bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis
Authors: Tang Wenwu , Yuan Xinzhu , Wang Zhixin , Zhang Ying , Chen Xiaoxia , Yang Xiaohua , Qi Zhirui , Zhang Ju , Li Jie , Xie Xisheng 
Published: March 2023

AbstractBackgroundHeart failure (HF) is a common cardiovascular disease in patients receiving maintenance hemodialysis (MHD). Once these patients on MHD exhibit HF, their hospitalization rate, mortality, and economic burden will be significantly increased. Early identification and prediction of hospitalization and death are of great importance for reducing hospitalization and mortality. This study used multicenter clinical data to develop and externally validate clinical risk models to predict expected mortality and HF hospitalization rates in MHD patients with HF.Materials and MethodsFrom January 2017 to October 2022, 348 patients receiving MHD from four participating centers were enrolled. Demographic data, MHD treatment modalities, laboratory tests, and echocardiography data were collected when the initial event occurred. Three centers were randomly assigned to the modeling dataset (n=258), and one center was assigned to the external validation set (n=90). Considering a composite outcome of HF hospitalization and death as the primary endpoint and hospitalization due to HF or death as the secondary endpoint, a COX clinical prediction model was constructed and verified using internal and external datasets.ResultsThe median age of patients in the modeling cohort was 63 years old, 41.5% of patients were women; 165 (61%) had a history of HF; 81 (31.4%) were hospitalized for HF; and 39 (15.1%) patients had died. The c-statistic values for composite outcome, hospitalization for HF, and mortality were 0.812, 0.808, and 0.811, respectively. The predictors of death and hospitalization outcomes caused by HF are significantly different. The strongest predictors of HF hospitalization outcomes were advanced age, multiple HF hospitalizations, hyponatremia, high levels of NT-proBNP and hs-cTnT, and larger MVe values. The strongest predictors of mortality were longer dialysis age, combined atrial fibrillation, calcification of the aortic or mitral valve (especially calcification, and in particular aortic valve calcification), pleural effusion, low serum sodium, and higher levels of hs-cTnT. The median age of the patients in the external validation cohort was 63 years old; 28.8% were female; 35 (38.1%) had a history of HF; 11 (12.2%) were hospitalized for HF; and 5 (5.6%) died. The c-statistic of the predictive models for composite outcome, hospitalisation for HF, and mortality was comparable to that of the modelling cohort.ConclusionThe model established in this study is stable and reliable and the included variables are easily obtained from the routine clinical environment. The model can provide useful risk factors and prognostic information for patients with MHD combined with HF. Keywords: heart failure, MHD patients, mortality, predictive model, external validation.
Hox genes modulate physical forces to differentially shape small and large intestinal epithelia
Authors: Gill Hasreet K. , Yin Sifan , Nerurkar Nandan L. , Lawlor John C. , Huycke Tyler R. , Mahadevan L. , Tabin Clifford J. 
Published: March 2023

ABSTRACTThe small and large intestines arise from a common primordial gut tube but ultimately become specialized in both form and function. While the midgut forms villi, the hindgut develops flat, brain-like sulci that resolve into heterogeneous outgrowths. Gut compartment identities are demarcated early in development via Hox genes, which are highly conserved, master regulators of spatial patterning in the embryo. Yet, how these factors trigger regional morphogenesis has remained a mystery. Combining mechanical measurements and mathematical modeling, we demonstrate that the posterior Hox geneHoxd13regulates biophysical phenomena that shape the hindgut lumen. We further show thatHoxd13acts through the TGFβ pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme; together, these features generate hindgut surface patterns. TGFβ, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of genetic identity that direct posterior intestinal morphogenesis.
CRAPS: Chromosomal-Repair-Assisted Pathway Shuffling in yeast
Authors: Dykstra Christien B. , Pyne Michael E. , Martin Vincent J.J. 
Published: March 2023

ABSTRACTA fundamental challenge of metabolic engineering involves assembling and screening vast combinations of orthologous enzymes across a multi-step biochemical pathway. Current pathway assembly workflows involve combining genetic partsex vivoand assembling one pathway configuration per tube or well. Here we present CRAPS,Chromosomal-Repair-AssistedPathwayShuffling, anin vivopathway engineering technique that enables the self-assembly of one pathway configuration per cell. CRAPS leverages the yeast chromosomal repair pathway and utilizes a pool of inactive, chromosomally integrated orthologous gene variants corresponding to a target multi-step pathway. Supplying gRNAs to the CRAPS host activates the expression of one gene variant per pathway step, resulting in a unique pathway configuration in each cell. We deployed CRAPS to build more than 1,000 combinations of a four-step carotenoid biosynthesis network. Sampling the CRAPS pathway space yielded strains with distinct color phenotypes and carotenoid product profiles. We anticipate that CRAPS will expedite strain engineering campaigns by enabling the generation and sampling of vast biochemical spaces.
Comparative mitogenomics of native European and alien Ponto-Caspian amphipods
Authors: Macher Jan-Niklas , Šidagytė-Copilas Eglė , Copilaş-Ciocianu Denis 
Published: March 2023

AbstractEuropean inland surface waters harbor an extensive diversity of native amphipod crustaceans with many species facing threats from invasive counterparts of Ponto-Caspian origin. Herein, we examine mitochondrial genomes to infer phylogenetic relationships and compare gene order and nucleotide composition between representative native European and invasive Ponto-Caspian taxa belonging to five families, ten genera, and 20 species (13 newly sequenced herein). We observe diverse gene rearrangement patterns in the phylogenetically disparate native species pool.Pallaseopsis quadrispinosaandSynurella ambulansshow significant departures from the typical organization, with extensive translocations of tRNAs and the nad1 gene, as well as a tRNA-F polarity switch in the latter. The monophyletic alien Ponto-Caspian gammarids display a conserved gene order, mainly differing from the native species by a tRNA-E and tRNA-R translocation, which strengthens previous findings. However, extensive rearrangement is observed inChaetogammarus warpachowskyiwith translocations of six tRNAs. The alien corophiid,Chelicorophium curvispinum, displays a very conserved gene order despite its distant phylogenetic position. We also find that native species have a significantly higher GC and lower AT content than invasive ones. The observed mitogenomic differences between native and invasive amphipods need further investigation and could shed light on the mechanisms underlying invasion success.
Cysteine: an ancestral Cu binding ligand in green algae?
Authors: Strenkert Daniela , Schmollinger Stefan , Hu Yuntao , Hofmann Christian , Holbrook Kristen , Liu Helen W. , Purvine Samuel O. , Nicora Carrie D. , Chen Si , Lipton Mary S. , Northen Trent R. , Clemens Stephan , Merchant Sabeeha S. 
Published: March 2023

ABSTRACTGrowth ofChlamydomonas reinhardtiiin zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding “first responder” proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ~80-fold, corresponding to ~ 2.8 × 109molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is anin vivoCu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.
«In vitroandin vivocombination of lytic phages and octapeptin OPX10053 against β-lactamase-producing clinical isolates ofKlebsiella pneumoniae»
Authors: Pacios Olga , Blasco Lucia , Bleriot Ines , Fernández-García Laura , López María , Ortiz-Cartagena Concha , Barrio-Pujante Antonio , Fernández Cuenca Felipe , Aracil Belen , Oteo-Iglesias Jesús , Hansford Karl A. , Tomás María 
Published: March 2023

AbstractBackgroundnovel approaches to treatKlebsiella pneumoniaeinfections are desperately needed, such as the use of rationally designed combination therapies.Objectivesto evaluate thein vitroandin vivotherapeutic potential of lytic phages againstK. pneumoniaein combination with octapeptin, a promising class of lipopeptides with broad spectrum Gram-negative activity.Methodswe determined the MICs to twenty-two lipopeptide compounds and chose one octapeptin (OPX10053) for evaluation of potential synergism in combination with lytic phages using checkerboard assays, optical density growth curves and time-kill (CFU enumeration). Toxicity and efficacyin vivoassays were conducted onGalleria mellonellalarvae.Resultsthis study reports the synergy foundin vitrobetween the octapeptin OPX10053 and two lytic phages previously characterized by our research group (vB_KpnM-VAC13 and vB_KpnM-VAC66) against clinical isolates ofK. pneumoniae. This synergy was validated by the FIC index, OD growth curves and time-kill assay when OPX10053 was added following 4 hours of phage exposure. Preliminary evaluation of toxicity revealed that OPX10053, even at subinhibitory concentrations and in phage combinations, exerts a toxic effect on larvae, which requires further investigation.ConclusionsThein vitroapplication of lytic phages in combination with octapeptin OPX10053 showed synergistic activity. Exposure ofG. mellonellato the lytic phages was well tolerated, whereas combination treatment with subinhibitory concentrations of OPX10053 did not attenuate toxicity. Even so, this innovative approach of combining lytic phages could open the door to some interesting associations between chemically synthesized drugs and biological entities. Sequential or simultaneous application alongside time, dosing and stewardship warrants further research.
Shared gene targets of the ATF4 and p53 transcriptional networks
Authors: Baniulyte Gabriele , Durham Serene A. , Merchant Lauren E. , Sammons Morgan A. 
Published: March 2023

AbstractThe master tumor suppressor p53 regulates multiple cell fate decisions, like cell cycle arrest and apoptosis, via transcriptional control of a broad gene network. Dysfunction in the p53 network is common in cancer, often through mutations that inactivate p53 or other members of the pathway. Induction of tumor-specific cell death by restoration of p53 activity without off-target effects has gained significant interest in the field. In this study, we explore the gene regulatory mechanisms underlying a putative anti-cancer strategy involving stimulation of the p53-independent Integrated Stress Response (ISR). Our data demonstrate the p53 and ISR pathways converge to independently regulate common metabolic and pro-apoptotic genes. We investigated the architecture of multiple gene regulatory elements bound by p53 and the ISR effector ATF4 controlling this shared regulation. We identified additional key transcription factors that control basal and stress-induced regulation of these shared p53 and ATF4 target genes. Thus, our results provide significant new molecular and genetic insight into gene regulatory networks and transcription factors that are the target of numerous antitumor therapies.
Cracking the floral quartet code: How do multimers of MIKCC-type MADS-domain transcription factors recognize their target genes?
Authors: Käppel Sandra , Rümpler Florian , Theißen Günter 
Published: March 2023

AbstractMADS-domain transcription factors (MTFs) are involved in the control of many important processes in eukaryotes. They are defined by the presence of a unique and highly conserved DNA-binding domain, the MADS-domain. MTFs bind to double-stranded DNA as dimers and recognize specific sequences termed CArG-boxes (such as 5’-CC(A/T)6GG-3’) and similar sequences that occur hundreds of thousand times in a typical flowering plant genome. The number of MTF-encoding genes increased by about two orders of magnitude during land plant evolution, resulting in roughly about 100 genes in flowering plant genomes. This raises the question as to how dozens of different, but highly similar MTFs accurately recognize thecis-regulatory elements of diverse target genes when the core binding sequence (CArG-box) occurs at such a high frequency. Besides the usual processes, such as base and shape readout of individual DNA sequences by dimers of MTFs, an important sublineage of MTFs in plants, termed MIKCC-type MTFs (MC-MTFs) has evolved an additional mechanism to increase the accurate recognition of target genes: the formation of heterotetramers of closely related proteins that bind to two CArG-boxes on the same DNA strand involving DNA-looping. MC-MTFs control important developmental processes in flowering plants, ranging from root and shoot to flower, fruit and seed development. The way MC-MTFs bind to DNA and select their target genes is hence not only of high biological interest, but also of great agronomic and economic importance. In this article we review the interplay of the different mechanisms of target gene recognition, from the ordinary (base readout) via the extravagant (shape readout) to the idiosyncratic (recognition of the distance and orientation of two CArG-boxes by heterotetramers of MC-MTFs). A special focus of our treatment is on the structural prerequisites of MC-MTFs that enable the specific recognition of target genes.
Distribution ofblaCTX-M-gene variants inE. colifrom different origins in Ecuador
Authors: Valenzuela Xavier , Hedman Hayden , Villagomez Alma , Cardenas Paul , Eisenberg Joseph N. S. , Levy Karen , Zhang Lixin , Trueba Gabriel 
Published: March 2023

ABSTRACTThe increasing abundance of extended spectrum β-lactamase (ESBL) genes inE. coli, and other commensal and pathogenic bacteria, endangers the utility of third or more recent generation cephalosporins, which are major tools for fighting deadly infections. The role of domestic animals in the transmission of ESBL carrying bacteria has been recognized, especially in low- and middle-income countries, however the horizontal gene transfer of these genes is difficult to assess. Here we investigateblaCTX-Mgene diversity (and flanking nucleotide sequences) inE. colifrom chicken and humans, in an Ecuadorian rural community and from chickens in another location in Ecuador. TheblaCTX-Massociated sequences in isolates from humans and chickens in the same remote community showed greater similarity from those found inE. coliin a chicken industrial operation 200 km away. Our study may provide evidence ofblaCTX-Mtransfer between chickens and humans in the community.
Deactivation and Collective Phasic Muscular Tuning for Pointing Direction: Insights from Machine Learning
Authors: Chambellant Florian , Gaveau Jeremie , Papaxanthis Charalambos , Thomas Elizabeth 
Published: March 2023

AbstractArm movements in our daily lives have to be adjusted for several factors in response to the demands of the environment, for example, speed, direction or distance. Previously, we had shown that arm movement kinematics is optimally tuned to take advantage of gravity effects and minimize muscle effort in various pointing directions and gravity contexts (Gaveau et al., 2016). Here we build upon these results and focus on muscular adjustments. We used Machine Learning to analyze the ensemble activities of multiple muscles recorded during pointing in various directions. The advantage of such a technique would be the observation of patterns in collective muscular activity that may not be noticed using univariate statistics. By providing an index of multimuscle activity, the Machine Learning analysis brought to light several features of tuning for pointing direction. In attempting to trace tuning curves, all comparisons were done with respects to pointing in the horizontal, gravity free plane. We demonstrated that tuning for direction does not take place in a uniform fashion but in a modular manner in which some muscle groups play a primary role. The antigravity muscles were more finely tuned to pointing direction than the gravity muscles. Of note, was their tuning during the first half of downward pointing. As the antigravity muscles were deactivated during this phase, it supported the idea that deactivation is not an on-off function but is tuned to pointing direction. Further support for the tuning of the portions of the phasic EMG containing only negative activity was provided by progressively improving classification accuracies with increasing angular distance from the horizontal. Overall, these results show that the motor system tunes muscle commands to exploit gravity effects and reduce muscular effort. It quantitatively demonstrates that phasic EMG negativity is an essential feature of muscle control.
Hyperspectral Oblique Plane Microscopy Enables Spontaneous, Label-Free Imaging of Biological Dynamic Processes in Live Animals
Authors: Guo Ke , Kalyviotis Konstantinos , Pantazis Periklis , Rowlands Christopher J 
Published: March 2023

AbstractSpontaneous Raman imaging has emerged as powerful label-free technique for investigating the molecular composition of biological specimens. Although Raman imaging can facilitate understanding of complex biological phenomenain vivo, current imaging modalities are limited in speed and sample compatibility. Here, we introduce a single-objective light-sheet microscope, namedλ-OPM, which records Raman images on a timescale of minutes to milliseconds. To demonstrate its function, we useλ-OPM to map and identify micro-plastic particles based on their Raman spectral characteristics. In live zebrafish embryos, we show thatλ-OPM can capture wound dynamics at five-minute intervals, revealing rapid changes in cellular and extracellular matrix composition in the wounded region. Finally, we useλ-OPM to obtain Raman scattering maps of a zebrafish embryo’s beating heart at an effective 28 frames per second, recording compositional changes at different points in the cardiac cycle.
Spiny but photogenic: amateur sightings complement herbarium specimens to reveal the bioregions of cacti
Authors: Calvente Alice , da Silva Ana Paula Alves , Edler Daniel , Carvalho Fernanda Antunes , Fantinati Mariana Ramos , Zizka Alexander , Antonelli Alexandre 
Published: March 2023

AbstractPremiseCacti are characteristic elements of the Neotropical flora and of major interest for biogeographic, evolutionary, and ecological studies. Here we test global biogeographic boundaries for Neotropical Cactaceae using specimen-based occurrences coupled with data from visual observations, including citizen science records, as a means to tackle the known collection biases in the family.MethodsSpecies richness and record density were assessed separately for preserved specimens and human observations and a bioregional scheme tailored to Cactaceae was produced using the interactive web application Infomap Bioregions based on data from 261,272 point records cleaned through automated and manual steps.Key ResultsWe find that areas in Mexico and southwestern USA, Eastern Brazil and along the Andean region have the greatest density of records and the highest species richness. Human observations complement information from preserved specimens substantially, especially along the Andes. We propose 24 cacti bioregions, among which the most species-rich are, in decreasing order: northern Mexico/southwestern USA, central Mexico, southern central Mexico, Central America, Mexican Pacific coast, central and southern Andes, northwestern Mexico/extreme southwestern USA, southwestern Bolivia, northeastern Brazil, Mexico/Baja California.ConclusionsThe bioregionalization proposed shows novel or modified biogeographical boundaries specific to cacti, and can thereby aid further evolutionary, biogeographic, and ecological studies by providing a validated framework for further analyses. This classification builds upon, and is distinctive from, other expert-derived regionalization schemes for other taxa. Our results showcase how observation data, including citizen-science records, can complement traditional specimen-based data for biogeographic research, particularly for taxa with specific specimen collection and preservation challenges and those that are threatened or internationally protected.
Single-molecule acceptor rise time (smART) FRET for nanoscale distance sensitivity
Authors: Guo Jiajia , Chen Xuyan , Manna Premashis , Lin Xingcheng , Scott Madelyn N. , Chen Wei Jia , Hoffman Mikaila , Zhang Bin , Schlau-Cohen Gabriela S. 
Published: March 2023

AbstractThe structure, dynamics, and binding of individual biomolecules have been extensively investigated using single-molecule Förster resonance energy transfer (smFRET) as a ‘spectroscopic ruler.’ The FRET efficiency between a fluorophore pair is used to measure distances in the several nanometer range. Existing approaches to detect closer distances come at the expense of sensitivity to longer distances. Here, we introduce single-molecule acceptor rise-time (smART) FRET that spans closer and longer distances. The acceptor rise time encodes the FRET rate, which scales polynomially with distance and thus has a steep dependence that expands the working range by 50%. High precision and accuracy is achieved through the spectroscopic separation between the rise time and the photophysical fluctuations that obfuscate other FRET readouts. Using the nanoscale sensitivity, we resolved the architectures of DNA bound to the single-stranded binding protein fromE. coli, demonstrating the ability of smART FRET to elucidate the complex behaviors of biomolecules.