bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate and fast graph-based pangenome annotation and clustering with ggCaller
Authors: Horsfield Samuel T. , Croucher Nicholas J. , Lees John A. 
Published: January 2023

AbstractBacterial genomes differ in both gene content and sequence mutations, which can cause important clinical phenotypic differences such as vaccine escape or antimicrobial resistance. To identify and quantify important variants, all genes within a population must be predicted, functionally annotated and clustered, representing the ‘pangenome’. Despite the volume of genome data available, gene prediction and annotation are currently conducted in isolation on individual genomes, which is computationally inefficient and frequently inconsistent across genomes. Here, we introduce the open-source software graph-gene-caller (ggCaller;https://github.com/samhorsfield96/ggCaller). ggCaller combines gene prediction, functional annotation and clustering into a single step using population-wide de Bruijn Graphs, removing redundancy in gene annotation, and resulting in more accurate gene predictions and orthologue clustering. We applied ggCaller to simulated and real-world bacterial genome datasets, comparing it to current state-of-the-art tools. ggCaller is ~50x faster with equivalent or greater accuracy, particularly in datasets with complex sources of error, such as assembly contamination or fragmentation. ggCaller is also an important extension to bacterial genome-wide association studies, enabling querying of annotated graphs for functional analyses. We highlight this application by functionally annotating DNA sequences with significant associations to tetracycline and macrolide resistance inStreptococcus pneumoniae, identifying key resistance determinants that were missed when using only a single reference genome. ggCaller is a novel bacterial genome analysis tool with applications in bacterial epidemiology and evolutionary study.
UL135 and UL136 Epistasis Controls Reactivation of Human Cytomegalovirus
Authors: Moy Melissa A. , Collins-McMillen Donna , Crawford Lindsey , Parkins Christopher , Zeltzer Sebastian , Caviness Katie , Caposio Patrizia , Goodrum Felicia 
Published: January 2023

ABSTRACTHuman cytomegalovirus (HCMV) is beta herpesvirus that persists indefinitely in the human host through a protracted, latent infection. The polycistronicUL133-UL138gene locus of HCMV encodes genes regulating latency and reactivation. While UL138 is pro-latency, restricting virus replication in CD34+ hematopoietic progenitor cells (HPCs), UL135 overcomes this restriction for reactivation. By contrast, UL136 is expressed with later kinetics and encodes multiple protein isoforms with differential roles in latency and reactivation. Like UL135, the largest UL136 isoform, UL136p33, is required for reactivation from latency in hematopoietic cells. Furthermore, UL136p33 is unstable, and its instability is important for the establishment of latency and sufficient accumulation of UL136p33 is a checkpoint for reactivation. We hypothesized that stabilizing UL136p33 might overcome the requirement of UL135 for reactivation. To test this, we generated recombinant viruses lacking UL135 that expressed a stabilized variant of UL136p33. Stabilizing UL136p33 did not impact replication of the UL135-mutant virus in fibroblasts. However, in the context of infection in hematopoietic cells, stabilization of UL136p33 strikingly compensated for the loss ofUL135,resulting in increased replication in CD34+ HPCs and in humanized NOD-scidIL2Rγcnull(NSG) mice. This finding suggests that while UL135 is essential for reactivation, it functions at steps preceding the accumulation of UL136p33 and that stabilized expression of UL136p33 largely overcomes the requirement for UL135 in reactivation. Taken together, our genetic evidence indicates an epistatic relationship between UL136p33 and UL135 whereby UL135 may initiate events early in reactivation that will result in the accumulation of UL136p33 to a threshold required for productive reactivation.SIGNIFICANCEHuman cytomegalovirus (HCMV) is one of nine human herpesviruses and a significant human pathogen. While HCMV establishes a life-long latent infection that is typically asymptomatic in healthy individuals, its reactivation from latency can have devastating consequences in the immune compromised. Defining virus-host and virus-virus interactions important for HCMV latency, reactivation and replication is critical to defining the molecular basis of latent and replicative states and in controlling infection and CMV disease. Here we define a genetic relationship between two viral genes in controlling virus reactivation from latency using primary human hematopoietic progenitor cell and humanized mouse models.
Description of three new species of predatory GenusHexacentrus(Orthoptera: Tettigoniidae) from India, with bioacoustic and morphological characterization
Authors: Ghosh Aarini , Jaiswara Ranjana , Monaal  , Sabharwal Shagun , Dasoju Vivek , Bhattacharjee Anubhab , Rajaraman Bittu Kaveri 
Published: January 2023

AbstractHexacentrusis a genus of predatory katydids. In India, the genusHexacentrusis represented by 7 species of which 6 are morphologically characterized while one is only acoustically characterized. In this study, we describe three new species under the genus from India based on detailed morphological, stridulatory, and acoustic features.
Ramped V1 transcranial ultrasonic stimulation modulates but does not evoke visual evoked potentials
Authors: Nandi Tulika , Johnstone Ainslie , Martin Eleanor , Cooper Robert , Bestmann Sven , Bergmann Til Ole , Treeby Bradley , Stagg Charlotte J. 
Published: January 2023

AbstractTranscranial ultrasonic stimulation (TUS), has been shown to evoke ‘visual evoked potential (VEP)-like’ potentials on EEG recordings, and also to modulate sensory evoked potentials. However, pulsed TUS is accompanied by an auditory confound, and it is possible that any observed effects were, in-part, evoked by this confound. Therefore, we used ramped TUS pulses, which are not as easily audible, to examine whether primary visual cortex (V1) TUS evokes VEP-like potentials, and modulates VEPs elicited using a checkerboard stimulus.MethodsWe tested 14 healthy participants (31 ± 4.3 yrs, 4 F and 10 M). TUS was applied to the left V1 using a 270 kHz transducer (H115-2AA, Sonic Concepts). Ramped pulses (1 ms ramp, 3.25 ms total pulse duration) were repeated at 250 Hz, with a pulse train duration of 300 ms, an effective duty cycle of 50%, and Isppa without ramping of 16 W/cm2in water. EEG was recorded from 16 channels using the g.USBamp amplifier (g.tec medical engineering GmbH). In two blocks (TUS-only), real and sham (100 each) TUS trials were repeated every 2 s. In another two blocks (TUS+checkerboard), a checkerboard stimulus was flipped every 0.5 s, and every fourth stimulus was associated with either a real or sham (100 each) TUS trial. The TUS trial started approx. 130 ms (0-5 ms jitter) before the checkerboard flip. All EEG data were analysed using Fieldtrip, and cluster-based permutation tests were used to test for differences between conditions.Results and discussionIn the TUS-only condition, in contrast to a previous study, we found no evoked potentials using ramped pulses which minimised the auditory artifact. In the TUS+checkerboard condition, we observed a modulation of the early-component of the VEP in real TUS, relative to no TUS trials. This suggests that, in line with in-vitro and animal data, there is a direct neuromodulatory effect of ultrasound, in addition to any confounding effects. Moving forward, ramping offers a relatively easy approach to minimise the auditory confound.
Recovery of protein synthesis to measure transcription-coupled DNA repair in living cells and tissues
Authors: van der Woude Melanie , Davó-Martínez Carlota , Thijssen Karen L. , Vermeulen Wim , Lans Hannes 
Published: January 2023

ABSTRACTTranscription-coupled nucleotide excision repair (TC-NER) is an important DNA repair mechanism that protects against the negative effects of transcription-blocking DNA lesions. Hereditary TC-NER deficiency causes pleiotropic and often severe neurodegenerative and progeroid symptoms. Multiple assays have been developed for the clinic and for research to measure TC-NER activity, which is hampered by the relatively low abundance of repair events taking place in transcribed DNA. ‘Recovery of RNA Synthesis’ is widely used as indirect TC-NER assay based on the notion that lesion-blocked transcription only resumes after successful TC-NER. Here, we show that measuring novel synthesis of a protein that has been degraded prior to DNA damage induction is an equally effective but more versatile manner to indirectly monitor TC-NER. This ‘Recovery of Protein Synthesis’ (RPS) assay is readily adaptable for use with different degradable proteins and readouts, including fluorescence imaging and immunoblot. Moreover, with the RPS assay TC-NER activity can be measured in real-time, in various living cells types and even in differentiated tissues of living organisms. As example, we show that TC-NER capacity declines in aging muscle tissue ofC. elegans. Therefore, the RPS assay constitutes an important novel clinical and research tool to investigate transcription-coupled DNA repair.
Microbe-derived indole tunes organ-function and links microbe metabolites to biological ageing
Authors: Xing Peter Yuli , Jayaraman Anusha , Zhang George Wei , Martin Katherine Ann , Faylon Llanto Elma , Kjelleberg Staffan , Rice Scott A. , Wang Yulan , Bello Adesola T. , Holmes Elaine , Nicholson Jeremy K , Whiley Luke , Pettersson Sven 
Published: January 2023

AbstractTo investigate the underlying molecular mechanisms on how the gut microbe metabolite, indoles, regulate host organ growth and function, germ-free male mice were mono-colonized with indole-producing wildtypeEscherichia colior tryptophanase-encodingtnaAknockout mutant indole-non-producingE. coli. The indole mutantE. colirecipient mice exhibited significant multiorgan decline and growth retardation combined with catabolism and energy deficiency despite increased food intake compared to control mice. In addition, indole mutant mice displayed malfunctional intestine, enlarged caecum, reduced numbers of colonic enterochromaffin cells and reduced circulating serotonin levels, resulting in reduced gut motility, diminished digestion, and lower energy harvest. Furthermore, indole mutant mice also displayed decreased expression ofKcnj12gene, suggesting reduced excitability of enteric neurons thus adding to intestinal dysfunctional phenotype. In conclusion, indoles are necessary to maintain adult metabolic homeostasis across multiple organs in vivo. Impairment of indole levels results in multiorgan functional decline suggesting a mechanism whereby gut microbe metabolites may regulate biological ageing and thus increase the risk for disease.Graphical summary
A Comparison of Lossless Compression Methods in Microscopy Data Storage Applications
Authors: Walker Logan A. , Li Ye , McGlothlin Maggie , Cai Dawen 
Published: January 2023

ABSTRACTModern high-throughput microscopy methods such as light-sheet imaging and electron microscopy are capable of producing petabytes of data inside of a single experiment. Storage of these large images, however, is challenging because of the difficulty of moving, storing, and analyzing such vast amounts of data, which is often collected at very high data rates (>1GBps). In this report, we provide a comparison of the performance of several compression algorithms using a collection of published and unpublished datasets including confocal, fMOST, and pathology images. We also use simulated data to demonstrate the efficiency of each algorithm as image content or entropy increases. As a result of this work, we recommend the use of theBLOSCalgorithm combined withZSTDfor various microscopy applications, as it produces the best compression ratio over a collection of conditions.CCS CONCEPTS• Applied computing → Bioinformatics; Imaging.
Transient Aurein 1.2 pores in prokaryotic model bilayers explored by coarse-grain molecular dynamics simulations: as glycolipid content increases, pore lifetime decreases
Authors: Balatti GE , Martini MF , Pickholz M 
Published: January 2023

ABSTRACTThe Aurein 1.2 is an anuran antimicrobial peptide (AMP) with a proven lytical activity against bacterial membranes. Previously, we found a differential action of aurein by both experimental and computational methods. This differential action was over membranes of two related probiotic strains, where the main differences between membranes were the number of glycolipids on lipid composition. In the present work, we focused on the differential behavior of the aurein 1.2 at its interaction with bacterium model membranes with different amounts of glycolipids in their composition. We carried out extensive molecular dynamics (MD) simulations by using the coarse-grain force field MARTINI and raising up differential mixtures of phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and monogalactosylglycerol (MG). We found a correlation between the presence of MG in PG/PE mixtures and the difficulty of aurein to stabilize pore structures, suggesting an AMPresistance factor encoded in the lipid composition of the membrane. Through this study, we hope to shed light on a possible resistance mechanism to AMPs related with the glycolipid content of diverse types of bacterial membranes.
Cholecystokinin-A Signaling Regulates Automaticity of Pacemaker Cardiomyocytes
Authors: Ruan Hongmei , Mandla Ravi , Ravi Namita , Galang Giselle , Soe Amanda W. , Olgin Jeffrey E. , Lang Di , Vedantham Vasanth 
Published: January 2023

ABSTRACTAimsThe behavior of pacemaker cardiomyocytes (PCs) in the sinoatrial node (SAN) is modulated by neurohormonal and paracrine factors, many of which signal through G-protein coupled receptors (GPCRs). The aims of the present study are to catalog GPCRs that are differentially expressed in the mammalian SAN and to define the acute physiological consequences of activating the cholecystokinin-A signaling system in isolated PCs.Methods and ResultsUsing bulk and single cell RNA sequencing datasets, we identify a set of GPCRs that are differentially expressed between SAN and right atrial tissue, including several whose roles in PCs and in the SAN have not been thoroughly characterized. Focusing on one such GPCR, Cholecystokinin-A receptor (CCKAR), we demonstrate expression ofCckarmRNA specifically in mouse PCs, and further demonstrate that subsets of SAN fibroblasts and neurons within the cardiac intrinsic nervous system express cholecystokinin, the ligand for CCKAR. Using mouse models, we find that while baseline SAN function is not dramatically affected by loss of CCKAR, the firing rate of individual PCs is slowed by exposure to sulfated cholecystokinin-8 (sCCK-8), the high affinity ligand for CCKAR. The effect of sCCK-8 on firing rate is mediated by reduction in the rate of spontaneous phase 4 depolarization of PCs and is mitigated by activation of beta-adrenergic signaling.Conclusions(1) PCs express many GPCRs whose specific roles in SAN function have not been characterized, (2) Activation of the the cholecystokinin-A signaling pathway regulates PC automaticity.
Artificial intelligence-driven morphology-based enrichment of malignant cells from body fluid
Authors: Mavropoulos Anastasia , Johnson Chassidy , Lu Vivian , Nieto Jordan , Schneider Emilie , Saini Kiran , Phelan Michael L. , Hsie Linda , Wang Maggie , Cruz Janifer , Mei Jeanette , Kim Julie , Lian Zhouyang , Li Nianzhen , Boutet Stephane C. , Wong-Thai Amy , Yu Weibo , Lu Qing-Yi , Kim Teresa , Geng Yipeng , Masaeli Maddison (Mahdokht) , Lee Thomas D. , Rao Jianyu 
Published: January 2023

ABSTRACTCell morphology is a fundamental feature used to evaluate patient specimens in pathological analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with high background of non-malignant cells, restricting the ability for downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multi-dimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low-levels or undetectable in pre-sort patient samples. Combined, our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multi-dimensional morphology analysis, and microfluidic sorting.
Stem cell factor and granulocyte colony-stimulating factor promote remyelination in the chronic phase of severe traumatic brain injury
Authors: Qiu Xuecheng , Ping Suning , Kyle Michele , Chin Lawrence , Zhao Li-Ru 
Published: January 2023

AbstractSevere traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination which is characterized by myelin sheath disruption and oligodendrocyte cell death leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colony–stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF+G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF+G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF+G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF+G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF+G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF+G-CSF-enhanced remyelination in chronic TBI.
Interleg coordination is not strictly controlled during walking
Authors: Arai Takahiro , Ota Kaiichiro , Funato Tetsuro , Tsuchiya Kazuo , Aoyagi Toshio , Aoi Shinya 
Published: January 2023

SummaryIn human walking, the left and right legs move alternately, half a stride out of phase with each other. Although various parameters, such as stride frequency, stride length, and duty factor, vary with walking speed, the antiphase relationship of the leg motion remains unchanged. This is the case even during running. However, during walking in left-right asymmetric situations, such as walking with unilateral leg loading, walking along a curved path, and walking on a split-belt treadmill, the relative phase between left and right leg motion shifts from the antiphase condition to compensate for the asymmetry. In addition, the phase relationship fluctuates significantly during walking of elderly people and patients with neurological disabilities, such as those caused by stroke or Parkinson’s disease. These observations suggest that appropriate interleg coordination is important for adaptive walking and that interleg coordination is strictly controlled during walking of healthy young people. However, the control mechanism of interleg coordination remains unclear. In the present study, we derive a quantity that models the control of interleg coordination during walking of healthy young people by taking advantage of a state-of-the-art method that combines big data science with nonlinear dynamics. This is done by modeling this control as the interaction between two coupled oscillators through the phase reduction theory and Bayesian inference method. However, the results were not what we expected. Specifically, we found that the relative phase between the motion of the legs is not actively controlled until the deviation from the antiphase condition exceeds a certain threshold. In other words, the control of interleg coordination has a dead zone like that in the case of the steering wheel of an automobile. Such forgoing of control presumably enhances energy efficiency and maneuverability during walking. Furthermore, the forgoing of control in specific situations, where we expect strict control, also appears in quiet standing. This suggests that interleg coordination in walking and quiet standing have a common characteristic strategy. Our discovery of the dead zone in the control of interleg coordination not only provides useful insight for understanding gait control in humans, but also should lead to the elucidation of the mechanisms involved in gait adaptation and disorders through further investigation of the dead zone.
Gestational diabetes mellitus dysregulates the PD-1/PD-L1 axis at the feto-maternal interface
Authors: Mihalic ZN. , Kindler O. , Raftopoulou S. , Santiso A. , Wadsack C. , Heinemann A. , Kargl J. 
Published: January 2023

ABSTRACTThe most common pregnancy complication is gestational diabetes mellitus (GDM), which is a glucose tolerance disorder. Obesity and older maternal age, which are associated with low-grade systemic inflammation, are the main risk factors for GDM. To evaluate the complexity and differences in the immune landscape at the fetal-maternal interface, we examined the maternally derived tissue, decidua basalis (DB), from healthy women, women with obesity, and women with GDM using flow cytometry, western blot, and gene expression analysis. Our results showed that the immune cell composition of DB is not altered by obesity; however, in GDM pregnancies, the DB displays a dysregulated PD-1/PD-L1 axis and significantly reduced regulatory T cell (Treg) infiltration, suggesting reduced local immunosuppression. Our study provides a detailed picture of the immune landscape at the fetal-maternal interface in normal, obese, and GDM pregnancies. This will aid our understanding of possible dysfunctional immune mechanisms in GDM.
Diatom phytochromes integrate the entire visible light spectra for photosensing in marine environments
Authors: Duchêne Carole , Bouly Jean-Pierre , Karlusich Juan José Pierella , Sellés Julien , Bailleul Benjamin , Bowler Chris , d’Alcalà Maurizio Ribera , Falciatore Angela , Jaubert Marianne 
Published: January 2023

AbstractAquatic life is strongly structured by light gradients, with gradual decrease in light intensity and differential attenuation of sunlight wavelengths with depth. How phytoplankton perceive these variations is unknown. By providing the firstin vivoquantitative assessment of the action of marine diatom phytochrome photoreceptors (DPH), we show that they efficiently trigger photoreversible responses across the entire light spectrum, unlike current models of phytochrome photosensing. The distribution and activity of DPHs in the environment indicate that they are extremely sensitive detectors of spectral light variations related to depth and optical properties of the water column in temperate and polar oceans, revealing a completely novel view of how light is perceived in the marine environment.