bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dating the photosynthetic organelle evolution in Archaeplastida,Paulinellaand secondary-plastid bearing lineages
Authors: Pietluch Filip , Mackiewicz Paweł , Sidorczuk Katarzyna , Gagat Przemysław 
Published: July 2022

AbstractPhotosynthetic eukaryotes have shaped the Earth’s biosphere by producing O2and converting light into organic compounds in specialized organelles called plastids. Plastids evolved from free-living cyanobacteria engulfed by heterotrophic unicellular eukaryotes in processes called cyanobacterial endosymbioses. Two independent such processes have been reported so far. The first gave rise to primary plastids and three Archaeplastida lineages: glaucophytes, red algae and green algae with land plants, whereas the second resulted in chromatophores in the rhizarian amoebaPaulinella. Importantly, archaeplastidans donated their plastids to many protist groups, thereby further spreading photosynthesis across the tree of life. To reveal the complex plastid evolution, we performed comprehensive phylogenetic and multi-clock analyses based on new fossil calibration points and the greatest number yet of plastid-encoded proteins from 108 taxa, representing a large diversity of photosynthetic organisms. Our results indicate that primary plastids evolved prior to 2.1 - 1.8 Bya, i.e. before glaucophytes diverged from the other archaeplastidans. Like the primary plastids before,Paulinellachromatophores evolved in low salinity habitats and possibly before 292 - 266 Mya. Red and green algae were engulfed by cryptophyte and chlorarachniophyte ancestors between 1.7 - 1.4 Bya, and 1.1 - 1.0 Bya, respectively; the former subsequently triggered plastid transfers to other eukaryotes. The diversification rate of the photosynthetic organisms increased with temperature and CO2but decreased with O2and volcanic activity. We also studied the impact of various molecular clocks and calibration sets on the age estimation and clearly indicate that the clocks are the source of greater differences.Significance StatementCyanobacteria and eukaryote endosymbioses created a multitude of photosynthetic organelles called plastids that feed most life on our planet. For decades scientists have been trying to untangle the puzzle of plastid evolution, i.e. when and how plastids were acquired and spread throughout the eukaryotic tree of life. To answer these questions we applied phylogenetic and multi-clock methods combined with new fossil calibration points on large data sets. Our results push back in the Earth’s history most key events concerning plastid evolution compared to previous reports. Additionally, we discovered a significant impact of climatic and atmospheric parameters on the diversification rate of plastid lineages. The estimated divergence times enabled us to reinterpret taxonomic classification of controversial fossils.
Gene Regulatory Network Reconfiguration in Direct Lineage Reprogramming
Authors: Kamimoto Kenji , Adil Mohd Tayyab , Jindal Kunal , Hoffmann Christy M. , Kong Wenjun , Yang Xue , Morris Samantha A. 
Published: July 2022

SummaryIn direct lineage reprogramming, transcription factor (TF) overexpression reconfigures Gene Regulatory Networks (GRNs) to convert cell identities between fully differentiated cell types. We previously developed CellOracle, a computational pipeline that integrates single-cell transcriptome and epigenome profiles to infer GRNs. CellOracle leverages these inferred GRNs to simulate gene expression changes in response to TF perturbation, enabling network re-configuration during reprogramming to be interrogated in silico. Here, we integrate CellOracle analysis with lineage tracing of fibroblast to induced endoderm progenitor (iEP) conversion, a prototypical direct lineage reprogramming paradigm. By linking early network state to reprogramming success or failure, we reveal distinct network configurations underlying different reprogramming outcomes. Using these network analyses and in silico simulation of TF perturbation, we identify new factors to coax cells into successfully converting cell identity, uncovering a central role for the AP-1 subunit Fos with the Hippo signaling effector, Yap1. Together, these results demonstrate the efficacy of CellOracle to infer and interpret cell-type-specific GRN configurations at high resolution, providing new mechanistic insights into the regulation and reprogramming of cell identity.
Convergent gene expression highlights shared vocal motor microcircuitry in songbirds and humans
Authors: Gedman Gregory L , Biegler Matthew T. , Haase Bettina , Wirthlin Morgan E. , Fedrigo Olivier , Pfenning Andreas R. , Jarvis Erich D. 
Published: July 2022

AbstractVocal learning is a skilled motor behavior observed in several mammalian and avian species and is critical for human speech. While convergent gene expression patterns have highlighted similar primary motor and striatal pathways for vocal imitation in songbirds and humans, the extent of molecular and circuit convergence remains unresolved. Here we profiled the four principal song nuclei of the zebra finch (HVC, LMAN, RA, Area X) and their surrounding brain regions using RNA-Seq and compared them with specialized markers we identified for human speech brain regions. Expanding previous work, both songbird RA and HVC exhibited convergent specialized gene expression of ∼350 genes with human laryngeal sensorimotor cortex. The songbird HVCRAintratelencephalic (IT) neurons were the predominant cell type that was convergent with human, specifically layer 2/3 IT neurons, while the songbird RA extratelencephalic (ET) projection neurons exhibited convergent expression with human layer 5 ET projection neurons. The molecular specializations of both songbird LMAN and human Broca’s area were more unique to each species. These findings demonstrate the extent of convergent molecular specializations in distantly related species for vocal imitation and emphasize important evolutionary constraints for this complex trait.One-Sentence SummaryOur data provide hundreds of candidate genes to study the molecular basis and evolution of song and speech across species.
Polyunsaturated fatty acids alter the formation of lipid droplets and eicosanoid production in Leishmania promatigotes
Authors: de Sousa Andrade Yasmin Monara Ferreira , de Castro Monara Viera , de Souza Tavares Victor , Oliveira Souza Rayane da Silva , Helena Faccioli Lúcia , Lima Jonilson Berlink , Sorgi Carlos Arterio , de Matos Borges Valéria , Araújo-Santos Théo 
Published: July 2022

AbstractLeishmania parasites contain lipid droplets (LD, or lipid bodies) and the molecular machinery responsible for synthesizing prostaglandins (PGs) and other bioactive lipids. We studied the effects of polyunsaturated fatty acids (PUFA) on LD biogenesis and eicosanoid production in distinct Leishmania species associated with different clinical forms of leishmaniasis. We also compared structural models of human-like cyclooxygenase-2 (GP63) and prostaglandin F synthase (PGFS) proteins of Leishmania, and we evaluated their enzymatic production in logarithmic and stationary growth phases of procyclic L. amazonensis, L. braziliensis and L. infantum. PUFAs modulate the formation of LDs in L. braziliensis and L. infantum. Leishmania species with equivalent clinical manifestations and tissue tropism had same protein mutations in GP63 and PGFS. No differences in GP63 production were observed among L. amazonensis, L. braziliensis and L. infantum, however increased PGFS production was detected during the parasite differentiation. Stimulation with arachidonic acid resulted in highly elevated production of hydroxyeicosatetraenoic acids compared to prostaglandins quantified by LC-MS/MS. The present findings open new perspectives on the role of eicosanoid metabolism in Leishmania and could contribute to the development of novel antiparasitic drugs.
Selection for increased post-infection survival ameliorates mating induced immune suppression in Drosophila melanogaster females
Authors: Basu Aabeer , Singh Aparajita , Ruchitha B G , Prasad Nagaraj Guru 
Published: July 2022

AbstractSexual activity (mating) negatively affects immune function in various insect species, in both sexes. In the experiments reported in this manuscript, we tested if hosts adapted to regular pathogen challenges are less susceptible to mating induced immune suppression, using experimentally evolved Drosophila melanogaster populations selected for increased post-infection survival when infected with a Gram-positive bacterium, Enterococcus faecalis. Mating increased susceptibility of females to bacterial pathogens, but in a pathogen specific manner. Mating-induced increase in susceptibility was also affected by host evolutionary history, with females from selected populations exhibiting similar post-infection survival irrespective of mating status, while females from control populations became more susceptible to bacterial infections after mating. Post-infection survival of males, irrespective of their evolutionary history, was not affected by their mating status. We therefore conclude that hosts evolved to better survive bacterial infections are also better at resisting mating-induced increase in susceptibility to infections in Drosophila melanogaster.
Optimization of information transmission through a noisy biochemical pathway explains the choice of reaction rates
Authors: Mahajan Anush , Ghosh Bhaswar 
Published: July 2022

AbstractLiving organisms are required to sense the environment accurately in order to ensure appropriate responses. The cells utilize specific signaling pathways to estimate the signal. The accuracy of estimating the input signal is severely limited by noise stemming from inherent stochasticity of the chemical reactions involved in signaling pathways. Cells employ multiple strategies to improve the accuracy by tuning the reaction rates, for instance amplifying the response, reducing the noise etc.. However, the pathway also consumes energy through incorporating ATP in phosphorylating key signaling proteins involved in the reaction pathways. In many instances, improvements in accuracy elicit extra energetic cost. For example, higher deactivation rate suppresses the basal pathway activity effectively amplifying the dynamic range of the response which leads to improvement in accuracy. However, higher deactivation rate also enhances the energy dissipation rate. Here, we employed a theoretical approach based on non-equilibrium thermodynamics of information to explore the role of accuracy and energetic cost in the performance of a MAPK signaling system. Our study shows that the accuracy-energy trade-off can explain the optimality of the reaction rates of the reaction pathways rather than accuracy alone. Our analysis elucidates the important role of the interplay between accuracy and related energetic cost in evolutionary shaping of the parameter space of signaling pathways.
Insight into diatoms diversity at two European coastal sites (LTER-MC in the Mediterranean Sea and SOMLIT-Astan in the Western English Channel) using a DNA Metabarcoding approach
Authors: Caracciolo Mariarita , Berney Cédric , Alric Benjamin , Piredda Roberta , Zingone Adriana , Sarno Diana , Percopo Isabella , Romac Sarah , Gall Florence Le , Rigaut-Jalabert Fabienne , Baudoux Anne-Claire , Simon Nathalie , Henry Nicolas 
Published: July 2022

AbstractDiatoms are among the most successful marine eukaryotic phytoplankton groups. Their diversity has been investigated in the world’s oceans through expeditions and observations carried out from the equator to the poles. Traditionally, diatom species have been distinguished based on morphological characters of their frustules, but high-throughput sequencing offers new, high-resolution data that can be used to re-examine spatial and/or temporal patterns of diversity. Here we investigated diatoms’ genetic diversity using metabarcoding (18S V4 rRNA gene) obtained along the years 2011 to 2013 at two coastal time series stations (SOMLIT-Astan and LTER-MareChiara) installed respectively off Roscoff in the Western English Channel and in the Gulf of Naples in the Mediterranean Sea. Diatom species pools detected were different, which fitted with previous observations and with our expectations, since these stations are installed in two contrasted pelagic habitats (permanently-mixed versus stratified in summer). However, this analysis also shows a pool of common ASVs among which some are persistent and dominant in both sites. The observed synchronous variations in relative read abundances of shared ASVs assigned to Chaetoceros socialis, C. tenuissimus, Cyclotella, Mediolabrus comicus and Leptocylindrus aporus at the two geographically distant sites could indicate that internal controls of growth rate and sexual reproduction, rather that external environmental parameters are at work.
The Fatty Acid Binding Protein Family Represents a Novel Target in Multiple Myeloma
Authors: Farrell Mariah , Fairfield Heather , Karam Michelle , D’Amico Anastasia , Murphy Connor S. , Falank Carolyne , Pistofidis Romanos Sklavenitis , Cao Amanda , Marinac Catherine R. , Dragon Julie A. , McGuinness Lauren , Gartner Carlos , Di Iorio Reagan , Jachimowicz Edward , DeMambro Victoria , Vary Calvin , Reagan Michaela R. 
Published: July 2022

ABSTRACTBackgroundMultiple myeloma is an incurable plasma cell malignancy with only a 53% 5-year survival rate, highlighting a critical need for new multiple myeloma vulnerabilities and therapeutic avenues. Herein, we explored a novel multiple myeloma target: the fatty acid binding protein (FABP) family.MethodsMyeloma cells treated with FABP inhibitors (BMS3094013 and SBFI-26) were examined in vivo and in vitro for cell cycle, proliferation, apoptosis, mitochondrial membrane potential, cellular metabolism (oxygen consumption rates and fatty acid oxidation), and DNA methylation. Myeloma cell responses to BMS309403 and/or SBFI-26 were assessed with RNA-sequencing and proteomic analysis, and confirmed with western blotting and qRT-PCR. Myeloma cell dependency on FABPs was assessed using DepMap. Finally, MM patient datasets (CoMMpass and GEO) were mined for FABP expression correlations with clinical outcomes.ResultsMyeloma cells treated with FABPi or with FABP5 knockout (generated via CRISPR/Cas9 editing) exhibited diminished proliferation in vitro. FABPi had potent anti- tumor effects both in vitro and in vivo in two pre-clinical MM mouse models where increased mouse survival was observed. FABPi negatively impacted mitochondrial respiration and reduced expression of MYC and other key signaling pathways in MM cells. Clinical data demonstrated worse overall and progression-free survival in patients with high FABP5.ConclusionsThis study establishes the FABP family as a therapeutically actionable dependency in multiple myeloma with a multitude of actions and cellular roles that result in the support of myeloma progression.Statement of translational relevanceMultiple myeloma (MM) is an incurable disease of the plasma cell and MM patients require better treatments as soon as possible. The fatty acid binding protein (FABP) family plays a number of roles in cells, including supporting fatty acid oxidation, lipid shuttling and signal transduction. Here, we demonstrate with CoMMpass and other clinical data that FABPs represent a biomarker for aggressive disease in MM, and are a novel, targetable protein family expressed by myeloma cells. Pharmacologically inhibiting FABPs kills tumor cells and induces cell cycle arrest in vitro and in pre-clinical models. Mechanisms of action are multitudinous, as we discovered with RNA-sequencing, proteomic analysis, and phenotyping assays. Cell metabolism, cell signaling, cell stress, and epigenetic signatures were altered in MM cells when FABPs were inhibited. In summary, targeting FABP5 holds great therapeutic potential for killing diseased cells, with few negative off-target effects on healthy cells.
Loosenin-like proteins fromPhanerochaete carnosaimpact both cellulose and chitin fiber networks
Authors: Monschein Mareike , Ioannou Eleni , Amin Leamon AKM AL , Varis Jutta J. , Wagner Edward R. , Mikkonen Kirsi S. , Cosgrove Daniel J. , Master Emma R. 
Published: July 2022

AbstractMicrobial expansin-related proteins are ubiquitous across bacterial and fungal organisms, and reportedly play a role in the modification and deconstruction of cell wall polysaccharides including lignocellulose. So far, very few microbial expansin related proteins, including loosenins and loosenin-like (LOOL) proteins, have been functionally characterized. Herein, four LOOLs encoded byPhanerochaete carnosaand belonging to different subfamilies (i.e., PcaLOOL7 and PcaLOOL9 from subfamily A; PcaLOOL2 and PcaLOOL12 from subfamily B) were recombinantly produced and the purified proteins were characterized using diverse cellulose and chitin substrates. Whereas all of the purified PcaLOOLs weakened cellulose filter paper and cellulose nanofibril networks (CNF), none significantly boosted cellulase activity on the selected cellulose substrates (Avicel and Whatman paper). Binding of PcaLOOLs to alpha-chitin was higher than to cellulose (Avicel), and highest at pH 5.0. Notably, whereas PcaLOOL9 reduced the yield strain of chitin nanofibrils (ChNF) in a protein-dose dependent manner, the reverse pattern was observed for PcaLOOL7 despite belonging to the same LOOL subfamily. The current study reveals the potential of microbial expansin-related proteins to impact both cellulose and chitin networks, and provides further evidence pointing to a non-lytic mode of action.
Optimization and comparison of two methods for spike train estimation in an unfused tetanic contraction of low threshold motor units
Authors: Rohlén Robin , Antfolk Christian , Grönlund Christer 
Published: July 2022

AbstractBackgroundHuman movement is generated by activating motor units (MUs), i.e., the smallest structures that can be voluntarily controlled. Recent findings have shown imaging of voluntarily activated MUs using ultrafast ultrasound based on displacement velocity images and a decomposition algorithm. Given this, estimates of trains of twitches (unfused tetanic signals) evoked by the neural discharges (spikes) of spinal motor neurons are provided. Based on these signals, a band-pass filter method (BPM) has been used to estimate its spike train. In addition, an improved spike estimation method consisting of a continuous Haar wavelet transform method (HWM) has been suggested. However, the parameters of the two methods have not been optimized, and their performance has not been compared rigorously.MethodHWM and BPM were optimized using simulations. Their performance was evaluated based on simulations and two experimental datasets with 21 unfused tetanic contractions considering their rate of agreement, spike offset, and spike offset variability with respect to the simulated or experimental spikes.ResultsA range of parameter sets that resulted in the highest possible agreement with simulated spikes was provided. Both methods highly agreed with simulated and experimental spikes, but HWM was a better spike estimation method than BPM because it had a higher agreement, less bias, and less variation (p< 0.001).ConclusionsThe optimized HWM will be an important contributor to further developing the identification and analysis of MUs using imaging, providing indirect access to the neural drive of the spinal cord to the muscle by the unfused tetanic signals.
Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain and placenta
Authors: Husso Aleksi , Pessa-Morikawa Tiina , Koistinen Ville Mikael , Kärkkäinen Olli , Lahti Leo , Iivanainen Antti , Hanhineva Kati , Niku Mikael 
Published: July 2022

AbstractThe maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. We compared full-term fetuses from germ-free (GF) and normally colonized mouse dams by gene expression profiling and non-targeted metabolomics. The developing immune system was strongly dependent on the maternal microbial status. In the fetal intestine, critical components mediating host-microbe interactions were differentially expressed. In fetal brain and placenta, interferon and inflammatory signaling were downregulated in germ-free fetuses. Neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected at the gene expression level. These impacts were strongly associated with microbial metabolite concentrations in the fetal tissues, suggesting that they are largely, although perhaps not exclusively mediated by maternal microbial metabolites absorbed through placenta. Several aryl sulfates were among the compounds strongly associated with gene expression differences. The germ-free fetus may suffer from depletion of queuine, a bacterial hypermodified nucleobase essential for eukaryotic tRNA stability and function.
Voltage to Calcium Transformation Enhances Direction Selectivity in Drosophila T4 neurons
Authors: Mishra Abhishek , Borst Alexander , Haag Juergen 
Published: July 2022

AbstractA critical step in neural information processing is the transformation of membrane voltage into calcium signals leading to transmitter release. However, the effect of voltage to calcium transformation on neural responses to different sensory stimuli is not well understood. Here, we use in vivo two-photon imaging of genetically encoded voltage and calcium indicators, Arclight and GCaMP6f respectively, to measure responses in Drosophila direction-selective T4 neurons.Comparison between Arclight and GCaMP6f signals revealed calcium signals to have a significantly higher direction selectivity compared to voltage signals. Using these recordings we build a model which transforms T4 voltage responses to calcium responses. The model reproduces experimentally measured calcium responses across different visual stimuli using different temporal filtering steps and a stationary non-linearity. These findings provide a mechanistic underpinning of the voltage-to-calcium transformation and show how this processing step, in addition to synaptic mechanisms on the dendrites of T4 cells, enhances direction selectivity in the output signal of T4 neurons.