bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ring formation byVibriofusion protein composed of FliF and FliG, MS-ring and C-ring component of bacterial flagellar motor in membrane
Authors: Takahashi Kanji , Nishikino Tatsuro , Kajino Hiroki , Kojima Seiji , Uchihashi Takayuki , Homma Michio 
Published: February 2023

ABSTRACTThe marine bacteriumVibrio alginolyticushas a single flagellum as a locomotory organ at the cell pole, which is rotated by the Na+-motive force to swim in a liquid. The base of the flagella has a motor composed of a stator and rotor, which serves as a power engine to generate torque through the rotor–stator interaction coupled to Na+influx through the stator channel. The MS-ring, which is embedded in the membrane at the base of the flagella as part of the rotor, is the initial structure required for flagellum assembly. It comprises 34 molecules of the two-transmembrane protein FliF. FliG, FliM, and FliN form a C-ring just below the MS-ring. FliG is an important rotor protein that interacts with the stator PomA and directly contributes to force generation. We previously found that FliG promotes MS-ring formation inE. coli. In the present study, we constructed afliF–fliGfusion gene, which encodes an approximately 100 kDa protein, and the successfully production of this protein effectively formed the MS-ring inE. colicells. We observed fuzzy structures around the ring using either electron microscopy or high-speed atomic force microscopy (HS-AFM), suggesting that FliM and FliN are necessary for the formation of a stable ring structure. The HS-AFM movies revealed flexible movements at the FliG region. We speculate that this flexibility plays a crucial role in facilitating the interaction between the cytoplasmic region of PomA and FliG to generate force.IMPORTANCEMS-ring is the initial structure to be assembled in flagellar motors. It comprises a complex two-ring (M and S) structure composed of 34 FliF molecules. We prepared a FliF–FliG fusion protein, which is directly involved in force generation. We observed it enabled the efficient formation of the MS-ring. The FliG portion that usually comprises the C-ring along with FliM and FliN displayed high flexibility likely due to the lack of FliM and FliN in the fusion protein. This study represents a significant milestone in thein vitroreconstruction of Na+-driven motor complexes.
Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review
Authors: Thomas SJ , Enders J , Kaiser A , Rovenstine L , Heslop L , Hauser W , Chadwick A , Wright DE 
Published: February 2023

AbstractBackgroundIntraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique.MethodsWe conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5).ResultsWe analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 74 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of -47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of -31.6 % and - 34.7% respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents.InterpretationReduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.
A Systematic Review of the Association between the Age of Onset of Spinal-Bulbar Muscular Atrophy (Kennedy’s Disease) and the Length of CAG Repeats in the Androgen Receptor Gene
Authors: Bellai Dante J. , Rae Mark G. 
Published: February 2023

AbstractBackgroundSpinal bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disorder which is caused by the presence of ≥ 38 CAG repeats in the androgen receptor gene. Relatively little is known about SBMA, but existing literature indicates a relationship between CAG repeat number and the onset age of some motor symptoms of SBMA. This literature review explored the effect of larger CAG repeats on the age of weakness onset compared to shorter length CAG repeats in male SBMA patients.MethodsThree databases were searched (MEDLINE, SCOPUS, and Web of Science; Oct 2021) along with targeted searches in Cambridge University Press and Annals of Neurology. 514 articles were initially identified, of which 13 were included for qualitative synthesis.ResultsEleven of the thirteen articles identified a statistically significant inverse correlation between CAG repeat length and age of weakness onset in SBMA. Five studies indicated that SBMA patients with fewer CAG repeats (e.g. 35-37) had an older age of weakness onset than patients with a greater number (e.g. >40) of CAG repeats. The minimum number of CAG repeats associated with weakness was numbered in the mid-to-late thirties.ConclusionIdentification of a relationship between CAG repeat number and weakness may enable earlier detection and intervention for SBMA.Limitations of this review include the restriction to English-only studies and differences in statistical methodology used in each study. We recommend that future studies use interviews, chart reviews, and standardized scoring methods to reduce effects of retrospective bias on reporting SBMA signs and symptoms.
Lysis cassette-mediated exoprotein release inYersinia entomophagais controlled by a PhoB- like regulator
Authors: Schoof Marion , O’Callaghan Maureen , Hefer Charles , Glare Travis R. , Paulson Amber R. , Hurst Mark R.H. 
Published: February 2023

ABSTRACTSecretion of exoproteins is a key component of bacterial virulence and is tightly regulated in response to environmental stimuli and host-dependent signals. The entomopathogenic bacteriumYersinia entomophagaMH96 produces a wide range of exoproteins including its main virulence factor, the 2.46 MDa insecticidal Yen-Tc toxin complex. Previously, a high-throughput transposon-based screening assay identified the region of exoprotein release (YeRER) as essential to exoprotein release in MH96. The current study defines the role of the YeRER-associatedambiguous holin/endolysin-based lysiscluster (ALC) and the novel RoeA regulator in the regulation and release of exoproteins in MH96. A mutation in the ALC region abolished exoprotein release and caused cell elongation, a phenotype able to be restored throughtrans-complementation with an intact ALC region. Endogenous ALC did not impact cell growth of the wild type, while artificial expression of an optimised ALC caused cell lysis. Using HolA-sfGFP and Rz1-sfGFP reporter, Rz1 expression was observed in all cells while HolA expression was limited to a small proportion of cells, which increased over time. Transcriptomic assessments found expression of the genes encoding the prominent exoproteins, including the Yen-Tc, was reduced in theroeAmutant and identified a 220 ncRNA of the YeRER intergenic that, whentranscomplemented in the wildtype, abolished exoprotein release. A model forY. entomophagamediated exoprotein regulation and release is proposed.ImportanceWhile theoretical models exist, there is not yet any empirical data that links ALC phage-like lysis cassettes with the release of large macro-molecular toxin complexes such as Yen-Tc in Gram-negative bacteria. In this study, we demonstrate that the novelY. entomophagaRoeA activates the production of exoproteins (including Yen-Tc) and the ALC at the transcriptional level. The translation of the ALC holin is confined to a subpopulation of cells that then lyse over time, indicative of a complex hierarchical regulatory network. The presence of orthologous RoeA orthologue and a HolA like holin 5’ of an eCIS Afp element inPseudomonas chlororaphiscombined with the presented data suggests a shared mechanism is required for the release of some large macromolecular protein assemblies such as the Yen-Tc, and further supports classification of phage-like lysis clusters as type 10 secretion systems.
aweMAGs: a fully automated workflow for quality assessment and annotation of eukaryotic genomes from metagenomes
Authors: Albanese Davide , Coleine Claudia , Selbmann Laura , Donati Claudio 
Published: February 2023

AbstractMetagenomics is one of the most promising approaches to identify and characterize novel microbial species from environmental samples. While a large amount of prokaryotic metagenome assembled genomes (MAGs) have been published, only a few examples of eukaryotic MAGs have been reported. This is in part due to the absence of dedicated and easy-to-use processing pipelines. Quality assessment, annotation and phylogenomic placement of eukaryotic MAGs involve the use of several computational tools and reference databases that are often difficult to collect and maintain. We present metashot/aweMAGs, a fully automated workflow capable of performing all these steps. metashot/aweMAGs can run out-of-the-box on any platform that supports Docker, Singularity and Nextflow, including computing clusters or batch systems in the cloud.
Targeting the cell and non-cell autonomous regulation of 47S synthesis by GCN2 in colon cancer
Authors: Piecyk Marie , Triki Mouna , Laval Pierre-Alexandre , Duret Cedric , Fauvre Joelle , Cussonneau Laura , Machon Christelle , Guitton Jerôme , Rama Nicolas , Gibert Benjamin , Ichim Gabriel , Catez Frederic , Bourdelais Fleur , Durand Sebastien , Diaz Jean-Jacques , Coste Isabelle , Renno Toufic , Manié Serge N , Aznar Nicolas , Ansieau Stephane , Ferraro-Peyret Carole , Chaveroux Cedric 
Published: February 2023

AbstractNutrient availability is a key determinant of tumor cell behavior. While nutrient-rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor GCN2 represses the expression of the precursor of ribosomal RNA, 47S, under metabolic stress. We show that blockade of GCN2 triggers cell death by an irremediable nucleolar stress and subsequent TP53-mediated apoptosis in patient-derived models of colon adenocarcinoma (COAD). In nutrient-rich conditions, GCN2 activity supports cell proliferation through the transcription stimulation of 47S rRNA, independently of the canonical ISR axis. However, impairment of GCN2 activity prevents nuclear translocation of the methionyl tRNA synthetase (MetRS) underlying the generation of a nucleolar stress, mTORC1 inhibition and autophagy induction. Inhibition of the GCN2-MetRS axis drastically improves the cytotoxicity of RNA pol I inhibitors, including the first-line chemotherapy oxaliplatin, on patient-derived COAD tumoroids. Our data thus reveal that GCN2 differentially controls the ribosome biogenesis according the nutritional context. Furthermore, pharmacological co-inhibition of the two GCN2 branches and the RNA pol I activity may represent a valuable strategy for elimination of proliferative and metabolically-stressed COAD cell.
Comparative proteomics of vesicles essential for the egress ofPlasmodium falciparumgametocytes from red blood cells
Authors: Sassmannshausen Juliane , Bennink Sandra , Distler Ute , Küchenhoff Juliane , Minns Allen M. , Lindner Scott E. , Burda Paul-Christian , Tenzer Stefan , Gilberger Tim W. , Pradel Gabriele 
Published: February 2023

AbstractTransmission of malaria parasites to the mosquito is mediated by sexual precursor cells, the gametocytes. Upon entering the mosquito midgut, the gametocytes egress from the enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which the membrane of the parasitophorous vacuole ruptures prior to the erythrocyte membrane. Membrane rupture requires the exocytosis of specialized secretory vesicles of the parasites; i.e. the osmiophilic bodies (OBs) involved in rupturing the parasitophorous vacuole membrane, and vesicles (here termed g-exonemes) that harbour the perforin-like protein PPLP2 required for erythrocyte lysis. While several OB proteins are known, like G377 and MDV1/Peg3, the protein composition of the g-exonemes remains unclear. Here, we used high- resolution imaging and BioID methods to study the two types of egress vesicles inPlasmodium falciparumgametocytes. We show that OB exocytosis precedes discharge of the g-exonemes and that exocytosis of the g-exonemes, but not of the OBs, is calcium-sensitive. Further, the two types of vesicles exhibit distinct proteomes. In addition to known egress-related proteins, our analyses revealed novel components of OBs and g-exonemes, including proteins involved in vesicle trafficking. Our data provide insight into the immense molecular machinery required for the inside-out egress ofP. falciparumgametocytes.
A novel HERC4-dependent glue degrader targeting STING
Authors: Mutlu Merve , Schmidt Isabel , Morrison Andrew I. , Goretzki Benedikt , Freuler Felix , Begue Damien , Pythoud Nicolas , Ahrne Erik , Kapps Sandra , Roest Susan , Bonenfant Debora , Jeanpierre Delphine , Tran Thi-Thanh-Thao , Maher Rob , An Shaojian , Rietsch Amandine , Nigsch Florian , Hofmann Andreas , Reece-Hoyes John , Parker Christian N. , Guerini Danilo 
Published: February 2023

AbstractStimulator of interferon genes (STING) is a central component of the pathway sensing the presence of cytosolic nucleic acids, having a key role in type I interferon innate immune response. Localized at the endoplasmic reticulum (ER), STING becomes activated by cGAMP, which is generated by the intracellular DNA sensor cyclic GMP-AMP synthase (cGAS). Due to its critical role in physiological function and its ‘ involvement in a variety of diseases, STING has been a notable focus for drug discovery. Recent advances in drug discovery allow the targeting of proteins previously considered “un-druggable” by novel mechanism of actions. Molecular glue degraders are defined as the compounds leading targeted protein degradation (TPD) by creating novel ligase-substrate interactions. Here, we identified AK59 as a novel molecular glue degrader for STING. A genome-wide, CRISPR/Cas9 knockout screen showed that the compound-mediated degradation of STING by AK59 is compromised by the loss of HECT and RLD domain containing E3 ubiquitin protein ligase 4 (HERC4), ubiquitin-like modifier activating enzyme 5 (UBA5) and ubiquitin like modifier activating enzyme 6 (UBA6). While UBA5 and UBA6 could be the auxiliary factors for AK59 activity, our results indicate that HERC4 is the main E3 ligase for the observed degradation mechanism. Validation by individual CRISPR knockouts, co-immunoprecipitations, as well as proximity mediated reporter assays suggested that AK59 functions as a glue degrader by forming a novel interaction between STING and HERC4. Furthermore, our data reveals that AK59 was effective on the most common pathological STING mutations that cause STING-associated vasculopathy with onset in infancy (SAVI), suggesting a potential clinical application of this mechanism. Thus, these findings not only reveal a novel mechanism for compound-induced degradation of STING but also utilize HERC4 as potential E3 ligase that for TPD, enabling novel therapeutic applications.
Field and genetic evidence support the photosynthetic performance index (PIABS) as an indicator of rice grain yield
Authors: Rodríguez Andrés Alberto , Vilas Juan Manuel , Sartore Gustavo Daniel , Bezus Rodolfo , Colazo José , Maiale Santiago Javier 
Published: February 2023

ABSTRACTThe effective increase of the rice breeding process for grain yield could be sustained by developing efficient tools to accelerate plant selection through the rapid determination of reliable predictors. Here, we have described different associations between grain yield and photosynthetic parameters simply and fast obtainable by a non-invasive technique in flag leaf during the anthesis stage. Among the analyzed photosynthetic parameters, the photosynthetic performance index (PIABS) stood out for its strong association with grain yield. A genome-wide association analysis determined in plants from a rice diversity panel at tillering stage indicated the presence of a quantitative trait locus on chromosome 9 characterized by a set of candidate chloroplastic genes with contrasting haplotypes for PIABS. An analysis of these haplotypes indicated a separation into two groups. One with haplotypes linked to high values of PIABS, which were associated almost exclusively withJaponicaspp. subpopulations, and another with haplotypes linked to low values of PIABS, which were associated exclusively withIndicaspp. subpopulations. Genotypes of theJaponicaspp. subpopulations showed high values in panicle weight, a yield components parameter, compared with theIndicaspp. subpopulations genotypes. The results of this work suggested that PIABScould be an early predictor of grain yield at the tillering stage in rice breeding processes.
8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla
Authors: Rios Nibardo Lopez , Gilbert Kyle M. , Papp Daniel , Cereza Gaspard , Foias Alexandru , Rangaprakash D. , May Markus W. , Guerin Bastien , Wald Lawrence L. , Keil Boris , Stockmann Jason P. , Barry Robert L. , Cohen-Adad Julien 
Published: February 2023

AbstractThe quality of cervical spinal cord images can be improved by the use of tailored radiofrequency coil solutions for ultra-high field imaging; however, very few commercial and research 7 Tesla radiofrequency coils currently exist for the spinal cord, and in particular those with parallel transmit capabilities. This work presents the design, testing and validation of a pTx/Rx coil for the human neck and cervical/upper-thoracic spinal cord. The pTx portion is composed of 8 dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made of 20 semi-adaptable overlapping loops to produce high Signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1+uniformity, power efficiency and/or specific absorption rate (SAR) efficiency. B1+homogeneity, SNR and g-factor was evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper-thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.
Out of sight, out of mind: Responses in primate ventral visual cortex track individual fixations during natural vision
Authors: Xiao Will , Sharma Saloni , Kreiman Gabriel , Livingstone Margaret S. 
Published: February 2023

AbstractDuring natural vision, primates shift their gaze several times per second with large, ballistic eye movements known as saccades. Open questions remain as to whether visual neurons retain their classical retinotopic response properties during natural vision or whether neurons integrate information across fixations and predict the consequences of impending saccades. Answers are especially wanting for vision in complex scenes relevant to natural behavior. We let 13 monkeys freely view thousands of large natural images, recorded over 883 hours of neuronal responses throughout the ventral visual pathway across 4.7 million fixations, and designed flexible analyses to reveal the spatial, temporal, and feature selectivity of the responses. Ventral visual responses followed each fixation and did not become gaze-invariant as monkeys examined an image over seconds. Computational models revealed that neuronal responses corresponded to eye-centered receptive fields. The results suggest that ventral visual cortex remains predominantly retinotopic during natural vision and does not establish a gaze-independent representation of the world.
The impossible challenge of estimating non-existent moments of the Chemical Master Equation
Authors: Wagner Vincent , Radde Nicole 
Published: February 2023

MotivationThe Chemical Master Equation is a set of linear differential equations that describes the evolution of the probability distribution on all possible configurations of a (bio-)chemical reaction system. Since the number of configurations and therefore the dimension of the CME rapidly increases with the number of molecules, its applicability is restricted to small systems. A widely applied remedy for this challenge are moment-based approaches which consider the evolution of the first few moments of the distribution as summary statistics for the complete distribution. Here, we investigate the performance of two moment-estimation methods for reaction systems whose equilibrium distributions encounter heavy-tailedness and hence do not possess statistical moments.ResultsWe show that estimation via Stochastic Simulation Algorithm trajectories lose consistency over time and estimated moment values span a wide range of values even for large sample sizes. In comparison, the Method of Moments returns smooth moment estimates but is not able to indicate the nonexistence of the allegedly predicted moments. We furthermore analyze the negative effect of a CME solution’s heavy-tailedness on SSA run times and explain inherent difficulties.While moment estimation techniques are a commonly applied tool in the simulation of (bio-)chemical reaction networks, we conclude that they should be used with care, as neither the system definition nor the moment estimation techniques themselves reliably indicate the potential heavy-tailedness of the CME’s solution.