orsucci Marion , Rosa Stefanie , Lenhard Michael , Kopka Joachim , Sicard Adrien 
Published: October 2022

AbstractThe study of the independent evolution of similar characters can highlight important ecological and genetic factors that drive phenotypic evolution. The transition from reproduction by outcrossing to self-fertilization has occurred frequently throughout plant evolution. A common trend in this transition is the reduction of flower features in the selfing lineages, including display size, flower signals and pollinators’ rewards. These changes are believed to evolve because resources invested in building attractive flowers are reallocated to other fitness functions as the pressures to attract pollinators decrease. We investigated the similarities in the evolution of flower fragrance after independent transitions to self-fertilization in Capsella. We identified a large number of compounds that are similarly changed in different selfer lineages, such that the composition of the flower scent can predict the mating system in this genus. We further demonstrate that the emission of some of these compounds convergently evolved based on mutations in different genes. In one of the Capsella selfing lineages, the loss of β-ocimene emission was caused by a mutation altering subcellular localization of the ortholog of TERPENE SYNTHASE 2 without apparent effects on its biosynthetic activity. This mutation appears to have been selected at the early stage of this selfing lineage establishment through the capture of a variant segregating in the ancestral outcrossing population. The large extent of convergence in the independent evolution of flower scent, together with the evolutionary history and molecular consequences of a causal mutation, suggest that the emission of specific volatiles has important fitness consequences in self-fertilizing plants without obvious energetic benefits.
Increased sampling and intra-complex homologies favor vertical over horizontal inheritance of the Dam1 complex
Authors: van Rooijen Laura E. , Tromer Eelco C. , van Hooff Jolien J. E. , Kops Geert J. P. L. , Snel Berend 
Published: October 2022

AbstractKinetochores connect chromosomes to spindle microtubules to ensure their correct segregation during cell division. Kinetochores of human and yeast are largely homologous, their ability to track depolymerizing microtubules however is carried out by the non-homologous complexes Ska1-C and Dam1-C, respectively. We previously reported the unique anti-correlating phylogenetic profiles of Dam1-C and Ska-C found amongst a wide variety of eukaryotes. Based on these profiles and the limited presence of Dam1-C, we speculated that horizontal gene transfer (HGT) could have played a role in the evolutionary history of Dam1-C.Here, we present expanded analyses of Dam1-c evolution, using additional genome as well as transcriptome sequences and recently acquired 3D structure data. This analysis revealed a wider and more complete presence of Dam1-C in Cryptista, Rhizaria, Ichthyosporea, CRuMs, and Colponemidia. The fungal Dam1-C cryo-EM structure supports earlier hypothesized intra-complex homologies, which enables the reconstruction of rooted and unrooted phylogenies. The rooted tree of concatenated Dam1-C subunits is statistically consistent with the species tree of eukaryotes, suggesting that Dam1-C is ancient, and that the present-day phylogenetic distribution is best explained by multiple, independent losses and no HGT was involved. Furthermore, we investigated the ancient origin of Dam1-C via profile-profile searches. Homology among eight out of the ten Dam1-C subunits suggested that the complex largely evolved from a single multimerizing subunit that diversified into an octameric core via stepwise duplication and sub-functionalization of the subunits before the origin of the Last Common Ancestor.SignificanceThe Dam1 complex has a crucial role in cell division yet its distribution across species is very patchy. To resolve the evolutionary origin of this peculiar distribution, we used the recently acquired 3D structure to obtain a rooted phylogeny. This study makes an important step in discovering the evolutionary history of the Dam1 complex, by determining that Dam1-C was part of the Last eukaryotic Common Ancestor and arose via stepwise duplications during the transition from prokaryotes to eukaryotes.
A galanin-positive population of lumbar spinal cord neurons modulates sexual arousal and copulatory behavior
Authors: Lenschow Constanze , Mendes Ana Rita P. , Ferreira Liliana , Lacoste Bertrand , Marques Hugo , Quilgars Camille , Bertrand Sandrine S. , Lima Susana Q. 
Published: October 2022

SummaryDuring sex, male arousal increases to the ejaculatory threshold, allowing genital sensory input to trigger ejaculation. While copulation and sexual arousal are thought to be centrally regulated by the brain, ejaculation is considered a reflex controlled by a spinal circuit. In this framework, the spinal cord is assumed to be strongly inhibited by descending input from the brain until the ejaculatory threshold, playing no role in the regulation of copulatory behavior. However, this remains untested. Here, we mapped the spinal circuit controlling the bulbospongiosus muscle, which is involved in sperm expulsion in mice. Our findings reveal that bulbospongiosus muscle-motor neurons receive input from galanin-expressing interneurons. This galanin-positive population receives genital input and, while its stimulation leads to bulbospongiosus muscle activity, the evoked muscle-potentials are dependent on spinalization, the male’s internal state and decrease with repeated stimulation. Moreover, ablation of galanin neurons affected the latency to ejaculate and altered the copulatory pattern. These results suggest an unexpected role of spinal circuits in the control of copulation and arousal, in addition to its established role in ejaculation.
Evaluation of K-Ras4B dimer interfaces and the role of Raf effectors
Authors: Chatzigoulas Alexios , Andreadelis Ioannis , Doerr Stefan , Lamprakis Christos , Theodoropoulou Anastasia , Manchester John , Velez-Vega Camilo , Duca Jose , Cournia Zoe 
Published: October 2022

ABSTRACTK-Ras4B is one the most frequently mutated proteins in cancer, yet mechanistic details of its activation such as its homodimerization on the membrane remain elusive. The structural determinants of K-Ras4B homodimerization have been debated with different conformations being proposed in the literature. Here, we perform microsecond all-atom Molecular Dynamics (MD) simulations on the K-Ras4B monomer in solution, the K-Ras4B monomer on the membrane, and two experimentally-based K-Ras4B dimer models of the α4-α5 interface to investigate the stability of these structures bound to GTP on a model cell membrane. We then evaluate the complexes for their propensity to form stable dimers on the plasma membrane in the presence and absence of Raf[RBD–CRD] effectors. We find that Raf[RBD-CRD] effectors enhance dimer stability, suggesting that the presence of effectors is necessary for K-Ras4B dimers stabilization on the cell membrane. Moreover, we observe, for the first time, a dynamic water channel at the K-Ras4B dimer interface, and identify putative allosteric connections in the K-Ras4B dimer interface. To discover novel K-Ras4B interfaces, we perform coarse-grained MD simulations in two dissociated K-Ras4B monomers on the membrane, which reveal that the dominant dimer interface is the α4-α5 interface. Finally, a druggability analysis is performed in the different K-Ras4B structures in the monomeric states. Strikingly, all known binding pockets of K-Ras4B are identified only in the structure that is membrane-bound, but not in the solution structure. Based on these results, we propose that modulating the protein-membrane interactions can be an alternative strategy for inhibiting K-Ras4B signaling.